GP1BA

Last updated
GP1BA
Protein GP1BA PDB 1gwb.png
Available structures
PDB Ortholog search: PDBe RCSB
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
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 Mb Chr 11: 70.53 – 70.53 Mb
PubMed search [3] [4]
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. [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

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

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. [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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000185245 Ensembl, May 2017
  2. 1 2 3 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

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