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Database: UniProt
Entry: P07225
LinkDB: P07225
Original site: P07225 
ID   PROS_HUMAN              Reviewed;         676 AA.
AC   P07225; A8KAC9; D3DN28; Q15518; Q7Z715; Q9UCZ8;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   31-JUL-2019, entry version 232.
DE   RecName: Full=Vitamin K-dependent protein S;
DE   Flags: Precursor;
GN   Name=PROS1; Synonyms=PROS;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND GAMMA-CARBOXYGLUTAMATION AT GLU-47;
RP   GLU-48; GLU-55; GLU-57; GLU-60; GLU-61; GLU-66; GLU-67; GLU-70; GLU-73
RP   AND GLU-77.
RX   PubMed=2820795; DOI=10.1016/0014-5793(87)80217-X;
RA   Ploos van Amstel H.K., van der Zanden A.L., Reitsma P.H.,
RA   Bertina R.M.;
RT   "Human protein S cDNA encodes Phe-16 and Tyr 222 in consensus
RT   sequences for the post-translational processing.";
RL   FEBS Lett. 222:186-190(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3467362; DOI=10.1073/pnas.84.2.349;
RA   Hoskins J., Norman D.K., Beckmann R.J., Long G.L.;
RT   "Cloning and characterization of human liver cDNA encoding a protein S
RT   precursor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:349-353(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2148110; DOI=10.1021/bi00486a010;
RA   Schmidel D.K., Tatro A.V., Phelps L.G., Tomczak J.A., Long G.L.;
RT   "Organization of the human protein S genes.";
RL   Biochemistry 29:7845-7852(1990).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Liver;
RX   PubMed=2148111; DOI=10.1021/bi00486a011;
RA   Ploos van Amstel H.K., Reitsma P.H., der Logt C.P., Bertina R.M.;
RT   "Intron-exon organization of the active human protein S gene PS alpha
RT   and its pseudogene PS beta: duplication and silencing during primate
RT   evolution.";
RL   Biochemistry 29:7853-7861(1990).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Trachea;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   SeattleSNPs variation discovery resource;
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Uterus;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 27-676.
RX   PubMed=2944113; DOI=10.1073/pnas.83.18.6716;
RA   Lundwall A., Dackowski W., Cohen E., Shaffer M., Mahr A., Dahlback B.,
RA   Stenflo J., Wydro R.;
RT   "Isolation and sequence of the cDNA for human protein S, a regulator
RT   of blood coagulation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:6716-6720(1986).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-519, AND VARIANTS THPH5
RP   VAL-381 AND GLY-508.
RX   PubMed=7482398;
RA   Gomez E., Poort S.R., Bertina R.M., Reitsma P.H.;
RT   "Identification of eight point mutations in protein S deficiency type
RT   I -- analysis of 15 pedigrees.";
RL   Thromb. Haemost. 73:750-755(1995).
RN   [11]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-530.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA   Moore R.J., Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [13]
RP   STRUCTURE BY NMR OF 200-286, AND DISULFIDE BONDS.
RX   PubMed=15952784; DOI=10.1021/bi050101f;
RA   Drakenberg T., Ghasriani H., Thulin E., Thamlitz A.M., Muranyi A.,
RA   Annila A., Stenflo J.;
RT   "Solution structure of the Ca2+-binding EGF3-4 pair from vitamin K-
RT   dependent protein S: identification of an unusual fold in EGF3.";
RL   Biochemistry 44:8782-8789(2005).
RN   [14]
RP   VARIANT PRO-501.
RX   PubMed=2143091;
RA   Bertina R.M., Ploos van Amstel H.K., van Wijngaarden A., Coenen J.,
RA   Leemhuis M.P., Deutz-Terlouw P.P., van der Linden I.K., Reitsma P.H.;
RT   "Heerlen polymorphism of protein S, an immunologic polymorphism due to
RT   dimorphism of residue 460.";
RL   Blood 76:538-548(1990).
RN   [15]
RP   VARIANT THPH5 SER-258.
RA   Cooper D.N.;
RL   Unpublished observations (SEP-1993).
RN   [16]
RP   VARIANT THPH5 TOKUSHIMA GLU-196.
RX   PubMed=8298131;
RA   Hayashi T., Nishioka J., Shigekiyo T., Saito S., Suzuki K.;
RT   "Protein S Tokushima: abnormal molecule with a substitution of Glu for
RT   Lys-155 in the second epidermal growth factor-like domain of protein
RT   S.";
RL   Blood 83:683-690(1994).
RN   [17]
RP   VARIANTS THPH5 LEU-40; HIS-41; ALA-67; CYS-72; MET-78; HIS-90;
RP   ASN-144; GLY-245; LYS-249; TRP-265; ARG-265 AND ASN-376, AND VARIANTS
RP   LEU-76 AND VAL-385.
RX   PubMed=7803790;
RA   Gandrille S., Borgel D., Eschwege-Gufflet V., Aillaud M., Dreyfus M.,
RA   Matheron C., Gaussem P., Abgrall J.F., Jude B., Sie P., Toulon P.,
RA   Aiach M.;
RT   "Identification of 15 different candidate causal point mutations and
RT   three polymorphisms in 19 patients with protein S deficiency using a
RT   scanning method for the analysis of the protein S active gene.";
RL   Blood 85:130-138(1995).
RN   [18]
RP   VARIANTS THPH5 SER-258 AND THR-611.
RX   PubMed=7545463;
RA   Formstone C.J., Wacey A.I., Berg L.-P., Rahman S., Bevan D.,
RA   Rowley M., Voke J., Bernardi F., Legnani C., Simioni P., Girolami A.,
RA   Tuddenham E.G.D., Kakkar V.V., Cooper D.N.;
RT   "Detection and characterization of seven novel protein S (PROS) gene
RT   lesions: evaluation of reverse transcript-polymerase chain reaction as
RT   a mutation screening strategy.";
RL   Blood 86:2632-2641(1995).
RN   [19]
RP   VARIANTS THPH5 PRO-351; SER-552; GLN-584 AND PRO-616.
RX   PubMed=7579449;
RA   Mustafa S., Pabinger I., Mannhalter C.;
RT   "Protein S deficiency type I: identification of point mutations in 9
RT   of 10 families.";
RL   Blood 86:3444-3451(1995).
RN   [20]
RP   VARIANT THPH5 SER-644.
RX   PubMed=8977443; DOI=10.1161/01.ATV.16.12.1407;
RA   Li M., Long G.L.;
RT   "Identification of two novel point mutations in the human protein S
RT   gene associated with familial protein S deficiency and thrombosis.";
RL   Arterioscler. Thromb. Vasc. Biol. 16:1407-1415(1996).
RN   [21]
RP   VARIANT THPH5 CYS-515, CHARACTERIZATION OF VARIANT PROS1 DEFICIENCY
RP   CYS-515, AND MUTAGENESIS OF ARG-515.
RX   PubMed=8639833;
RA   Yamazaki T., Katsumi A., Kagami K., Okamoto Y., Sugiura I.,
RA   Hamaguchi M., Kojima T., Takamatsu J., Saito H.;
RT   "Molecular basis of a hereditary type I protein S deficiency caused by
RT   a substitution of Cys for Arg474.";
RL   Blood 87:4643-4650(1996).
RN   [22]
RP   VARIANTS THPH5 TYR-186; THR-611 AND LEU-665.
RX   PubMed=8781426;
RA   Beauchamp N.J., Daly M.E., Cooper P.C., Makris M., Preston F.E.,
RA   Peake I.R.;
RT   "Molecular basis of protein S deficiency in three families also
RT   showing independent inheritance of factor V Leiden.";
RL   Blood 88:1700-1707(1996).
RN   [23]
RP   VARIANTS THPH5 GLU-50; ALA-67; GLU-95; TYR-186; SER-241; PRO-324;
RP   ASP-381; SER-449 AND ARG-666, AND VARIANT PRO-501.
RX   PubMed=8943854;
RG   Protein S study group;
RA   Simmonds R.E., Ireland H., Kunz G., Lane D.A.;
RT   "Identification of 19 protein S gene mutations in patients with
RT   phenotypic protein S deficiency and thrombosis.";
RL   Blood 88:4195-4204(1996).
RN   [24]
RP   VARIANTS THPH5 SER-111; GLY-157; GLY-161; GLU-364; PRO-446; ARG-475;
RP   ALA-501; MET-508; CYS-515; PRO-525; ALA-532; TYR-568; ARG-575 AND
RP   ARG-666, AND VARIANT PRO-501.
RX   PubMed=8765219; DOI=10.1016/S0022-2143(96)90015-3;
RG   The French network on molecular abnormalities responsible for protein C and protein S deficiencies;
RA   Borgel D., Duchemin J., Alhenc-Gelas M., Matheron C., Aiach M.,
RA   Gandrille S.;
RT   "Molecular basis for protein S hereditary deficiency: genetic defects
RT   observed in 118 patients with type I and type IIa deficiencies.";
RL   J. Lab. Clin. Med. 128:218-227(1996).
RN   [25]
RP   VARIANTS THPH5 PRO-300 AND ARG-666.
RX   PubMed=8701404;
RA   Duchemin J., Borg J.-Y., Borgel D., Vasse M., Leveque H., Aiach M.,
RA   Gandrille S.;
RT   "Five novel mutations of the protein S active gene (PROS 1) in 8
RT   Norman families.";
RL   Thromb. Haemost. 75:437-444(1996).
RN   [26]
RP   VARIANT THPH5 PHE-639.
RX   PubMed=9031443;
RA   Bustorff T.C., Freire I., Gago T., Crespo F., David D.;
RT   "Identification of three novel mutations in hereditary protein S
RT   deficiency.";
RL   Thromb. Haemost. 77:21-25(1997).
RN   [27]
RP   VARIANTS THPH5 ASP-68; ARG-95 AND SER-336.
RX   PubMed=9241758;
RG   Plasma coagulation inhibitors subcommittee of the scientific and standardization committee of the international society on thrombosis and haemostasis;
RA   Gandrille S., Borgel D., Ireland H., Lane D.A., Simmonds R.,
RA   Reitsma P.H., Mannhalter C., Pabinger I., Saito H., Suzuki K.,
RA   Formstone C., Cooper D.N., Espinosa Y., Sala N., Bernardi F.,
RA   Aiach M.;
RT   "Protein S deficiency: a database of mutations.";
RL   Thromb. Haemost. 77:1201-1214(1997).
RN   [28]
RP   VARIANTS THPH5 CYS-482; CYS-485 AND GLY-561, AND VARIANTS PRO-501 AND
RP   MET-559.
RX   PubMed=10447256;
RX   DOI=10.1002/(SICI)1098-1004(1999)14:1<30::AID-HUMU4>3.0.CO;2-X;
RA   Espinosa-Parrilla Y., Morell M., Souto J.C., Tirado I.,
RA   Fontcuberta J., Estivill X., Sala N.;
RT   "Protein S gene analysis reveals the presence of a cosegregating
RT   mutation in most pedigrees with type I but not type III PS
RT   deficiency.";
RL   Hum. Mutat. 14:30-39(1999).
RN   [29]
RP   VARIANTS THPH5 ALA-67; GLY-129; PHE-175; PRO-515; LEU-562 AND ASP-638,
RP   AND VARIANTS LEU-76 AND ASP-638.
RX   PubMed=10613647;
RA   Hermida J., Faioni E.M., Mannucci P.M.;
RT   "Poor relationship between phenotypes of protein S deficiency and
RT   mutations in the protein S alpha gene.";
RL   Thromb. Haemost. 82:1634-1638(1999).
RN   [30]
RP   VARIANTS THPH5 TYR-166; GLY-247; THR-611; ARG-622 AND ARG-666.
RX   PubMed=10706858;
RA   Makris M., Leach M., Beauchamp N.J., Daly M.E., Cooper P.C.,
RA   Hampton K.K., Bayliss P., Peake I.R., Miller G.J., Preston F.E.;
RT   "Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis
RT   in families with inherited deficiencies of protein S.";
RL   Blood 95:1935-1941(2000).
RN   [31]
RP   VARIANTS THPH5 HIS-15; THR-640 AND LEU-667, AND VARIANTS SER-98;
RP   LYS-233 AND MET-559.
RX   PubMed=10790208;
RX   DOI=10.1002/(SICI)1098-1004(200005)15:5<463::AID-HUMU8>3.3.CO;2-5;
RA   Espinosa-Parrilla Y., Morell M., Borrell M., Souto J.C.,
RA   Fontcuberta J., Estivill X., Sala N.;
RT   "Optimization of a simple and rapid single-strand conformation
RT   analysis for detection of mutations in the PROS1 gene: identification
RT   of seven novel mutations and three novel, apparently neutral,
RT   variants.";
RL   Hum. Mutat. 15:463-473(2000).
RN   [32]
RP   VARIANTS THPH5 ASN-243 AND PRO-339.
RX   PubMed=11372770; DOI=10.1055/s-2001-14075;
RA   Iwaki T., Mastushita T., Kobayashi T., Yamamoto Y., Nomura Y.,
RA   Kagami K., Nakayama T., Sugiura I., Kojima T., Takamatsu J.,
RA   Kanayama N., Saito H.;
RT   "DNA sequence analysis of protein S deficiency -- identification of
RT   four point mutations in twelve Japanese subjects.";
RL   Semin. Thromb. Hemost. 27:155-160(2001).
RN   [33]
RP   VARIANTS THPH5 CYS-149; ARG-383; LYS-390 AND SER-526.
RX   PubMed=11776305;
RA   Andersen B.D., Bisgaard M.L., Lind B., Philips M., Villoutreix B.O.,
RA   Thorsen S.;
RT   "Characterization and structural impact of five novel PROS1 mutations
RT   in eleven protein S-deficient families.";
RL   Thromb. Haemost. 86:1392-1399(2001).
RN   [34]
RP   VARIANTS THPH5 ASP-52 AND MET-78, AND CHARACTERIZATION OF VARIANTS
RP   THPH5 ASP-52 AND MET-78.
RX   PubMed=12351389; DOI=10.1182/blood-2002-03-0909;
RA   Rezende S.M., Lane D.A., Mille-Baker B., Samama M.M., Conard J.,
RA   Simmonds R.E.;
RT   "Protein S Gla-domain mutations causing impaired Ca(2+)-induced
RT   phospholipid binding and severe functional protein S deficiency.";
RL   Blood 100:2812-2819(2002).
RN   [35]
RP   VARIANTS THPH5 GLU-18; CYS-90; SER-258; VAL-336 AND PRO-664, AND
RP   CHARACTERIZATION OF VARIANTS THPH5 GLU-18; CYS-90; SER-258 VAL-336 AND
RP   PRO-664.
RX   PubMed=11858485;
RA   Rezende S.M., Lane D.A., Zoeller B., Mille-Baker B., Laffan M.,
RA   Dalhbaeck B., Simmonds R.E.;
RT   "Genetic and phenotypic variability between families with hereditary
RT   protein S deficiency.";
RL   Thromb. Haemost. 87:258-265(2002).
RN   [36]
RP   VARIANTS THPH5 ARG-95; GLU-196; ILE-630 AND CYS-636, AND
RP   CHARACTERIZATION OF VARIANTS THPH5 ARG-95; GLU-196; ILE-630 AND
RP   CYS-636.
RX   PubMed=11927129; DOI=10.1016/S0049-3848(02)00015-4;
RA   Tsuda H., Urata M., Tsuda T., Wakiyama M., Iida H., Nakahara M.,
RA   Kinoshita S., Hamasaki N.;
RT   "Four missense mutations identified in the protein S gene of
RT   thrombosis patients with protein S deficiency: effects on secretion
RT   and anticoagulant activity of protein S.";
RL   Thromb. Res. 105:233-239(2002).
RN   [37]
RP   VARIANTS THPH5 CYS-101 AND ASN-144, AND VARIANT SER-168.
RX   PubMed=12632031; DOI=10.1097/00001721-200302000-00012;
RA   Boinot C., Borgel D., Kitzis A., Guicheteau M., Aiach M.,
RA   Alhenc-Gelas M.;
RT   "Familial thrombophilia is an oligogenetic disease: involvement of the
RT   prothrombin G20210A, PROC and PROS gene mutations.";
RL   Blood Coagul. Fibrinolysis 14:191-196(2003).
RN   [38]
RP   VARIANTS THPH5 LEU-87; TYR-121; GLU-196; HIS-355 AND LEU-667.
RX   PubMed=15238143; DOI=10.1111/j.1365-2141.2004.05026.x;
RA   Okada H., Takagi A., Murate T., Adachi T., Yamamoto K., Matsushita T.,
RA   Takamatsu J., Sugita K., Sugimoto M., Yoshioka A., Yamazaki T.,
RA   Saito H., Kojima T.;
RT   "Identification of protein Salpha gene mutations including four novel
RT   mutations in eight unrelated patients with protein S deficiency.";
RL   Br. J. Haematol. 126:219-225(2004).
RN   [39]
RP   VARIANTS THPH5 ALA-67; TYR-88; GLY-129; ASN-144; PHE-175; GLY-204;
RP   CYS-266; SER-267; ASP-336; ARG-357; PRO-446; PRO-515; ASP-521;
RP   LYS-611; ASP-638 AND TYR-639, VARIANTS LEU-76; PRO-501; MET-559;
RP   LEU-562 AND HIS-583, CHARACTERIZATION OF VARIANTS PROS1 DEFICIENCY
RP   ALA-67; TYR-88; GLY-129; PHE-175; GLY-204; CYS-266; SER-267; ASP-336;
RP   ARG-357; PRO-446; PRO-515; ASP-521; LYS-611; ASP-638 AND TYR-639, AND
RP   CHARACTERIZATION OF VARIANTS LEU-76; LEU-562 AND HIS-583.
RX   PubMed=15712227; DOI=10.1002/humu.20136;
RG   Protein S Italian team (PROSIT);
RA   Biguzzi E., Razzari C., Lane D.A., Castaman G., Cappellari A.,
RA   Bucciarelli P., Fontana G., Margaglione M., D'Andrea G.,
RA   Simmonds R.E., Rezende S.M., Preston R., Prisco D., Faioni E.M.;
RT   "Molecular diversity and thrombotic risk in protein S deficiency: the
RT   PROSIT study.";
RL   Hum. Mutat. 25:259-269(2005).
RN   [40]
RP   VARIANT [LARGE SCALE ANALYSIS] GLY-545.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
RN   [41]
RP   CHARACTERIZATION OF VARIANTS THPH5 HIS-15 AND THR-640, AND
RP   CHARACTERIZATION OF VARIANT LYS-233.
RX   PubMed=18322254; DOI=10.3324/haematol.12090;
RA   Hurtado B., Munoz X., Mulero M.C., Navarro G., Domenech P.,
RA   Garcia de Frutos P., Perez-Riba M., Sala N.;
RT   "Functional characterization of twelve natural PROS1 mutations
RT   associated with anticoagulant protein S deficiency.";
RL   Haematologica 93:574-580(2008).
RN   [42]
RP   VARIANT THPH6 CYS-234.
RX   PubMed=20484936; DOI=10.1159/000298282;
RA   Fischer D., Porto L., Stoll H., Geisen C., Schloesser R.L.;
RT   "Intracerebral mass bleeding in a term neonate: manifestation of
RT   hereditary protein S deficiency with a new mutation in the PROS1
RT   gene.";
RL   Neonatology 98:337-340(2010).
RN   [43]
RP   VARIANT LYS-233.
RX   PubMed=27535533; DOI=10.1038/nature19057;
RG   Exome Aggregation Consortium;
RA   Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E.,
RA   Fennell T., O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B.,
RA   Tukiainen T., Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K.,
RA   Zhao F., Zou J., Pierce-Hoffman E., Berghout J., Cooper D.N.,
RA   Deflaux N., DePristo M., Do R., Flannick J., Fromer M., Gauthier L.,
RA   Goldstein J., Gupta N., Howrigan D., Kiezun A., Kurki M.I.,
RA   Moonshine A.L., Natarajan P., Orozco L., Peloso G.M., Poplin R.,
RA   Rivas M.A., Ruano-Rubio V., Rose S.A., Ruderfer D.M., Shakir K.,
RA   Stenson P.D., Stevens C., Thomas B.P., Tiao G., Tusie-Luna M.T.,
RA   Weisburd B., Won H.H., Yu D., Altshuler D.M., Ardissino D.,
RA   Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA   Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S.,
RA   Laakso M., McCarroll S., McCarthy M.I., McGovern D., McPherson R.,
RA   Neale B.M., Palotie A., Purcell S.M., Saleheen D., Scharf J.M.,
RA   Sklar P., Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C.,
RA   Wilson J.G., Daly M.J., MacArthur D.G.;
RT   "Analysis of protein-coding genetic variation in 60,706 humans.";
RL   Nature 536:285-291(2016).
CC   -!- FUNCTION: Anticoagulant plasma protein; it is a cofactor to
CC       activated protein C in the degradation of coagulation factors Va
CC       and VIIIa. It helps to prevent coagulation and stimulating
CC       fibrinolysis.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Plasma.
CC   -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of
CC       aspartate and asparagine is (R) stereospecific within EGF domains.
CC       {ECO:0000250}.
CC   -!- DISEASE: Thrombophilia due to protein S deficiency, autosomal
CC       dominant (THPH5) [MIM:612336]: A hemostatic disorder characterized
CC       by impaired regulation of blood coagulation and a tendency to
CC       recurrent venous thrombosis. Based on the plasma levels of total
CC       and free PROS1 as well as the serine protease-activated protein C
CC       cofactor activity, three types of THPH5 have been described: type
CC       I, characterized by reduced total and free PROS1 levels together
CC       with reduced anticoagulant activity; type III, in which only free
CC       PROS1 antigen and PROS1 activity levels are reduced; and the rare
CC       type II which is characterized by normal concentrations of both
CC       total and free PROS1 antigen, but low cofactor activity.
CC       {ECO:0000269|PubMed:10447256, ECO:0000269|PubMed:10613647,
CC       ECO:0000269|PubMed:10706858, ECO:0000269|PubMed:10790208,
CC       ECO:0000269|PubMed:11372770, ECO:0000269|PubMed:11776305,
CC       ECO:0000269|PubMed:11858485, ECO:0000269|PubMed:11927129,
CC       ECO:0000269|PubMed:12351389, ECO:0000269|PubMed:12632031,
CC       ECO:0000269|PubMed:15238143, ECO:0000269|PubMed:15712227,
CC       ECO:0000269|PubMed:18322254, ECO:0000269|PubMed:7482398,
CC       ECO:0000269|PubMed:7545463, ECO:0000269|PubMed:7579449,
CC       ECO:0000269|PubMed:7803790, ECO:0000269|PubMed:8298131,
CC       ECO:0000269|PubMed:8639833, ECO:0000269|PubMed:8701404,
CC       ECO:0000269|PubMed:8765219, ECO:0000269|PubMed:8781426,
CC       ECO:0000269|PubMed:8943854, ECO:0000269|PubMed:8977443,
CC       ECO:0000269|PubMed:9031443, ECO:0000269|PubMed:9241758,
CC       ECO:0000269|Ref.15}. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Thrombophilia due to protein S deficiency, autosomal
CC       recessive (THPH6) [MIM:614514]: A very rare and severe hematologic
CC       disorder resulting in thrombosis and secondary hemorrhage usually
CC       beginning in early infancy. Some affected individuals develop
CC       neonatal purpura fulminans, multifocal thrombosis, or intracranial
CC       hemorrhage. {ECO:0000269|PubMed:20484936}. Note=The disease is
CC       caused by mutations affecting the gene represented in this entry.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAP45054.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/pros1/";
DR   EMBL; Y00692; CAA68687.1; -; mRNA.
DR   EMBL; Y00692; CAA68688.1; ALT_SEQ; mRNA.
DR   EMBL; M15036; AAA36479.1; -; mRNA.
DR   EMBL; M57853; AAA60357.1; -; Genomic_DNA.
DR   EMBL; M57840; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57841; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57842; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57844; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57845; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57846; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57847; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57848; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57849; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57850; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57851; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; M57852; AAA60357.1; JOINED; Genomic_DNA.
DR   EMBL; AH002948; AAA60180.1; -; Genomic_DNA.
DR   EMBL; AK292994; BAF85683.1; -; mRNA.
DR   EMBL; AY308744; AAP45054.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; CH471052; EAW79903.1; -; Genomic_DNA.
DR   EMBL; CH471052; EAW79905.1; -; Genomic_DNA.
DR   EMBL; BC015801; AAH15801.1; -; mRNA.
DR   CCDS; CCDS2923.1; -.
DR   PIR; A35610; KXHUS.
DR   RefSeq; NP_000304.2; NM_000313.3.
DR   RefSeq; NP_001301006.1; NM_001314077.1.
DR   PDB; 1Z6C; NMR; -; A=200-286.
DR   PDBsum; 1Z6C; -.
DR   SMR; P07225; -.
DR   BioGrid; 111611; 18.
DR   IntAct; P07225; 4.
DR   STRING; 9606.ENSP00000377783; -.
DR   DrugBank; DB00055; Drotrecogin alfa.
DR   DrugBank; DB00170; Menadione.
DR   DrugBank; DB00464; Sodium Tetradecyl Sulfate.
DR   GlyConnect; 2090; -.
DR   iPTMnet; P07225; -.
DR   PhosphoSitePlus; P07225; -.
DR   BioMuta; PROS1; -.
DR   DMDM; 131086; -.
DR   CPTAC; non-CPTAC-2705; -.
DR   EPD; P07225; -.
DR   jPOST; P07225; -.
DR   MaxQB; P07225; -.
DR   PaxDb; P07225; -.
DR   PeptideAtlas; P07225; -.
DR   PRIDE; P07225; -.
DR   ProteomicsDB; 51975; -.
DR   ABCD; P07225; -.
DR   DNASU; 5627; -.
DR   Ensembl; ENST00000348974; ENSP00000330021; ENSG00000184500.
DR   Ensembl; ENST00000394236; ENSP00000377783; ENSG00000184500.
DR   GeneID; 5627; -.
DR   KEGG; hsa:5627; -.
DR   UCSC; uc003drb.5; human.
DR   CTD; 5627; -.
DR   DisGeNET; 5627; -.
DR   GeneCards; PROS1; -.
DR   HGNC; HGNC:9456; PROS1.
DR   HPA; HPA007724; -.
DR   HPA; HPA023974; -.
DR   MalaCards; PROS1; -.
DR   MIM; 176880; gene.
DR   MIM; 612336; phenotype.
DR   MIM; 614514; phenotype.
DR   neXtProt; NX_P07225; -.
DR   OpenTargets; ENSG00000184500; -.
DR   Orphanet; 64738; NON RARE IN EUROPE: Non rare thrombophilia.
DR   Orphanet; 743; Severe hereditary thrombophilia due to congenital protein S deficiency.
DR   PharmGKB; PA33809; -.
DR   eggNOG; ENOG410IGF6; Eukaryota.
DR   eggNOG; ENOG410ZTGU; LUCA.
DR   GeneTree; ENSGT00940000154035; -.
DR   HOGENOM; HOG000065758; -.
DR   InParanoid; P07225; -.
DR   KO; K03908; -.
DR   OMA; YPKYLGC; -.
DR   OrthoDB; 317733at2759; -.
DR   PhylomeDB; P07225; -.
DR   TreeFam; TF352157; -.
DR   Reactome; R-HSA-114608; Platelet degranulation.
DR   Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation.
DR   Reactome; R-HSA-159740; Gamma-carboxylation of protein precursors.
DR   Reactome; R-HSA-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
DR   Reactome; R-HSA-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins.
DR   Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR   Reactome; R-HSA-977606; Regulation of Complement cascade.
DR   SIGNOR; P07225; -.
DR   ChiTaRS; PROS1; human.
DR   EvolutionaryTrace; P07225; -.
DR   GeneWiki; Protein_S; -.
DR   GenomeRNAi; 5627; -.
DR   PRO; PR:P07225; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Bgee; ENSG00000184500; Expressed in 227 organ(s), highest expression level in choroid plexus epithelium.
DR   ExpressionAtlas; P07225; baseline and differential.
DR   Genevisible; P07225; HS.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR   GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR   GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; TAS:Reactome.
DR   GO; GO:0042730; P:fibrinolysis; IEA:UniProtKB-KW.
DR   GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR   GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR   GO; GO:0030449; P:regulation of complement activation; TAS:Reactome.
DR   Gene3D; 4.10.740.10; -; 1.
DR   InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
DR   InterPro; IPR013320; ConA-like_dom_sf.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR   InterPro; IPR018097; EGF_Ca-bd_CS.
DR   InterPro; IPR035972; GLA-like_dom_SF.
DR   InterPro; IPR000294; GLA_domain.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR001791; Laminin_G.
DR   InterPro; IPR033189; PROS1.
DR   PANTHER; PTHR24040:SF10; PTHR24040:SF10; 1.
DR   Pfam; PF00008; EGF; 1.
DR   Pfam; PF07645; EGF_CA; 2.
DR   Pfam; PF00594; Gla; 1.
DR   Pfam; PF00054; Laminin_G_1; 1.
DR   Pfam; PF02210; Laminin_G_2; 1.
DR   PRINTS; PR00001; GLABLOOD.
DR   SMART; SM00181; EGF; 4.
DR   SMART; SM00179; EGF_CA; 4.
DR   SMART; SM00069; GLA; 1.
DR   SMART; SM00282; LamG; 2.
DR   SUPFAM; SSF49899; SSF49899; 2.
DR   SUPFAM; SSF57184; SSF57184; 1.
DR   SUPFAM; SSF57630; SSF57630; 1.
DR   PROSITE; PS00010; ASX_HYDROXYL; 4.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 3.
DR   PROSITE; PS50026; EGF_3; 4.
DR   PROSITE; PS01187; EGF_CA; 3.
DR   PROSITE; PS00011; GLA_1; 1.
DR   PROSITE; PS50998; GLA_2; 1.
DR   PROSITE; PS50025; LAM_G_DOMAIN; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Blood coagulation; Calcium;
KW   Cleavage on pair of basic residues; Complete proteome;
KW   Disease mutation; Disulfide bond; EGF-like domain; Fibrinolysis;
KW   Gamma-carboxyglutamic acid; Glycoprotein; Hemostasis; Hydroxylation;
KW   Polymorphism; Reference proteome; Repeat; Secreted; Signal;
KW   Thrombophilia; Zymogen.
FT   SIGNAL        1     24
FT   PROPEP       25     41
FT                                /FTId=PRO_0000022119.
FT   CHAIN        42    676       Vitamin K-dependent protein S.
FT                                /FTId=PRO_0000022120.
FT   DOMAIN       42     87       Gla. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   DOMAIN      117    155       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      157    200       EGF-like 2; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      201    242       EGF-like 3; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      243    283       EGF-like 4; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      299    475       Laminin G-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00122}.
FT   DOMAIN      484    666       Laminin G-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00122}.
FT   REGION       88    116       Thrombin-sensitive.
FT   SITE        499    499       Not glycosylated; in variant Heerlen.
FT   MOD_RES      47     47       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      48     48       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      55     55       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      57     57       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      60     60       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      61     61       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      66     66       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      67     67       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      70     70       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      73     73       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES      77     77       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:2820795}.
FT   MOD_RES     136    136       (3R)-3-hydroxyaspartate. {ECO:0000250}.
FT   CARBOHYD    499    499       N-linked (GlcNAc...) asparagine.
FT   CARBOHYD    509    509       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    530    530       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:16335952}.
FT   DISULFID     58     63       {ECO:0000250}.
FT   DISULFID    121    134       {ECO:0000250}.
FT   DISULFID    126    143       {ECO:0000250}.
FT   DISULFID    145    154       {ECO:0000250}.
FT   DISULFID    161    175       {ECO:0000250}.
FT   DISULFID    171    184       {ECO:0000250}.
FT   DISULFID    186    199       {ECO:0000250}.
FT   DISULFID    205    217       {ECO:0000269|PubMed:15952784}.
FT   DISULFID    212    226       {ECO:0000269|PubMed:15952784}.
FT   DISULFID    228    241       {ECO:0000269|PubMed:15952784}.
FT   DISULFID    247    256       {ECO:0000269|PubMed:15952784}.
FT   DISULFID    252    265       {ECO:0000269|PubMed:15952784}.
FT   DISULFID    267    282       {ECO:0000269|PubMed:15952784}.
FT   DISULFID    449    475       {ECO:0000250}.
FT   DISULFID    639    666       {ECO:0000250}.
FT   VARIANT      15     15       L -> H (in THPH5; reduced mutant protein
FT                                levels and secretion).
FT                                {ECO:0000269|PubMed:10790208,
FT                                ECO:0000269|PubMed:18322254}.
FT                                /FTId=VAR_046802.
FT   VARIANT      18     18       V -> E (in THPH5; expresses very low/
FT                                undetectable PROS1 levels compared to
FT                                wild-type; has impaired secretion;
FT                                intracellular degradation of unsecreted
FT                                material is found).
FT                                {ECO:0000269|PubMed:11858485}.
FT                                /FTId=VAR_046803.
FT   VARIANT      40     40       R -> L (in THPH5; dbSNP:rs7614835).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046804.
FT   VARIANT      41     41       R -> H (in THPH5; dbSNP:rs963668412).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046805.
FT   VARIANT      50     50       K -> E (in THPH5; dbSNP:rs748630360).
FT                                {ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046806.
FT   VARIANT      52     52       G -> D (in THPH5; does not affect PROS1
FT                                production but results in 15.2-fold
FT                                reduced PROS1 activity; has 5.4 fold
FT                                reduced affinity for anionic phospholipid
FT                                vesicles (P < 0.0001) and decreased
FT                                affinity for an antibody specific for the
FT                                Ca(2+)-dependent conformation of the
FT                                PROS1 Gla domain).
FT                                {ECO:0000269|PubMed:12351389}.
FT                                /FTId=VAR_046807.
FT   VARIANT      67     67       E -> A (in THPH5; dbSNP:rs766423432).
FT                                {ECO:0000269|PubMed:10613647,
FT                                ECO:0000269|PubMed:15712227,
FT                                ECO:0000269|PubMed:7803790,
FT                                ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046808.
FT   VARIANT      68     68       A -> D (in THPH5).
FT                                {ECO:0000269|PubMed:9241758}.
FT                                /FTId=VAR_046809.
FT   VARIANT      72     72       F -> C (in THPH5).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046810.
FT   VARIANT      76     76       P -> L (in dbSNP:rs73846070).
FT                                {ECO:0000269|PubMed:10613647,
FT                                ECO:0000269|PubMed:15712227,
FT                                ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046811.
FT   VARIANT      78     78       T -> M (in THPH5; reduces expression of
FT                                PROS1 by 33.2% (P < 0.001) and activity
FT                                by 3.6-fold; has only a modest 1.5-fold
FT                                (P < 0.001) reduced affinity for
FT                                phospholipid and an antibody specific for
FT                                the Ca(2+)-dependent conformation of the
FT                                PROS1 Gla domain; dbSNP:rs6122).
FT                                {ECO:0000269|PubMed:12351389,
FT                                ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_014666.
FT   VARIANT      87     87       V -> L (in THPH5; dbSNP:rs557733421).
FT                                {ECO:0000269|PubMed:15238143}.
FT                                /FTId=VAR_046812.
FT   VARIANT      88     88       C -> Y (in THPH5).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046813.
FT   VARIANT      90     90       R -> C (in THPH5; produces around 50% of
FT                                PROS1 levels compared to wild-type; has
FT                                impaired secretion; intracellular
FT                                degradation of unsecreted material is
FT                                found; dbSNP:rs765935815).
FT                                {ECO:0000269|PubMed:11858485}.
FT                                /FTId=VAR_046814.
FT   VARIANT      90     90       R -> H (in THPH5; dbSNP:rs200886866).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046815.
FT   VARIANT      95     95       G -> E (in THPH5; dbSNP:rs144526169).
FT                                {ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046816.
FT   VARIANT      95     95       G -> R (in THPH5; the activated protein
FT                                cofactor activity is inhibited by C4BPB
FT                                with a dose dependency similar to that of
FT                                wild-type PROS1).
FT                                {ECO:0000269|PubMed:11927129,
FT                                ECO:0000269|PubMed:9241758}.
FT                                /FTId=VAR_046817.
FT   VARIANT      98     98       T -> S (in dbSNP:rs142805170).
FT                                {ECO:0000269|PubMed:10790208}.
FT                                /FTId=VAR_046818.
FT   VARIANT     101    101       R -> C (in THPH5; dbSNP:rs778731080).
FT                                {ECO:0000269|PubMed:12632031}.
FT                                /FTId=VAR_046819.
FT   VARIANT     111    111       R -> S (in THPH5).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046820.
FT   VARIANT     121    121       C -> Y (in THPH5).
FT                                {ECO:0000269|PubMed:15238143}.
FT                                /FTId=VAR_046821.
FT   VARIANT     129    129       D -> G (in THPH5; dbSNP:rs749024073).
FT                                {ECO:0000269|PubMed:10613647,
FT                                ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046822.
FT   VARIANT     144    144       T -> N (in THPH5; dbSNP:rs146366248).
FT                                {ECO:0000269|PubMed:12632031,
FT                                ECO:0000269|PubMed:15712227,
FT                                ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046823.
FT   VARIANT     149    149       W -> C (in THPH5).
FT                                {ECO:0000269|PubMed:11776305}.
FT                                /FTId=VAR_046824.
FT   VARIANT     157    157       D -> G (in THPH5; dbSNP:rs751090951).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046825.
FT   VARIANT     161    161       C -> G (in THPH5).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046826.
FT   VARIANT     166    166       N -> Y (in THPH5).
FT                                {ECO:0000269|PubMed:10706858}.
FT                                /FTId=VAR_046827.
FT   VARIANT     168    168       N -> S (in dbSNP:rs144430063).
FT                                {ECO:0000269|PubMed:12632031}.
FT                                /FTId=VAR_046828.
FT   VARIANT     175    175       C -> F (in THPH5).
FT                                {ECO:0000269|PubMed:10613647,
FT                                ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046829.
FT   VARIANT     186    186       C -> Y (in THPH5; dbSNP:rs779391826).
FT                                {ECO:0000269|PubMed:8781426,
FT                                ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046830.
FT   VARIANT     196    196       K -> E (in THPH5; Tokushima; the specific
FT                                activity decreases to 58% of that of the
FT                                wild-type PROS1; the activated protein
FT                                cofactor activity is inhibited by C4BPB
FT                                with a dose dependency similar to that of
FT                                wild-type PROS1; dbSNP:rs121918474).
FT                                {ECO:0000269|PubMed:11927129,
FT                                ECO:0000269|PubMed:15238143,
FT                                ECO:0000269|PubMed:8298131}.
FT                                /FTId=VAR_005566.
FT   VARIANT     204    204       E -> G (in THPH5).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046831.
FT   VARIANT     233    233       R -> K (neutral polymorphism; does not
FT                                affect protein levels; the mutant is
FT                                normally secreted; dbSNP:rs41267007).
FT                                {ECO:0000269|PubMed:10790208,
FT                                ECO:0000269|PubMed:18322254,
FT                                ECO:0000269|PubMed:27535533}.
FT                                /FTId=VAR_046832.
FT   VARIANT     234    234       Y -> C (in THPH6; dbSNP:rs387906675).
FT                                {ECO:0000269|PubMed:20484936}.
FT                                /FTId=VAR_067302.
FT   VARIANT     241    241       C -> S (in THPH5).
FT                                {ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046833.
FT   VARIANT     243    243       D -> N (in THPH5).
FT                                {ECO:0000269|PubMed:11372770}.
FT                                /FTId=VAR_046834.
FT   VARIANT     245    245       D -> G (in THPH5; dbSNP:rs1211117206).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046835.
FT   VARIANT     247    247       C -> G (in THPH5).
FT                                {ECO:0000269|PubMed:10706858}.
FT                                /FTId=VAR_046836.
FT   VARIANT     249    249       E -> K (in THPH5; dbSNP:rs1455675811).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046837.
FT   VARIANT     258    258       N -> S (in THPH5; produces around 30% of
FT                                PROS1 levels compared to wild-type; has
FT                                impaired secretion; intracellular
FT                                degradation of unsecreted material is
FT                                found; dbSNP:rs121918473).
FT                                {ECO:0000269|PubMed:11858485,
FT                                ECO:0000269|PubMed:7545463,
FT                                ECO:0000269|Ref.15}.
FT                                /FTId=VAR_005567.
FT   VARIANT     265    265       C -> R (in THPH5).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046838.
FT   VARIANT     265    265       C -> W (in THPH5).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046839.
FT   VARIANT     266    266       Y -> C (in THPH5; dbSNP:rs777616039).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046840.
FT   VARIANT     267    267       C -> S (in THPH5).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046841.
FT   VARIANT     300    300       L -> P (in THPH5).
FT                                {ECO:0000269|PubMed:8701404}.
FT                                /FTId=VAR_046842.
FT   VARIANT     324    324       S -> P (in THPH5).
FT                                {ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046843.
FT   VARIANT     336    336       G -> D (in THPH5).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046844.
FT   VARIANT     336    336       G -> S (in THPH5).
FT                                {ECO:0000269|PubMed:9241758}.
FT                                /FTId=VAR_046845.
FT   VARIANT     336    336       G -> V (in THPH5; expresses very low/
FT                                undetectable PROS1 levels compared to
FT                                wild-type; has impaired secretion;
FT                                intracellular degradation of unsecreted
FT                                material is found).
FT                                {ECO:0000269|PubMed:11858485}.
FT                                /FTId=VAR_046846.
FT   VARIANT     339    339       L -> P (in THPH5).
FT                                {ECO:0000269|PubMed:11372770}.
FT                                /FTId=VAR_046847.
FT   VARIANT     351    351       L -> P (in THPH5).
FT                                {ECO:0000269|PubMed:7579449}.
FT                                /FTId=VAR_046848.
FT   VARIANT     355    355       R -> H (in THPH5; dbSNP:rs780863931).
FT                                {ECO:0000269|PubMed:15238143}.
FT                                /FTId=VAR_046849.
FT   VARIANT     357    357       G -> R (in THPH5; dbSNP:rs941433523).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046850.
FT   VARIANT     364    364       K -> E (in THPH5).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046851.
FT   VARIANT     376    376       D -> N (in THPH5).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046852.
FT   VARIANT     381    381       G -> D (in THPH5; dbSNP:rs1223579199).
FT                                {ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046853.
FT   VARIANT     381    381       G -> V (in THPH5).
FT                                {ECO:0000269|PubMed:7482398}.
FT                                /FTId=VAR_046854.
FT   VARIANT     383    383       W -> R (in THPH5).
FT                                {ECO:0000269|PubMed:11776305}.
FT                                /FTId=VAR_046855.
FT   VARIANT     385    385       M -> V (in dbSNP:rs767653920).
FT                                {ECO:0000269|PubMed:7803790}.
FT                                /FTId=VAR_046856.
FT   VARIANT     390    390       E -> K (in THPH5).
FT                                {ECO:0000269|PubMed:11776305}.
FT                                /FTId=VAR_046857.
FT   VARIANT     446    446       L -> P (in THPH5).
FT                                {ECO:0000269|PubMed:15712227,
FT                                ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046858.
FT   VARIANT     449    449       C -> S (in THPH5).
FT                                {ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046859.
FT   VARIANT     475    475       C -> R (in THPH5).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046860.
FT   VARIANT     482    482       G -> C (in THPH5).
FT                                {ECO:0000269|PubMed:10447256}.
FT                                /FTId=VAR_014116.
FT   VARIANT     485    485       Y -> C (in THPH5; dbSNP:rs1323663956).
FT                                {ECO:0000269|PubMed:10447256}.
FT                                /FTId=VAR_014117.
FT   VARIANT     501    501       S -> A (in THPH5; dbSNP:rs121918472).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046862.
FT   VARIANT     501    501       S -> P (variant Heerlen; could be
FT                                associated with THPH5;
FT                                dbSNP:rs121918472).
FT                                {ECO:0000269|PubMed:10447256,
FT                                ECO:0000269|PubMed:15712227,
FT                                ECO:0000269|PubMed:2143091,
FT                                ECO:0000269|PubMed:8765219,
FT                                ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_005568.
FT   VARIANT     508    508       V -> G (in THPH5).
FT                                {ECO:0000269|PubMed:7482398}.
FT                                /FTId=VAR_046863.
FT   VARIANT     508    508       V -> M (in THPH5).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046864.
FT   VARIANT     515    515       R -> C (in THPH5; secretion of the mutant
FT                                markedly decreased compared with that of
FT                                the wild-type; intracellular degradation
FT                                and impaired secretion of the mutant;
FT                                dbSNP:rs199469500).
FT                                {ECO:0000269|PubMed:8639833,
FT                                ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046865.
FT   VARIANT     515    515       R -> P (in THPH5).
FT                                {ECO:0000269|PubMed:10613647,
FT                                ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046866.
FT   VARIANT     521    521       G -> D (in THPH5).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046867.
FT   VARIANT     525    525       A -> P (in THPH5).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046868.
FT   VARIANT     526    526       L -> S (in THPH5).
FT                                {ECO:0000269|PubMed:11776305}.
FT                                /FTId=VAR_046869.
FT   VARIANT     532    532       T -> A (in THPH5; dbSNP:rs371028997).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046870.
FT   VARIANT     545    545       E -> G (in a colorectal cancer sample;
FT                                somatic mutation; dbSNP:rs1396452003).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035981.
FT   VARIANT     552    552       L -> S (in THPH5).
FT                                {ECO:0000269|PubMed:7579449}.
FT                                /FTId=VAR_046871.
FT   VARIANT     559    559       I -> M (in dbSNP:rs184798444).
FT                                {ECO:0000269|PubMed:10447256,
FT                                ECO:0000269|PubMed:10790208,
FT                                ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_014118.
FT   VARIANT     561    561       R -> G (in THPH5; dbSNP:rs121918476).
FT                                {ECO:0000269|PubMed:10447256}.
FT                                /FTId=VAR_014119.
FT   VARIANT     562    562       I -> L (in THPH5; unknown pathological
FT                                significance; dbSNP:rs1380889353).
FT                                {ECO:0000269|PubMed:10613647,
FT                                ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046872.
FT   VARIANT     568    568       C -> Y (in THPH5).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046873.
FT   VARIANT     575    575       L -> R (in THPH5).
FT                                {ECO:0000269|PubMed:8765219}.
FT                                /FTId=VAR_046874.
FT   VARIANT     583    583       N -> H (in dbSNP:rs139479630).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046875.
FT   VARIANT     584    584       L -> Q (in THPH5).
FT                                {ECO:0000269|PubMed:7579449}.
FT                                /FTId=VAR_046876.
FT   VARIANT     611    611       M -> K (in THPH5).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046877.
FT   VARIANT     611    611       M -> T (in THPH5; dbSNP:rs750531364).
FT                                {ECO:0000269|PubMed:10706858,
FT                                ECO:0000269|PubMed:7545463,
FT                                ECO:0000269|PubMed:8781426}.
FT                                /FTId=VAR_046878.
FT   VARIANT     616    616       A -> P (in THPH5).
FT                                {ECO:0000269|PubMed:7579449}.
FT                                /FTId=VAR_046879.
FT   VARIANT     622    622       L -> R (in THPH5).
FT                                {ECO:0000269|PubMed:10706858}.
FT                                /FTId=VAR_046880.
FT   VARIANT     630    630       T -> I (in THPH5; the activated protein
FT                                cofactor activity is inhibited by C4BPB
FT                                with a dose dependency similar to that of
FT                                wild-type PROS1; dbSNP:rs202190731).
FT                                {ECO:0000269|PubMed:11927129}.
FT                                /FTId=VAR_046881.
FT   VARIANT     636    636       Y -> C (in THPH5; shows intracellular
FT                                degradation and decreased secretion;
FT                                dbSNP:rs368173480).
FT                                {ECO:0000269|PubMed:11927129}.
FT                                /FTId=VAR_046882.
FT   VARIANT     638    638       G -> D (in THPH5).
FT                                {ECO:0000269|PubMed:10613647,
FT                                ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046883.
FT   VARIANT     639    639       C -> F (in THPH5).
FT                                {ECO:0000269|PubMed:9031443}.
FT                                /FTId=VAR_046884.
FT   VARIANT     639    639       C -> Y (in THPH5).
FT                                {ECO:0000269|PubMed:15712227}.
FT                                /FTId=VAR_046885.
FT   VARIANT     640    640       M -> T (in THPH5; does not affect protein
FT                                levels; the mutant is secreted at lower
FT                                levels compared to wild-type).
FT                                {ECO:0000269|PubMed:10790208,
FT                                ECO:0000269|PubMed:18322254}.
FT                                /FTId=VAR_046886.
FT   VARIANT     644    644       I -> S (in THPH5).
FT                                {ECO:0000269|PubMed:8977443}.
FT                                /FTId=VAR_046887.
FT   VARIANT     664    664       H -> P (in THPH5; expresses very low/
FT                                undetectable PROS1 levels compared to
FT                                wild-type; has impaired secretion;
FT                                intracellular degradation of unsecreted
FT                                material is found).
FT                                {ECO:0000269|PubMed:11858485}.
FT                                /FTId=VAR_046888.
FT   VARIANT     665    665       S -> L (in THPH5; dbSNP:rs778685576).
FT                                {ECO:0000269|PubMed:8781426}.
FT                                /FTId=VAR_046889.
FT   VARIANT     666    666       C -> R (in THPH5; dbSNP:rs1302089144).
FT                                {ECO:0000269|PubMed:10706858,
FT                                ECO:0000269|PubMed:8701404,
FT                                ECO:0000269|PubMed:8765219,
FT                                ECO:0000269|PubMed:8943854}.
FT                                /FTId=VAR_046890.
FT   VARIANT     667    667       P -> L (in THPH5; dbSNP:rs1220553873).
FT                                {ECO:0000269|PubMed:10790208,
FT                                ECO:0000269|PubMed:15238143}.
FT                                /FTId=VAR_046891.
FT   MUTAGEN     515    515       R->A,E: Markedly reduced secretion of the
FT                                mutant. {ECO:0000269|PubMed:8639833}.
FT   MUTAGEN     515    515       R->K: No change in secretion of the
FT                                mutant. {ECO:0000269|PubMed:8639833}.
FT   CONFLICT     11     11       L -> P (in Ref. 2; AAA36479).
FT                                {ECO:0000305}.
FT   CONFLICT     26     26       F -> L (in Ref. 2; AAA36479).
FT                                {ECO:0000305}.
FT   STRAND      204    212       {ECO:0000244|PDB:1Z6C}.
FT   STRAND      227    229       {ECO:0000244|PDB:1Z6C}.
FT   STRAND      233    235       {ECO:0000244|PDB:1Z6C}.
FT   TURN        236    239       {ECO:0000244|PDB:1Z6C}.
FT   STRAND      240    242       {ECO:0000244|PDB:1Z6C}.
FT   HELIX       246    249       {ECO:0000244|PDB:1Z6C}.
FT   STRAND      253    256       {ECO:0000244|PDB:1Z6C}.
FT   STRAND      260    262       {ECO:0000244|PDB:1Z6C}.
FT   STRAND      269    271       {ECO:0000244|PDB:1Z6C}.
FT   STRAND      279    281       {ECO:0000244|PDB:1Z6C}.
SQ   SEQUENCE   676 AA;  75123 MW;  2B88A04F85403F25 CRC64;
     MRVLGGRCGA LLACLLLVLP VSEANFLSKQ QASQVLVRKR RANSLLEETK QGNLERECIE
     ELCNKEEARE VFENDPETDY FYPKYLVCLR SFQTGLFTAA RQSTNAYPDL RSCVNAIPDQ
     CSPLPCNEDG YMSCKDGKAS FTCTCKPGWQ GEKCEFDINE CKDPSNINGG CSQICDNTPG
     SYHCSCKNGF VMLSNKKDCK DVDECSLKPS ICGTAVCKNI PGDFECECPE GYRYNLKSKS
     CEDIDECSEN MCAQLCVNYP GGYTCYCDGK KGFKLAQDQK SCEVVSVCLP LNLDTKYELL
     YLAEQFAGVV LYLKFRLPEI SRFSAEFDFR TYDSEGVILY AESIDHSAWL LIALRGGKIE
     VQLKNEHTSK ITTGGDVINN GLWNMVSVEE LEHSISIKIA KEAVMDINKP GPLFKPENGL
     LETKVYFAGF PRKVESELIK PINPRLDGCI RSWNLMKQGA SGIKEIIQEK QNKHCLVTVE
     KGSYYPGSGI AQFHIDYNNV SSAEGWHVNV TLNIRPSTGT GVMLALVSGN NTVPFAVSLV
     DSTSEKSQDI LLSVENTVIY RIQALSLCSD QQSHLEFRVN RNNLELSTPL KIETISHEDL
     QRQLAVLDKA MKAKVATYLG GLPDVPFSAT PVNAFYNGCM EVNINGVQLD LDEAISKHND
     IRAHSCPSVW KKTKNS
//
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