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

35-89 (Pancreatic trypsin inhibitor Kunitz domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q9WU03

Entry ID Method Resolution Chain Position Source
AF-Q9WU03-F1 Predicted AlphaFoldDB

12 variants for Q9WU03

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3388878760 45 G>R No EVA
rs3545570687 48 R>W No EVA
rs3388855582 79 Q>R No EVA
rs3388891895 102 N>S No EVA
rs3388871297 112 S>T No EVA
rs240750205 121 D>E No EVA
rs226011340 153 T>A No EVA
rs3545643381 166 C>G No EVA
rs237682750 189 H>Y No EVA
rs219001834 216 S>A No EVA
rs3388891718 233 R>C No EVA
rs211813594 248 N>D No EVA

No associated diseases with Q9WU03

4 regional properties for Q9WU03

Type Name Position InterPro Accession
domain Pancreatic trypsin inhibitor Kunitz domain 35 - 89 IPR002223-1
domain Pancreatic trypsin inhibitor Kunitz domain 131 - 184 IPR002223-2
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 66 - 84 IPR020901-1
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 161 - 179 IPR020901-2

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Single-pass type I membrane protein
  • Cytoplasm
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

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.

7 GO annotations of biological process

Name Definition
basement membrane organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the basement membrane.
epithelial cell morphogenesis involved in placental branching The change in form (cell shape and size) that occurs when a trophoblast cell elongates to contribute to the branching of the placenta.
establishment or maintenance of cell polarity Any cellular process that results in the specification, formation or maintenance of anisotropic intracellular organization or cell growth patterns.
negative regulation of cell motility Any process that stops, prevents, or reduces the frequency, rate or extent of cell motility.
negative regulation of cell-cell adhesion Any process that stops, prevents or reduces the rate or extent of cell adhesion to another cell.
negative regulation of neural precursor cell proliferation Any process that stops, prevents, or reduces the frequency, rate or extent of neural precursor cell proliferation.
neural tube closure The last step in the formation of the neural tube, where the paired neural folds are brought together and fuse at the dorsal midline.

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
P48307 TFPI2 Tissue factor pathway inhibitor 2 Homo sapiens (Human) SS
P10646 TFPI Tissue factor pathway inhibitor Homo sapiens (Human) SS
O43278 SPINT1 Kunitz-type protease inhibitor 1 Homo sapiens (Human) EV
O43291 SPINT2 Kunitz-type protease inhibitor 2 Homo sapiens (Human) EV
Q9R097 Spint1 Kunitz-type protease inhibitor 1 Mus musculus (Mouse) SS
O35536 Tfpi2 Tissue factor pathway 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
MAQLCELRRG RALLALVASL LLSGAQVASR ELDVHESCGV SKVVGKCRAS IPRWWYNITD
70 80 90 100 110 120
GSCQPFVYGG CEGNGNNYQS KEECLDKCAG VTENTTDDMA RNRNGADSSV LSVPRKQSAE
130 140 150 160 170 180
DLSAEIFNYE EYCVPKAVTG PCRAAFPRWY YDTEKNSCIS FIYGGCRGNK NSYLSQEACM
190 200 210 220 230 240
QHCSGKQMHP FLTPGLKAVI LVGLFLMVLI LLLGTSMVCL IRVVRRKQER ALRTVWSTAD
250
DKEQLVKNTC VL