Q8CIZ8

SS
Gene name
Vwf
Protein name
von Willebrand factor
Names
vWF [Cleaved into: von Willebrand antigen 2 , von Willebrand antigen II]
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:22371
EC number
Protein Class

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)

1238-1260 (N-terminal autoinhibitory module) SS

Target domain

1275-1458 (A1 domain)

Relief mechanism

Others

Assay

1467-1493 (C-terminal autoinhibitory module) SS

Target domain

1275-1458 (A1 domain)

Relief mechanism

Others

Assay

1496-1669 (A2 domain) SS

Target domain

1275-1458 (A1 domain)

Relief mechanism

Others

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q8CIZ8

Entry ID Method Resolution Chain Position Source
1U0O X-ray 270 A C 1261-1468 PDB

No variants for Q8CIZ8

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q8CIZ8

No associated diseases with Q8CIZ8

23 regional properties for Q8CIZ8

Type Name Position InterPro Accession
domain VWFC domain 350 - 418 IPR001007-1
domain VWFC domain 829 - 898 IPR001007-2
domain VWFC domain 1879 - 1946 IPR001007-3
domain VWFC domain 2255 - 2328 IPR001007-4
domain VWFC domain 2429 - 2499 IPR001007-5
domain VWFC domain 2510 - 2574 IPR001007-6
domain VWFC domain 2580 - 2645 IPR001007-7
domain von Willebrand factor, type D domain 20 - 201 IPR001846-1
domain von Willebrand factor, type D domain 377 - 560 IPR001846-2
domain von Willebrand factor, type D domain 856 - 1032 IPR001846-3
domain von Willebrand factor, type D domain 1938 - 2124 IPR001846-4
domain von Willebrand factor, type A 1275 - 1458 IPR002035-1
domain von Willebrand factor, type A 1496 - 1669 IPR002035-2
domain von Willebrand factor, type A 1689 - 1872 IPR002035-3
domain Trypsin Inhibitor-like, cysteine rich domain 295 - 348 IPR002919-1
domain Trypsin Inhibitor-like, cysteine rich domain 652 - 707 IPR002919-2
domain Trypsin Inhibitor-like, cysteine rich domain 1145 - 1196 IPR002919-3
domain Cystine knot, C-terminal 2724 - 2812 IPR006207
domain VWF/SSPO/Zonadhesin-like, cysteine-rich domain 218 - 292 IPR014853-1
domain VWF/SSPO/Zonadhesin-like, cysteine-rich domain 577 - 649 IPR014853-2
domain VWF/SSPO/Zonadhesin-like, cysteine-rich domain 1053 - 1127 IPR014853-3
domain VWF/SSPO/Zonadhesin-like, cysteine-rich domain 2132 - 2200 IPR014853-4
domain von Willebrand factor, VWA N-terminal domain 1198 - 1276 IPR032361

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

7 GO annotations of cellular component

Name Definition
collagen-containing extracellular matrix An extracellular matrix consisting mainly of proteins (especially collagen) and glycosaminoglycans (mostly as proteoglycans) that provides not only essential physical scaffolding for the cellular constituents but can also initiate crucial biochemical and biomechanical cues required for tissue morphogenesis, differentiation and homeostasis. The components are secreted by cells in the vicinity and form a sheet underlying or overlying cells such as endothelial and epithelial cells.
endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
external side of plasma membrane The leaflet of the plasma membrane that faces away from the cytoplasm and any proteins embedded or anchored in it or attached to its surface.
extracellular matrix A structure lying external to one or more cells, which provides structural support, biochemical or biomechanical cues for cells or tissues.
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.
extracellular space That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.
Weibel-Palade body A large, elongated, rod-shaped secretory granule characteristic of vascular endothelial cells that contain a number of structurally and functionally distinct proteins, of which the best characterized are von Willebrand factor (VWF) and P-selectin. Weibel-Palade bodies are formed from the trans-Golgi network in a process that depends on VWF, which is densely packed in a highly organized manner, and on coat proteins that remain associated with the granules. Upon cell stimulation, regulated exocytosis releases the contained proteins to the cell surface, where they act in the recruitment of platelets and leukocytes and in inflammatory and vasoactive responses.

6 GO annotations of molecular function

Name Definition
collagen binding Binding to collagen, a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals. Collagen is highly enriched in glycine (some regions are 33% glycine) and proline, occurring predominantly as 3-hydroxyproline (about 20%).
identical protein binding Binding to an identical protein or proteins.
immunoglobulin binding Binding to an immunoglobulin.
integrin binding Binding to an integrin.
protease binding Binding to a protease or a peptidase.
protein-folding chaperone binding Binding to a chaperone protein, a class of proteins that bind to nascent or unfolded polypeptides and ensure correct folding or transport.

9 GO annotations of biological process

Name Definition
activation of blood coagulation via clotting cascade Any process that initiates the clotting cascade of blood coagulation, a cascade of plasma enzymes that is triggered following damage to blood vessels, leading to formation of a clot.
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
cell adhesion The attachment of a cell, either to another cell or to an underlying substrate such as the extracellular matrix, via cell adhesion molecules.
cell-substrate adhesion The attachment of a cell to the underlying substrate via adhesion molecules.
hemostasis The stopping of bleeding (loss of body fluid) or the arrest of the circulation to an organ or part.
inflammatory response The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
liver development The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes.
placenta development The process whose specific outcome is the progression of the placenta over time, from its formation to the mature structure. The placenta is an organ of metabolic interchange between fetus and mother, partly of embryonic origin and partly of maternal origin.
platelet activation A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.

6 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q28295 VWF von Willebrand factor Canis lupus familiaris (Dog) (Canis familiaris) SS
P04275 VWF von Willebrand factor [Cleaved into: von Willebrand antigen 2 ] Homo sapiens (Human) EV
Q28833 VWF von Willebrand factor Sus scrofa (Pig) SS
Q62935 Vwf von Willebrand factor Rattus norvegicus (Rat) SS
Q69V36 Os06g0194400 B3 domain-containing protein Os06g0194400 Oryza sativa subsp japonica (Rice) PR
Q9FHB2 At5g58280 Putative B3 domain-containing protein At5g58280 Arabidopsis thaliana (Mouse-ear cress) PR
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