Descriptions

Kunitz-type protease inhibitor 2 (or hepatocyte growth factor activator inhibitor type 2 (HAI-2)) is an integral membrane Kunitz-type serine protease inhibitor that regulates the proteolysis of matriptase and prostasin in a cell-type selective manner. The vast majority of non-glycosylated HAI-2 is synthesized into multiple disulfide-linked oligomers, which lack protease inhibitory function, likely due to distorted conformations caused by the disarrayed disulfide linkages. N-glycosylation on Asn-57 is required for folding into a functional HAI-2 with full protease suppressive activity and correct subcellular targeting signal.

Autoinhibitory domains (AIDs)

Target domain

33-87 (Pancreatic trypsin inhibitor Kunitz domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for O35536

Entry ID Method Resolution Chain Position Source
AF-O35536-F1 Predicted AlphaFoldDB

13 variants for O35536

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388813426 3 P>H No EVA
rs37026717 8 Q>R No EVA
rs3388815282 21 L>H No EVA
rs249673599 58 Q>H No EVA
rs3388813328 64 F>V No EVA
rs238647899 83 Q>E No EVA
rs263720055 94 P>Q No EVA
rs265943979 111 R>Q No EVA
rs36318687 133 I>M No EVA
rs255970186 140 A>T No EVA
rs1135179125 171 R>C No EVA
rs3396010315 202 C>* No EVA
rs3396418179 204 R>G No EVA

No associated diseases with O35536

5 regional properties for O35536

Type Name Position InterPro Accession
domain Pancreatic trypsin inhibitor Kunitz domain 33 - 87 IPR002223-1
domain Pancreatic trypsin inhibitor Kunitz domain 94 - 147 IPR002223-2
domain Pancreatic trypsin inhibitor Kunitz domain 154 - 207 IPR002223-3
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 64 - 82 IPR020901-1
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 184 - 202 IPR020901-2

Functions

Description
EC Number
Subcellular Localization
  • Secreted
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

1 GO annotations of cellular component

Name Definition
extracellular space That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.

1 GO annotations of molecular function

Name Definition
serine-type endopeptidase inhibitor activity Binds to and stops, prevents or reduces the activity of a serine-type endopeptidase.

2 GO annotations of biological process

Name Definition
blood coagulation The sequential process in which the multiple coagulation factors of the blood interact, ultimately resulting in the formation of an insoluble fibrin clot; it may be divided into three stages
cellular response to fluid shear stress Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a fluid shear stress stimulus. Fluid shear stress is the force acting on an object in a system where the fluid is moving across a solid surface.

13 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q7YRQ8 TFPI2 Tissue factor pathway inhibitor 2 Bos taurus (Bovine) SS
Q868Z9 Ppn Papilin Drosophila melanogaster (Fruit fly) SS
M9PE65 axo Axotactin Drosophila melanogaster (Fruit fly) SS
P49223 SPINT3 Kunitz-type protease inhibitor 3 Homo sapiens (Human) SS
O43291 SPINT2 Kunitz-type protease inhibitor 2 Homo sapiens (Human) EV
O43278 SPINT1 Kunitz-type protease inhibitor 1 Homo sapiens (Human) EV
P10646 TFPI Tissue factor pathway inhibitor Homo sapiens (Human) SS
P48307 TFPI2 Tissue factor pathway inhibitor 2 Homo sapiens (Human) SS
Q9R097 Spint1 Kunitz-type protease inhibitor 1 Mus musculus (Mouse) SS
Q9WU03 Spint2 Kunitz-type protease inhibitor 2 Mus musculus (Mouse) SS
O54819 Tfpi Tissue factor pathway inhibitor Mus musculus (Mouse) SS
Q02445 Tfpi Tissue factor pathway inhibitor Rattus norvegicus (Rat) SS
Q28864 TFPI Tissue factor pathway inhibitor Macaca mulatta (Rhesus macaque) SS
10 20 30 40 50 60
MDPAMPLQLW NLPLLLVGSV LGLTSVSAQG NNLEICLLPL DAGPCQALIP KFYYDRDQQK
70 80 90 100 110 120
CRRFNYGGCL GNANNFHSRD LCQQTCGSIE KVPPVCRSEL KTYPCDKPNI RFFFNLNTMT
130 140 150 160 170 180
CEPLRPGLCS RTINVFSEEA TCKGLCEPRK HIPSFCSSPK DEGLCSANVT RFYFNSRNKT
190 200 210 220
CETFTYTGCG GNENNFYYLD ACHRACVKGW KKPKRWKIGD FLPRFWKHLS