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GP1BA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GWB, 1M0Z, 1M10, 1OOK, 1P8V, 1P9A, 1QYY, 1SQ0, 1U0N, 2BP3, 3P72, 3PMH, 4C2A, 4C2B, 4CH2, 4CH8, 4MGX, 4YR6
Identifiers
Aliases	GP1BA, BDPLT1, BDPLT3, BSS, CD42B, CD42b-alpha, DBPLT3, GP1B, GPIbA, VWDP, GPIbalpha, glycoprotein Ib platelet alpha subunit, glycoprotein Ib platelet subunit alpha
External IDs	OMIM: 606672; MGI: 1333744; HomoloGene: 143; GeneCards: GP1BA; OMA:GP1BA - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17p13.2 Start 4,932,277 bp End 4,935,023 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B3|11 43.2 cM Start 70,529,948 bp End 70,532,862 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte lymph node buccal mucosa cell secondary oocyte trabecular bone granulocyte blood bone marrow cells mucosa of ileum tibialis anterior muscle Top expressed in blood tibiofemoral joint granulocyte embryo muscle of thigh neural layer of retina yolk sac morula spleen lumbar subsegment of spinal cord More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein kinase inhibitor activity thrombin-activated receptor activity protein binding Cellular component cytoplasm integral component of membrane membrane plasma membrane integral component of plasma membrane cell surface anchored component of external side of plasma membrane extracellular exosome extracellular space extracellular matrix Biological process blood coagulation, intrinsic pathway hemostasis fibrinolysis negative regulation of protein kinase activity cytokine-mediated signaling pathway blood coagulation platelet activation cell surface receptor signaling pathway cell adhesion cell morphogenesis regulation of blood coagulation negative regulation of receptor signaling pathway via JAK-STAT thrombin-activated receptor signaling pathway platelet aggregation regulation of megakaryocyte differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2811 14723 Ensembl ENSG00000185245 ENSMUSG00000050675 UniProt P07359 O35930 RefSeq (mRNA) NM_000173 NM_010326 RefSeq (protein) NP_000164 NP_034456 Location (UCSC) Chr 17: 4.93 – 4.94 Mb Chr 11: 70.53 – 70.53 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Platelet glycoprotein Ib alpha chain also known as glycoprotein Ib (platelet), alpha polypeptide or CD42b (Cluster of Differentiation 42b), is a protein that in humans is encoded by the GP1BA gene.

Function

Glycoprotein Ib (GP Ib) is a platelet surface membrane glycoprotein receptor composed of a heterodimer, an alpha chain and a beta chain, that are linked by disulfide bonds. The Gp Ib functions as a receptor for von Willebrand factor (VWF). The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX and platelet glycoprotein V to form the glycoprotein Ib-IX-V complex. Binding of the GP Ib-IX-V complex to VWF facilitates initial platelet adhesion to vascular subendothelium after vascular injury, and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis. This gene encodes the alpha subunit. Several polymorphisms and mutations have been described in this gene, some of which are the cause of Bernard–Soulier syndromes and platelet-type von Willebrand disease.

Interactions

GP1BA has been shown to interact with YWHAZ and FLNB.

Inhibitors

CCP-224, a short PEG-conjugated form of the cyclic peptide OS-1, binds to human GPIb alpha with high affinity and can prevents neutrophil-platelet aggregation in Sickle Cell Disease. In vivo, platelet-mediated thrombus formation can be greatly reduced in arterioles of mice, injured by laser, following an infusion of the OS-1 peptide. The OS-1 peptide prevents binding of GPIb alpha to the VWF A1 domain. The co-crystal structure of GPIb alpha and OS-1 has been reported.

See also

• Cluster of differentiation

References

1. ^ GRCh38: Ensembl release 89: ENSG00000185245 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000050675 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lopez JA, Chung DW, Fujikawa K, Hagen FS, Papayannopoulou T, Roth GJ (August 1987). "Cloning of the alpha chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich alpha 2-glycoprotein". Proceedings of the National Academy of Sciences of the United States of America. 84 (16): 5615–5619. Bibcode:1987PNAS...84.5615L. doi:10.1073/pnas.84.16.5615. PMC 298913. PMID 3303030.
6. Arya M, Anvari B, Romo GM, Cruz MA, Dong JF, McIntire LV, et al. (June 2002). "Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers". Blood. 99 (11): 3971–3977. doi:10.1182/blood-2001-11-0060. PMID 12010796. S2CID 24850350. Retrieved 2023-09-08.
7. Jackson SP, Nesbitt WS, Kulkarni S (July 2003). "Signaling events underlying thrombus formation". Journal of Thrombosis and Haemostasis. 1 (7): 1602–1612. doi:10.1046/j.1538-7836.2003.00267.x. PMID 12871297. S2CID 22088432.
8. "Entrez Gene: GP1BA glycoprotein Ib (platelet), alpha polypeptide".
9. Calverley DC, Kavanagh TJ, Roth GJ (February 1998). "Human signaling protein 14-3-3zeta interacts with platelet glycoprotein Ib subunits Ibalpha and Ibbeta". Blood. 91 (4): 1295–1303. doi:10.1182/blood.V91.4.1295. PMID 9454760.
10. Du X, Fox JE, Pei S (March 1996). "Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha". The Journal of Biological Chemistry. 271 (13): 7362–7367. doi:10.1074/jbc.271.13.7362. PMID 8631758.
11. Feng S, Christodoulides N, Reséndiz JC, Berndt MC, Kroll MH (January 2000). "Cytoplasmic domains of GpIbalpha and GpIbbeta regulate 14-3-3zeta binding to GpIb/IX/V". Blood. 95 (2): 551–557. doi:10.1182/blood.V95.2.551. PMID 10627461. S2CID 77799615.
12. Takafuta T, Wu G, Murphy GF, Shapiro SS (July 1998). "Human beta-filamin is a new protein that interacts with the cytoplasmic tail of glycoprotein Ibalpha". The Journal of Biological Chemistry. 273 (28): 17531–17538. doi:10.1074/jbc.273.28.17531. PMID 9651345.
13. Jimenez, Maritza A.; Novelli, Enrico; Shaw, Gray D.; Sundd, Prithu (2017-09-12). "Glycoprotein Ibα inhibitor (CCP-224) prevents neutrophil-platelet aggregation in Sickle Cell Disease". Blood Advances. 1 (20): 1712–1716. doi:10.1182/bloodadvances.2017006742. ISSN 2473-9529. PMC 5617353. PMID 28966995.
14. Chen, Jianchung; Zhou, Hairu; Diacovo, Alexander; Zheng, X. Long; Emsley, Jonas; Diacovo, Thomas G. (2014-12-11). "Exploiting the kinetic interplay between GPIbα-VWF binding interfaces to regulate hemostasis and thrombosis". Blood. 124 (25): 3799–3807. doi:10.1182/blood-2014-04-569392. ISSN 1528-0020. PMC 4263987. PMID 25293780.
15. Benard, Susan Adam; Smith, Thomas M.; Cunningham, Kristina; Jacob, Jaison; DeSilva, Thamara; Lin, Laura; Shaw, Gray D.; Kriz, Ron; Kelleher, Kerry S. (2008-04-22). "Identification of peptide antagonists to glycoprotein Ibalpha that selectively inhibit von Willebrand factor dependent platelet aggregation". Biochemistry. 47 (16): 4674–4682. doi:10.1021/bi702428q. ISSN 0006-2960. PMID 18363340.
16. McEwan, Paul A.; Andrews, Robert K.; Emsley, Jonas (2009-11-26). "Glycoprotein Ibalpha inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism". Blood. 114 (23): 4883–4885. doi:10.1182/blood-2009-05-224170. ISSN 1528-0020. PMID 19726719.

Further reading

• Kunishima S, Kamiya T, Saito H (November 2002). "Genetic abnormalities of Bernard-Soulier syndrome". International Journal of Hematology. 76 (4): 319–327. doi:10.1007/BF02982690. PMID 12463594. S2CID 23635810.
• Du X (May 2007). "Signaling and regulation of the platelet glycoprotein Ib-IX-V complex". Current Opinion in Hematology. 14 (3): 262–269. doi:10.1097/MOH.0b013e3280dce51a. PMID 17414217. S2CID 39904506.
• Clemetson KJ (July 2007). "A short history of platelet glycoprotein Ib complex". Thrombosis and Haemostasis. 98 (1): 63–68. doi:10.1160/th07-05-0327. PMID 17597992. S2CID 958810.
• López JA, Ludwig EH, McCarthy BJ (May 1992). "Polymorphism of human glycoprotein Ib alpha results from a variable number of tandem repeats of a 13-amino acid sequence in the mucin-like macroglycopeptide region. Structure/function implications". The Journal of Biological Chemistry. 267 (14): 10055–10061. doi:10.1016/S0021-9258(19)50199-5. PMID 1577776.
• Murata M, Furihata K, Ishida F, Russell SR, Ware J, Ruggeri ZM (June 1992). "Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ib alpha involved in platelet transfusion refractoriness". Blood. 79 (11): 3086–3090. doi:10.1182/blood.V79.11.3086.3086. PMID 1586750.
• Girma JP, Takahashi Y, Yoshioka A, Diaz J, Meyer D (October 1990). "Ristocetin and botrocetin involve two distinct domains of von Willebrand factor for binding to platelet membrane glycoprotein Ib". Thrombosis and Haemostasis. 64 (2): 326–332. doi:10.1055/s-0038-1647310. PMID 1702906. S2CID 27425464.
• Miller JL, Lyle VA, Cunningham D (January 1992). "Mutation of leucine-57 to phenylalanine in a platelet glycoprotein Ib alpha leucine tandem repeat occurring in patients with an autosomal dominant variant of Bernard-Soulier disease". Blood. 79 (2): 439–446. doi:10.1182/blood.V79.2.439.439. PMID 1730088.
• Modderman PW, Admiraal LG, Sonnenberg A, von dem Borne AE (January 1992). "Glycoproteins V and Ib-IX form a noncovalent complex in the platelet membrane". The Journal of Biological Chemistry. 267 (1): 364–369. doi:10.1016/S0021-9258(18)48503-1. PMID 1730602.
• Miller JL, Cunningham D, Lyle VA, Finch CN (June 1991). "Mutation in the gene encoding the alpha chain of platelet glycoprotein Ib in platelet-type von Willebrand disease". Proceedings of the National Academy of Sciences of the United States of America. 88 (11): 4761–4765. Bibcode:1991PNAS...88.4761M. doi:10.1073/pnas.88.11.4761. PMC 51746. PMID 2052556.
• Hess D, Schaller J, Rickli EE, Clemetson KJ (July 1991). "Identification of the disulphide bonds in human platelet glycocalicin". European Journal of Biochemistry. 199 (2): 389–393. doi:10.1111/j.1432-1033.1991.tb16135.x. PMID 2070794.
• Du X, Beutler L, Ruan C, Castaldi PA, Berndt MC (May 1987). "Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane". Blood. 69 (5): 1524–1527. doi:10.1182/blood.V69.5.1524.1524. PMID 2436691.
• Andrews RK, Booth WJ, Gorman JJ, Castaldi PA, Berndt MC (October 1989). "Purification of botrocetin from Bothrops jararaca venom. Analysis of the botrocetin-mediated interaction between von Willebrand factor and the human platelet membrane glycoprotein Ib-IX complex". Biochemistry. 28 (21): 8317–8326. doi:10.1021/bi00447a009. PMID 2557900.
• Wenger RH, Wicki AN, Kieffer N, Adolph S, Hameister H, Clemetson KJ (December 1989). "The 5' flanking region and chromosomal localization of the gene encoding human platelet membrane glycoprotein Ib alpha". Gene. 85 (2): 517–524. doi:10.1016/0378-1119(89)90446-0. PMID 2628181.
• Wenger RH, Kieffer N, Wicki AN, Clemetson KJ (October 1988). "Structure of the human blood platelet membrane glycoprotein Ib alpha gene". Biochemical and Biophysical Research Communications. 156 (1): 389–395. doi:10.1016/S0006-291X(88)80853-2. PMID 2845978.
• Wicki AN, Clemetson KJ (November 1985). "Structure and function of platelet membrane glycoproteins Ib and V. Effects of leukocyte elastase and other proteases on platelets response to von Willebrand factor and thrombin". European Journal of Biochemistry. 153 (1): 1–11. doi:10.1111/j.1432-1033.1985.tb09259.x. PMID 2933256.
• Adelman B, Michelson AD, Greenberg J, Handin RI (December 1986). "Proteolysis of platelet glycoprotein Ib by plasmin is facilitated by plasmin lysine-binding regions". Blood. 68 (6): 1280–1284. doi:10.1182/blood.V68.6.1280.1280. PMID 2946332.
• Lopez JA, Chung DW, Fujikawa K, Hagen FS, Papayannopoulou T, Roth GJ (August 1987). "Cloning of the alpha chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich alpha 2-glycoprotein". Proceedings of the National Academy of Sciences of the United States of America. 84 (16): 5615–5619. Bibcode:1987PNAS...84.5615L. doi:10.1073/pnas.84.16.5615. PMC 298913. PMID 3303030.
• Lopez JA, Chung DW, Fujikawa K, Hagen FS, Davie EW, Roth GJ (April 1988). "The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence". Proceedings of the National Academy of Sciences of the United States of America. 85 (7): 2135–2139. Bibcode:1988PNAS...85.2135L. doi:10.1073/pnas.85.7.2135. PMC 279943. PMID 3353370.
• Titani K, Takio K, Handa M, Ruggeri ZM (August 1987). "Amino acid sequence of the von Willebrand factor-binding domain of platelet membrane glycoprotein Ib". Proceedings of the National Academy of Sciences of the United States of America. 84 (16): 5610–5614. Bibcode:1987PNAS...84.5610T. doi:10.1073/pnas.84.16.5610. PMC 298912. PMID 3497398.
• Harmon JT, Jamieson GA (October 1986). "The glycocalicin portion of platelet glycoprotein Ib expresses both high and moderate affinity receptor sites for thrombin. A soluble radioreceptor assay for the interaction of thrombin with platelets". The Journal of Biological Chemistry. 261 (28): 13224–13229. doi:10.1016/S0021-9258(18)69294-4. PMID 3759960.

External links

• GP1BA+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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