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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei260 – 2612Reactive bondBy similarity
Sitei401 – 4022Reactive bondBy similarity

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

ReactomeiR-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

PharmGKBiPA36076.

Polymorphism and mutation databases

BioMutaiSPINT1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 35351 PublicationAdd
BLAST
Chaini36 – 529494Kunitz-type protease inhibitor 1PRO_0000016883Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi66 – 661N-linked (GlcNAc...)Sequence analysis
Glycosylationi235 – 2351N-linked (GlcNAc...)Sequence analysis
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
Glycosylationi523 – 5231N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO43278.
MaxQBiO43278.
PaxDbiO43278.
PeptideAtlasiO43278.
PRIDEiO43278.

PTM databases

iPTMnetiO43278.
PhosphoSiteiO43278.
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 interactions.
DIPiDIP-37949N.
IntActiO43278. 3 interactions.
MINTiMINT-1190358.
STRINGi9606.ENSP00000342098.

Structurei

Secondary structure

1
529
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi50 – 534Combined sources
Beta strandi54 – 563Combined sources
Beta strandi61 – 633Combined sources
Helixi66 – 694Combined sources
Turni70 – 723Combined sources
Beta strandi75 – 773Combined sources
Helixi84 – 9310Combined sources
Beta strandi99 – 1046Combined sources
Beta strandi106 – 1083Combined sources
Beta strandi113 – 1197Combined sources
Beta strandi131 – 1333Combined sources
Beta strandi135 – 1428Combined sources
Turni143 – 1453Combined sources
Helixi146 – 1494Combined sources
Turni150 – 1523Combined sources
Helixi246 – 2505Combined sources
Beta strandi263 – 2686Combined sources
Turni270 – 2723Combined sources
Beta strandi273 – 2808Combined sources
Beta strandi282 – 2843Combined sources
Beta strandi290 – 2923Combined sources
Helixi293 – 3008Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 47-152, 245-444.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43278.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini57 – 14084MANSCPROSITE-ProRule annotationAdd
BLAST
Domaini250 – 30051BPTI/Kunitz inhibitor 1PROSITE-ProRule annotationAdd
BLAST
Domaini334 – 37037LDL-receptor class APROSITE-ProRule annotationAdd
BLAST
Domaini391 – 44151BPTI/Kunitz inhibitor 2PROSITE-ProRule annotationAdd
BLAST

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.
GeneTreeiENSGT00740000114929.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti469 – 4691A → T (Ref. 2) Curated
Sequence conflicti469 – 4691A → T (PubMed:12975309).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti123 – 1231Y → C.
Corresponds to variant rs11549915 [ dbSNP | Ensembl ].
VAR_050065
Natural varianti142 – 1421T → R.
Corresponds to variant rs12323939 [ dbSNP | Ensembl ].
VAR_050066
Natural varianti337 – 3371P → L.
Corresponds to variant rs7165897 [ dbSNP | Ensembl ].
VAR_050067

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei306 – 32116Missing in isoform 2. 2 PublicationsVSP_013019Add
BLAST

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
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. Positions 47-152, 245-444.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112570. 4 interactions.
DIPiDIP-37949N.
IntActiO43278. 3 interactions.
MINTiMINT-1190358.
STRINGi9606.ENSP00000342098.

Protein family/group databases

MEROPSiI02.007.

PTM databases

iPTMnetiO43278.
PhosphoSiteiO43278.
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.
GeneCardsiSPINT1.
HGNCiHGNC:11246. SPINT1.
HPAiHPA006903.
MIMi605123. gene.
neXtProtiNX_O43278.
PharmGKBiPA36076.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00740000114929.
HOGENOMiHOG000128104.
HOVERGENiHBG061664.
InParanoidiO43278.
KOiK15619.
OMAiECKLACR.
OrthoDBiEOG091G0612.
PhylomeDBiO43278.
TreeFamiTF325867.

Enzyme and pathway databases

ReactomeiR-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: September 7, 2016
This is version 163 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.