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Protein

Kunitz-type protease inhibitor 2

Gene

SPINT2

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 inhibits plasmin, plasma and tissue kallikrein, and factor XIa.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei48 – 492Reactive bondBy similarity
Sitei143 – 1442Reactive bondBy similarity

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: ProtInc
  • serine-type endopeptidase inhibitor activity Source: UniProtKB

GO - Biological processi

  • movement of cell or subcellular component Source: ProtInc
  • negative regulation of cell-cell adhesion Source: MGI
  • negative regulation of cell motility Source: MGI
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

MEROPSiI02.009.

Names & Taxonomyi

Protein namesi
Recommended name:
Kunitz-type protease inhibitor 2
Alternative name(s):
Hepatocyte growth factor activator inhibitor type 2
Short name:
HAI-2
Placental bikunin
Gene namesi
Name:SPINT2
Synonyms:HAI2, KOP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:11247. SPINT2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 197170ExtracellularSequence analysisAdd
BLAST
Transmembranei198 – 21821HelicalSequence analysisAdd
BLAST
Topological domaini219 – 25234CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: HGNC
  • extracellular region Source: ProtInc
  • integral component of membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies (DIAR3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by life-threatening secretory diarrhea, severe metabolic acidosis and hyponatremia. Hyponatremia is secondary to extraordinarily high fecal sodium loss, with low or normal excretion of urinary sodium, in the absence of infectious, autoimmune and endocrine causes.
See also OMIM:270420
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti163 – 1631Y → C in DIAR3; has a significantly reduced ability to inhibit trypsin compared to wild-type. 1 Publication
Corresponds to variant rs121908403 [ dbSNP | Ensembl ].
VAR_058718

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiSPINT2.
MIMi270420. phenotype.
Orphaneti103908. Congenital sodium diarrhea.
PharmGKBiPA36077.

Polymorphism and mutation databases

BioMutaiSPINT2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 27272 PublicationsAdd
BLAST
Chaini28 – 252225Kunitz-type protease inhibitor 2PRO_0000016885Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi38 ↔ 88PROSITE-ProRule annotation
Disulfide bondi47 ↔ 71PROSITE-ProRule annotation
Glycosylationi57 – 571N-linked (GlcNAc...)
Disulfide bondi63 ↔ 84PROSITE-ProRule annotation
Glycosylationi94 – 941N-linked (GlcNAc...)Sequence analysis
Disulfide bondi133 ↔ 183PROSITE-ProRule annotation
Disulfide bondi142 ↔ 166PROSITE-ProRule annotation
Disulfide bondi158 ↔ 179PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO43291.
PaxDbiO43291.
PeptideAtlasiO43291.
PRIDEiO43291.

PTM databases

iPTMnetiO43291.
PhosphoSiteiO43291.

Expressioni

Tissue specificityi

Expressed in placenta, kidney, pancreas, prostate, testis, thymus, and trachea.

Gene expression databases

BgeeiENSG00000167642.
CleanExiHS_SPINT2.
ExpressionAtlasiO43291. baseline and differential.
GenevisibleiO43291. HS.

Organism-specific databases

HPAiCAB018969.
HPA011101.

Interactioni

Protein-protein interaction databases

BioGridi115896. 105 interactions.
IntActiO43291. 1 interaction.
MINTiMINT-1366946.
STRINGi9606.ENSP00000301244.

Structurei

Secondary structure

1
252
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni36 – 383Combined sources
Beta strandi51 – 577Combined sources
Turni58 – 614Combined sources
Beta strandi62 – 687Combined sources
Beta strandi70 – 723Combined sources
Beta strandi78 – 803Combined sources
Helixi81 – 877Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4U32X-ray1.65X34-88[»]
ProteinModelPortaliO43291.
SMRiO43291. Positions 35-183.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini38 – 8851BPTI/Kunitz inhibitor 1PROSITE-ProRule annotationAdd
BLAST
Domaini133 – 18351BPTI/Kunitz inhibitor 2PROSITE-ProRule annotationAdd
BLAST

Domaini

This inhibitor contains two inhibitory domains.

Sequence similaritiesi

Contains 2 BPTI/Kunitz inhibitor domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00740000114929.
HOGENOMiHOG000013109.
HOVERGENiHBG079207.
InParanoidiO43291.
OMAiCDNFIYG.
OrthoDBiEOG091G09P2.
PhylomeDBiO43291.
TreeFamiTF326553.

Family and domain databases

Gene3Di4.10.410.10. 2 hits.
InterProiIPR002223. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PfamiPF00014. Kunitz_BPTI. 2 hits.
[Graphical view]
PRINTSiPR00759. BASICPTASE.
SMARTiSM00131. KU. 2 hits.
[Graphical view]
SUPFAMiSSF57362. SSF57362. 2 hits.
PROSITEiPS00280. BPTI_KUNITZ_1. 2 hits.
PS50279. BPTI_KUNITZ_2. 2 hits.
[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: O43291-1) [UniParc]FASTAAdd to basket

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
MAQLCGLRRS RAFLALLGSL LLSGVLAADR ERSIHDFCLV SKVVGRCRAS
60 70 80 90 100
MPRWWYNVTD GSCQLFVYGG CDGNSNNYLT KEECLKKCAT VTENATGDLA
110 120 130 140 150
TSRNAADSSV PSAPRRQDSE DHSSDMFNYE EYCTANAVTG PCRASFPRWY
160 170 180 190 200
FDVERNSCNN FIYGGCRGNK NSYRSEEACM LRCFRQQENP PLPLGSKVVV
210 220 230 240 250
LAGLFVMVLI LFLGASMVYL IRVARRNQER ALRTVWSSGD DKEQLVKNTY

VL
Length:252
Mass (Da):28,228
Last modified:February 21, 2001 - v2
Checksum:iA7D3360C0EECAB2B
GO
Isoform 2 (identifier: O43291-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     36-92: Missing.

Note: No experimental confirmation available.
Show »
Length:195
Mass (Da):21,828
Checksum:i7E046F218A22319B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 31Q → H in AAB84031 (PubMed:9434156).Curated
Sequence conflicti11 – 111R → P in BAA25024 (PubMed:9346890).Curated
Sequence conflicti53 – 531R → K in AAB84031 (PubMed:9434156).Curated
Sequence conflicti240 – 2401D → H in AAB84031 (PubMed:9434156).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti163 – 1631Y → C in DIAR3; has a significantly reduced ability to inhibit trypsin compared to wild-type. 1 Publication
Corresponds to variant rs121908403 [ dbSNP | Ensembl ].
VAR_058718
Natural varianti200 – 2001V → L.1 Publication
Corresponds to variant rs11548457 [ dbSNP | Ensembl ].
VAR_012482

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei36 – 9257Missing in isoform 2. 1 PublicationVSP_043680Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006534 mRNA. Translation: BAA25024.1.
U78095 mRNA. Translation: AAC02781.1.
AF027205 mRNA. Translation: AAB84031.1.
AK291532 mRNA. Translation: BAF84221.1.
AK297154 mRNA. Translation: BAG59653.1.
BT020115 mRNA. Translation: AAV38918.1.
BT020116 mRNA. Translation: AAV38919.1.
BT020117 mRNA. Translation: AAV38920.1.
AC011479 Genomic DNA. No translation available.
CH471126 Genomic DNA. Translation: EAW56766.1.
CH471126 Genomic DNA. Translation: EAW56767.1.
BC001668 mRNA. Translation: AAH01668.1.
BC007705 mRNA. Translation: AAH07705.1.
BC011951 mRNA. Translation: AAH11951.1.
BC011955 mRNA. Translation: AAH11955.1.
BC012868 mRNA. Translation: AAH12868.1.
CCDSiCCDS12510.1. [O43291-1]
CCDS54261.1. [O43291-2]
RefSeqiNP_001159575.1. NM_001166103.1. [O43291-2]
NP_066925.1. NM_021102.3. [O43291-1]
UniGeneiHs.31439.

Genome annotation databases

EnsembliENST00000301244; ENSP00000301244; ENSG00000167642. [O43291-1]
ENST00000454580; ENSP00000389788; ENSG00000167642. [O43291-2]
GeneIDi10653.
KEGGihsa:10653.
UCSCiuc002ohr.2. human. [O43291-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006534 mRNA. Translation: BAA25024.1.
U78095 mRNA. Translation: AAC02781.1.
AF027205 mRNA. Translation: AAB84031.1.
AK291532 mRNA. Translation: BAF84221.1.
AK297154 mRNA. Translation: BAG59653.1.
BT020115 mRNA. Translation: AAV38918.1.
BT020116 mRNA. Translation: AAV38919.1.
BT020117 mRNA. Translation: AAV38920.1.
AC011479 Genomic DNA. No translation available.
CH471126 Genomic DNA. Translation: EAW56766.1.
CH471126 Genomic DNA. Translation: EAW56767.1.
BC001668 mRNA. Translation: AAH01668.1.
BC007705 mRNA. Translation: AAH07705.1.
BC011951 mRNA. Translation: AAH11951.1.
BC011955 mRNA. Translation: AAH11955.1.
BC012868 mRNA. Translation: AAH12868.1.
CCDSiCCDS12510.1. [O43291-1]
CCDS54261.1. [O43291-2]
RefSeqiNP_001159575.1. NM_001166103.1. [O43291-2]
NP_066925.1. NM_021102.3. [O43291-1]
UniGeneiHs.31439.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4U32X-ray1.65X34-88[»]
ProteinModelPortaliO43291.
SMRiO43291. Positions 35-183.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115896. 105 interactions.
IntActiO43291. 1 interaction.
MINTiMINT-1366946.
STRINGi9606.ENSP00000301244.

Protein family/group databases

MEROPSiI02.009.

PTM databases

iPTMnetiO43291.
PhosphoSiteiO43291.

Polymorphism and mutation databases

BioMutaiSPINT2.

Proteomic databases

MaxQBiO43291.
PaxDbiO43291.
PeptideAtlasiO43291.
PRIDEiO43291.

Protocols and materials databases

DNASUi10653.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301244; ENSP00000301244; ENSG00000167642. [O43291-1]
ENST00000454580; ENSP00000389788; ENSG00000167642. [O43291-2]
GeneIDi10653.
KEGGihsa:10653.
UCSCiuc002ohr.2. human. [O43291-1]

Organism-specific databases

CTDi10653.
GeneCardsiSPINT2.
HGNCiHGNC:11247. SPINT2.
HPAiCAB018969.
HPA011101.
MalaCardsiSPINT2.
MIMi270420. phenotype.
605124. gene.
neXtProtiNX_O43291.
Orphaneti103908. Congenital sodium diarrhea.
PharmGKBiPA36077.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4295. Eukaryota.
ENOG410XQNP. LUCA.
GeneTreeiENSGT00740000114929.
HOGENOMiHOG000013109.
HOVERGENiHBG079207.
InParanoidiO43291.
OMAiCDNFIYG.
OrthoDBiEOG091G09P2.
PhylomeDBiO43291.
TreeFamiTF326553.

Enzyme and pathway databases

ReactomeiR-HSA-8852405. Signaling by MST1.

Miscellaneous databases

ChiTaRSiSPINT2. human.
GeneWikiiSPINT2.
GenomeRNAii10653.
PROiO43291.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167642.
CleanExiHS_SPINT2.
ExpressionAtlasiO43291. baseline and differential.
GenevisibleiO43291. HS.

Family and domain databases

Gene3Di4.10.410.10. 2 hits.
InterProiIPR002223. Kunitz_BPTI.
IPR020901. Prtase_inh_Kunz-CS.
[Graphical view]
PfamiPF00014. Kunitz_BPTI. 2 hits.
[Graphical view]
PRINTSiPR00759. BASICPTASE.
SMARTiSM00131. KU. 2 hits.
[Graphical view]
SUPFAMiSSF57362. SSF57362. 2 hits.
PROSITEiPS00280. BPTI_KUNITZ_1. 2 hits.
PS50279. BPTI_KUNITZ_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSPIT2_HUMAN
AccessioniPrimary (citable) accession number: O43291
Secondary accession number(s): A8K667
, B4DLU1, O00271, O14895, Q5TZQ3, Q969E0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: September 7, 2016
This is version 155 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 19
    Human chromosome 19: 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.