P49223

SS
Gene name
SPINT3
Protein name
Kunitz-type protease inhibitor 3
Names
HKIB9
Species
Homo sapiens (Human)
KEGG Pathway
hsa:10816
EC number
Protein Class

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)

55-56 (N-glycosylation site) SS

Target domain

33-87 (Pancreatic trypsin inhibitor Kunitz domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for P49223

Entry ID Method Resolution Chain Position Source
AF-P49223-F1 Predicted AlphaFoldDB

108 variants for P49223

Variant ID(s) Position Change Description Diseaes Association Provenance
rs1313122392 1 M>? Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
rs558255734 2 Q>* No 1000Genomes
TOPMed
gnomAD
rs558255734 2 Q>K No 1000Genomes
TOPMed
gnomAD
rs375957406 2 Q>L No 1000Genomes
ESP
ExAC
TOPMed
gnomAD
rs1426409058 4 Q>* No Ensembl
rs1333904465 5 A>T No gnomAD
rs1978852076 7 L>P No Ensembl
rs985823373 8 S>* No TOPMed
gnomAD
rs985823373 8 S>L No TOPMed
gnomAD
rs1404404623 11 L>R No gnomAD
rs572410069 11 L>V No 1000Genomes
ExAC
TOPMed
gnomAD
rs1028442756 12 I>V No TOPMed
gnomAD
rs1179309967 14 T>I No TOPMed
gnomAD
rs376249666 15 L>F No Ensembl
rs1468959241 16 C>R No gnomAD
rs977334887 18 E>A No TOPMed
gnomAD
rs1200802644 18 E>Q No TOPMed
gnomAD
rs1289688857 19 L>P No gnomAD
COSM1227386
COSM1227387
rs554197150
 20 R>* large_intestine [Cosmic] No cosmic curated
1000Genomes
TOPMed
gnomAD
rs371429401 20 R>L No ESP
TOPMed
gnomAD
rs371429401 20 R>P No ESP
TOPMed
gnomAD
COSM1592617
rs371429401
COSM1592618
 20 R>Q endometrium [Cosmic] No cosmic curated
ESP
TOPMed
gnomAD
rs151265860 21 S>* No 1000Genomes
TOPMed
rs151265860 21 S>L No 1000Genomes
TOPMed
rs2145528584 22 E>Q No Ensembl
rs1241709469 23 L>R No gnomAD
rs2145528582 23 L>V No Ensembl
rs888436313 24 A>P No Ensembl
rs999354455 25 R>* No TOPMed
gnomAD
rs1348455327
COSM5124698
COSM5124697
 25 R>Q Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
NCI-TCGA
TOPMed
gnomAD
rs1441676078 26 D>A No Ensembl
rs568339598 26 D>N No 1000Genomes
ExAC
TOPMed
gnomAD
rs1600861349 27 T>I No Ensembl
rs1600861349 27 T>N No Ensembl
rs1978774487 27 T>S No TOPMed
rs1978773910 29 K>N No Ensembl
rs1471198382 29 K>R No gnomAD
rs1600861344 30 D>V No TOPMed
rs990603726 34 N>D No TOPMed
gnomAD
rs953489376 35 V>A No TOPMed
rs950573306 36 C>* No TOPMed
gnomAD
rs1978773227 36 C>R No TOPMed
rs1176039969 37 A>S No TOPMed
gnomAD
rs1176039969 37 A>T No TOPMed
gnomAD
rs1429151750 37 A>V No gnomAD
TCGA novel 39 P>L Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1421779750 39 P>S No gnomAD
rs1464628649 40 M>T No gnomAD
rs201876626 40 M>V No TOPMed
gnomAD
rs1978772313 42 K>E No gnomAD
rs187227683 42 K>N No 1000Genomes
ESP
ExAC
TOPMed
gnomAD
rs1978772228 42 K>R No TOPMed
rs184344258 43 G>S No 1000Genomes
ExAC
TOPMed
gnomAD
rs1462523335 44 P>S No TOPMed
gnomAD
TCGA novel 46 Q>E Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs2145526849 46 Q>R No Ensembl
rs1232479273 47 T>I No gnomAD
rs1232479273 47 T>N No gnomAD
rs1978771050 48 Y>C No Ensembl
rs1978770763 49 M>K No Ensembl
rs1978770861 49 M>V No Ensembl
rs372278539 50 T>M No ESP
ExAC
TOPMed
gnomAD
rs148191315 51 R>* No 1000Genomes
ESP
ExAC
TOPMed
gnomAD
rs1315357830 51 R>Q No TOPMed
gnomAD
rs530253715 52 W>R No 1000Genomes
ExAC
gnomAD
rs960094338 53 F>L No TOPMed
gnomAD
rs367695635 54 F>L No ESP
TOPMed
gnomAD
rs73305953 54 F>S No 1000Genomes
ESP
ExAC
TOPMed
gnomAD
rs1325370716 55 N>D No TOPMed
rs766724366 55 N>S No ExAC
TOPMed
rs1978769485 56 F>S No gnomAD
rs1978769341 58 T>S No Ensembl
rs1449015013 59 G>S No gnomAD
rs1325666319 60 E>D No TOPMed
rs1319206946 60 E>K No TOPMed
gnomAD
rs1386065260 61 C>F No TOPMed
gnomAD
rs1978768874 61 C>R No TOPMed
rs763453592 62 E>D No ExAC
gnomAD
rs1476598254 63 L>F No gnomAD
rs1600861244 65 A>P No TOPMed
rs1600861244 65 A>T No TOPMed
TCGA novel 67 G>E Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs748269805 67 G>R No ExAC
TOPMed
gnomAD
rs1253073866 69 C>* No gnomAD
rs902742956 69 C>R No Ensembl
rs532406898 70 G>E No 1000Genomes
TOPMed
gnomAD
rs777486509 70 G>R No TOPMed
gnomAD
rs1022489132 71 G>D No Ensembl
rs1978767138 76 F>L No gnomAD
rs751739708 77 L>F No TOPMed
gnomAD
rs6032259
VAR_059443
 77 L>S No UniProt
1000Genomes
ExAC
TOPMed
dbSNP
gnomAD
rs1312479234 78 R>T No gnomAD
rs766390500 79 K>* No gnomAD
rs766390500 79 K>E No gnomAD
rs866920960 80 E>K No Ensembl
rs1376163935 81 K>I No gnomAD
rs2145526726 82 C>S No Ensembl
rs2145526723 82 C>Y No Ensembl
rs2145526715 83 E>D No Ensembl
rs1978765733 83 E>Q No TOPMed
rs1978765620 86 C>* No Ensembl
rs768976990 87 K>N No ExAC
gnomAD
rs1260554754 88 F>L No TOPMed
gnomAD
rs370265602 89 T>A No ESP
ExAC
gnomAD
rs1366302504 89 T>N No gnomAD
rs370265602 89 T>S No ESP
ExAC
gnomAD
rs1978764619 90 T>C No Ensembl
rs1245476662 90 T>R No gnomAD

No associated diseases with P49223

2 regional properties for P49223

Type Name Position InterPro Accession
domain Pancreatic trypsin inhibitor Kunitz domain 33 - 87 IPR002223
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 64 - 82 IPR020901

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.

No GO annotations of biological process

Name Definition
No GO annotations for biological process

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
P48307 TFPI2 Tissue factor pathway inhibitor 2 Homo sapiens (Human) SS
P10646 TFPI Tissue factor pathway inhibitor 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
Q9R097 Spint1 Kunitz-type protease inhibitor 1 Mus musculus (Mouse) SS
O35536 Tfpi2 Tissue factor pathway inhibitor 2 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
MQLQASLSFL LILTLCLELR SELARDTIKD LLPNVCAFPM EKGPCQTYMT RWFFNFETGE
70 80
CELFAYGGCG GNSNNFLRKE KCEKFCKFT