ID TMPSD_HUMAN Reviewed; 586 AA.
AC Q9BYE2; B4DTM9; E9PIJ5; E9PRA0; F8WAJ3; J3KQC6; Q1RMF8; Q86YM4; Q96JY8;
AC Q9BYE1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 5.
DT 27-MAR-2024, entry version 165.
DE RecName: Full=Transmembrane protease serine 13;
DE EC=3.4.21.- {ECO:0000269|PubMed:34562451, ECO:0000269|PubMed:35796294};
DE AltName: Full=Membrane-type mosaic serine protease;
DE Short=Mosaic serine protease;
GN Name=TMPRSS13; Synonyms=MSP, TMPRSS11;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY (ISOFORMS
RP 1 AND 2), POLYMORPHISM, AND VARIANTS ALA-SER-PRO-ALA-GLN-73 INS AND
RP 74-ALA--GLN-78 DEL.
RC TISSUE=Lung;
RX PubMed=11267681; DOI=10.1016/s0167-4781(01)00184-1;
RA Kim D.R., Sharmin S., Inoue M., Kido H.;
RT "Cloning and expression of novel mosaic serine proteases with and without a
RT transmembrane domain from human lung.";
RL Biochim. Biophys. Acta 1518:204-209(2001).
RN [2]
RP SEQUENCE REVISION TO 192; 259; 298 AND 496.
RA Kim D.R., Inoue M., Kido H.;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT 74-ALA--GLN-78 DEL.
RA Park T.J., Park W.J.;
RT "Homo sapiens transmembrane protease, serine 6 (TMPRSS6) mRNA.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 6).
RC TISSUE=Placenta;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6), AND VARIANT
RP 74-ALA--GLN-78 DEL.
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=20977675; DOI=10.1111/j.1742-4658.2010.07894.x;
RA Hashimoto T., Kato M., Shimomura T., Kitamura N.;
RT "TMPRSS13, a type II transmembrane serine protease, is inhibited by
RT hepatocyte growth factor activator inhibitor type 1 and activates pro-
RT hepatocyte growth factor.";
RL FEBS J. 277:4888-4900(2010).
RN [8]
RP FUNCTION, INTERACTION WITH SPINT1 AND SPINT2, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION, AND MUTAGENESIS OF ARG-325 AND SER-511.
RX PubMed=28710277; DOI=10.1074/jbc.m117.775999;
RA Murray A.S., Varela F.A., Hyland T.E., Schoenbeck A.J., White J.M.,
RA Tanabe L.M., Todi S.V., List K.;
RT "Phosphorylation of the type II transmembrane serine protease, TMPRSS13, in
RT hepatocyte growth factor activator inhibitor-1 and -2-mediated cell-surface
RT localization.";
RL J. Biol. Chem. 292:14867-14884(2017).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SPINT2, SUBCELLULAR
RP LOCATION, PROTEOLYTIC PROCESSING, PHOSPHORYLATION, GLYCOSYLATION AT ASN-405
RP AND ASN-445, AND MUTAGENESIS OF ASN-255; ASN-292; ARG-325; ASN-405; ASN-445
RP AND SER-511.
RX PubMed=34562451; DOI=10.1016/j.jbc.2021.101227;
RA Martin C.E., Murray A.S., Sala-Hamrick K.E., Mackinder J.R., Harrison E.C.,
RA Lundgren J.G., Varela F.A., List K.;
RT "Posttranslational modifications of serine protease TMPRSS13 regulate
RT zymogen activation, proteolytic activity, and cell surface localization.";
RL J. Biol. Chem. 297:101227-101227(2021).
RN [10]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS
RP OF ARG-196; ARG-201; ARG-210; ARG-228; ARG-325 AND SER-511.
RX PubMed=35796294; DOI=10.1515/hsz-2022-0129;
RA Martin C.E., Murray A.S., Mackinder J.R., Sala-Hamrick K.E., Flynn M.G.,
RA Lundgren J.G., Varela F.A., List K.;
RT "TMPRSS13 zymogen activation, surface localization, and shedding is
RT regulated by proteolytic cleavage within the non-catalytic stem region.";
RL Biol. Chem. 403:969-982(2022).
CC -!- FUNCTION: Serine protease (PubMed:20977675, PubMed:28710277,
CC PubMed:34562451). Cleaves the proform of PRSS8/prostasin to form the
CC active protein (PubMed:34562451). Cleaves the proform of HGF to form
CC the active protein which promotes MAPK signaling (PubMed:20977675).
CC Promotes the formation of the stratum corneum and subsequently the
CC epidermal barrier in embryos (By similarity).
CC {ECO:0000250|UniProtKB:Q5U405, ECO:0000269|PubMed:20977675,
CC ECO:0000269|PubMed:28710277, ECO:0000269|PubMed:34562451}.
CC -!- ACTIVITY REGULATION: Cleavage of HGF is inhibited by SPINT1/HAI-1 via
CC the BPTI/Kunitz inhibitor 1 domain. {ECO:0000269|PubMed:20977675}.
CC -!- SUBUNIT: Interacts with SPINT1/HAI-1; the interaction promotes the
CC phosphorylation and cell membrane localization of TMPRSS13
CC (PubMed:28710277). Interacts with SPINT2/HAI-2; the interaction
CC promotes the phosphorylation and cell membrane localization of TMPRSS13
CC (PubMed:28710277, PubMed:34562451). {ECO:0000269|PubMed:28710277,
CC ECO:0000269|PubMed:34562451}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28710277,
CC ECO:0000269|PubMed:34562451, ECO:0000269|PubMed:35796294}; Single-pass
CC type II membrane protein {ECO:0000255}. Secreted
CC {ECO:0000269|PubMed:35796294}. Cytoplasm {ECO:0000269|PubMed:28710277}.
CC Note=The non-phosphorylated, inactive full length protein localizes
CC intracellularly (PubMed:28710277). N-glycosylation and phosphorylation
CC is required for trafficking to the cell surface (PubMed:28710277,
CC PubMed:34562451, PubMed:35796294). Interaction with SPINT1/HAI-1 and
CC SPINT2/HAI-2 facilitate its translocation to the cell surface
CC (PubMed:34562451, PubMed:35796294). Proteolytic cleavage is required
CC for secretion (PubMed:35796294). {ECO:0000269|PubMed:28710277,
CC ECO:0000269|PubMed:34562451, ECO:0000269|PubMed:35796294}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=MSPL {ECO:0000303|PubMed:11267681};
CC IsoId=Q9BYE2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BYE2-2; Sequence=VSP_013103, VSP_013104;
CC Name=3; Synonyms=MSPS {ECO:0000303|PubMed:11267681};
CC IsoId=Q9BYE2-3; Sequence=VSP_013099, VSP_013102;
CC Name=4;
CC IsoId=Q9BYE2-4; Sequence=VSP_013100, VSP_013101;
CC Name=6;
CC IsoId=Q9BYE2-6; Sequence=VSP_013102;
CC -!- TISSUE SPECIFICITY: Expressed in placenta.
CC {ECO:0000269|PubMed:20977675}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Predominantly expressed in lung,
CC placenta, pancreas, and prostate. {ECO:0000269|PubMed:11267681}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in lung, placenta, pancreas,
CC and prostate (PubMed:11267681). Weakly expressed in testis and
CC peripheral blood lymphocytes (PubMed:11267681).
CC {ECO:0000269|PubMed:11267681}.
CC -!- PTM: The inactive zymogen is post-translationally modified and then
CC trafficked to the cell surface, whereby it undergoes autocatalytic
CC cleavage resulting in an activated form that is released
CC extracellularly. {ECO:0000269|PubMed:28710277,
CC ECO:0000269|PubMed:34562451}.
CC -!- PTM: Phosphorylation is required for localization at the cell surface
CC (PubMed:28710277, PubMed:34562451). Phosphorylation increases following
CC inhibition of protease activity by SPINT2/HAI-2 (PubMed:35796294).
CC {ECO:0000269|PubMed:28710277, ECO:0000269|PubMed:34562451,
CC ECO:0000269|PubMed:35796294}.
CC -!- PTM: N-glycosylation of Asn-405 and Asn-445 is required for exit from
CC the endoplasmic reticulum and trafficking to the cell surface
CC (PubMed:28710277, PubMed:34562451). Also required for autocleavage of
CC the zymogen, activation and secretion of the mature protein
CC (PubMed:34562451). {ECO:0000269|PubMed:28710277,
CC ECO:0000269|PubMed:34562451}.
CC -!- POLYMORPHISM: The repeat A-S-P-A-[GLQR] is polymorphic and the number
CC of copies varies between 12 to 14. {ECO:0000269|PubMed:11267681}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- CAUTION: Was termed TMPRSS6 (Ref.3). {ECO:0000305}.
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DR EMBL; AB048796; BAB39741.2; -; mRNA.
DR EMBL; AB048797; BAB39742.2; -; mRNA.
DR EMBL; AY190317; AAO38062.1; -; mRNA.
DR EMBL; AK027798; BAB55376.1; -; mRNA.
DR EMBL; AK300283; BAG62041.1; -; mRNA.
DR EMBL; AP002962; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC114928; AAI14929.1; -; mRNA.
DR CCDS; CCDS41721.1; -. [Q9BYE2-6]
DR CCDS; CCDS55788.1; -. [Q9BYE2-3]
DR CCDS; CCDS55789.1; -. [Q9BYE2-4]
DR CCDS; CCDS58185.1; -. [Q9BYE2-2]
DR RefSeq; NP_001070731.1; NM_001077263.2. [Q9BYE2-6]
DR RefSeq; NP_001193718.1; NM_001206789.1. [Q9BYE2-3]
DR RefSeq; NP_001193719.1; NM_001206790.1. [Q9BYE2-4]
DR RefSeq; NP_001231924.1; NM_001244995.1. [Q9BYE2-2]
DR AlphaFoldDB; Q9BYE2; -.
DR SMR; Q9BYE2; -.
DR BioGRID; 123845; 140.
DR IntAct; Q9BYE2; 4.
DR STRING; 9606.ENSP00000434279; -.
DR MEROPS; S01.087; -.
DR TCDB; 8.A.131.1.13; the transmembrane protease serine 3 (tmprss3) family.
DR GlyCosmos; Q9BYE2; 4 sites, No reported glycans.
DR GlyGen; Q9BYE2; 5 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BYE2; -.
DR PhosphoSitePlus; Q9BYE2; -.
DR SwissPalm; Q9BYE2; -.
DR BioMuta; TMPRSS13; -.
DR DMDM; 313104278; -.
DR jPOST; Q9BYE2; -.
DR MassIVE; Q9BYE2; -.
DR PaxDb; 9606-ENSP00000434279; -.
DR PeptideAtlas; Q9BYE2; -.
DR ProteomicsDB; 20829; -.
DR ProteomicsDB; 23254; -.
DR ProteomicsDB; 30511; -.
DR ProteomicsDB; 79624; -. [Q9BYE2-1]
DR ProteomicsDB; 79625; -. [Q9BYE2-2]
DR ProteomicsDB; 79626; -. [Q9BYE2-3]
DR ProteomicsDB; 79627; -. [Q9BYE2-4]
DR Antibodypedia; 32401; 112 antibodies from 17 providers.
DR DNASU; 84000; -.
DR Ensembl; ENST00000430170.6; ENSP00000387702.2; ENSG00000137747.16. [Q9BYE2-2]
DR Ensembl; ENST00000445164.6; ENSP00000394114.2; ENSG00000137747.16. [Q9BYE2-1]
DR Ensembl; ENST00000524993.6; ENSP00000434279.1; ENSG00000137747.16. [Q9BYE2-6]
DR Ensembl; ENST00000526090.1; ENSP00000436502.1; ENSG00000137747.16. [Q9BYE2-4]
DR Ensembl; ENST00000528626.5; ENSP00000435813.1; ENSG00000137747.16. [Q9BYE2-3]
DR GeneID; 84000; -.
DR KEGG; hsa:84000; -.
DR MANE-Select; ENST00000524993.6; ENSP00000434279.1; NM_001077263.3; NP_001070731.1. [Q9BYE2-6]
DR UCSC; uc001pru.3; human. [Q9BYE2-1]
DR AGR; HGNC:29808; -.
DR CTD; 84000; -.
DR DisGeNET; 84000; -.
DR GeneCards; TMPRSS13; -.
DR HGNC; HGNC:29808; TMPRSS13.
DR HPA; ENSG00000137747; Tissue enhanced (esophagus, skin).
DR MIM; 610050; gene.
DR neXtProt; NX_Q9BYE2; -.
DR OpenTargets; ENSG00000137747; -.
DR PharmGKB; PA142670732; -.
DR VEuPathDB; HostDB:ENSG00000137747; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000159197; -.
DR HOGENOM; CLU_006842_19_2_1; -.
DR InParanoid; Q9BYE2; -.
DR OMA; AIHYDEH; -.
DR OrthoDB; 4629979at2759; -.
DR TreeFam; TF351678; -.
DR PathwayCommons; Q9BYE2; -.
DR SignaLink; Q9BYE2; -.
DR BioGRID-ORCS; 84000; 14 hits in 1146 CRISPR screens.
DR ChiTaRS; TMPRSS13; human.
DR GenomeRNAi; 84000; -.
DR Pharos; Q9BYE2; Tbio.
DR PRO; PR:Q9BYE2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BYE2; Protein.
DR Bgee; ENSG00000137747; Expressed in upper arm skin and 132 other cell types or tissues.
DR ExpressionAtlas; Q9BYE2; baseline and differential.
DR Genevisible; Q9BYE2; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004252; F:serine-type endopeptidase activity; NAS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00112; LDLa; 1.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 3.10.250.10; SRCR-like domain; 1.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR017327; Peptidase_S1A_TMPRSS13.
DR InterPro; IPR001190; SRCR.
DR InterPro; IPR017448; SRCR-like_dom.
DR InterPro; IPR036772; SRCR-like_dom_sf.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24252; ACROSIN-RELATED; 1.
DR PANTHER; PTHR24252:SF14; TRANSMEMBRANE PROTEASE SERINE 3-LIKE; 1.
DR Pfam; PF15494; SRCR_2; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF037935; TMPRSS13; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00202; SR; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF56487; SRCR-like; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR PROSITE; PS50287; SRCR_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 Alternative splicing; Cell membrane; Cytoplasm; Disulfide bond;
KW Glycoprotein; Hydrolase; Membrane; Protease; Reference proteome; Repeat;
KW Secreted; Serine protease; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..586
FT /note="Transmembrane protease serine 13"
FT /id="PRO_0000088698"
FT TOPO_DOM 1..165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 187..586
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REPEAT 9..13
FT /note="1-1"
FT REPEAT 14..18
FT /note="2-1; approximate"
FT REPEAT 19..23
FT /note="1-2"
FT REPEAT 24..28
FT /note="1-3"
FT REPEAT 29..33
FT /note="2-2"
FT REPEAT 34..38
FT /note="1-4"
FT REPEAT 39..43
FT /note="1-5"
FT REPEAT 44..48
FT /note="1-6"
FT REPEAT 49..53
FT /note="2-3"
FT REPEAT 54..58
FT /note="1-7"
FT REPEAT 59..63
FT /note="1-8"
FT REPEAT 64..68
FT /note="2-4"
FT REPEAT 69..78
FT /note="1-9; approximate"
FT REPEAT 79..83
FT /note="1-10"
FT REPEAT 84..88
FT /note="1-11"
FT REPEAT 89..93
FT /note="1-12"
FT DOMAIN 195..325
FT /note="SRCR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 204..226
FT /note="LDL-receptor class A"
FT DOMAIN 326..559
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 1..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 9..93
FT /note="13 X 5 AA repeats of A-S-P-A-[GLQR]"
FT REGION 14..68
FT /note="4 X 5 AA repeats of T-P-P-G-R"
FT REGION 131..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 565..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..157
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 366
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 414
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 511
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:34562451,
FT ECO:0000269|PubMed:35796294"
FT SITE 228..229
FT /note="Cleavage; by autolysis; required for cell surface
FT localization and secretion"
FT /evidence="ECO:0000269|PubMed:35796294"
FT SITE 325
FT /note="Required for autocleavage and PRSS8 cleavage"
FT /evidence="ECO:0000269|PubMed:34562451,
FT ECO:0000269|PubMed:35796294"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 405
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:34562451"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:34562451"
FT DISULFID 250..314
FT /evidence="ECO:0000250"
FT DISULFID 263..317
FT /evidence="ECO:0000250"
FT DISULFID 351..367
FT /evidence="ECO:0000250"
FT DISULFID 448..517
FT /evidence="ECO:0000250"
FT DISULFID 480..496
FT /evidence="ECO:0000250"
FT DISULFID 507..535
FT /evidence="ECO:0000250"
FT VAR_SEQ 151..186
FT /note="GTSLPKFTWREGQKQLPLIGCVLLLIALVVSLIILF -> V (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:11267681,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_013099"
FT VAR_SEQ 428..491
FT /note="AHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLIDFKK
FT CNDYLVYDSYLT -> GEGICTPRSPAPQPQHPLQPSHLSASVNSYPGPKASAGQKSKT
FT LKDPYMEHFCFIIRETEAQGL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013100"
FT VAR_SEQ 492..586
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013101"
FT VAR_SEQ 560..586
FT /note="VRSLQQDTAPSRLGTSSGGDPGGAPRL -> SEVRFRKS (in isoform
FT 3 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11267681,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013102"
FT VAR_SEQ 560..563
FT /note="VRSL -> SSAG (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_013103"
FT VAR_SEQ 564..586
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_013104"
FT VARIANT 73
FT /note="R -> RASPAQ"
FT /evidence="ECO:0000303|PubMed:11267681"
FT /id="VAR_081354"
FT VARIANT 74..78
FT /note="Missing"
FT /evidence="ECO:0000303|PubMed:11267681,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VAR_081355"
FT MUTAGEN 196
FT /note="R->Q: No effect on autocleavage."
FT /evidence="ECO:0000269|PubMed:35796294"
FT MUTAGEN 201
FT /note="R->Q: No effect on autocleavage."
FT /evidence="ECO:0000269|PubMed:35796294"
FT MUTAGEN 210
FT /note="R->Q: No effect on autocleavage."
FT /evidence="ECO:0000269|PubMed:35796294"
FT MUTAGEN 228
FT /note="R->Q: Significantly reduces autocleavage and
FT cleavage of substrates. Abolishes phosphorylation when
FT inhibited by SPINT2/HAI-2, also reduces localization to the
FT cell surface and is instead localized to the endoplasmic
FT reticulum."
FT /evidence="ECO:0000269|PubMed:35796294"
FT MUTAGEN 255
FT /note="N->Q: No effect on autocleavage. No effect on PRSS8
FT cleavage and activation."
FT /evidence="ECO:0000269|PubMed:34562451"
FT MUTAGEN 292
FT /note="N->Q: No effect on autocleavage. No effect on PRSS8
FT cleavage and activation."
FT /evidence="ECO:0000269|PubMed:34562451"
FT MUTAGEN 325
FT /note="R->Q: Abolishes autocleavage. Abolishes PRSS8
FT cleavage and activation. Increases localization to the cell
FT surface. No effect on glycosylation."
FT /evidence="ECO:0000269|PubMed:28710277,
FT ECO:0000269|PubMed:34562451, ECO:0000269|PubMed:35796294"
FT MUTAGEN 405
FT /note="N->Q: Loss of localization to the cell surface even
FT in the presence of the inhibitor SPINT2. Reduces PRSS8
FT cleavage and activation. No effect on interaction with
FT SPINT2."
FT /evidence="ECO:0000269|PubMed:34562451"
FT MUTAGEN 445
FT /note="N->Q: Reduces autocleavage. Loss of localization to
FT the cell surface even in the presence of the inhibitor
FT SPINT2. Reduces PRSS8 cleavage and activation. No effect on
FT interaction with SPINT2."
FT /evidence="ECO:0000269|PubMed:34562451"
FT MUTAGEN 511
FT /note="S->A: Abolishes autocleavage. Abolishes serine
FT protease activity including PRSS8 cleavage and activation.
FT Increases localization to the cell surface. No effect on
FT glycosylation."
FT /evidence="ECO:0000269|PubMed:28710277,
FT ECO:0000269|PubMed:34562451, ECO:0000269|PubMed:35796294"
FT CONFLICT 192
FT /note="H -> Y (in Ref. 3; AAO38062)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="K -> E (in Ref. 3; AAO38062)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="C -> R (in Ref. 3; AAO38062)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="D -> G (in Ref. 4; BAG62041)"
FT /evidence="ECO:0000305"
FT CONFLICT 586
FT /note="L -> V (in Ref. 1; BAB39741)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 586 AA; 63167 MW; EDA2E3B7509FB1C6 CRC64;
MERDSHGNAS PARTPSAGAS PAQASPAGTP PGRASPAQAS PAQASPAGTP PGRASPAQAS
PAGTPPGRAS PGRASPAQAS PAQASPARAS PALASLSRSS SGRSSSARSA SVTTSPTRVY
LVRATPVGAV PIRSSPARSA PATRATRESP GTSLPKFTWR EGQKQLPLIG CVLLLIALVV
SLIILFQFWQ GHTGIRYKEQ RESCPKHAVR CDGVVDCKLK SDELGCVRFD WDKSLLKIYS
GSSHQWLPIC SSNWNDSYSE KTCQQLGFES AHRTTEVAHR DFANSFSILR YNSTIQESLH
RSECPSQRYI SLQCSHCGLR AMTGRIVGGA LASDSKWPWQ VSLHFGTTHI CGGTLIDAQW
VLTAAHCFFV TREKVLEGWK VYAGTSNLHQ LPEAASIAEI IINSNYTDEE DDYDIALMRL
SKPLTLSAHI HPACLPMHGQ TFSLNETCWI TGFGKTRETD DKTSPFLREV QVNLIDFKKC
NDYLVYDSYL TPRMMCAGDL RGGRDSCQGD SGGPLVCEQN NRWYLAGVTS WGTGCGQRNK
PGVYTKVTEV LPWIYSKMEV RSLQQDTAPS RLGTSSGGDP GGAPRL
//
