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GP1BA

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GP1BA
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGP1BA, BDPLT1, BDPLT3, BSS, CD42B, CD42b-alpha, DBPLT3, GP1B, GPIbA, VWDP, GPIbalpha, glycoprotein Ib platelet alpha subunit, glycoprotein Ib platelet subunit alpha
External IDsOMIM: 606672; MGI: 1333744; HomoloGene: 143; GeneCards: GP1BA; OMA:GP1BA - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000173

NM_010326

RefSeq (protein)

NP_000164

NP_034456

Location (UCSC)Chr 17: 4.93 – 4.94 MbChr 11: 70.53 – 70.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.

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Function

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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.[5] 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,[6] and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis.[7] 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.[8]

Interactions

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GP1BA has been shown to interact with YWHAZ[9][10][11] and FLNB.[12]

Inhibitors

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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.[13] 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.[14] The OS-1 peptide prevents binding of GPIb alpha to the VWF A1 domain.[15] The co-crystal structure of GPIb alpha and OS-1 has been reported.[16]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000185245Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000050675Ensembl, 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

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.