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UniProtKB - O43291 (SPIT2_HUMAN)
Protein
Kunitz-type protease inhibitor 2
Gene
SPINT2
Organism
Homo sapiens (Human)
Status
Functioni
Inhibitor of HGF activator. Also inhibits plasmin, plasma and tissue kallikrein, and factor XIa.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 48 – 49 | Reactive bondBy similarity | 2 | |
Sitei | 143 – 144 | Reactive bondBy similarity | 2 |
GO - Molecular functioni
- endopeptidase inhibitor activity Source: ProtInc
- serine-type endopeptidase inhibitor activity Source: UniProtKB
GO - Biological processi
- basement membrane organization Source: Ensembl
- cellular response to BMP stimulus Source: Ensembl
- epithelial cell morphogenesis involved in placental branching Source: Ensembl
- establishment or maintenance of cell polarity Source: Ensembl
- negative regulation of cell-cell adhesion Source: MGI
- negative regulation of cell motility Source: MGI
- negative regulation of neural precursor cell proliferation Source: Ensembl
- neural tube closure Source: Ensembl
Keywordsi
Molecular function | Protease inhibitor, Serine protease inhibitor |
Enzyme and pathway databases
PathwayCommonsi | O43291 |
Reactomei | R-HSA-6806942, MET Receptor Activation R-HSA-8852405, Signaling by MST1 |
SignaLinki | O43291 |
Protein family/group databases
MEROPSi | I02.009 |
Names & Taxonomyi
Protein namesi | Recommended name: Kunitz-type protease inhibitor 2Alternative name(s): Hepatocyte growth factor activator inhibitor type 2 Short name: HAI-2 Placental bikunin |
Gene namesi | Name:SPINT2 Synonyms:HAI2, KOP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11247, SPINT2 |
MIMi | 605124, gene |
neXtProti | NX_O43291 |
VEuPathDBi | HostDB:ENSG00000167642 |
Subcellular locationi
Other locations
- Membrane Curated; Single-pass type I membrane protein Curated
Extracellular region or secreted
- extracellular region Source: ProtInc
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- cytoplasm Source: HGNC-UCL
- integral component of membrane Source: ProtInc
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 28 – 197 | ExtracellularSequence analysisAdd BLAST | 170 | |
Transmembranei | 198 – 218 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 219 – 252 | CytoplasmicSequence analysisAdd BLAST | 34 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Involvement in diseasei
Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies (DIAR3)1 Publication
The disease is caused by variants 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_058718 | 163 | Y → C in DIAR3; has a significantly reduced ability to inhibit trypsin compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs121908403EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 10653 |
MalaCardsi | SPINT2 |
MIMi | 270420, phenotype |
OpenTargetsi | ENSG00000167642 |
Orphaneti | 563708, Syndromic congenital sodium diarrhea |
PharmGKBi | PA36077 |
Miscellaneous databases
Pharosi | O43291, Tbio |
Genetic variation databases
BioMutai | SPINT2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 27 | 2 PublicationsAdd BLAST | 27 | |
ChainiPRO_0000016885 | 28 – 252 | Kunitz-type protease inhibitor 2Add BLAST | 225 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 38 ↔ 88 | PROSITE-ProRule annotation | ||
Disulfide bondi | 47 ↔ 71 | PROSITE-ProRule annotation | ||
Glycosylationi | 57 | N-linked (GlcNAc...) asparagine | 1 | |
Disulfide bondi | 63 ↔ 84 | PROSITE-ProRule annotation | ||
Glycosylationi | 94 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 133 ↔ 183 | PROSITE-ProRule annotation | ||
Disulfide bondi | 142 ↔ 166 | PROSITE-ProRule annotation | ||
Disulfide bondi | 158 ↔ 179 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | O43291 |
jPOSTi | O43291 |
MassIVEi | O43291 |
MaxQBi | O43291 |
PaxDbi | O43291 |
PeptideAtlasi | O43291 |
PRIDEi | O43291 |
ProteomicsDBi | 48859 [O43291-1] 48860 [O43291-2] |
PTM databases
GlyGeni | O43291, 3 sites, 1 O-linked glycan (1 site) |
iPTMneti | O43291 |
PhosphoSitePlusi | O43291 |
Expressioni
Tissue specificityi
Expressed in placenta, kidney, pancreas, prostate, testis, thymus, and trachea.
Gene expression databases
Bgeei | ENSG00000167642, Expressed in pituitary gland and 238 other tissues |
ExpressionAtlasi | O43291, baseline and differential |
Genevisiblei | O43291, HS |
Organism-specific databases
HPAi | ENSG00000167642, Low tissue specificity |
Interactioni
Protein-protein interaction databases
BioGRIDi | 115896, 136 interactors |
IntActi | O43291, 76 interactors |
MINTi | O43291 |
STRINGi | 9606.ENSP00000301244 |
Miscellaneous databases
RNActi | O43291, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O43291 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 38 – 88 | BPTI/Kunitz inhibitor 1PROSITE-ProRule annotationAdd BLAST | 51 | |
Domaini | 133 – 183 | BPTI/Kunitz inhibitor 2PROSITE-ProRule annotationAdd BLAST | 51 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 100 – 122 | DisorderedSequence analysisAdd BLAST | 23 |
Domaini
This inhibitor contains two inhibitory domains.
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4295, Eukaryota |
GeneTreei | ENSGT00940000160348 |
HOGENOMi | CLU_140751_0_0_1 |
InParanoidi | O43291 |
OMAi | KEECMHR |
OrthoDBi | 1282068at2759 |
PhylomeDBi | O43291 |
TreeFami | TF326553 |
Family and domain databases
CDDi | cd00109, KU, 2 hits |
Gene3Di | 4.10.410.10, 2 hits |
InterProi | View protein in InterPro IPR002223, Kunitz_BPTI IPR036880, Kunitz_BPTI_sf IPR020901, Prtase_inh_Kunz-CS |
Pfami | View protein in Pfam PF00014, Kunitz_BPTI, 2 hits |
PRINTSi | PR00759, BASICPTASE |
SMARTi | View protein in SMART SM00131, KU, 2 hits |
SUPFAMi | SSF57362, SSF57362, 2 hits |
PROSITEi | View protein in PROSITE PS00280, BPTI_KUNITZ_1, 2 hits PS50279, BPTI_KUNITZ_2, 2 hits |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: O43291-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketK7EM91 | K7EM91_HUMAN | Kunitz-type protease inhibitor 2 | SPINT2 | 202 | Annotation score: | ||
K7EKQ0 | K7EKQ0_HUMAN | Kunitz-type protease inhibitor 2 | SPINT2 | 174 | Annotation score: | ||
K7ES27 | K7ES27_HUMAN | Kunitz-type protease inhibitor 2 | SPINT2 | 106 | Annotation score: | ||
K7EJS4 | K7EJS4_HUMAN | Kunitz-type protease inhibitor 2 | SPINT2 | 52 | Annotation score: | ||
K7EKC8 | K7EKC8_HUMAN | Kunitz-type protease inhibitor 2 | SPINT2 | 62 | Annotation score: | ||
K7ESI5 | K7ESI5_HUMAN | Kunitz-type protease inhibitor 2 | SPINT2 | 130 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 3 | Q → H in AAB84031 (PubMed:9434156).Curated | 1 | |
Sequence conflicti | 11 | R → P in BAA25024 (PubMed:9346890).Curated | 1 | |
Sequence conflicti | 53 | R → K in AAB84031 (PubMed:9434156).Curated | 1 | |
Sequence conflicti | 240 | D → H in AAB84031 (PubMed:9434156).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_058718 | 163 | Y → C in DIAR3; has a significantly reduced ability to inhibit trypsin compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs121908403EnsemblClinVar. | 1 | |
Natural variantiVAR_012482 | 200 | V → L1 PublicationCorresponds to variant dbSNP:rs11548457Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_043680 | 36 – 92 | Missing in isoform 2. 1 PublicationAdd BLAST | 57 |
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 |
CCDSi | CCDS12510.1 [O43291-1] CCDS54261.1 [O43291-2] |
RefSeqi | NP_001159575.1, NM_001166103.1 [O43291-2] NP_066925.1, NM_021102.3 [O43291-1] |
Genome annotation databases
Ensembli | ENST00000301244; ENSP00000301244; ENSG00000167642 ENST00000454580; ENSP00000389788; ENSG00000167642 [O43291-2] |
GeneIDi | 10653 |
KEGGi | hsa:10653 |
MANE-Selecti | ENST00000301244.12; ENSP00000301244.5; NM_021102.4; NP_066925.1 |
UCSCi | uc002ohr.2, human [O43291-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS12510.1 [O43291-1] CCDS54261.1 [O43291-2] |
RefSeqi | NP_001159575.1, NM_001166103.1 [O43291-2] NP_066925.1, NM_021102.3 [O43291-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4U32 | X-ray | 1.65 | X | 34-88 | [»] | |
SMRi | O43291 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 115896, 136 interactors |
IntActi | O43291, 76 interactors |
MINTi | O43291 |
STRINGi | 9606.ENSP00000301244 |
Protein family/group databases
MEROPSi | I02.009 |
PTM databases
GlyGeni | O43291, 3 sites, 1 O-linked glycan (1 site) |
iPTMneti | O43291 |
PhosphoSitePlusi | O43291 |
Genetic variation databases
BioMutai | SPINT2 |
Proteomic databases
EPDi | O43291 |
jPOSTi | O43291 |
MassIVEi | O43291 |
MaxQBi | O43291 |
PaxDbi | O43291 |
PeptideAtlasi | O43291 |
PRIDEi | O43291 |
ProteomicsDBi | 48859 [O43291-1] 48860 [O43291-2] |
Protocols and materials databases
Antibodypediai | 2598, 401 antibodies from 33 providers |
DNASUi | 10653 |
Genome annotation databases
Ensembli | ENST00000301244; ENSP00000301244; ENSG00000167642 ENST00000454580; ENSP00000389788; ENSG00000167642 [O43291-2] |
GeneIDi | 10653 |
KEGGi | hsa:10653 |
MANE-Selecti | ENST00000301244.12; ENSP00000301244.5; NM_021102.4; NP_066925.1 |
UCSCi | uc002ohr.2, human [O43291-1] |
Organism-specific databases
CTDi | 10653 |
DisGeNETi | 10653 |
GeneCardsi | SPINT2 |
HGNCi | HGNC:11247, SPINT2 |
HPAi | ENSG00000167642, Low tissue specificity |
MalaCardsi | SPINT2 |
MIMi | 270420, phenotype 605124, gene |
neXtProti | NX_O43291 |
OpenTargetsi | ENSG00000167642 |
Orphaneti | 563708, Syndromic congenital sodium diarrhea |
PharmGKBi | PA36077 |
VEuPathDBi | HostDB:ENSG00000167642 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4295, Eukaryota |
GeneTreei | ENSGT00940000160348 |
HOGENOMi | CLU_140751_0_0_1 |
InParanoidi | O43291 |
OMAi | KEECMHR |
OrthoDBi | 1282068at2759 |
PhylomeDBi | O43291 |
TreeFami | TF326553 |
Enzyme and pathway databases
PathwayCommonsi | O43291 |
Reactomei | R-HSA-6806942, MET Receptor Activation R-HSA-8852405, Signaling by MST1 |
SignaLinki | O43291 |
Miscellaneous databases
BioGRID-ORCSi | 10653, 19 hits in 1039 CRISPR screens |
ChiTaRSi | SPINT2, human |
GeneWikii | SPINT2 |
GenomeRNAii | 10653 |
Pharosi | O43291, Tbio |
PROi | PR:O43291 |
RNActi | O43291, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167642, Expressed in pituitary gland and 238 other tissues |
ExpressionAtlasi | O43291, baseline and differential |
Genevisiblei | O43291, HS |
Family and domain databases
CDDi | cd00109, KU, 2 hits |
Gene3Di | 4.10.410.10, 2 hits |
InterProi | View protein in InterPro IPR002223, Kunitz_BPTI IPR036880, Kunitz_BPTI_sf IPR020901, Prtase_inh_Kunz-CS |
Pfami | View protein in Pfam PF00014, Kunitz_BPTI, 2 hits |
PRINTSi | PR00759, BASICPTASE |
SMARTi | View protein in SMART SM00131, KU, 2 hits |
SUPFAMi | SSF57362, SSF57362, 2 hits |
PROSITEi | View protein in PROSITE PS00280, BPTI_KUNITZ_1, 2 hits PS50279, BPTI_KUNITZ_2, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | SPIT2_HUMAN | |
Accessioni | O43291Primary (citable) accession number: O43291 Secondary accession number(s): A8K667 Q969E0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 21, 2001 |
Last sequence update: | February 21, 2001 | |
Last modified: | February 23, 2022 | |
This is version 192 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references