Descriptions

Von Willebrand Factor (VWF) is a giant extracellular protein playing a key role in blood clotting. Activated by shear-stress, VWF crosslinks the endothelial extracellular matrix with blood platelets at the site of vascular injury. Functional VWF is a linear multimer of tens of covalently linked monomers, extending up to 15 mm. Autoinhibition of VWF is mediated by the A1-A2 domain-domain interaction. The VWF A2 domain targets and blocks specific regions of the VWF A1 domain that correspond to the binding site of the platelet glycoprotein Iba (GPIba) receptor. A stretching force unblocks the GPIba binding site by dissociating the A1A2 complex. Also, the autoinhibitory modules (AIMs) flanking the VWF-A1 domain contribute to autoinhibition of the VWF. The N-terminal AIM cooperates with the C-terminal AIM to form a joint Rotini-like structure, partially autoinhibiting the VWF-A1-GPIba interaction.

Autoinhibitory domains (AIDs)

Target domain

125-185 (v-SNARE coiled-coil homology)

Relief mechanism

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q9JHW5

Entry ID Method Resolution Chain Position Source
AF-Q9JHW5-F1 Predicted AlphaFoldDB

No variants for Q9JHW5

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9JHW5

No associated diseases with Q9JHW5

3 regional properties for Q9JHW5

Type Name Position InterPro Accession
binding_site IQ motif, EF-hand binding site 159 - 181 IPR000048-1
binding_site IQ motif, EF-hand binding site 205 - 235 IPR000048-2
domain ATPase, AAA-type, core 563 - 680 IPR003959

Functions

Description
EC Number
Subcellular Localization
  • Secreted
  • Secreted, extracellular space, extracellular matrix
  • Localized to storage granules
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

26 GO annotations of cellular component

Name Definition
apical part of cell The region of a polarized cell that forms a tip or is distal to a base. For example, in a polarized epithelial cell, the apical region has an exposed surface and lies opposite to the basal lamina that separates the epithelium from other tissue.
azurophil granule membrane The lipid bilayer surrounding an azurophil granule, a primary lysosomal granule found in neutrophil granulocytes that contains a wide range of hydrolytic enzymes and is released into the extracellular fluid.
cell surface The external part of the cell wall and/or plasma membrane.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
endoplasmic reticulum membrane The lipid bilayer surrounding the endoplasmic reticulum.
filopodium Thin, stiff, actin-based protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal or dendritic growth cone, or a dendritic shaft.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
hippocampal mossy fiber to CA3 synapse One of the giant synapses that form between the mossy fiber axons of dentate gyrus granule cells and the large complex spines of CA3 pyramidal cells. It consists of a giant bouton known as the mossy fiber expansion, synapsed to the complex, multiheaded spine (thorny excresence) of a CA3 pyramidal cell.
lamellipodium A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments.
late endosome membrane The lipid bilayer surrounding a late endosome.
lysosomal membrane The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.
neuron projection A prolongation or process extending from a nerve cell, e.g. an axon or dendrite.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
phagocytic vesicle A membrane-bounded intracellular vesicle that arises from the ingestion of particulate material by phagocytosis.
phagocytic vesicle membrane The lipid bilayer surrounding a phagocytic vesicle.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
platelet alpha granule A secretory organelle found in blood platelets, which is unique in that it exhibits further compartmentalization and acquires its protein content via two distinct mechanisms
pseudopodium A temporary protrusion or retractile process of a cell, associated with flowing movements of the protoplasm, and serving for locomotion and feeding.
secretory granule A small subcellular vesicle, surrounded by a membrane, that is formed from the Golgi apparatus and contains a highly concentrated protein destined for secretion. Secretory granules move towards the periphery of the cell and upon stimulation, their membranes fuse with the cell membrane, and their protein load is exteriorized. Processing of the contained protein may take place in secretory granules.
secretory granule membrane The lipid bilayer surrounding a secretory granule.
SNARE complex A protein complex involved in membrane fusion; a stable ternary complex consisting of a four-helix bundle, usually formed from one R-SNARE and three Q-SNAREs with an ionic layer sandwiched between hydrophobic layers. One well-characterized example is the neuronal SNARE complex formed of synaptobrevin 2, syntaxin 1a, and SNAP-25.
synaptic vesicle A secretory organelle, typically 50 nm in diameter, of presynaptic nerve terminals; accumulates in high concentrations of neurotransmitters and secretes these into the synaptic cleft by fusion with the 'active zone' of the presynaptic plasma membrane.
synaptic vesicle membrane The lipid bilayer surrounding a synaptic vesicle.
trans-Golgi network The network of interconnected tubular and cisternal structures located within the Golgi apparatus on the side distal to the endoplasmic reticulum, from which secretory vesicles emerge. The trans-Golgi network is important in the later stages of protein secretion where it is thought to play a key role in the sorting and targeting of secreted proteins to the correct destination.
transport vesicle Any of the vesicles of the constitutive secretory pathway, which carry cargo from the endoplasmic reticulum to the Golgi, between Golgi cisternae, from the Golgi to the ER (retrograde transport) or to destinations within or outside the cell.

3 GO annotations of molecular function

Name Definition
SNAP receptor activity Acting as a marker to identify a membrane and interacting selectively with one or more SNAREs on another membrane to mediate membrane fusion.
SNARE binding Binding to a SNARE (soluble N-ethylmaleimide-sensitive factor attached protein receptor) protein.
syntaxin binding Binding to a syntaxin, a SNAP receptor involved in the docking of synaptic vesicles at the presynaptic zone of a synapse.

18 GO annotations of biological process

Name Definition
calcium-ion regulated exocytosis The release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle by fusion of the vesicle with the plasma membrane of a cell, induced by a rise in cytosolic calcium-ion levels.
endoplasmic reticulum to Golgi vesicle-mediated transport The directed movement of substances from the endoplasmic reticulum (ER) to the Golgi, mediated by COP II vesicles. Small COP II coated vesicles form from the ER and then fuse directly with the cis-Golgi. Larger structures are transported along microtubules to the cis-Golgi.
endosome to lysosome transport The directed movement of substances from endosomes to lysosomes.
eosinophil degranulation The regulated exocytosis of secretory granules containing preformed mediators such as major basic protein, eosinophil peroxidase, and eosinophil cationic protein by an eosinophil.
exocytosis A process of secretion by a cell that results in the release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle. Exocytosis can occur either by full fusion, when the vesicle collapses into the plasma membrane, or by a kiss-and-run mechanism that involves the formation of a transient contact, a pore, between a granule (for exemple of chromaffin cells) and the plasma membrane. The latter process most of the time leads to only partial secretion of the granule content. Exocytosis begins with steps that prepare vesicles for fusion with the membrane (tethering and docking) and ends when molecules are secreted from the cell.
Golgi to plasma membrane protein transport The directed movement of proteins from the Golgi to the plasma membrane in transport vesicles that move from the trans-Golgi network to the plasma membrane.
natural killer cell degranulation The regulated exocytosis of secretory granules containing preformed mediators such as perforin and granzymes by a natural killer cell.
neutrophil degranulation The regulated exocytosis of secretory granules containing preformed mediators such as proteases, lipases, and inflammatory mediators by a neutrophil.
phagocytosis, engulfment The internalization of bacteria, immune complexes and other particulate matter or of an apoptotic cell by phagocytosis, including the membrane and cytoskeletal processes required, which involves one of three mechanisms
positive regulation of dendrite morphogenesis Any process that activates or increases the frequency, rate or extent of dendrite morphogenesis.
positive regulation of histamine secretion by mast cell Any process that activates or increases the frequency, rate or extent of histamine secretion by mast cell.
regulation of protein targeting to vacuolar membrane Any process that modulates the frequency, rate or extent of protein targeting to vacuolar membrane.
SNARE complex assembly The aggregation, arrangement and bonding together of a set of components to form a SNARE complex, a protein complex involved in membrane fusion; a stable ternary complex consisting of a four-helix bundle, usually formed from one R-SNARE and three Q-SNAREs with an ionic layer sandwiched between hydrophobic layers.
triglyceride transport The directed movement of triglyceride into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Triglycerides are important components of plant oils, animal fats and animal plasma lipoproteins.
vesicle fusion Fusion of the membrane of a transport vesicle with its target membrane.
vesicle fusion with Golgi apparatus The joining of the lipid bilayer membrane around a vesicle to the lipid bilayer membrane around the Golgi.
vesicle transport along microtubule The directed movement of a vesicle along a microtubule, mediated by motor proteins. This process begins with the attachment of a vesicle to a microtubule, and ends when the vesicle reaches its final destination.
vesicle-mediated transport A cellular transport process in which transported substances are moved in membrane-bounded vesicles; transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. The process begins with a step that directs a substance to the forming vesicle, and includes vesicle budding and coating. Vesicles are then targeted to, and fuse with, an acceptor membrane.

10 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q12255 NYV1 Vacuolar v-SNARE NYV1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
Q17QI5 VAMP7 Vesicle-associated membrane protein 7 Bos taurus (Bovine) SS
Q5ZL74 VAMP7 Vesicle-associated membrane protein 7 Gallus gallus (Chicken) SS
P51809 VAMP7 Vesicle-associated membrane protein 7 Homo sapiens (Human) EV
P70280 Vamp7 Vesicle-associated membrane protein 7 Mus musculus (Mouse) SS
O49377 VAMP711 Vesicle-associated membrane protein 711 Arabidopsis thaliana (Mouse-ear cress) SS
Q9FMR5 VAMP714 Vesicle-associated membrane protein 714 Arabidopsis thaliana (Mouse-ear cress) PR
Q9LFP1 VAMP713 Vesicle-associated membrane protein 713 Arabidopsis thaliana (Mouse-ear cress) SS
Q9M376 VAMP727 Vesicle-associated membrane protein 727 Arabidopsis thaliana (Mouse-ear cress) SS
Q9SIQ9 VAMP712 Vesicle-associated membrane protein 712 Arabidopsis thaliana (Mouse-ear cress) SS
10 20 30 40 50 60
MNPFRYEICL LVLALTWPGT LCTEKPRDRP STARCSLFGD DFINTFDETM YSFAGGCSYL
70 80 90 100 110 120
LAGDCQKRSF SILGNFQDGK RMSLSVYLGE FFDIHLFANG TVMQGDQSIS MPYASQGLYL
130 140 150 160 170 180
ELEAGYYKLS SETFGFAARI DGNGNFQVLM SDRHFNKTCG LCGDFNIFAE DDFRTQEGTL
190 200 210 220 230 240
TSDPYDFANS WALSSEEQRC KRASPPSRNC ESSSGDMHQA MWEQCQLLKT ASVFARCHPL
250 260 270 280 290 300
VDPESFVALC EKILCTCATG PECACPVLLE YARTCAQEGM VLYGWTDHSA CRPACPAGME
310 320 330 340 350 360
YKECVSPCPR TCQSLSINEV CQQQCVDGCS CPEGELLDED RCVQSSDCPC VHAGKRYPPG
370 380 390 400 410 420
TSLSQDCNTC ICRNSLWICS NEECPGECLV TGQSHFKSFD NRYFTFSGIC QYLLARDCED
430 440 450 460 470 480
HTFSIVIETM QCADDPDAVC TRSVSVRLSA LHNSLVKLKH GGAVGIDGQD VQLPFLQGDL
490 500 510 520 530 540
RIQHTVMASV RLSYAEDLQM DWDGRGRLLV KLSPVYSGKT CGLCGNYNGN KGDDFLTPAG
550 560 570 580 590 600
LVEPLVVDFG NAWKLQGDCS DLRRQHSDPC SLNPRLTRFA EEACALLTSS KFEACHHAVS
610 620 630 640 650 660
PLPYLQNCRY DVCSCSDSRD CLCNAVANYA AECARKGVHI GWREPGFCAL GCPQGQVYLQ
670 680 690 700 710 720
CGNSCNLTCR SLSLPDEECS EVCLEGCYCP PGLYQDERGD CVPKAQCPCY YDGELFQPAD
730 740 750 760 770 780
IFSDHHTMCY CEDGFMHCTT SGTLGSLLPD TVLSSPLSHR SKRSLSCRPP MVKLVCPADN
790 800 810 820 830 840
PRAQGLECAK TCQNYDLERM SLGCVSGCLC PPGMVRHENK CVALERCPCF HQGAEYAPGD
850 860 870 880 890 900
TVKIGCNTCV CRERKWNCTN HVCDATRSAI GMAHYLTFDG LKYLFPGECQ YVLVYDYCGS
910 920 930 940 950 960
NPGTFQILVG NEGCSYPSVK CRKRVTILVD GGELELFDGE VNVKRPLRDE SHFEVVESGR
970 980 990 1000 1010 1020
YVILLLGQAL SVVWDHHLSI SVVLKHTYQE QVCGLCGNFD GIQNNDSTTS SLQVEEDPVN
1030 1040 1050 1060 1070 1080
FGNSWKVSSQ CADTRKLSLD VSPATCHNNI MKQTMVDSAC RILTSDVFQG CNRLVDPEPY
1090 1100 1110 1120 1130 1140
LDICIYDTCS CESIGDCACF CDTIAAYAHV CAQHGQVVAW RTPTLCPQSC EEKNVRENGY
1150 1160 1170 1180 1190 1200
ECEWRYNSCA PACPVTCQHP EPLACPVQCV EGCHAHCPPG RILDELLQTC VDPQDCPVCE
1210 1220 1230 1240 1250 1260
VAGRRLAPGK KITLSPDDPA HCQNCHCDGV NLTCEACQEP GGLVAPPTDA PVSSTTPYVE
1270 1280 1290 1300 1310 1320
DTPEPPLHNF YCSKLLDLVF LLDGSSMLSE AEFEVLKAFV VGMMERLHIS QKRIRVAVVE
1330 1340 1350 1360 1370 1380
YHDGSRAYLE LKARKRPSEL RRITSQIKYT GSQVASTSEV LKYTLFQIFG KIDRPEASHI
1390 1400 1410 1420 1430 1440
TLLLTASQEP PRMARNLVRY VQGLKKKKVI VIPVGIGPHA SLKQIRLIEK QAPENKAFLL
1450 1460 1470 1480 1490 1500
SGVDELEQRR DEIVSYLCDL APEAPAPTQP PQVAHVTVSP GIAGISSPGP KRKSMVLDVV
1510 1520 1530 1540 1550 1560
FVLEGSDEVG EANFNKSKEF VEEVIQRMDV SPDATRISVL QYSYTVTMEY AFNGAQSKEE
1570 1580 1590 1600 1610 1620
VLRHVREIRY QGGNRTNTGQ ALQYLSEHSF SPSQGDRVEA PNLVYMVTGN PASDEIKRLP
1630 1640 1650 1660 1670 1680
GDIQVVPIGV GPHANMQELE RISRPIAPIF IRDFETLPRE APDLVLQTCC SKEGLQLPTL
1690 1700 1710 1720 1730 1740
PPLPDCSQPL DVVLLLDGSS SLPESSFDKM KSFAKAFISK ANIGPHLTQV SVIQYGSINT
1750 1760 1770 1780 1790 1800
IDVPWNVVQE KAHLQSLVDL MQQEGGPSQI GDALAFAVRY VTSQIHGARP GASKAVVIII
1810 1820 1830 1840 1850 1860
MDTSLDPVDT AADAARSNRV AVFPVGVGDR YDEAQLRILA GPGASSNVVK LQQVEDLSTM
1870 1880 1890 1900 1910 1920
ATLGNSFFHK LCSGFSGVCV DEDGNEKRPG DVWTLPDQCH TVTCLANGQT LLQSHRVNCD
1930 1940 1950 1960 1970 1980
HGPRPSCANS QSPVRVEETC GCRWTCPCVC TGSSTRHIVT FDGQNFKLTG SCSYVIFQNK
1990 2000 2010 2020 2030 2040
EQDLEVLLHN GACSPGAKQA CMKSIEIKHA GVSAELHSNM EMAVDGRLVL APYVGENMEV
2050 2060 2070 2080 2090 2100
SIYGAIMYEV RFTHLGHILT YTPQNNEFQL QLSPKTFASK MHGLCGICDE NGANDFTLRD
2110 2120 2130 2140 2150 2160
GTVTTDWKRL VQEWTVQQPG YTCQAVPEEQ CPVSDSSHCQ VLLSASFAEC HKVIAPATFH
2170 2180 2190 2200 2210 2220
TICQQDSCHQ ERVCEVIASY AHLCRTSGVC VDWRTTDFCA MSCPPSLVYN HCERGCPRHC
2230 2240 2250 2260 2270 2280
DGNTSFCGDH PSEGCFCPQH QVFLEGSCVP EEACTQCVGE DGVRHQFLET WVPDHQPCQI
2290 2300 2310 2320 2330 2340
CMCLSGRKIN CTAQPCPTAR APTCGPCEVA RLKQSTNLCC PEYECVCDLF NCNLPPVPPC
2350 2360 2370 2380 2390 2400
EGGLQPTLTN PGECRPTFTC DCRKEECKRV SPPSCPPHRT PTLRKTQCCD EYECACSCVN
2410 2420 2430 2440 2450 2460
STLSCPLGYL ASATTNDCGC TTTTCLPDKV CVHRGTVYPV GQFWEEGCDT CTCTDMEDTV
2470 2480 2490 2500 2510 2520
VGLRVVQCSQ RPCEDSCQPG FSYVLHEGEC CGRCLPSACK VVAGSLRGDS HSSWKSVGSR
2530 2540 2550 2560 2570 2580
WAVPENPCLV NECVRVEDAV FVQQRNISCP QLAVPTCPTG FQLNCETSEC CPSCHCEPVE
2590 2600 2610 2620 2630 2640
ACLLNGTIIG PGKSVMVDLC TTCRCIVQTD AISRFKLECR KTTCEACPMG YREEKSQGEC
2650 2660 2670 2680 2690 2700
CGRCLPTACT IQLRGGRIMT LKQDETFQDG CDSHLCRVNE RGEYIWEKRV TGCPPFDEHK
2710 2720 2730 2740 2750 2760
CLAEGGKIVK IPGTCCDTCE EPDCKDITAK VQYIKVGDCK SQEEVDIHYC QGKCASKAVY
2770 2780 2790 2800 2810
SIDIEDVQEQ CSCCLPSRTE PMRVPLHCTN GSVVYHEVIN AMQCRCSPRN CSK