ID SPIT1_HUMAN Reviewed; 529 AA. AC O43278; Q7Z7D2; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2005, sequence version 2. DT 13-FEB-2019, entry version 183. DE RecName: Full=Kunitz-type protease inhibitor 1; DE AltName: Full=Hepatocyte growth factor activator inhibitor type 1; DE Short=HAI-1; DE Flags: Precursor; GN Name=SPINT1; Synonyms=HAI1; ORFNames=UNQ223/PRO256; 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] (ISOFORM 2). RX PubMed=9045658; DOI=10.1074/jbc.272.10.6370; RA Shimomura T., Denda K., Kitamura A., Kawaguchi T., Kito M., Kondo J., RA Kagaya S., Qin L., Takata H., Miyazawa K., Kitamura N.; RT "Hepatocyte growth factor activator inhibitor, a novel Kunitz-type RT serine protease inhibitor."; RL J. Biol. Chem. 272:6370-6376(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Kirchhofer D., Peek M., Li W., Stamos J., Eigenbrot C., RA Kadkhodayan S., Eliott J.M., Corpuz R.T., Lazarus R.A., Moran P.; RT "Tissue-expression, protease-specificity and Kunitz domain functions RT of HAI-1B, a new splice variant of hepatocyte growth factor activator RT inhibitor-1."; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Colon, and Placenta; 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 [6] RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION. RC TISSUE=Milk; RX PubMed=10373425; DOI=10.1074/jbc.274.26.18237; RA Lin C.Y., Anders J., Johnson M., Dickson R.B.; RT "Purification and characterization of a complex containing matriptase RT and a Kunitz-type serine protease inhibitor from human milk."; RL J. Biol. Chem. 274:18237-18242(1999). RN [7] RP PROTEIN SEQUENCE OF 36-50. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 245-303 IN COMPLEX WITH RP HGFAC, AND DISULFIDE BONDS. RX PubMed=15713485; DOI=10.1016/j.jmb.2004.12.048; RA Shia S., Stamos J., Kirchhofer D., Fan B., Wu J., Corpuz R.T., RA Santell L., Lazarus R.A., Eigenbrot C.; RT "Conformational lability in serine protease active sites: structures RT of hepatocyte growth factor activator (HGFA) alone and with the RT inhibitory domain from HGFA inhibitor-1B."; RL J. Mol. Biol. 346:1335-1349(2005). CC -!- FUNCTION: Inhibitor of HGF activator. Also acts as an inhibitor of CC matriptase (ST14). CC -!- SUBUNIT: Interacts with HGFAC. {ECO:0000269|PubMed:15713485}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=HAI-1B; CC IsoId=O43278-1; Sequence=Displayed; CC Name=2; Synonyms=HAI-1A; CC IsoId=O43278-2; Sequence=VSP_013019; CC -!- DOMAIN: This inhibitor contains two inhibitory domains. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/SPINT1ID44384ch15q15.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AB000095; BAA25014.1; -; mRNA. DR EMBL; AY296715; AAP44001.1; -; mRNA. DR EMBL; AY358969; AAQ89328.1; -; mRNA. DR EMBL; BT007425; AAP36093.1; -; mRNA. DR EMBL; BC004140; AAH04140.1; -; mRNA. DR EMBL; BC018702; AAH18702.1; -; mRNA. DR CCDS; CCDS10067.1; -. [O43278-1] DR CCDS; CCDS45231.1; -. [O43278-2] DR RefSeq; NP_001027539.1; NM_001032367.1. [O43278-2] DR RefSeq; NP_003701.1; NM_003710.3. [O43278-2] DR RefSeq; NP_857593.1; NM_181642.2. [O43278-1] DR RefSeq; XP_006720720.1; XM_006720657.1. [O43278-1] DR UniGene; Hs.233950; -. DR PDB; 1YC0; X-ray; 2.60 A; I=245-303. DR PDB; 2MSX; NMR; -; A=47-152. DR PDB; 4ISL; X-ray; 2.29 A; B=245-304. DR PDB; 4ISN; X-ray; 2.45 A; B=245-307. DR PDB; 4ISO; X-ray; 2.01 A; B=245-304. DR PDB; 5EZD; X-ray; 2.10 A; A/B=168-303. DR PDB; 5H7V; X-ray; 3.82 A; A=36-457. DR PDBsum; 1YC0; -. DR PDBsum; 2MSX; -. DR PDBsum; 4ISL; -. DR PDBsum; 4ISN; -. DR PDBsum; 4ISO; -. DR PDBsum; 5EZD; -. DR PDBsum; 5H7V; -. DR ProteinModelPortal; O43278; -. DR SMR; O43278; -. DR BioGrid; 112570; 5. DR DIP; DIP-37949N; -. DR IntAct; O43278; 17. DR MINT; O43278; -. DR STRING; 9606.ENSP00000342098; -. DR MEROPS; I02.007; -. DR iPTMnet; O43278; -. DR PhosphoSitePlus; O43278; -. DR SwissPalm; O43278; -. DR BioMuta; SPINT1; -. DR EPD; O43278; -. DR jPOST; O43278; -. DR MaxQB; O43278; -. DR PaxDb; O43278; -. DR PeptideAtlas; O43278; -. DR PRIDE; O43278; -. DR ProteomicsDB; 48846; -. DR ProteomicsDB; 48847; -. [O43278-2] DR DNASU; 6692; -. DR Ensembl; ENST00000344051; ENSP00000342098; ENSG00000166145. [O43278-1] DR Ensembl; ENST00000562057; ENSP00000457076; ENSG00000166145. [O43278-2] DR GeneID; 6692; -. DR KEGG; hsa:6692; -. DR UCSC; uc001zna.4; human. [O43278-1] DR CTD; 6692; -. DR DisGeNET; 6692; -. DR EuPathDB; HostDB:ENSG00000166145.14; -. DR GeneCards; SPINT1; -. DR HGNC; HGNC:11246; SPINT1. DR HPA; HPA006903; -. DR HPA; HPA031178; -. DR MIM; 605123; gene. DR neXtProt; NX_O43278; -. DR OpenTargets; ENSG00000166145; -. DR PharmGKB; PA36076; -. DR eggNOG; KOG4295; Eukaryota. DR eggNOG; ENOG410XQNP; LUCA. DR GeneTree; ENSGT00940000161683; -. DR HOGENOM; HOG000128104; -. DR HOVERGEN; HBG061664; -. DR InParanoid; O43278; -. DR KO; K15619; -. DR OMA; ECKLACR; -. DR OrthoDB; 687721at2759; -. DR PhylomeDB; O43278; -. DR TreeFam; TF325867; -. DR Reactome; R-HSA-6806942; MET Receptor Activation. DR Reactome; R-HSA-8852405; Signaling by MST1. DR ChiTaRS; SPINT1; human. DR EvolutionaryTrace; O43278; -. DR GeneWiki; SPINT1; -. DR GenomeRNAi; 6692; -. DR PRO; PR:O43278; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; ENSG00000166145; Expressed in 171 organ(s), highest expression level in lower esophagus mucosa. DR ExpressionAtlas; O43278; baseline and differential. DR Genevisible; O43278; HS. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:ProtInc. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; TAS:ProtInc. DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl. DR GO; GO:0071773; P:cellular response to BMP stimulus; IEA:Ensembl. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; IEA:Ensembl. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0060674; P:placenta blood vessel development; IEA:Ensembl. DR GO; GO:0045687; P:positive regulation of glial cell differentiation; IEA:Ensembl. DR CDD; cd00109; KU; 2. DR CDD; cd00112; LDLa; 1. DR Gene3D; 2.60.40.10; -; 1. DR Gene3D; 4.10.410.10; -; 2. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR002223; Kunitz_BPTI. DR InterPro; IPR036880; Kunitz_BPTI_sf. DR InterPro; IPR036055; LDL_receptor-like_sf. DR InterPro; IPR023415; LDLR_class-A_CS. DR InterPro; IPR002172; LDrepeatLR_classA_rpt. DR InterPro; IPR013980; MANSC_dom. DR InterPro; IPR011106; MANSC_N. DR InterPro; IPR020901; Prtase_inh_Kunz-CS. DR Pfam; PF00014; Kunitz_BPTI; 2. DR Pfam; PF00057; Ldl_recept_a; 1. DR Pfam; PF07502; MANEC; 1. DR PRINTS; PR00759; BASICPTASE. DR SMART; SM00131; KU; 2. DR SMART; SM00192; LDLa; 1. DR SMART; SM00765; MANEC; 1. DR SUPFAM; SSF57362; SSF57362; 2. DR SUPFAM; SSF57424; SSF57424; 1. DR PROSITE; PS00280; BPTI_KUNITZ_1; 2. DR PROSITE; PS50279; BPTI_KUNITZ_2; 2. DR PROSITE; PS01209; LDLRA_1; 1. DR PROSITE; PS50068; LDLRA_2; 1. DR PROSITE; PS50986; MANSC; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Polymorphism; KW Protease inhibitor; Reference proteome; Repeat; Secreted; KW Serine protease inhibitor; Signal. FT SIGNAL 1 35 {ECO:0000269|PubMed:15340161}. FT CHAIN 36 529 Kunitz-type protease inhibitor 1. FT /FTId=PRO_0000016883. FT DOMAIN 57 140 MANSC. {ECO:0000255|PROSITE- FT ProRule:PRU00341}. FT DOMAIN 250 300 BPTI/Kunitz inhibitor 1. FT {ECO:0000255|PROSITE-ProRule:PRU00031}. FT DOMAIN 334 370 LDL-receptor class A. FT {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DOMAIN 391 441 BPTI/Kunitz inhibitor 2. FT {ECO:0000255|PROSITE-ProRule:PRU00031}. FT SITE 260 261 Reactive bond. {ECO:0000250}. FT SITE 401 402 Reactive bond. {ECO:0000250}. FT CARBOHYD 66 66 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 235 235 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 523 523 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 250 300 {ECO:0000269|PubMed:15713485}. FT DISULFID 259 283 {ECO:0000269|PubMed:15713485}. FT DISULFID 275 296 {ECO:0000269|PubMed:15713485}. FT DISULFID 335 347 {ECO:0000250}. FT DISULFID 342 360 {ECO:0000250}. FT DISULFID 354 369 {ECO:0000250}. FT DISULFID 391 441 {ECO:0000250}. FT DISULFID 400 424 {ECO:0000250}. FT DISULFID 416 437 {ECO:0000250}. FT VAR_SEQ 306 321 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9045658}. FT /FTId=VSP_013019. FT VARIANT 123 123 Y -> C (in dbSNP:rs11549915). FT /FTId=VAR_050065. FT VARIANT 142 142 T -> R (in dbSNP:rs12323939). FT /FTId=VAR_050066. FT VARIANT 337 337 P -> L (in dbSNP:rs7165897). FT /FTId=VAR_050067. FT CONFLICT 469 469 A -> T (in Ref. 2 and 3). {ECO:0000305}. FT HELIX 50 53 {ECO:0000244|PDB:2MSX}. FT STRAND 54 56 {ECO:0000244|PDB:2MSX}. FT STRAND 61 63 {ECO:0000244|PDB:2MSX}. FT HELIX 66 69 {ECO:0000244|PDB:2MSX}. FT TURN 70 72 {ECO:0000244|PDB:2MSX}. FT STRAND 75 77 {ECO:0000244|PDB:2MSX}. FT HELIX 84 93 {ECO:0000244|PDB:2MSX}. FT STRAND 99 104 {ECO:0000244|PDB:2MSX}. FT STRAND 106 108 {ECO:0000244|PDB:2MSX}. FT STRAND 113 119 {ECO:0000244|PDB:2MSX}. FT STRAND 131 133 {ECO:0000244|PDB:2MSX}. FT STRAND 135 142 {ECO:0000244|PDB:2MSX}. FT TURN 143 145 {ECO:0000244|PDB:2MSX}. FT HELIX 146 149 {ECO:0000244|PDB:2MSX}. FT TURN 150 152 {ECO:0000244|PDB:2MSX}. FT STRAND 169 173 {ECO:0000244|PDB:5EZD}. FT STRAND 177 180 {ECO:0000244|PDB:5EZD}. FT STRAND 190 196 {ECO:0000244|PDB:5EZD}. FT STRAND 199 201 {ECO:0000244|PDB:5EZD}. FT STRAND 209 212 {ECO:0000244|PDB:5EZD}. FT STRAND 215 222 {ECO:0000244|PDB:5EZD}. FT STRAND 234 240 {ECO:0000244|PDB:5EZD}. FT HELIX 246 250 {ECO:0000244|PDB:4ISO}. FT STRAND 263 268 {ECO:0000244|PDB:4ISO}. FT TURN 270 272 {ECO:0000244|PDB:4ISO}. FT STRAND 273 280 {ECO:0000244|PDB:4ISO}. FT STRAND 282 284 {ECO:0000244|PDB:4ISO}. FT STRAND 290 292 {ECO:0000244|PDB:4ISO}. FT HELIX 293 300 {ECO:0000244|PDB:4ISO}. SQ SEQUENCE 529 AA; 58398 MW; A87F286C23C73422 CRC64; MAPARTMARA RLAPAGIPAV ALWLLCTLGL QGTQAGPPPA PPGLPAGADC LNSFTAGVPG FVLDTNASVS NGATFLESPT VRRGWDCVRA CCTTQNCNLA LVELQPDRGE DAIAACFLIN CLYEQNFVCK FAPREGFINY LTREVYRSYR QLRTQGFGGS GIPKAWAGID LKVQPQEPLV LKDVENTDWR LLRGDTDVRV ERKDPNQVEL WGLKEGTYLF QLTVTSSDHP EDTANVTVTV LSTKQTEDYC LASNKVGRCR GSFPRWYYDP TEQICKSFVY GGCLGNKNNY LREEECILAC RGVQGGPLRG SSGAQATFPQ GPSMERRHPV CSGTCQPTQF RCSNGCCIDS FLECDDTPNC PDASDEAACE KYTSGFDELQ RIHFPSDKGH CVDLPDTGLC KESIPRWYYN PFSEHCARFT YGGCYGNKNN FEEEQQCLES CRGISKKDVF GLRREIPIPS TGSVEMAVAV FLVICIVVVV AILGYCFFKN QRKDFHGHHH HPPPTPASST VSTTEDTEHL VYNHTTRPL //