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FLASH GENE

Symbol

VWF

contributors: mct/pgu - updated : 05-09-2016

HGNC name	von Willebrand factor
HGNC id	12726

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000552 52 - 8833 NP_000543 - 2813 - 2008 18600088

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive pharynx       highly   stomach       highly Lymphoid/Immune spleen           thymus         Nervous nerve       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic megakaryocyte Homo sapiens Blood/Hematopoietic platelet Cardiovascular endothelial cell Homo sapiens

cell lineage
cell lines
fluid/secretion	plasma

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal peptide, a large propeptide of 100kDa (the A2 domain required for multimerization of VWF and for its targeting
	to storage granules)
	the mature subunit cysteine rich with four distinct types of repeat domains
	three VWFA domains, A1 domain contains the binding site of chloride ions that control allosterically the proteolysis by ADAMTS13, a novel Ca(²+)-binding site at the A2 domain, regulating its cleavage by ADAMTS13
	four VWFD domains
	three VWFC domains
	a c-terminal cystine knot-like (ctck) domain

conjugated

GlycoP

mono polymer

heptamer

isoforms

Precursor

HOMOLOGY

Homologene

FAMILY

CATEGORY

immunity/defense

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic,granule
	intracellular,nucleus

basic FUNCTION	antihemophilic factor carrier and a platelet-vessel wall mediator in the blood coagulation system playing a crucial role in the hemostasis process
	; may reduce the immunogenicity of FVIII by inhibiting the uptake of F8 by antigen presenting cells, the first step in the development of an immune response against a foreign antigen (PMID :
	pathogenetic role for VWF-platelet interaction in flow disturbance-induced venous thrombosis
	having function in endothelial cells
	required for platelet adhesion to sites of vessel injury, a process vital for both hemostasis and thrombosis
	large, multimeric plasma glycoprotein that critically mediates hemostasis at sites of vascular injury
	binds calcium at physiologic calcium concentrations and calcium stabilizes VWF A2 domain by accelerating refolding
	VWFpropeptide binding to mature VWF occurs in the circulation, which can regulate the hemostatic potential of VWF by reducing VWF binding to platelet GP1BA
	risk factor for bleeding and thrombosis
	platelet-vessel wall interaction is mediated by VWF, which thereby plays a major role in physiological hemostasis and thrombotic disease
	large, multimeric protein that regulates hemostasis by tethering platelets to the subendothelial matrix at sites of vascular damage
	is one of the most important proteins of the hemostatic systemand its multimeric state is essential for its natural function to guide platelets to sites of injury
	possible role of complementary mechanisms that are capable of modifying the thrombogenic potential of VWF
	large multidomain, multimeric glycoprotein that plays an essential role in regulating the balance between blood clotting and bleeding

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

coagulation/hemostasis

PATHWAY

metabolism

signaling

a component

released into the plasma forming disulfide-linked multimeric structure, assembled from dimers

INTERACTION

DNA

RNA

small molecule

protein	binding to collagen via the VWF-A3 domain
	binding GP1BA by its A1 and A3 domain
	domain A2 is cleaved by ADAMTS13(cleavage stimulated by GP1BA)
	PLD1 is a specific regulator of VWF secretion
	interacting with THBS1 (THBS1 played competitively inhibitory role in ADAMTS13 binding and cleaving of VWF, and the potential competition might happen within A2 and A3 domains)
	F8 accelerates proteolytic cleavage of VWF by ADAMTS13 under fluid shear stress
	interacting with ADAMTS13 (regulation of VWF multimeric size and platelet-tethering function is carried out by ADAMTS13, a plasma metalloprotease that is constitutively active)
	interacting with ADAMTS13 (ADAMTS13 regulates the platelet aggregation function of VWF via proteolysis)
	light chain, particularly the a3 region in the light chain of F8, contains the major binding site for VWF
	GNA12 plays a prominent role in endothelial cells (ECs) VWF secretion required for hemostasis and thrombosis
	ADAMTS13 proteolytically regulates the platelet-tethering function of von Willebrand factor (VWF)
	procoagulant activity of plasma VWF correlates with the length of VWF multimers, which is proteolytically controlled by the metalloprotease ADAMTS13
	ADAMTS13 is a specific von Willebrand factor (VWF)-cleaving protease, preventing microvascular thrombosis of VWF/platelet thrombi
	VWF modulates the internalization and presentation of F8-derived peptides on major histocompatibility complex class II
	RGS4 controls secretion of von Willebrand factor (VWF) to the subendothelial matrix

cell & other

REGULATION

Other	neutrophil oxidant hypochlorous acid (HOCl) inhibits VWF proteolysis by ADAMTS13 by oxidizing VWF methionine 1606 (M1606) in the A2 domain
	cleavage of VWF by granzyme M destroys its factor VIII binding capacity

ASSOCIATED DISORDERS

corresponding disease(s)

VWF

related resource

VonWillebranddisease

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function plasma VWF antigen and VWF RCO were significantly elevated in preeclampsia

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	VWF-deficient mice were protected from thrombosis induced by complete (stasis) or partial (stenosis) flow restriction in the inferior vena cava