4C2A

Crystal Structure of High-Affinity von Willebrand Factor A1 domain with R1306Q and I1309V Mutations in Complex with High Affinity GPIb alpha

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d4c2aa_	Alpha and beta proteins (a/b)	vWA-like	vWA-like	Integrin A (or I) domain	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4c2ab_	Alpha and beta proteins (a/b)	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	L domain-like	Ngr ectodomain-like	automated matches	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	vWA-like	8032264	3000832	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	L domain-like	8034703	3001010	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	UNK_F_TYPE	e4c2aA1	A: a/b three-layered sandwiches	X: HAD domain-like	H: HAD domain-related	T: vWA-like	F: UNK_F_TYPE	ECOD (1.6)
B	LRR_8_1	e4c2aB1	A: beta duplicates or obligate multimers	X: Single-stranded right-handed beta-helix	H: Leucine-rich repeats (From Topology)	T: Leucine-rich repeats	F: LRR_8_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.410	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	von Willebrand factor, type A domain	CATH (4.3.0)
B	3.80.10.10	Alpha Beta	Alpha-Beta Horseshoe	Leucine-rich repeat, LRR (right-handed beta-alpha superhelix)	Ribonuclease Inhibitor	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00092	von Willebrand factor type A domain (VWA)	von Willebrand factor type A domain	-	Domain
B	PF13855	Leucine rich repeat (LRR_8)	Leucine rich repeat	-	Repeat
B	PF01462	Leucine rich repeat N-terminal domain (LRRNT)	Leucine rich repeat N-terminal domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	VON WILLEBRAND FACTOR	protein binding binding enzyme binding protease binding collagen binding protein-containing complex binding protein-folding chaperone binding cell adhesion molecule binding integrin binding signaling receptor binding immunoglobulin binding identical protein binding	multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding cell activation cellular process platelet activation multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding cell activation cellular process platelet activation cellular response to stimulus positive regulation of cell communication regulation of biological process regulation of signaling regulation of cellular process positive regulation of signal transduction signaling positive regulation of biological process positive regulation of intracellular signal transduction regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction regulation of response to stimulus regulation of cell communication signal transduction positive regulation of cellular process positive regulation of signaling cell adhesion cell-substrate adhesion	extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix intracellular anatomical structure intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle Weibel-Palade body secretory granule clathrin-coated vesicle secretory vesicle coated vesicle cytoplasm platelet alpha granule vesicle lumen membrane-enclosed lumen cytoplasmic vesicle lumen secretory granule lumen intracellular organelle lumen organelle lumen platelet alpha granule lumen endoplasmic reticulum
B	PLATELET GLYCOPROTEIN IB ALPHA CHAIN	peptide receptor activity molecular transducer activity G protein-coupled receptor activity thrombin-activated receptor activity proteinase-activated receptor activity G protein-coupled peptide receptor activity transmembrane signaling receptor activity signaling receptor activity	multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding developmental process cellular developmental process hemopoiesis multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding developmental process cellular developmental process hemopoiesis megakaryocyte differentiation cell development myeloid cell differentiation cell differentiation megakaryocyte development anatomical structure development myeloid cell development cellular process regulation of response to external stimulus negative regulation of biological process regulation of response to wounding regulation of coagulation regulation of response to stress regulation of multicellular organismal process regulation of hemostasis regulation of biological process negative regulation of response to stimulus negative regulation of wound healing regulation of blood coagulation negative regulation of blood coagulation response to external stimulus negative regulation of response to wounding negative regulation of hemostasis fibrinolysis negative regulation of coagulation regulation of response to stimulus negative regulation of response to external stimulus regulation of wound healing negative regulation of multicellular organismal process cell activation platelet activation cellular response to stimulus regulation of cellular process cell surface receptor signaling pathway signaling signal transduction cell communication anatomical structure morphogenesis cell morphogenesis regulation of cell motility positive regulation of biological process positive regulation of leukocyte cell-cell adhesion regulation of leukocyte adhesion to vascular endothelial cell leukocyte cell-cell adhesion leukocyte tethering or rolling positive regulation of cell-cell adhesion cell adhesion cell-cell adhesion positive regulation of leukocyte tethering or rolling cellular extravasation regulation of cell migration regulation of cell-cell adhesion cell migration regulation of immune system process cell motility locomotion positive regulation of cellular process positive regulation of cell adhesion regulation of cell adhesion regulation of leukocyte migration positive regulation of leukocyte adhesion to vascular endothelial cell leukocyte migration regulation of leukocyte tethering or rolling leukocyte adhesion to vascular endothelial cell immune system process regulation of locomotion regulation of leukocyte cell-cell adhesion regulation of cellular extravasation regulation of localization cellular localization inorganic ion homeostasis intracellular calcium ion homeostasis transport homeostatic process monoatomic ion transmembrane transport calcium ion homeostasis negative regulation of sequestering of calcium ion calcium ion transport metal ion transport maintenance of location in cell monoatomic cation transmembrane transport localization intracellular monoatomic cation homeostasis monoatomic ion homeostasis negative regulation of cellular process monoatomic ion transport intracellular chemical homeostasis monoatomic cation homeostasis monoatomic cation transport regulation of sequestering of calcium ion intracellular monoatomic ion homeostasis calcium ion transmembrane import into cytosol sequestering of calcium ion inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport maintenance of location transmembrane transport release of sequestered calcium ion into cytosol cellular homeostasis chemical homeostasis calcium ion transmembrane transport protein maturation blood coagulation, intrinsic pathway blood coagulation, fibrin clot formation protein metabolic process protein activation cascade primary metabolic process gene expression macromolecule biosynthetic process biosynthetic process metabolic process macromolecule metabolic process regulation of cell activation positive regulation of platelet activation positive regulation of cell activation regulation of platelet activation positive regulation of multicellular organismal process	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle extracellular matrix external encapsulating structure protein-containing complex plasma membrane protein complex membrane protein complex glycoprotein Ib-IX-V complex receptor complex glycoprotein complex plasma membrane signaling receptor complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR050780	Mucin/von Willebrand/Thrombospondin superfamily	Family
A	IPR002919	Trypsin Inhibitor-like, cysteine rich domain	Domain
A	IPR001007	VWFC domain	Domain
A	IPR037578	Von Willebrand factor	Family
A	IPR036465	von Willebrand factor A-like domain superfamily	Homologous Superfamily
A	IPR001846	von Willebrand factor, type D domain	Domain
A	IPR014853	VWF/SSPO/Zonadhesin-like, cysteine-rich domain	Domain
A	IPR032361	von Willebrand factor, VWA N-terminal domain	Domain
A	IPR036084	Serine protease inhibitor-like superfamily	Homologous Superfamily
A	IPR002035	von Willebrand factor, type A	Domain
A	IPR006207	Cystine knot, C-terminal	Domain
B	IPR000372	Leucine-rich repeat N-terminal domain	Domain
B	IPR003591	Leucine-rich repeat, typical subtype	Repeat
B	IPR051432	Voltage and calcium-activated potassium channel auxiliary protein	Family
B	IPR001611	Leucine-rich repeat	Repeat
B	IPR032675	Leucine-rich repeat domain superfamily	Homologous Superfamily
B	IPR000483	Cysteine-rich flanking region, C-terminal	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P04275	von Willebrand disease 1 von Willebrand disease 2 von Willebrand disease 3 atrial fibrillation hypertensive disorder hereditary von Willebrand disease thrombotic disease intracranial thrombosis cardiovascular disease Liver Cirrhosis, Experimental congestive heart failure Down syndrome ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia drug-induced liver injury von Willebrand disease 1 von Willebrand disease 2 von Willebrand disease 3 atrial fibrillation hypertensive disorder hereditary von Willebrand disease thrombotic disease intracranial thrombosis cardiovascular disease Liver Cirrhosis, Experimental congestive heart failure Down syndrome ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia drug-induced liver injury peripheral neuropathy gastric carcinoma thrombocytopenia heart failure acquired von willebrand syndrome transitional cell carcinoma herpes zoster interstitial cystitis von Willebrand disease type 2A kidney disease von Willebrand disease type 2N lung adenocarcinoma coronary artery disease non-small cell lung carcinoma pancreatic intraductal papillary-mucinous carcinoma ductal breast carcinoma in situ thrombophilia thrombotic thrombocytopenic purpura adrenal cortex carcinoma ulcerative colitis angiodysplasia Bernard-Soulier syndrome von Willebrand disease type 2B breast carcinoma lung cancer medulloblastoma osteosarcoma pancreatic intraductal papillary-mucinous neoplasm peripheral nervous system disease familial atrial fibrillation pulmonary embolism heart disease hemophilia A vascular disease atherosclerosis inborn carbohydrate metabolic disorder invasive ductal breast carcinoma von Willebrand disease type 2M cerebrovascular disorder lung carcinoma
B	Pharos: P07359	Bernard-Soulier syndrome Bernard-Soulier syndrome, type A2, autosomal dominant pseudo-von Willebrand disease nonarteritic anterior ischemic optic neuropathy, susceptibility to thrombotic disease hypertensive disorder Von Willebrand disease, platelet type attention deficit hyperactivity disorder, inattentive type brain aneurysm hereditary von Willebrand disease non-arteritic anterior ischemic optic neuropathy thrombocytopenia osteosarcoma

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.