Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Kunitz-type protease inhibitor 2

Gene

SPINT2

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

Functioni

Inhibitor of HGF activator. Also inhibits plasmin, plasma and tissue kallikrein, and factor XIa.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei48 – 49Reactive bondBy similarity2
Sitei143 – 144Reactive bondBy similarity2

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

ReactomeiR-HSA-6806942 MET Receptor Activation
R-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

EuPathDBiHostDB:ENSG00000167642.12
HGNCiHGNC:11247 SPINT2
MIMi605124 gene
neXtProtiNX_O43291

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 197ExtracellularSequence analysisAdd BLAST170
Transmembranei198 – 218HelicalSequence analysisAdd BLAST21
Topological domaini219 – 252CytoplasmicSequence analysisAdd BLAST34

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_058718163Y → 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 mutation

Organism-specific databases

DisGeNETi10653
MalaCardsiSPINT2
MIMi270420 phenotype
OpenTargetsiENSG00000167642
Orphaneti103908 Congenital sodium diarrhea
PharmGKBiPA36077

Polymorphism and mutation databases

BioMutaiSPINT2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 272 PublicationsAdd BLAST27
ChainiPRO_000001688528 – 252Kunitz-type protease inhibitor 2Add BLAST225

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi38 ↔ 88PROSITE-ProRule annotation
Disulfide bondi47 ↔ 71PROSITE-ProRule annotation
Glycosylationi57N-linked (GlcNAc...) asparagine1
Disulfide bondi63 ↔ 84PROSITE-ProRule annotation
Glycosylationi94N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi133 ↔ 183PROSITE-ProRule annotation
Disulfide bondi142 ↔ 166PROSITE-ProRule annotation
Disulfide bondi158 ↔ 179PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO43291
MaxQBiO43291
PaxDbiO43291
PeptideAtlasiO43291
PRIDEiO43291
ProteomicsDBi48859
48860 [O43291-2]

PTM databases

iPTMnetiO43291
PhosphoSitePlusiO43291

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000167642 Expressed in 225 organ(s), highest expression level in pituitary gland
CleanExiHS_SPINT2
ExpressionAtlasiO43291 baseline and differential
GenevisibleiO43291 HS

Organism-specific databases

HPAiCAB018969
HPA011101

Interactioni

Protein-protein interaction databases

BioGridi115896, 109 interactors
IntActiO43291, 1 interactor
MINTiO43291
STRINGi9606.ENSP00000301244

Structurei

Secondary structure

1252
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO43291
SMRiO43291
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini38 – 88BPTI/Kunitz inhibitor 1PROSITE-ProRule annotationAdd BLAST51
Domaini133 – 183BPTI/Kunitz inhibitor 2PROSITE-ProRule annotationAdd BLAST51

Domaini

This inhibitor contains two inhibitory domains.

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

CDDicd00109 KU, 2 hits
Gene3Di4.10.410.10, 2 hits
InterProiView protein in InterPro
IPR002223 Kunitz_BPTI
IPR036880 Kunitz_BPTI_sf
IPR020901 Prtase_inh_Kunz-CS
PfamiView protein in Pfam
PF00014 Kunitz_BPTI, 2 hits
PRINTSiPR00759 BASICPTASE
SMARTiView protein in SMART
SM00131 KU, 2 hits
SUPFAMiSSF57362 SSF57362, 2 hits
PROSITEiView protein in PROSITE
PS00280 BPTI_KUNITZ_1, 2 hits
PS50279 BPTI_KUNITZ_2, 2 hits

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

This 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 '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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EM91K7EM91_HUMAN
Kunitz-type protease inhibitor 2
SPINT2
202Annotation score:
K7EKQ0K7EKQ0_HUMAN
Kunitz-type protease inhibitor 2
SPINT2
174Annotation score:
K7ES27K7ES27_HUMAN
Kunitz-type protease inhibitor 2
SPINT2
106Annotation score:
K7EKC8K7EKC8_HUMAN
Kunitz-type protease inhibitor 2
SPINT2
62Annotation score:
K7EJS4K7EJS4_HUMAN
Kunitz-type protease inhibitor 2
SPINT2
52Annotation score:
K7ESI5K7ESI5_HUMAN
Kunitz-type protease inhibitor 2
SPINT2
130Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3Q → H in AAB84031 (PubMed:9434156).Curated1
Sequence conflicti11R → P in BAA25024 (PubMed:9346890).Curated1
Sequence conflicti53R → K in AAB84031 (PubMed:9434156).Curated1
Sequence conflicti240D → H in AAB84031 (PubMed:9434156).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_058718163Y → C in DIAR3; has a significantly reduced ability to inhibit trypsin compared to wild-type. 1 PublicationCorresponds to variant dbSNP:rs121908403EnsemblClinVar.1
Natural variantiVAR_012482200V → L1 PublicationCorresponds to variant dbSNP:rs11548457Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04368036 – 92Missing in isoform 2. 1 PublicationAdd BLAST57

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

Similar 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
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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4U32X-ray1.65X34-88[»]
ProteinModelPortaliO43291
SMRiO43291
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115896, 109 interactors
IntActiO43291, 1 interactor
MINTiO43291
STRINGi9606.ENSP00000301244

Protein family/group databases

MEROPSiI02.009

PTM databases

iPTMnetiO43291
PhosphoSitePlusiO43291

Polymorphism and mutation databases

BioMutaiSPINT2

Proteomic databases

EPDiO43291
MaxQBiO43291
PaxDbiO43291
PeptideAtlasiO43291
PRIDEiO43291
ProteomicsDBi48859
48860 [O43291-2]

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
DisGeNETi10653
EuPathDBiHostDB:ENSG00000167642.12
GeneCardsiSPINT2
HGNCiHGNC:11247 SPINT2
HPAiCAB018969
HPA011101
MalaCardsiSPINT2
MIMi270420 phenotype
605124 gene
neXtProtiNX_O43291
OpenTargetsiENSG00000167642
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-6806942 MET Receptor Activation
R-HSA-8852405 Signaling by MST1

Miscellaneous databases

ChiTaRSiSPINT2 human
GeneWikiiSPINT2
GenomeRNAii10653
PROiPR:O43291
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167642 Expressed in 225 organ(s), highest expression level in pituitary gland
CleanExiHS_SPINT2
ExpressionAtlasiO43291 baseline and differential
GenevisibleiO43291 HS

Family and domain databases

CDDicd00109 KU, 2 hits
Gene3Di4.10.410.10, 2 hits
InterProiView protein in InterPro
IPR002223 Kunitz_BPTI
IPR036880 Kunitz_BPTI_sf
IPR020901 Prtase_inh_Kunz-CS
PfamiView protein in Pfam
PF00014 Kunitz_BPTI, 2 hits
PRINTSiPR00759 BASICPTASE
SMARTiView protein in SMART
SM00131 KU, 2 hits
SUPFAMiSSF57362 SSF57362, 2 hits
PROSITEiView protein in PROSITE
PS00280 BPTI_KUNITZ_1, 2 hits
PS50279 BPTI_KUNITZ_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiSPIT2_HUMAN
AccessioniPrimary (citable) accession number: O43291
Secondary accession number(s): A8K667
, B4DLU1, O00271, O14895, Q5TZQ3, Q969E0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: September 12, 2018
This is version 172 of the entry and version 2 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again