GenomeNet

Database: UniProt
Entry: O43278
LinkDB: O43278
Original site: O43278 
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   08-MAY-2019, entry version 184.
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";
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   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   SMR; O43278; -.
DR   BioGrid; 112570; 6.
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   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   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; 4.10.400.10; -; 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
//
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