GenomeNet

Database: UniProt
Entry: P00748
LinkDB: P00748
Original site: P00748 
ID   FA12_HUMAN              Reviewed;         615 AA.
AC   P00748; P78339;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 3.
DT   13-FEB-2019, entry version 224.
DE   RecName: Full=Coagulation factor XII;
DE            EC=3.4.21.38;
DE   AltName: Full=Hageman factor;
DE            Short=HAF;
DE   Contains:
DE     RecName: Full=Coagulation factor XIIa heavy chain;
DE   Contains:
DE     RecName: Full=Beta-factor XIIa part 1;
DE   Contains:
DE     RecName: Full=Coagulation factor XIIa light chain;
DE     AltName: Full=Beta-factor XIIa part 2;
DE   Flags: Precursor;
GN   Name=F12;
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 [GENOMIC DNA], AND VARIANT PRO-207.
RX   PubMed=2888762;
RA   Cool D.E., McGillivray R.T.A.;
RT   "Characterization of the human blood coagulation factor XII gene.
RT   Intron/exon gene organization and analysis of the 5'-flanking
RT   region.";
RL   J. Biol. Chem. 262:13662-13673(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-207; ASP-545 AND
RP   HIS-605.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA   Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA   Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA   Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA   Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA   Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA   Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA   Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA   Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4-615, AND VARIANT PRO-207.
RX   PubMed=3754331; DOI=10.1093/nar/14.7.3146;
RA   Tripodi M., Citarella F., Guida S., Galeffi P., Fantoni A.,
RA   Cortese R.;
RT   "cDNA sequence coding for human coagulation factor XII (Hageman).";
RL   Nucleic Acids Res. 14:3146-3146(1986).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 14-615, AND VARIANT PRO-207.
RX   PubMed=3877053;
RA   Cool D.E., Edgell C.-J.S., Louie G.V., Zoller M.J., Brayer G.D.,
RA   McGillivray R.T.A.;
RT   "Characterization of human blood coagulation factor XII cDNA.
RT   Prediction of the primary structure of factor XII and the tertiary
RT   structure of beta-factor XIIa.";
RL   J. Biol. Chem. 260:13666-13676(1985).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 146-615, AND VARIANT PRO-207.
RX   PubMed=3011063; DOI=10.1021/bi00355a009;
RA   Que B.G., Davie E.W.;
RT   "Characterization of a cDNA coding for human factor XII (Hageman
RT   factor).";
RL   Biochemistry 25:1525-1528(1986).
RN   [7]
RP   PROTEIN SEQUENCE OF 20-379, GLYCOSYLATION AT ASN-249; THR-299;
RP   THR-305; SER-308; THR-328; THR-329 AND THR-337, AND VARIANT PRO-207.
RX   PubMed=3886654;
RA   McMullen B.A., Fujikawa K.;
RT   "Amino acid sequence of the heavy chain of human alpha-factor XIIa
RT   (activated Hageman factor).";
RL   J. Biol. Chem. 260:5328-5341(1985).
RN   [8]
RP   PROTEIN SEQUENCE OF 354-362 AND 373-615.
RX   PubMed=6604055;
RA   Fujikawa K., McMullen B.A.;
RT   "Amino acid sequence of human beta-factor XIIa.";
RL   J. Biol. Chem. 258:10924-10933(1983).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 561-615, AND VARIANT FA12D
RP   ARG-589.
RC   TISSUE=Blood;
RX   PubMed=8528215; DOI=10.1093/hmg/4.7.1235;
RA   Schloesser M., Hofferbert S., Bartz U., Lutze G., Lammle B., Engel W.;
RT   "The novel acceptor splice site mutation 11396(G-->A) in the factor
RT   XII gene causes a truncated transcript in cross-reacting material
RT   negative patients.";
RL   Hum. Mol. Genet. 4:1235-1237(1995).
RN   [10]
RP   GLYCOSYLATION AT THR-109.
RX   PubMed=1544894;
RA   Harris R.J., Ling V.T., Spellman M.W.;
RT   "O-linked fucose is present in the first epidermal growth factor
RT   domain of factor XII but not protein C.";
RL   J. Biol. Chem. 267:5102-5107(1992).
RN   [11]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-433.
RC   TISSUE=Plasma;
RX   PubMed=14760718; DOI=10.1002/pmic.200300556;
RA   Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT   "Screening for N-glycosylated proteins by liquid chromatography mass
RT   spectrometry.";
RL   Proteomics 4:454-465(2004).
RN   [12]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-249 AND ASN-433.
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   [13]
RP   INVOLVEMENT IN FA12D.
RX   PubMed=2882793;
RA   Bernardi F., Marchetti G., Patracchini P., del Senno L., Tripodi M.,
RA   Fantoni A., Bartolai S., Vannini F., Felloni L., Rossi L.,
RA   Panicucci F., Conconi F.;
RT   "Factor XII gene alteration in Hageman trait detected by TaqI
RT   restriction enzyme.";
RL   Blood 69:1421-1424(1987).
RN   [14]
RP   INTERACTION WITH HRG, AND FUNCTION.
RX   PubMed=21304106; DOI=10.1182/blood-2010-07-290551;
RA   Macquarrie J.L., Stafford A.R., Yau J.W., Leslie B.A., Vu T.T.,
RA   Fredenburgh J.C., Weitz J.I.;
RT   "Histidine-rich glycoprotein binds factor XIIa with high affinity and
RT   inhibits contact-initiated coagulation.";
RL   Blood 117:4134-4141(2011).
RN   [15]
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   [16]
RP   X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) OF 133-213, AND DISULFIDE
RP   BONDS.
RX   PubMed=23385745; DOI=10.1107/S1744309113000286;
RA   Beringer D.X., Kroon-Batenburg L.M.;
RT   "The structure of the FnI-EGF-like tandem domain of coagulation factor
RT   XII solved using SIRAS.";
RL   Acta Crystallogr. F 69:94-102(2013).
RN   [17]
RP   VARIANT FA12D SER-590.
RX   PubMed=2510163; DOI=10.1073/pnas.86.21.8319;
RA   Miyata T., Kawabata S., Iwanaga S., Takahashi I., Alving B., Saito H.;
RT   "Coagulation factor XII (Hageman factor) Washington D.C.: inactive
RT   factor XIIa results from Cys-571-->Ser substitution.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:8319-8322(1989).
RN   [18]
RP   VARIANT FA12D PRO-372.
RX   PubMed=8049433;
RA   Hovinga J.K., Schaller J., Stricker H., Wuillemin W.A., Furlan M.,
RA   Laemmle B.;
RT   "Coagulation factor XII Locarno: the functional defect is caused by
RT   the amino acid substitution Arg-353-->Pro leading to loss of a
RT   kallikrein cleavage site.";
RL   Blood 84:1173-1181(1994).
RN   [19]
RP   VARIANTS FA12D MET-414; GLN-417; ASN-461 AND ARG-589.
RX   PubMed=9354665;
RA   Schloesser M., Zeerleder S., Lutze G., Halbmayer W.-M., Hofferbert S.,
RA   Hinney B., Koestering H., Laemmle B., Pindur G., Thies K., Koehler M.,
RA   Engel W.;
RT   "Mutations in the human factor XII gene.";
RL   Blood 90:3967-3977(1997).
RN   [20]
RP   VARIANT FA12D CYS-53.
RX   PubMed=10361128;
RA   Kondo S., Tokunaga F., Kawano S., Oono Y., Kumagai S., Koide T.;
RT   "Factor XII Tenri, a novel cross-reacting material negative factor XII
RT   deficiency, occurs through a proteasome-mediated degradation.";
RL   Blood 93:4300-4308(1999).
RN   [21]
RP   VARIANTS FA12D PRO-142 AND LYS-440, AND CHARACTERIZATION OF VARIANTS
RP   FA12D PRO-142 AND LYS-440.
RX   PubMed=11776307;
RA   Kanaji T., Kanaji S., Osaki K., Kuroiwa M., Sakaguchi M., Mihara K.,
RA   Niho Y., Okamura T.;
RT   "Identification and characterization of two novel mutations (Q421K and
RT   R123P) in congenital factor XII deficiency.";
RL   Thromb. Haemost. 86:1409-1415(2001).
RN   [22]
RP   VARIANT FA12D CYS-505, AND CHARACTERIZATION OF VARIANT FA12D CYS-505.
RX   PubMed=15205584; DOI=10.1097/01.mbc.0000114447.59147.d1;
RA   Ishii K., Oguchi S., Moriki T., Yatabe Y., Takeshita E., Murata M.,
RA   Ikeda Y., Watanabe K.;
RT   "Genetic analyses and expression studies identified a novel mutation
RT   (W486C) as a molecular basis of congenital coagulation factor XII
RT   deficiency.";
RL   Blood Coagul. Fibrinolysis 15:367-373(2004).
RN   [23]
RP   VARIANT FA12D THR-411, AND CHARACTERIZATION OF VARIANT FA12D THR-411.
RX   PubMed=15617741; DOI=10.1016/j.thromres.2004.08.027;
RA   Oguchi S., Ishii K., Moriki T., Takeshita E., Murata M., Ikeda Y.,
RA   Watanabe K.;
RT   "Factor XII Shizuoka, a novel mutation (Ala392Thr) identified and
RT   characterized in a patient with congenital coagulation factor XII
RT   deficiency.";
RL   Thromb. Res. 115:191-197(2005).
RN   [24]
RP   VARIANTS HAE3 LYS-328 AND ARG-328.
RX   PubMed=16638441; DOI=10.1016/j.bbrc.2006.03.092;
RA   Dewald G., Bork K.;
RT   "Missense mutations in the coagulation factor XII (Hageman factor)
RT   gene in hereditary angioedema with normal C1 inhibitor.";
RL   Biochem. Biophys. Res. Commun. 343:1286-1289(2006).
RN   [25]
RP   VARIANT HAE3 LYS-328.
RX   PubMed=17186468; DOI=10.1086/509899;
RA   Cichon S., Martin L., Hennies H.C., Mueller F., Van Driessche K.,
RA   Karpushova A., Stevens W., Colombo R., Renne T., Drouet C., Bork K.,
RA   Noethen M.M.;
RT   "Increased activity of coagulation factor XII (Hageman factor) causes
RT   hereditary angioedema type III.";
RL   Am. J. Hum. Genet. 79:1098-1104(2006).
CC   -!- FUNCTION: Factor XII is a serum glycoprotein that participates in
CC       the initiation of blood coagulation, fibrinolysis, and the
CC       generation of bradykinin and angiotensin. Prekallikrein is cleaved
CC       by factor XII to form kallikrein, which then cleaves factor XII
CC       first to alpha-factor XIIa and then trypsin cleaves it to beta-
CC       factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa.
CC       {ECO:0000269|PubMed:21304106}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Selective cleavage of Arg-|-Ile bonds in factor VII to
CC         form factor VIIa and factor XI to form factor XIa.;
CC         EC=3.4.21.38;
CC   -!- SUBUNIT: Interacts with HRG; the interaction, which is enhanced in
CC       the presence of zinc ions and inhibited by heparin-binding,
CC       inhibits factor XII autoactivation and contact-initiated
CC       coagulation. {ECO:0000269|PubMed:21304106}.
CC   -!- INTERACTION:
CC       Q07021:C1QBP; NbExp=2; IntAct=EBI-6378830, EBI-347528;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- PTM: Factor XII is activated by kallikrein in alpha-factor XIIa,
CC       which is further converted by trypsin into beta-factor XIIa.
CC       Alpha-factor XIIa is composed of an NH2-terminal heavy chain,
CC       called coagulation factor XIIa heavy chain, and a COOH-terminal
CC       light chain, called coagulation factor XIIa light chain, connected
CC       by a disulfide bond. Beta-factor XIIa is composed of 2 chains
CC       linked by a disulfide bond, an N-terminal nonapeptide, called
CC       beta-factor XIIa part 1, and coagulation factor XIIa light chain,
CC       also known in this context as beta-factor XIIa part 2.
CC   -!- PTM: O- and N-glycosylated. The O-linked polysaccharides were not
CC       identified, but are probably the mucin type linked to GalNAc.
CC       {ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:1544894,
CC       ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:3886654}.
CC   -!- DISEASE: Factor XII deficiency (FA12D) [MIM:234000]: An
CC       asymptomatic anomaly of in vitro blood coagulation. Its diagnosis
CC       is based on finding a low plasma activity of the factor in
CC       coagulating assays. It is usually only accidentally discovered
CC       through pre-operative blood tests. Factor XII deficiency is
CC       divided into two categories, a cross-reacting material (CRM)-
CC       negative group (negative F12 antigen detection) and a CRM-positive
CC       group (positive F12 antigen detection).
CC       {ECO:0000269|PubMed:10361128, ECO:0000269|PubMed:11776307,
CC       ECO:0000269|PubMed:15205584, ECO:0000269|PubMed:15617741,
CC       ECO:0000269|PubMed:2510163, ECO:0000269|PubMed:2882793,
CC       ECO:0000269|PubMed:8049433, ECO:0000269|PubMed:8528215,
CC       ECO:0000269|PubMed:9354665}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Hereditary angioedema 3 (HAE3) [MIM:610618]: An
CC       hereditary angioedema occurring only in women. Hereditary
CC       angioedema is an autosomal dominant disorder characterized by
CC       episodic local swelling involving subcutaneous or submucous tissue
CC       of the upper respiratory and gastrointestinal tracts, face,
CC       extremities, and genitalia. Hereditary angioedema type 3 differs
CC       from types 1 and 2 in that both concentration and function of C1
CC       esterase inhibitor are normal. Hereditary angioedema type 3 is
CC       precipitated or worsened by high estrogen levels (e.g., during
CC       pregnancy or treatment with oral contraceptives).
CC       {ECO:0000269|PubMed:16638441, ECO:0000269|PubMed:17186468}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Factor XII entry;
CC       URL="https://en.wikipedia.org/wiki/Factor_XII";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/f12/";
DR   EMBL; M17466; AAB59490.1; -; Genomic_DNA.
DR   EMBL; M17464; AAB59490.1; JOINED; Genomic_DNA.
DR   EMBL; M17465; AAB59490.1; JOINED; Genomic_DNA.
DR   EMBL; AF538691; AAM97932.1; -; Genomic_DNA.
DR   EMBL; AC145098; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; M31315; AAA70225.1; -; mRNA.
DR   EMBL; M11723; AAA51986.1; -; mRNA.
DR   EMBL; M13147; AAA70224.1; -; mRNA.
DR   EMBL; U71274; AAB51203.1; -; Genomic_DNA.
DR   CCDS; CCDS34302.1; -.
DR   PIR; A29411; KFHU12.
DR   RefSeq; NP_000496.2; NM_000505.3.
DR   UniGene; Hs.1321; -.
DR   PDB; 4BDW; X-ray; 2.50 A; A=133-215.
DR   PDB; 4BDX; X-ray; 1.62 A; A=133-213.
DR   PDB; 4XDE; X-ray; 2.14 A; A=373-615.
DR   PDB; 4XE4; X-ray; 2.40 A; A=373-615.
DR   PDB; 6B74; X-ray; 2.32 A; A=354-362, B=373-615.
DR   PDB; 6B77; X-ray; 2.37 A; A=354-362, B=373-615.
DR   PDBsum; 4BDW; -.
DR   PDBsum; 4BDX; -.
DR   PDBsum; 4XDE; -.
DR   PDBsum; 4XE4; -.
DR   PDBsum; 6B74; -.
DR   PDBsum; 6B77; -.
DR   ProteinModelPortal; P00748; -.
DR   SMR; P00748; -.
DR   BioGrid; 108459; 15.
DR   IntAct; P00748; 3.
DR   STRING; 9606.ENSP00000253496; -.
DR   BindingDB; P00748; -.
DR   ChEMBL; CHEMBL2821; -.
DR   DrugBank; DB06404; C1 Esterase Inhibitor (Human).
DR   DrugBank; DB09228; C1 Esterase Inhibitor (Recombinant).
DR   DrugBank; DB06689; Ethanolamine Oleate.
DR   GuidetoPHARMACOLOGY; 2361; -.
DR   MEROPS; S01.211; -.
DR   GlyConnect; 1121; -.
DR   iPTMnet; P00748; -.
DR   PhosphoSitePlus; P00748; -.
DR   BioMuta; F12; -.
DR   DMDM; 317373446; -.
DR   jPOST; P00748; -.
DR   PaxDb; P00748; -.
DR   PeptideAtlas; P00748; -.
DR   PRIDE; P00748; -.
DR   ProteomicsDB; 51278; -.
DR   DNASU; 2161; -.
DR   Ensembl; ENST00000253496; ENSP00000253496; ENSG00000131187.
DR   GeneID; 2161; -.
DR   KEGG; hsa:2161; -.
DR   UCSC; uc003mgo.5; human.
DR   CTD; 2161; -.
DR   DisGeNET; 2161; -.
DR   EuPathDB; HostDB:ENSG00000131187.9; -.
DR   GeneCards; F12; -.
DR   H-InvDB; HIX0005461; -.
DR   HGNC; HGNC:3530; F12.
DR   HPA; HPA003825; -.
DR   MalaCards; F12; -.
DR   MIM; 234000; phenotype.
DR   MIM; 610618; phenotype.
DR   MIM; 610619; gene.
DR   neXtProt; NX_P00748; -.
DR   OpenTargets; ENSG00000131187; -.
DR   Orphanet; 330; Congenital factor XII deficiency.
DR   Orphanet; 100054; Hereditary angioedema type 3.
DR   Orphanet; 64738; NON RARE IN EUROPE: Non rare thrombophilia.
DR   PharmGKB; PA161; -.
DR   eggNOG; KOG1217; Eukaryota.
DR   eggNOG; KOG3627; Eukaryota.
DR   eggNOG; COG5640; LUCA.
DR   GeneTree; ENSGT00940000161657; -.
DR   HOGENOM; HOG000237314; -.
DR   HOVERGEN; HBG004345; -.
DR   InParanoid; P00748; -.
DR   KO; K01328; -.
DR   OMA; EKCFEPQ; -.
DR   OrthoDB; 1340284at2759; -.
DR   PhylomeDB; P00748; -.
DR   TreeFam; TF329901; -.
DR   BRENDA; 3.4.21.38; 2681.
DR   Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR   SIGNOR; P00748; -.
DR   GeneWiki; Factor_XII; -.
DR   GenomeRNAi; 2161; -.
DR   PMAP-CutDB; P00748; -.
DR   PRO; PR:P00748; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   Bgee; ENSG00000131187; Expressed in 128 organ(s), highest expression level in liver.
DR   Genevisible; P00748; HS.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
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:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005791; C:rough endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0051787; F:misfolded protein binding; IC:BHF-UCL.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR   GO; GO:0007597; P:blood coagulation, intrinsic pathway; TAS:Reactome.
DR   GO; GO:0002542; P:Factor XII activation; IDA:BHF-UCL.
DR   GO; GO:0042730; P:fibrinolysis; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; TAS:BHF-UCL.
DR   GO; GO:0002353; P:plasma kallikrein-kinin cascade; IDA:BHF-UCL.
DR   GO; GO:0030194; P:positive regulation of blood coagulation; IDA:BHF-UCL.
DR   GO; GO:0051919; P:positive regulation of fibrinolysis; IDA:BHF-UCL.
DR   GO; GO:0010756; P:positive regulation of plasminogen activation; IDA:BHF-UCL.
DR   GO; GO:0016540; P:protein autoprocessing; IDA:BHF-UCL.
DR   GO; GO:0016485; P:protein processing; IDA:BHF-UCL.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   GO; GO:0051788; P:response to misfolded protein; IDA:BHF-UCL.
DR   GO; GO:0031638; P:zymogen activation; IDA:BHF-UCL.
DR   CDD; cd00061; FN1; 1.
DR   CDD; cd00062; FN2; 1.
DR   CDD; cd00108; KR; 1.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 2.10.10.10; -; 1.
DR   Gene3D; 2.40.20.10; -; 1.
DR   InterPro; IPR014394; Coagulation_fac_XII/HGFA.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR000083; Fibronectin_type1.
DR   InterPro; IPR000562; FN_type2_dom.
DR   InterPro; IPR036943; FN_type2_sf.
DR   InterPro; IPR000001; Kringle.
DR   InterPro; IPR013806; Kringle-like.
DR   InterPro; IPR018056; Kringle_CS.
DR   InterPro; IPR038178; Kringle_sf.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   Pfam; PF00008; EGF; 2.
DR   Pfam; PF00039; fn1; 1.
DR   Pfam; PF00040; fn2; 1.
DR   Pfam; PF00051; Kringle; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PIRSF; PIRSF001146; Factor_XII_HGFA; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00181; EGF; 2.
DR   SMART; SM00179; EGF_CA; 2.
DR   SMART; SM00058; FN1; 1.
DR   SMART; SM00059; FN2; 1.
DR   SMART; SM00130; KR; 1.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; SSF50494; 1.
DR   SUPFAM; SSF57440; SSF57440; 2.
DR   PROSITE; PS00022; EGF_1; 2.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 2.
DR   PROSITE; PS01253; FN1_1; 1.
DR   PROSITE; PS51091; FN1_2; 1.
DR   PROSITE; PS00023; FN2_1; 1.
DR   PROSITE; PS51092; FN2_2; 1.
DR   PROSITE; PS00021; KRINGLE_1; 1.
DR   PROSITE; PS50070; KRINGLE_2; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Blood coagulation; Complete proteome;
KW   Direct protein sequencing; Disease mutation; Disulfide bond;
KW   EGF-like domain; Fibrinolysis; Glycoprotein; Hemostasis; Hydrolase;
KW   Kringle; Polymorphism; Protease; Reference proteome; Repeat; Secreted;
KW   Serine protease; Signal; Zymogen.
FT   SIGNAL        1     19       {ECO:0000269|PubMed:3886654}.
FT   CHAIN        20    372       Coagulation factor XIIa heavy chain.
FT                                /FTId=PRO_0000027833.
FT   CHAIN       354    362       Beta-factor XIIa part 1.
FT                                /FTId=PRO_0000027834.
FT   CHAIN       373    615       Coagulation factor XIIa light chain.
FT                                /FTId=PRO_0000027835.
FT   DOMAIN       42     90       Fibronectin type-II.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00478,
FT                                ECO:0000255|PROSITE-ProRule:PRU00479}.
FT   DOMAIN       94    131       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      133    173       Fibronectin type-I. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00478}.
FT   DOMAIN      174    210       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      217    295       Kringle. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00121}.
FT   DOMAIN      373    614       Peptidase S1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00274}.
FT   COMPBIAS    296    349       Pro-rich.
FT   ACT_SITE    412    412       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    461    461       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    563    563       Charge relay system. {ECO:0000250}.
FT   CARBOHYD    109    109       O-linked (Fuc) threonine.
FT                                {ECO:0000269|PubMed:1544894}.
FT   CARBOHYD    249    249       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:16335952,
FT                                ECO:0000269|PubMed:3877053,
FT                                ECO:0000269|PubMed:3886654}.
FT   CARBOHYD    299    299       O-linked (GalNAc...) threonine.
FT                                {ECO:0000269|PubMed:3886654}.
FT   CARBOHYD    305    305       O-linked (GalNAc...) threonine.
FT                                {ECO:0000269|PubMed:3886654}.
FT   CARBOHYD    308    308       O-linked (GalNAc...) serine.
FT                                {ECO:0000269|PubMed:3886654}.
FT   CARBOHYD    328    328       O-linked (GalNAc...) threonine.
FT                                {ECO:0000269|PubMed:3886654}.
FT   CARBOHYD    329    329       O-linked (GalNAc...) threonine.
FT                                {ECO:0000269|PubMed:3886654}.
FT   CARBOHYD    337    337       O-linked (GalNAc...) threonine.
FT                                {ECO:0000269|PubMed:3886654}.
FT   CARBOHYD    433    433       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:14760718,
FT                                ECO:0000269|PubMed:16335952}.
FT   DISULFID     47     73       {ECO:0000250}.
FT   DISULFID     61     88       {ECO:0000250}.
FT   DISULFID     98    110       {ECO:0000250}.
FT   DISULFID    104    119       {ECO:0000250}.
FT   DISULFID    121    130       {ECO:0000250}.
FT   DISULFID    135    163       {ECO:0000269|PubMed:23385745}.
FT   DISULFID    161    170       {ECO:0000269|PubMed:23385745}.
FT   DISULFID    178    189       {ECO:0000269|PubMed:23385745}.
FT   DISULFID    183    198       {ECO:0000269|PubMed:23385745}.
FT   DISULFID    200    209       {ECO:0000269|PubMed:23385745}.
FT   DISULFID    217    295       {ECO:0000250}.
FT   DISULFID    238    277       {ECO:0000250}.
FT   DISULFID    266    290       {ECO:0000250}.
FT   DISULFID    359    486       {ECO:0000250}.
FT   DISULFID    397    413       {ECO:0000250}.
FT   DISULFID    405    475       {ECO:0000250}.
FT   DISULFID    436    439       {ECO:0000250}.
FT   DISULFID    500    569       {ECO:0000250}.
FT   DISULFID    532    548       {ECO:0000250}.
FT   DISULFID    559    590       {ECO:0000250}.
FT   VARIANT      53     53       Y -> C (in FA12D; Tenri; inactive;
FT                                dbSNP:rs118204455).
FT                                {ECO:0000269|PubMed:10361128}.
FT                                /FTId=VAR_014426.
FT   VARIANT     142    142       R -> P (in FA12D; CRM-negative phenotype;
FT                                low levels of accumulation in the cell;
FT                                not secreted).
FT                                {ECO:0000269|PubMed:11776307}.
FT                                /FTId=VAR_031500.
FT   VARIANT     207    207       A -> P (in dbSNP:rs17876030).
FT                                {ECO:0000269|PubMed:2888762,
FT                                ECO:0000269|PubMed:3011063,
FT                                ECO:0000269|PubMed:3754331,
FT                                ECO:0000269|PubMed:3877053,
FT                                ECO:0000269|PubMed:3886654,
FT                                ECO:0000269|Ref.2}.
FT                                /FTId=VAR_014336.
FT   VARIANT     328    328       T -> K (in HAE3; dbSNP:rs118204456).
FT                                {ECO:0000269|PubMed:16638441,
FT                                ECO:0000269|PubMed:17186468}.
FT                                /FTId=VAR_031501.
FT   VARIANT     328    328       T -> R (in HAE3; dbSNP:rs118204456).
FT                                {ECO:0000269|PubMed:16638441}.
FT                                /FTId=VAR_031502.
FT   VARIANT     342    342       P -> Q (in dbSNP:rs2230939).
FT                                /FTId=VAR_029191.
FT   VARIANT     372    372       R -> P (in FA12D; Locarno; inactive;
FT                                dbSNP:rs118204454).
FT                                {ECO:0000269|PubMed:8049433}.
FT                                /FTId=VAR_006623.
FT   VARIANT     411    411       A -> T (in FA12D; Shizuoka; CRM-negative
FT                                phenotype; transcribed and synthesized at
FT                                wild-type levels; not secreted;
FT                                dbSNP:rs865853663).
FT                                {ECO:0000269|PubMed:15617741}.
FT                                /FTId=VAR_031503.
FT   VARIANT     414    414       L -> M (in FA12D; CRM-negative
FT                                phenotype). {ECO:0000269|PubMed:9354665}.
FT                                /FTId=VAR_031504.
FT   VARIANT     417    417       R -> Q (in FA12D; CRM-negative phenotype;
FT                                dbSNP:rs932430490).
FT                                {ECO:0000269|PubMed:9354665}.
FT                                /FTId=VAR_031505.
FT   VARIANT     440    440       Q -> K (in FA12D; CRM-negative phenotype;
FT                                accumulation in the cell; low secretion).
FT                                {ECO:0000269|PubMed:11776307}.
FT                                /FTId=VAR_031506.
FT   VARIANT     461    461       D -> N (in FA12D; CRM-positive
FT                                phenotype). {ECO:0000269|PubMed:9354665}.
FT                                /FTId=VAR_031507.
FT   VARIANT     505    505       W -> C (in FA12D; CRM-negative phenotype;
FT                                transcribed and synthesized at wild-type
FT                                levels; not secreted).
FT                                {ECO:0000269|PubMed:15205584}.
FT                                /FTId=VAR_031508.
FT   VARIANT     545    545       G -> D (in dbSNP:rs17876034).
FT                                {ECO:0000269|Ref.2}.
FT                                /FTId=VAR_014337.
FT   VARIANT     589    589       G -> R (in FA12D; CRM-positive phenotype;
FT                                dbSNP:rs766505234).
FT                                {ECO:0000269|PubMed:8528215,
FT                                ECO:0000269|PubMed:9354665}.
FT                                /FTId=VAR_031509.
FT   VARIANT     590    590       C -> S (in FA12D; Washington D.C.;
FT                                inactive; dbSNP:rs1157280571).
FT                                {ECO:0000269|PubMed:2510163}.
FT                                /FTId=VAR_006624.
FT   VARIANT     605    605       Y -> H (in dbSNP:rs17876035).
FT                                {ECO:0000269|Ref.2}.
FT                                /FTId=VAR_014338.
FT   CONFLICT    333    333       P -> S (in Ref. 5; AAA51986).
FT                                {ECO:0000305}.
FT   CONFLICT    379    379       A -> G (in Ref. 6; AAA70224).
FT                                {ECO:0000305}.
FT   STRAND      135    137       {ECO:0000244|PDB:4BDX}.
FT   TURN        138    141       {ECO:0000244|PDB:4BDX}.
FT   STRAND      142    144       {ECO:0000244|PDB:4BDX}.
FT   STRAND      149    153       {ECO:0000244|PDB:4BDX}.
FT   STRAND      158    163       {ECO:0000244|PDB:4BDX}.
FT   STRAND      165    173       {ECO:0000244|PDB:4BDX}.
FT   STRAND      188    192       {ECO:0000244|PDB:4BDX}.
FT   STRAND      195    199       {ECO:0000244|PDB:4BDX}.
FT   STRAND      204    206       {ECO:0000244|PDB:4BDX}.
FT   STRAND      380    383       {ECO:0000244|PDB:4XDE}.
FT   STRAND      387    392       {ECO:0000244|PDB:4XDE}.
FT   STRAND      395    403       {ECO:0000244|PDB:4XDE}.
FT   STRAND      406    409       {ECO:0000244|PDB:4XDE}.
FT   HELIX       411    414       {ECO:0000244|PDB:4XDE}.
FT   HELIX       420    422       {ECO:0000244|PDB:4XDE}.
FT   STRAND      424    428       {ECO:0000244|PDB:4XDE}.
FT   STRAND      440    449       {ECO:0000244|PDB:4XDE}.
FT   TURN        455    457       {ECO:0000244|PDB:4XDE}.
FT   STRAND      463    467       {ECO:0000244|PDB:4XDE}.
FT   TURN        471    473       {ECO:0000244|PDB:4XE4}.
FT   STRAND      490    492       {ECO:0000244|PDB:4XDE}.
FT   STRAND      499    504       {ECO:0000244|PDB:4XDE}.
FT   HELIX       513    515       {ECO:0000244|PDB:4XDE}.
FT   STRAND      520    527       {ECO:0000244|PDB:4XDE}.
FT   HELIX       529    532       {ECO:0000244|PDB:4XDE}.
FT   TURN        535    538       {ECO:0000244|PDB:4XDE}.
FT   HELIX       539    541       {ECO:0000244|PDB:4XDE}.
FT   STRAND      546    550       {ECO:0000244|PDB:4XDE}.
FT   TURN        558    560       {ECO:0000244|PDB:4XDE}.
FT   STRAND      566    570       {ECO:0000244|PDB:4XDE}.
FT   STRAND      572    586       {ECO:0000244|PDB:4XDE}.
FT   STRAND      588    591       {ECO:0000244|PDB:6B74}.
FT   STRAND      597    601       {ECO:0000244|PDB:4XDE}.
FT   HELIX       602    605       {ECO:0000244|PDB:4XDE}.
FT   HELIX       606    611       {ECO:0000244|PDB:4XDE}.
SQ   SEQUENCE   615 AA;  67792 MW;  F5B861BF635EB480 CRC64;
     MRALLLLGFL LVSLESTLSI PPWEAPKEHK YKAEEHTVVL TVTGEPCHFP FQYHRQLYHK
     CTHKGRPGPQ PWCATTPNFD QDQRWGYCLE PKKVKDHCSK HSPCQKGGTC VNMPSGPHCL
     CPQHLTGNHC QKEKCFEPQL LRFFHKNEIW YRTEQAAVAR CQCKGPDAHC QRLASQACRT
     NPCLHGGRCL EVEGHRLCHC PVGYTGAFCD VDTKASCYDG RGLSYRGLAR TTLSGAPCQP
     WASEATYRNV TAEQARNWGL GGHAFCRNPD NDIRPWCFVL NRDRLSWEYC DLAQCQTPTQ
     AAPPTPVSPR LHVPLMPAQP APPKPQPTTR TPPQSQTPGA LPAKREQPPS LTRNGPLSCG
     QRLRKSLSSM TRVVGGLVAL RGAHPYIAAL YWGHSFCAGS LIAPCWVLTA AHCLQDRPAP
     EDLTVVLGQE RRNHSCEPCQ TLAVRSYRLH EAFSPVSYQH DLALLRLQED ADGSCALLSP
     YVQPVCLPSG AARPSETTLC QVAGWGHQFE GAEEYASFLQ EAQVPFLSLE RCSAPDVHGS
     SILPGMLCAG FLEGGTDACQ GDSGGPLVCE DQAAERRLTL QGIISWGSGC GDRNKPGVYT
     DVAYYLAWIR EHTVS
//
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