VWF

Protein identityUniProt · HPA

UniProt accession

P04275

Gene

VWF

Ensembl

ENSG00000110799

Chromosome

12

Canonical length

2813 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a glycoprotein involved in hemostasis. The encoded preproprotein is proteolytically processed following assembly into large multimeric complexes. These complexes function in the adhesion of platelets to sites of vascular injury and the transport of various proteins in the blood. Mutations in this gene result in von Willebrand disease, an inherited bleeding disorder. An unprocessed pseudogene has been found on chromosome 22. [provided by RefSeq, Oct 2015]

Canonical amino-acid sequenceUniProt

2813 residues, UniProt reviewed canonical sequence.

>P04275|VWF
     1  MIPARFAGVL LALALILPGT LCAEGTRGRS STARCSLFGS DFVNTFDGSM YSFAGYCSYL
    61  LAGGCQKRSF SIIGDFQNGK RVSLSVYLGE FFDIHLFVNG TVTQGDQRVS MPYASKGLYL
   121  ETEAGYYKLS GEAYGFVARI DGSGNFQVLL SDRYFNKTCG LCGNFNIFAE DDFMTQEGTL
   181  TSDPYDFANS WALSSGEQWC ERASPPSSSC NISSGEMQKG LWEQCQLLKS TSVFARCHPL
   241  VDPEPFVALC EKTLCECAGG LECACPALLE YARTCAQEGM VLYGWTDHSA CSPVCPAGME
   301  YRQCVSPCAR TCQSLHINEM CQERCVDGCS CPEGQLLDEG LCVESTECPC VHSGKRYPPG
   361  TSLSRDCNTC ICRNSQWICS NEECPGECLV TGQSHFKSFD NRYFTFSGIC QYLLARDCQD
   421  HSFSIVIETV QCADDRDAVC TRSVTVRLPG LHNSLVKLKH GAGVAMDGQD VQLPLLKGDL
   481  RIQHTVTASV RLSYGEDLQM DWDGRGRLLV KLSPVYAGKT CGLCGNYNGN QGDDFLTPSG
   541  LAEPRVEDFG NAWKLHGDCQ DLQKQHSDPC ALNPRMTRFS EEACAVLTSP TFEACHRAVS
   601  PLPYLRNCRY DVCSCSDGRE CLCGALASYA AACAGRGVRV AWREPGRCEL NCPKGQVYLQ
   661  CGTPCNLTCR SLSYPDEECN EACLEGCFCP PGLYMDERGD CVPKAQCPCY YDGEIFQPED
   721  IFSDHHTMCY CEDGFMHCTM SGVPGSLLPD AVLSSPLSHR SKRSLSCRPP MVKLVCPADN
   781  LRAEGLECTK TCQNYDLECM SMGCVSGCLC PPGMVRHENR CVALERCPCF HQGKEYAPGE
   841  TVKIGCNTCV CQDRKWNCTD HVCDATCSTI GMAHYLTFDG LKYLFPGECQ YVLVQDYCGS
   901  NPGTFRILVG NKGCSHPSVK CKKRVTILVE GGEIELFDGE VNVKRPMKDE THFEVVESGR
   961  YIILLLGKAL SVVWDRHLSI SVVLKQTYQE KVCGLCGNFD GIQNNDLTSS NLQVEEDPVD
  1021  FGNSWKVSSQ CADTRKVPLD SSPATCHNNI MKQTMVDSSC RILTSDVFQD CNKLVDPEPY
  1081  LDVCIYDTCS CESIGDCACF CDTIAAYAHV CAQHGKVVTW RTATLCPQSC EERNLRENGY
  1141  ECEWRYNSCA PACQVTCQHP EPLACPVQCV EGCHAHCPPG KILDELLQTC VDPEDCPVCE
  1201  VAGRRFASGK KVTLNPSDPE HCQICHCDVV NLTCEACQEP GGLVVPPTDA PVSPTTLYVE
  1261  DISEPPLHDF YCSRLLDLVF LLDGSSRLSE AEFEVLKAFV VDMMERLRIS QKWVRVAVVE
  1321  YHDGSHAYIG LKDRKRPSEL RRIASQVKYA GSQVASTSEV LKYTLFQIFS KIDRPEASRI
  1381  TLLLMASQEP QRMSRNFVRY VQGLKKKKVI VIPVGIGPHA NLKQIRLIEK QAPENKAFVL
  1441  SSVDELEQQR DEIVSYLCDL APEAPPPTLP PDMAQVTVGP GLLGVSTLGP KRNSMVLDVA
  1501  FVLEGSDKIG EADFNRSKEF MEEVIQRMDV GQDSIHVTVL QYSYMVTVEY PFSEAQSKGD
  1561  ILQRVREIRY QGGNRTNTGL ALRYLSDHSF LVSQGDREQA PNLVYMVTGN PASDEIKRLP
  1621  GDIQVVPIGV GPNANVQELE RIGWPNAPIL IQDFETLPRE APDLVLQRCC SGEGLQIPTL
  1681  SPAPDCSQPL DVILLLDGSS SFPASYFDEM KSFAKAFISK ANIGPRLTQV SVLQYGSITT
  1741  IDVPWNVVPE KAHLLSLVDV MQREGGPSQI GDALGFAVRY LTSEMHGARP GASKAVVILV
  1801  TDVSVDSVDA AADAARSNRV TVFPIGIGDR YDAAQLRILA GPAGDSNVVK LQRIEDLPTM
  1861  VTLGNSFLHK LCSGFVRICM DEDGNEKRPG DVWTLPDQCH TVTCQPDGQT LLKSHRVNCD
  1921  RGLRPSCPNS QSPVKVEETC GCRWTCPCVC TGSSTRHIVT FDGQNFKLTG SCSYVLFQNK
  1981  EQDLEVILHN GACSPGARQG CMKSIEVKHS ALSVELHSDM EVTVNGRLVS VPYVGGNMEV
  2041  NVYGAIMHEV RFNHLGHIFT FTPQNNEFQL QLSPKTFASK TYGLCGICDE NGANDFMLRD
  2101  GTVTTDWKTL VQEWTVQRPG QTCQPILEEQ CLVPDSSHCQ VLLLPLFAEC HKVLAPATFY
  2161  AICQQDSCHQ EQVCEVIASY AHLCRTNGVC VDWRTPDFCA MSCPPSLVYN HCEHGCPRHC
  2221  DGNVSSCGDH PSEGCFCPPD KVMLEGSCVP EEACTQCIGE DGVQHQFLEA WVPDHQPCQI
  2281  CTCLSGRKVN CTTQPCPTAK APTCGLCEVA RLRQNADQCC PEYECVCDPV SCDLPPVPHC
  2341  ERGLQPTLTN PGECRPNFTC ACRKEECKRV SPPSCPPHRL PTLRKTQCCD EYECACNCVN
  2401  STVSCPLGYL ASTATNDCGC TTTTCLPDKV CVHRSTIYPV GQFWEEGCDV CTCTDMEDAV
  2461  MGLRVAQCSQ KPCEDSCRSG FTYVLHEGEC CGRCLPSACE VVTGSPRGDS QSSWKSVGSQ
  2521  WASPENPCLI NECVRVKEEV FIQQRNVSCP QLEVPVCPSG FQLSCKTSAC CPSCRCERME
  2581  ACMLNGTVIG PGKTVMIDVC TTCRCMVQVG VISGFKLECR KTTCNPCPLG YKEENNTGEC
  2641  CGRCLPTACT IQLRGGQIMT LKRDETLQDG CDTHFCKVNE RGEYFWEKRV TGCPPFDEHK
  2701  CLAEGGKIMK IPGTCCDTCE EPECNDITAR LQYVKVGSCK SEVEVDIHYC QGKCASKAMY
  2761  SIDINDVQDQ CSCCSPTRTE PMQVALHCTN GSVVYHEVLN AMECKCSPRK CSK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VWF can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

142 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VWF.

Disease | AllUniProt

Conditions VWF is implicated in, by any mechanism.

• von Willebrand disease 1 (VWD1) MIM:193400
• von Willebrand disease 2 (VWD2) MIM:613554
• von Willebrand disease 3 (VWD3) MIM:277480

Disease | GeneticClinVar

464 pathogenic / likely-pathogenic of 2,100 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• von Willebrand disease type 3
• von Willebrand disease type 2
• von Willebrand disease type 1
• Hereditary von Willebrand disease
• von Willebrand disorder

Disease | ImmuneIEDB

Conditions an epitope on VWF was assayed in.

• brain glioblastoma multiforme T cell
• rheumatoid arthritis B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against VWF are reported. Each links to that disease's full target list.

• Purpura, Thrombotic Thrombocytopenic 11
• Lupus Erythematosus, Systemic 9
• Paraproteinemias 4
• Lymphoproliferative Disorders 3
• Thrombosis 3

Showing 5 of 8 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for VWF from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.59

gnomAD pLI

0

gnomAD missense Z

0.99

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• cell adhesion
• cell-substrate adhesion
• hemostasis
• platelet activation
• positive regulation of intracellular signal transduction
• response to wounding

Molecular functions

• collagen binding
• extracellular matrix structural constituent
• identical protein binding
• immunoglobulin binding
• integrin binding
• protease binding
• protein-folding chaperone binding

Cellular components

• endoplasmic reticulum
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• platelet alpha granule
• platelet alpha granule lumen
• Weibel-Palade body

Protein domainsUniProt · Pfam · InterPro

• VWFC domain
• von Willebrand factor, type D domain
• von Willebrand factor, type A
• Trypsin Inhibitor-like, cysteine rich domain
• Cystine knot, C-terminal
• VWF/SSPO/Zonadhesin-like, cysteine-rich domain
• Serine protease inhibitor-like superfamily
• von Willebrand factor A-like domain superfamily
• Mucin/von Willebrand/Thrombospondin superfamily
• Otogelin-like/Mucin, TIL domain
• von Willebrand factor type A domain
• von Willebrand factor type C domain
• von Willebrand factor type D domain
• Trypsin Inhibitor like cysteine rich domain
• C8 domain
• Von Willebrand factor-like domain
• Otogelin-like/Mucin TIL domain
• von Willebrand factor, VWA N-terminal domain
• Von Willebrand factor
• VWA N-terminal

KeywordsUniProt

• Blood coagulation
• Cell adhesion
• Cleavage on pair of basic residues
• Disulfide bond
• Extracellular matrix
• Glycoprotein
• Hemostasis
• Repeat
• Secreted
• Signal
• von Willebrand disease

InteractionsUniProt · HPA

Protein binding partners of VWF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• F8
• GP1BA
• OPTN