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

50-104 (Pancreatic trypsin inhibitor Kunitz domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q02445

Entry ID Method Resolution Chain Position Source
AF-Q02445-F1 Predicted AlphaFoldDB

1 variants for Q02445

Variant ID(s) Position Change Description Diseaes Association Provenance
rs197267875 187 V>I No EVA

No associated diseases with Q02445

6 regional properties for Q02445

Type Name Position InterPro Accession
domain Pancreatic trypsin inhibitor Kunitz domain 50 - 104 IPR002223-1
domain Pancreatic trypsin inhibitor Kunitz domain 122 - 175 IPR002223-2
domain Pancreatic trypsin inhibitor Kunitz domain 220 - 273 IPR002223-3
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 81 - 99 IPR020901-1
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 152 - 170 IPR020901-2
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 250 - 268 IPR020901-3

Functions

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

3 GO annotations of cellular component

Name Definition
caveola A membrane raft that forms small pit, depression, or invagination that communicates with the outside of a cell and extends inward, indenting the cytoplasm and the cell membrane. Examples include flask-shaped invaginations of the plasma membrane in adipocytes associated with caveolin proteins, and minute pits or incuppings of the cell membrane formed during pinocytosis. Caveolae may be pinched off to form free vesicles within the cytoplasm.
cell surface The external part of the cell wall and/or plasma membrane.
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.

7 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 interleukin-1 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 an interleukin-1 stimulus.
cellular response to lipopolysaccharide 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 lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
cellular response to steroid hormone stimulus 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 steroid hormone stimulus.
negative regulation of blood coagulation Any process that stops, prevents, or reduces the frequency, rate or extent of blood coagulation.
response to estradiol Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by estradiol, a C18 steroid hormone hydroxylated at C3 and C17 that acts as a potent estrogen.
response to lipopolysaccharide Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.

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
P48307 TFPI2 Tissue factor pathway inhibitor 2 Homo sapiens (Human) SS
P10646 TFPI Tissue factor pathway inhibitor 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
O35536 Tfpi2 Tissue factor pathway inhibitor 2 Mus musculus (Mouse) SS
O54819 Tfpi Tissue factor pathway inhibitor Mus musculus (Mouse) SS
Q28864 TFPI Tissue factor pathway inhibitor Macaca mulatta (Rhesus macaque) SS
10 20 30 40 50 60
MTNKLKKDHA FWAAVCLLLS IVPELLNALP EEDDDTINTD SELRPMKPLH TFCAMKAEDG
70 80 90 100 110 120
PCKAMIRSYY FNMNSHQCEE FIYGGCRGNK NRFDTLEECR KTCIPGYKKT TIKTTSGAEK
130 140 150 160 170 180
PDFCFLEEDP GICRGFMTRY FYNNQSKQCE QFKYGGCLGN SNNFETLEEC RNTCEDPVNE
190 200 210 220 230 240
VQKGDYVTNQ ITVTDRTTVN NVVIPQATKA PSQWDYDGPS WCLEPADSGL CKASEKRFYY
250 260 270 280 290 300
NPAIGKCRQF NYTGCGGNNN NFTTKQDCNR ACKKDSSKKS SKRAKTQRRR KSFVKVMYEN
IH