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

1846-1900 (Pancreatic trypsin inhibitor Kunitz domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

0 structures for Q868Z9

Entry ID Method Resolution Chain Position Source

No variants for Q868Z9

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q868Z9

No associated diseases with Q868Z9

17 regional properties for Q868Z9

Type Name Position InterPro Accession
domain Protein kinase domain 582 - 910 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 582 - 910 IPR001245
conserved_site Tyrosine-protein kinase, receptor class III, conserved site 641 - 654 IPR001824
domain Immunoglobulin subtype 2 215 - 285 IPR003598-1
domain Immunoglobulin subtype 2 410 - 492 IPR003598-2
domain Immunoglobulin subtype 27 - 102 IPR003599-1
domain Immunoglobulin subtype 112 - 196 IPR003599-2
domain Immunoglobulin subtype 209 - 296 IPR003599-3
domain Immunoglobulin subtype 308 - 399 IPR003599-4
domain Immunoglobulin subtype 404 - 504 IPR003599-5
domain Immunoglobulin-like domain 21 - 85 IPR007110-1
domain Immunoglobulin-like domain 203 - 290 IPR007110-2
domain Immunoglobulin-like domain 402 - 502 IPR007110-3
active_site Tyrosine-protein kinase, active site 774 - 786 IPR008266
domain Immunoglobulin 209 - 292 IPR013151
binding_site Protein kinase, ATP binding site 588 - 616 IPR017441
domain Tyrosine-protein kinase, catalytic domain 582 - 910 IPR020635

Functions

Description
EC Number
Subcellular Localization
  • Secreted, extracellular space, extracellular matrix, basement membrane
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
basement membrane A collagen-containing extracellular matrix consisting of a thin layer of dense material found in various animal tissues interposed between the cells and the adjacent connective tissue. It consists of the basal lamina plus an associated layer of reticulin fibers.
extracellular region The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite.

3 GO annotations of molecular function

Name Definition
extracellular matrix structural constituent The action of a molecule that contributes to the structural integrity of the extracellular matrix.
metalloendopeptidase activity Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which water acts as a nucleophile, one or two metal ions hold the water molecule in place, and charged amino acid side chains are ligands for the metal ions.
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
extracellular matrix organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an extracellular matrix.
proteolysis The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds.

26 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q7YRQ8 TFPI2 Tissue factor pathway inhibitor 2 Bos taurus (Bovine) SS
M9PE65 axo Axotactin Drosophila melanogaster (Fruit fly) SS
Q04721 NOTCH2 Neurogenic locus notch homolog protein 2 Homo sapiens (Human) EV
P46531 NOTCH1 Neurogenic locus notch homolog protein 1 Homo sapiens (Human) EV
P21941 MATN1 Cartilage matrix protein Homo sapiens (Human) PR
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
O43291 SPINT2 Kunitz-type protease inhibitor 2 Homo sapiens (Human) EV
O43278 SPINT1 Kunitz-type protease inhibitor 1 Homo sapiens (Human) EV
Q6GUQ1 Egfl8 Epidermal growth factor-like protein 8 Mus musculus (Mouse) PR
Q01705 Notch1 Neurogenic locus notch homolog protein 1 Mus musculus (Mouse) SS
Q91V88 Npnt Nephronectin Mus musculus (Mouse) PR
O35516 Notch2 Neurogenic locus notch homolog protein 2 Mus musculus (Mouse) SS
P51942 Matn1 Cartilage matrix protein Mus musculus (Mouse) PR
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
Q9QW30 Notch2 Neurogenic locus notch homolog protein 2 Rattus norvegicus (Rat) SS
Q07008 Notch1 Neurogenic locus notch homolog protein 1 Rattus norvegicus (Rat) SS
Q02445 Tfpi Tissue factor pathway inhibitor Rattus norvegicus (Rat) SS
Q28864 TFPI Tissue factor pathway inhibitor Macaca mulatta (Rhesus macaque) SS
P13508 glp-1 Protein glp-1 Caenorhabditis elegans EV
A2RUV0 notch1 Neurogenic locus notch homolog protein 1 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
P46530 notch1a Neurogenic locus notch homolog protein 1 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MDLSRRLCST ALVAFIVLAS IHDSQSRFPG LRQKRQYGAN MYLPESSVTP GGEGNDPDEW
70 80 90 100 110 120
TPWSSPSDCS RTCGGGVSYQ TRECLRRDDR GEAVCSGGSR RYFSCNTQDC PEEESDFRAQ
130 140 150 160 170 180
QCSRFDRQQF DGVFYEWVPY TNAPNPCELN CMPKGERFYY RQREKVVDGT RCNDKDLDVC
190 200 210 220 230 240
VNGECMPVGC DMMLGSDAKE DKCRKCGGDG STCKTIRNTI TTKDLAPGYN DLLLLPEGAT
250 260 270 280 290 300
NIRIEETVPS SNYLACRNHS GHYYLNGDWR IDFPRPMFFA NSWWNYQRKP MGFAAPDQLT
310 320 330 340 350 360
CSGPISESLF IVMLVQEKNI SLDYEYSIPE SLSHSQQDTH TWTHHQFNAC SASCGGGSQS
370 380 390 400 410 420
RKVTCNNRIT LAEVNPSLCD QKSKPVEEQA CGTEPCAPHW VEGEWSKCSK GCGSDGFQNR
430 440 450 460 470 480
SITCERISSS GEHTVEEDAV CLKEVGNKPA TKQECNRDVK NCPKYHLGPW TPCDKLCGDG
490 500 510 520 530 540
KQTRKVTCFI EENGHKRVLP EEDCVEEKPE TEKSCLLTPC EGVDWIISQW SGCNACGQNT
550 560 570 580 590 600
ETRTAICGNK EGKVYPEEFC EPEVPTLSRP CKSPKCEAQW FSSEWSKCSA PCGKGVKSRI
610 620 630 640 650 660
VICGEFDGKT VTPADDDSKC NKETKPESEQ DCEGEEKVCP GEWFTGPWGK CSKPCGGGER
670 680 690 700 710 720
VREVLCLSNG TKSVNCDEEK VEPLSEKCNS EACTEDEILP LTSTDKPIED DEEDCDEDGI
730 740 750 760 770 780
ELISDGLSDD EKSEDVIDLE GTAKTETTPE AEDLMQSDSP TPYDEFESTG TTFEGSGYDS
790 800 810 820 830 840
ESTTDSGIST EGSGDDEETS EASTDLSSST DSGSTSSDST SSDSSSSISS DATSEAPASS
850 860 870 880 890 900
VSDSSDSTDA STETTGVSDD STDVSSSTEA SASESTDVSG ASDSTGSTNA SDSTPESSTE
910 920 930 940 950 960
ASSSTDDSTD SSDNSSNVSE SSTEASSSSV SDSNDSSDGS TDGVSSTTEN SSDSTSDATS
970 980 990 1000 1010 1020
DSTASSDSTD STSDQTTETT PESSTDSTES STLDASSTTD ASSTSESSSE SSTDGSSTTS
1030 1040 1050 1060 1070 1080
NSASSETTGL SSDGSTTDAT TAASDNTDIT TDGSTDESTD GSSNASTEGS TEGASEDTTI
1090 1100 1110 1120 1130 1140
STESSGSTES TDAIASDGST TEGSTVEDLS SSTSSDVTSD STITDSSPST EVSGSTDSSS
1150 1160 1170 1180 1190 1200
STDGSSTDAS STEASSTDVT ESTDSTVSGG TSDTTESGPT EESTTEGSTE STTEGSTDST
1210 1220 1230 1240 1250 1260
QSTDLDSTTS DIWSTSDKDD ESESSTPYSF DSEVTKSKPR KCKPKKSTCA KSEYGCCPDG
1270 1280 1290 1300 1310 1320
KSTPKGPFDE GCPIAKTCAD TKYGCCLDGV SPAKGKNNKG CPKSQCAETL FGCCPDKFTA
1330 1340 1350 1360 1370 1380
ADGENDEGCP ETTTVPPTTT TEETQPETTT EIEGSGQDST TSEPDTKKSC SFSEFGCCPD
1390 1400 1410 1420 1430 1440
AETSAKGPDF EGCGLASPVA KGCAESENGC CPDGQTPASG PNGEGCSGCT RERFGCCPDS
1450 1460 1470 1480 1490 1500
QTPAHGPNKE GCCLDTQFGC CPDNILAARG PNNEGCECHY TPYGCCPDNK SAATGYNQEG
1510 1520 1530 1540 1550 1560
CACETTQYGC CPDKITAAKG PKHEGCPCET TQFGCCPDGL TFAKGPHHHG CHCTQTEFKC
1570 1580 1590 1600 1610 1620
CDDEKTPAKG PNGDGCTCVE SKFGCCPDGV TKATDEKFGG CENVQEPPQK ACGLPKETGT
1630 1640 1650 1660 1670 1680
CNNYSVKYYF DTSYGGCARF WYGGCDGNDN RFESEAECKD TCQDYTGKHV CLLPKSAGPC
1690 1700 1710 1720 1730 1740
TGFTKKWYFD VDRNRCEEFQ YGGCYGTNNR FDSLEQCQGT CAASENLPTC EQPVESGPCA
1750 1760 1770 1780 1790 1800
GNFERWYYDN ETDICRPFTY GGCKGNKNNY PTEHACNYNC RQPGVLKDRC ALPKQTGDCS
1810 1820 1830 1840 1850 1860
EKLAKWHFSE SEKRCVPFYY SGCGGNKNNF PTLESCEDHC PRQVAKDICE IPAEVGECAN
1870 1880 1890 1900 1910 1920
YVTSWYYDTQ DQACRQFYYG GCGGNENRFP TEESCLARCD RKPEPTTTTP ATRPQPSRQD
1930 1940 1950 1960 1970 1980
VCDEEPAPGE CSTWVLKWHF DRKIGACRQF YYGNCGGNGN RFETENDCQQ RCLSQEPPAP
1990 2000 2010 2020 2030 2040
TPPRAPAPTR QPDPAPTVAQ CSQPADPGQC DKWALHWNYN ETEGRCQSFY YGGCGGNDNR
2050 2060 2070 2080 2090 2100
FATEEECSAR CSVNIDIRIG ADPVEHDTSK CFLAFEPGNC YNNVTRWFYN SAEGLCDEFV
2110 2120 2130 2140 2150 2160
YTGCGGNANN YATEEECQNE CNDAQTTCAL PPVRGRCSDL SRRWYFDERS GECHEFEFTG
2170 2180 2190 2200 2210 2220
CRGNRNNFVS QSDCLNFCIG EPVVEPSAPT YSVCAEPPEA GECDNRTTAW FYDSENMACT
2230 2240 2250 2260 2270 2280
AFTYTGCGGN GNRFETRDQC ERQCGEFKGV DVCNEPVTTG PCTDWQTKYY FNTASQACEP
2290 2300 2310 2320 2330 2340
FTYGGCDGTG NRFSDLFECQ TVCLAGREPR VGSAKEICLL PVATGRCNGP SVHERRWYYD
2350 2360 2370 2380 2390 2400
DEAGNCVSFI YAGCSGNQNN FRSFEACTNQ CRPEPNKQDN EIGQNPCDTF DAECQELRCP
2410 2420 2430 2440 2450 2460
YGVRRVAARS QPECTQCICE NPCEGYSCPE GQQCAIDVAS SDDRQFAPVC RDIYKPGECP
2470 2480 2490 2500 2510 2520
ALSANASGCA RECYTDADCR GDNKCCSDGC GQLCVHPARP TQPPRTQAPV VSYPGDARAA
2530 2540 2550 2560 2570 2580
LEPKEAHELD VQTAIGGIAV LRCFATGNPA PNITWSLKNL VINTNKGRYV LTANGDLTIV
2590 2600 2610 2620 2630 2640
QVRQTDDGTY VCVASNGLGE PVRREVALQV TEPVSQPAYI YGDKNVTQIV ELNRPAVIRC
2650 2660 2670 2680 2690 2700
PAGGFPEPHV SWWRNGQMFG LKNNLMARDY SLVFNSIQLS DLGLYTCEVY NQRRPVSLRV
2710 2720 2730 2740 2750 2760
TLKAVGPVRP LSPEEEQYMQ YVLNPATRPV TQRPSYPYRP TRPAYVPEPT VNVHAVLALE
2770 2780 2790 2800 2810 2820
PKNSYTPGST IVMSCSVQGY PEPNVTWIKD DVPLYNNERV QITYQPHRLV LSDVTSADSG
2830 2840 2850 2860 2870 2880
KYTCRASNAY TYANGEANVS IQSVVPVSPE CVDNPYFANC KLIVKGRYCS NPYYTQFCCR
2890
SCTLAGQVAS PPLHPNAV