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Protein

Kunitz-type protease inhibitor 1

Gene

SPINT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Inhibitor of HGF activator. Also acts as an inhibitor of matriptase (ST14).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei260 – 261Reactive bondBy similarity2
Sitei401 – 402Reactive bondBy similarity2

GO - Molecular functioni

  • serine-type endopeptidase inhibitor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166145-MONOMER.
ReactomeiR-HSA-6806942. MET Receptor Activation.
R-HSA-8852405. Signaling by MST1.

Protein family/group databases

MEROPSiI02.007.

Names & Taxonomyi

Protein namesi
Recommended name:
Kunitz-type protease inhibitor 1
Alternative name(s):
Hepatocyte growth factor activator inhibitor type 1
Short name:
HAI-1
Gene namesi
Name:SPINT1
Synonyms:HAI1
ORF Names:UNQ223/PRO256
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:11246. SPINT1.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: ProtInc
  • extracellular space Source: UniProtKB
  • membrane Source: ProtInc
  • plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi6692.
OpenTargetsiENSG00000166145.
PharmGKBiPA36076.

Polymorphism and mutation databases

BioMutaiSPINT1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 351 PublicationAdd BLAST35
ChainiPRO_000001688336 – 529Kunitz-type protease inhibitor 1Add BLAST494

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi66N-linked (GlcNAc...)Sequence analysis1
Glycosylationi235N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi250 ↔ 3001 Publication
Disulfide bondi259 ↔ 2831 Publication
Disulfide bondi275 ↔ 2961 Publication
Disulfide bondi335 ↔ 347By similarity
Disulfide bondi342 ↔ 360By similarity
Disulfide bondi354 ↔ 369By similarity
Disulfide bondi391 ↔ 441By similarity
Disulfide bondi400 ↔ 424By similarity
Disulfide bondi416 ↔ 437By similarity
Glycosylationi523N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO43278.
MaxQBiO43278.
PaxDbiO43278.
PeptideAtlasiO43278.
PRIDEiO43278.

PTM databases

iPTMnetiO43278.
PhosphoSitePlusiO43278.
SwissPalmiO43278.

Expressioni

Gene expression databases

BgeeiENSG00000166145.
CleanExiHS_SPINT1.
ExpressionAtlasiO43278. baseline and differential.
GenevisibleiO43278. HS.

Organism-specific databases

HPAiHPA006903.

Interactioni

Subunit structurei

Interacts with HGFAC.1 Publication

Protein-protein interaction databases

BioGridi112570. 4 interactors.
DIPiDIP-37949N.
IntActiO43278. 4 interactors.
MINTiMINT-1190358.
STRINGi9606.ENSP00000342098.

Structurei

Secondary structure

1529
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi50 – 53Combined sources4
Beta strandi54 – 56Combined sources3
Beta strandi61 – 63Combined sources3
Helixi66 – 69Combined sources4
Turni70 – 72Combined sources3
Beta strandi75 – 77Combined sources3
Helixi84 – 93Combined sources10
Beta strandi99 – 104Combined sources6
Beta strandi106 – 108Combined sources3
Beta strandi113 – 119Combined sources7
Beta strandi131 – 133Combined sources3
Beta strandi135 – 142Combined sources8
Turni143 – 145Combined sources3
Helixi146 – 149Combined sources4
Turni150 – 152Combined sources3
Beta strandi169 – 173Combined sources5
Beta strandi177 – 180Combined sources4
Beta strandi190 – 196Combined sources7
Beta strandi199 – 201Combined sources3
Beta strandi209 – 212Combined sources4
Beta strandi215 – 222Combined sources8
Beta strandi234 – 240Combined sources7
Helixi246 – 250Combined sources5
Beta strandi263 – 268Combined sources6
Turni270 – 272Combined sources3
Beta strandi273 – 280Combined sources8
Beta strandi282 – 284Combined sources3
Beta strandi290 – 292Combined sources3
Helixi293 – 300Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YC0X-ray2.60I245-303[»]
2MSXNMR-A47-152[»]
4ISLX-ray2.29B245-304[»]
4ISNX-ray2.45B245-307[»]
4ISOX-ray2.01B245-304[»]
5EZDX-ray2.10A/B168-303[»]
ProteinModelPortaliO43278.
SMRiO43278.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43278.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini57 – 140MANSCPROSITE-ProRule annotationAdd BLAST84
Domaini250 – 300BPTI/Kunitz inhibitor 1PROSITE-ProRule annotationAdd BLAST51
Domaini334 – 370LDL-receptor class APROSITE-ProRule annotationAdd BLAST37
Domaini391 – 441BPTI/Kunitz inhibitor 2PROSITE-ProRule annotationAdd BLAST51

Domaini

This inhibitor contains two inhibitory domains.

Sequence similaritiesi

Contains 2 BPTI/Kunitz inhibitor domains.PROSITE-ProRule annotation
Contains 1 LDL-receptor class A domain.PROSITE-ProRule annotation
Contains 1 MANSC domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00860000133796.
HOGENOMiHOG000128104.
HOVERGENiHBG061664.
InParanoidiO43278.
KOiK15619.
OMAiECKLACR.
OrthoDBiEOG091G0612.
PhylomeDBiO43278.
TreeFamiTF325867.

Family and domain databases

Gene3Di4.10.400.10. 1 hit.
4.10.410.10. 2 hits.
InterProiIPR002223. Kunitz_BPTI.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR013980. MANSC_dom.
IPR011106. MANSC_N.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PfamiPF00014. Kunitz_BPTI. 2 hits.
PF00057. Ldl_recept_a. 1 hit.
PF07502. MANEC. 1 hit.
[Graphical view]
PRINTSiPR00759. BASICPTASE.
SMARTiSM00131. KU. 2 hits.
SM00192. LDLa. 1 hit.
SM00765. MANEC. 1 hit.
[Graphical view]
SUPFAMiSSF57362. SSF57362. 2 hits.
SSF57424. SSF57424. 1 hit.
PROSITEiPS00280. BPTI_KUNITZ_1. 2 hits.
PS50279. BPTI_KUNITZ_2. 2 hits.
PS01209. LDLRA_1. 1 hit.
PS50068. LDLRA_2. 1 hit.
PS50986. MANSC. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43278-1) [UniParc]FASTAAdd to basket
Also known as: HAI-1B

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAPARTMARA RLAPAGIPAV ALWLLCTLGL QGTQAGPPPA PPGLPAGADC
60 70 80 90 100
LNSFTAGVPG FVLDTNASVS NGATFLESPT VRRGWDCVRA CCTTQNCNLA
110 120 130 140 150
LVELQPDRGE DAIAACFLIN CLYEQNFVCK FAPREGFINY LTREVYRSYR
160 170 180 190 200
QLRTQGFGGS GIPKAWAGID LKVQPQEPLV LKDVENTDWR LLRGDTDVRV
210 220 230 240 250
ERKDPNQVEL WGLKEGTYLF QLTVTSSDHP EDTANVTVTV LSTKQTEDYC
260 270 280 290 300
LASNKVGRCR GSFPRWYYDP TEQICKSFVY GGCLGNKNNY LREEECILAC
310 320 330 340 350
RGVQGGPLRG SSGAQATFPQ GPSMERRHPV CSGTCQPTQF RCSNGCCIDS
360 370 380 390 400
FLECDDTPNC PDASDEAACE KYTSGFDELQ RIHFPSDKGH CVDLPDTGLC
410 420 430 440 450
KESIPRWYYN PFSEHCARFT YGGCYGNKNN FEEEQQCLES CRGISKKDVF
460 470 480 490 500
GLRREIPIPS TGSVEMAVAV FLVICIVVVV AILGYCFFKN QRKDFHGHHH
510 520
HPPPTPASST VSTTEDTEHL VYNHTTRPL
Length:529
Mass (Da):58,398
Last modified:March 15, 2005 - v2
Checksum:iA87F286C23C73422
GO
Isoform 2 (identifier: O43278-2) [UniParc]FASTAAdd to basket
Also known as: HAI-1A

The sequence of this isoform differs from the canonical sequence as follows:
     306-321: Missing.

Show »
Length:513
Mass (Da):56,885
Checksum:iD6E05F3A5885CDDD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti469A → T (Ref. 2) Curated1
Sequence conflicti469A → T (PubMed:12975309).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050065123Y → C.Corresponds to variant rs11549915dbSNPEnsembl.1
Natural variantiVAR_050066142T → R.Corresponds to variant rs12323939dbSNPEnsembl.1
Natural variantiVAR_050067337P → L.Corresponds to variant rs7165897dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013019306 – 321Missing in isoform 2. 2 PublicationsAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000095 mRNA. Translation: BAA25014.1.
AY296715 mRNA. Translation: AAP44001.1.
AY358969 mRNA. Translation: AAQ89328.1.
BT007425 mRNA. Translation: AAP36093.1.
BC004140 mRNA. Translation: AAH04140.1.
BC018702 mRNA. Translation: AAH18702.1.
CCDSiCCDS10067.1. [O43278-1]
CCDS45231.1. [O43278-2]
RefSeqiNP_001027539.1. NM_001032367.1. [O43278-2]
NP_003701.1. NM_003710.3. [O43278-2]
NP_857593.1. NM_181642.2. [O43278-1]
XP_006720720.1. XM_006720657.1. [O43278-1]
UniGeneiHs.233950.

Genome annotation databases

EnsembliENST00000344051; ENSP00000342098; ENSG00000166145. [O43278-1]
ENST00000562057; ENSP00000457076; ENSG00000166145. [O43278-2]
GeneIDi6692.
KEGGihsa:6692.
UCSCiuc001zna.4. human. [O43278-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000095 mRNA. Translation: BAA25014.1.
AY296715 mRNA. Translation: AAP44001.1.
AY358969 mRNA. Translation: AAQ89328.1.
BT007425 mRNA. Translation: AAP36093.1.
BC004140 mRNA. Translation: AAH04140.1.
BC018702 mRNA. Translation: AAH18702.1.
CCDSiCCDS10067.1. [O43278-1]
CCDS45231.1. [O43278-2]
RefSeqiNP_001027539.1. NM_001032367.1. [O43278-2]
NP_003701.1. NM_003710.3. [O43278-2]
NP_857593.1. NM_181642.2. [O43278-1]
XP_006720720.1. XM_006720657.1. [O43278-1]
UniGeneiHs.233950.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1YC0X-ray2.60I245-303[»]
2MSXNMR-A47-152[»]
4ISLX-ray2.29B245-304[»]
4ISNX-ray2.45B245-307[»]
4ISOX-ray2.01B245-304[»]
5EZDX-ray2.10A/B168-303[»]
ProteinModelPortaliO43278.
SMRiO43278.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112570. 4 interactors.
DIPiDIP-37949N.
IntActiO43278. 4 interactors.
MINTiMINT-1190358.
STRINGi9606.ENSP00000342098.

Protein family/group databases

MEROPSiI02.007.

PTM databases

iPTMnetiO43278.
PhosphoSitePlusiO43278.
SwissPalmiO43278.

Polymorphism and mutation databases

BioMutaiSPINT1.

Proteomic databases

EPDiO43278.
MaxQBiO43278.
PaxDbiO43278.
PeptideAtlasiO43278.
PRIDEiO43278.

Protocols and materials databases

DNASUi6692.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344051; ENSP00000342098; ENSG00000166145. [O43278-1]
ENST00000562057; ENSP00000457076; ENSG00000166145. [O43278-2]
GeneIDi6692.
KEGGihsa:6692.
UCSCiuc001zna.4. human. [O43278-1]

Organism-specific databases

CTDi6692.
DisGeNETi6692.
GeneCardsiSPINT1.
HGNCiHGNC:11246. SPINT1.
HPAiHPA006903.
MIMi605123. gene.
neXtProtiNX_O43278.
OpenTargetsiENSG00000166145.
PharmGKBiPA36076.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00860000133796.
HOGENOMiHOG000128104.
HOVERGENiHBG061664.
InParanoidiO43278.
KOiK15619.
OMAiECKLACR.
OrthoDBiEOG091G0612.
PhylomeDBiO43278.
TreeFamiTF325867.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166145-MONOMER.
ReactomeiR-HSA-6806942. MET Receptor Activation.
R-HSA-8852405. Signaling by MST1.

Miscellaneous databases

ChiTaRSiSPINT1. human.
EvolutionaryTraceiO43278.
GeneWikiiSPINT1.
GenomeRNAii6692.
PROiO43278.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166145.
CleanExiHS_SPINT1.
ExpressionAtlasiO43278. baseline and differential.
GenevisibleiO43278. HS.

Family and domain databases

Gene3Di4.10.400.10. 1 hit.
4.10.410.10. 2 hits.
InterProiIPR002223. Kunitz_BPTI.
IPR023415. LDLR_class-A_CS.
IPR002172. LDrepeatLR_classA_rpt.
IPR013980. MANSC_dom.
IPR011106. MANSC_N.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PfamiPF00014. Kunitz_BPTI. 2 hits.
PF00057. Ldl_recept_a. 1 hit.
PF07502. MANEC. 1 hit.
[Graphical view]
PRINTSiPR00759. BASICPTASE.
SMARTiSM00131. KU. 2 hits.
SM00192. LDLa. 1 hit.
SM00765. MANEC. 1 hit.
[Graphical view]
SUPFAMiSSF57362. SSF57362. 2 hits.
SSF57424. SSF57424. 1 hit.
PROSITEiPS00280. BPTI_KUNITZ_1. 2 hits.
PS50279. BPTI_KUNITZ_2. 2 hits.
PS01209. LDLRA_1. 1 hit.
PS50068. LDLRA_2. 1 hit.
PS50986. MANSC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSPIT1_HUMAN
AccessioniPrimary (citable) accession number: O43278
Secondary accession number(s): Q7Z7D2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: March 15, 2005
Last modified: November 30, 2016
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.