GP1BA

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)
End	4,935,023 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	70,532,862 bp
RNA expression pattern
	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
	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
	2811
	14723
	ENSG00000185245
	ENSMUSG00000050675
	P07359
	O35930
	NM_000173
	NM_010326
	NP_000164
	NP_034456
	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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000185245 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000050675 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ 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.
^ "Entrez Gene: GP1BA glycoprotein Ib (platelet), alpha polypeptide".
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

External links

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

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

This membrane protein–related article is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000185245 – Ensembl, May 2017

[refGRCm38Ensembl-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".

[pmid9454760-9] 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.

[pmid8631758-10] 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.

[pmid10627461-11] 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.

[pmid9651345-12] 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.

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