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

47-101 (Pancreatic trypsin inhibitor Kunitz domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for O54819

Entry ID Method Resolution Chain Position Source
AF-O54819-F1 Predicted AlphaFoldDB

19 variants for O54819

Variant ID(s) Position Change Description Diseaes Association Provenance
rs6187124 9 Y>H No EVA
rs3388560568 24 E>G No EVA
rs28010515 24 E>K No EVA
rs3388560545 27 N>S No EVA
rs3388564352 39 E>V No EVA
rs3388566585 40 L>V No EVA
rs3388560610 64 R>S No EVA
rs3388555678 66 Y>D No EVA
rs3388564067 77 E>K No EVA
rs3388568404 82 G>* No EVA
rs3388565134 100 C>R No EVA
rs3388565134 100 C>S No EVA
rs3391886289 127 P>H No EVA
rs3391852129 128 G>V No EVA
rs3391835213 130 C>G No EVA
rs3388564061 159 N>S No EVA
rs3388568509 281 K>N No EVA
rs3388568390 290 I>F No EVA
rs3388564234 302 Y>* No EVA

No associated diseases with O54819

5 regional properties for O54819

Type Name Position InterPro Accession
domain Formin, FH3 domain 231 - 429 IPR010472
domain Formin, GTPase-binding domain 40 - 228 IPR010473
domain Diaphanous autoregulatory (DAD) domain 1025 - 1055 IPR014767
domain Rho GTPase-binding/formin homology 3 (GBD/FH3) domain 40 - 416 IPR014768
domain Formin, FH2 domain 605 - 1058 IPR015425

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.

3 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 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.

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
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
MTYKMKKEYA FWATVCLLLS LVPEFLNALS EEADDTDSEL GSMKPLHTFC AMKADDGPCK
70 80 90 100 110 120
AMIRSYFFNM YTHQCEEFIY GGCEGNENRF DTLEECKKTC IPGYEKTAVK AASGAERPDF
130 140 150 160 170 180
CFLEEDPGLC RGYMKRYLYN NQTKQCERFV YGGCLGNRNN FETLDECKKI CENPVHSPSP
190 200 210 220 230 240
VNEVQMSDYV TDGNTVTDRS TVNNIVVPQS PKVPRRRDYR GRPWCLQPAD SGLCKASERR
250 260 270 280 290 300
FYYNSATGKC HRFNYTGCGG NNNNFTTRRR CLRSCKTGLI KNKSKGVVKI QRRKAPFVKV
VYESIN