Descriptions
Autoinhibitory domains (AIDs)
Target domain |
50-233 (A1 domain) |
Relief mechanism |
Others |
Assay |
|
Target domain |
50-233 (A1 domain) |
Relief mechanism |
Others |
Assay |
|
Target domain |
50-233 (A1 domain) |
Relief mechanism |
Others |
Assay |
|
Accessory elements
No accessory elements
References
- Zhao YC et al. (2022) "The N-terminal autoinhibitory module of the A1 domain in von Willebrand factor stabilizes the mechanosensor catch bond", RSC chemical biology, 3, 707-720
- Aponte-Santamaría C et al. (2015) "Force-sensitive autoinhibition of the von Willebrand factor is mediated by interdomain interactions", Biophysical journal, 108, 2312-21
- Legan ER et al. (2023) "Type 2B von Willebrand disease mutations differentially perturb autoinhibition of the A1 domain", Blood, 141, 1221-1232
- Emsley J et al. (1998) "Crystal structure of the von Willebrand Factor A1 domain and implications for the binding of platelet glycoprotein Ib", The Journal of biological chemistry, 273, 10396-401
Autoinhibited structure
Activated structure
1 structures for Q62935
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q62935-F1 | Predicted | AlphaFoldDB |
No variants for Q62935
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q62935 | |||||
4 associated diseases with Q62935
[MIM: 609265]: Li-Fraumeni syndrome 2 (LFS2)
A highly penetrant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers
[MIM: 176807]: Prostate cancer (PC)
A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:12533788}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
[MIM: 259500]: Osteogenic sarcoma (OSRC)
A sarcoma originating in bone-forming cells, affecting the ends of long bones. Note=The gene represented in this entry may be involved in disease pathogenesis.
[MIM: 114480]: Breast cancer (BC)
A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:12094328, ECO:0000269|PubMed:12454775, ECO:0000269|PubMed:12610780, ECO:0000269|PubMed:15818573, ECO:0000269|PubMed:21618645, ECO:0000269|PubMed:25619829}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Without disease ID
- A highly penetrant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers
- A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:12533788}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
- A sarcoma originating in bone-forming cells, affecting the ends of long bones. Note=The gene represented in this entry may be involved in disease pathogenesis.
- A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:12094328, ECO:0000269|PubMed:12454775, ECO:0000269|PubMed:12610780, ECO:0000269|PubMed:15818573, ECO:0000269|PubMed:21618645, ECO:0000269|PubMed:25619829}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
6 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 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. |
16 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. |
| cellular response to cold | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cold stimulus, a temperature stimulus below the optimal temperature for that organism. |
| cellular response to lipopolysaccharide | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. |
| 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. |
| liver regeneration | The regrowth of lost or destroyed liver. |
| 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. |
| positive regulation of intracellular signal transduction | Any process that activates or increases the frequency, rate or extent of intracellular signal transduction. |
| response to immobilization stress | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of being rendered immobile. |
| response to L-ascorbic acid | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an L-ascorbic acid (vitamin C) stimulus. |
| response to X-ray | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of X-ray radiation. An X-ray is a form of electromagnetic radiation with a wavelength in the range of 10 nanometers to 100 picometers (corresponding to frequencies in the range 30 PHz to 3 EHz). |
5 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P04275 | VWF | von Willebrand factor [Cleaved into: von Willebrand antigen 2 ] | Homo sapiens (Human) | EV |
| Q8CIZ8 | Vwf | von Willebrand factor | Mus musculus (Mouse) | SS |
| Q28833 | VWF | von Willebrand factor | Sus scrofa (Pig) | 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 |
| HCDGVNLTCE | ACQEPGGLVV | PPTDAPVSST | TPYVEDTPEP | PLHNFYCSKL | LDLVFLLDGS |
| 70 | 80 | 90 | 100 | 110 | 120 |
| YRLSEAEFEV | LKAFVVGTME | RLHISQKRIR | VAVVEYHDGS | HAYLELRARK | RPSELRRIAS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| QIKYVGSQLA | STSEVLKYTL | FQIFGKIDRP | EASRVILLLT | ASQEPQRMAR | YFTRYLQGFK |
| 190 | 200 | 210 | 220 | 230 | 240 |
| KKKVILIPVG | IGPHANLKQI | RLIEKQAPEN | KAFLLSGVDE | LEQRRDEIIN | YLCDLAPEAP |
| 250 | 260 | 270 | 280 | 290 | 300 |
| APSKPPQVAH | ITVSPGISGV | SSPGPKRKSL | VLDVVFVLEA | SDEVGEANFN | KSKEFLEEVI |
| 310 | 320 | 330 | 340 | 350 | 360 |
| QRMDVSPAGT | HIAVLQYSYT | VNVEYTFKEA | QSKEDVLRHV | REIRYQGGNR | TNTGQALQYL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| SEHSFSPSQG | DREQAPNLVY | MVTGNPASDE | IRRLPGDIQV | VPIGVGSRAN | LQELERISRP |
| ITPIFIQDFE |