PA2G4

Proliferation-associated protein 2G4 (PA2G4) also known as ErbB3-binding protein 1 (EBP1) is a protein that in humans is encoded by the PA2G4 gene.[5]

PA2G4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2Q8K, 3J2I
Identifiers
Aliases	PA2G4, EBP1, HG4-1, p38-2G4, proliferation-associated 2G4
External IDs	OMIM: 602145 MGI: 894684 HomoloGene: 4513 GeneCards: PA2G4
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.2 Start 56,104,537 bp[1] End 56,113,910 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 D3 Start 128,557,766 bp[2] End 128,565,987 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0001948 protein binding • ubiquitin protein ligase binding • RNA binding • nucleic acid binding Cellular component • cytoplasm • membrane • nucleolus • extracellular exosome • cell nucleus • extracellular region • azurophil granule lumen Biological process • regulation of transcription, DNA-templated • transcription, DNA-templated • cell cycle arrest • rRNA processing • cellular proliferation • negative regulation of transcription, DNA-templated • regulation of translation • neutrophil degranulation • negative regulation of apoptotic process • positive regulation of cell differentiation • ribosomal large subunit export from nucleus Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5036	18813
Ensembl	ENSG00000170515	ENSMUSG00000025364
UniProt	Q9UQ80	P50580
RefSeq (mRNA)	NM_006191	NM_011119
RefSeq (protein)	NP_006182	NP_035249
Location (UCSC)	Chr 12: 56.1 – 56.11 Mb	Chr 10: 128.56 – 128.57 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes an RNA-binding protein that is involved in growth regulation. This protein is present in pre-ribosomal ribonucleoprotein complexes and may be involved in ribosome assembly and the regulation of intermediate and late steps of rRNA processing. This protein can interact with the cytoplasmic domain of the ErbB3 receptor and may contribute to transducing growth regulatory signals. This protein is also a transcriptional corepressor of androgen receptor-regulated genes and other cell cycle regulatory genes through its interactions with histone deacetylases. This protein has been implicated in growth inhibition and the induction of differentiation of human cancer cells. Paradoxically, the expression of EBP1 is decreased in prostate cancer [6], but increased in Acute Myelogneous Leukemia.[7] Six pseudogenes, located on chromosomes 3, 6, 9, 18, 20 and X, have been identified.[8]

Interactions

PA2G4 has been shown to interact with ERBB3,[9][10] retinoblastoma protein,[11] and androgen receptor.[12]

References

1. GRCh38: Ensembl release 89: ENSG00000170515 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025364 - 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. Lamartine J, Seri M, Cinti R, Heitzmann F, Creaven M, Radomski N, Jost E, Lenoir GM, Romeo G, Sylla BS (November 1997). "Molecular cloning and mapping of a human cDNA (PA2G4) that encodes a protein highly homologous to the mouse cell cycle protein p38-2G4". Cytogenetics and Cell Genetics. 78 (1): 31–5. doi:10.1159/000134621. PMID 9345902.
6. Zhang Y, Linn D, Liu Z, Melamed J, Tavora F, Young CY, Burger AM, Hamburger AW (October 2008). "EBP1, an ErbB3-binding protein, is decreased in prostate cancer and implicated in hormone resistance". Molecular Cancer Therapeutics. 7 (10): 3176–86. doi:10.1158/1535-7163.MCT-08-0526. PMC 2629587. PMID 18852121.
7. Nguyen le XT, Zhu L, Lee Y, Ta L, Mitchell BS (July 2016). "Expression and Role of the ErbB3-Binding Protein 1 in Acute Myelogenous Leukemic Cells". Clinical Cancer Research. 22 (13): 3320–7. doi:10.1158/1078-0432.CCR-15-2282. PMID 26813358.
8. "Entrez Gene: PA2G4 proliferation-associated 2G4, 38kDa".
9. Lessor TJ, Hamburger AW (April 2001). "Regulation of the ErbB3 binding protein Ebp1 by protein kinase C". Molecular and Cellular Endocrinology. 175 (1–2): 185–91. doi:10.1016/S0303-7207(01)00387-2. PMID 11325528.
10. Yoo JY, Wang XW, Rishi AK, Lessor T, Xia XM, Gustafson TA, Hamburger AW (February 2000). "Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin". British Journal of Cancer. 82 (3): 683–90. doi:10.1054/bjoc.1999.0981. PMC 2363329. PMID 10682683.
11. Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW (May 2001). "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation". Journal of Cellular Physiology. 187 (2): 209–17. doi:10.1002/jcp.1075. PMID 11268000.
12. Zhang Y, Fondell JD, Wang Q, Xia X, Cheng A, Lu ML, Hamburger AW (August 2002). "Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1". Oncogene. 21 (36): 5609–18. doi:10.1038/sj.onc.1205638. PMID 12165860.

Further reading

• Radomski N, Jost E (October 1995). "Molecular cloning of a murine cDNA encoding a novel protein, p38-2G4, which varies with the cell cycle". Experimental Cell Research. 220 (2): 434–45. doi:10.1006/excr.1995.1335. PMID 7556453.
• Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Froesch BA, Takayama S, Reed JC (May 1998). "BAG-1L protein enhances androgen receptor function". The Journal of Biological Chemistry. 273 (19): 11660–6. doi:10.1074/jbc.273.19.11660. PMID 9565586.
• Kim ST, Lim DS, Canman CE, Kastan MB (December 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". The Journal of Biological Chemistry. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID 10608806.
• Yoo JY, Wang XW, Rishi AK, Lessor T, Xia XM, Gustafson TA, Hamburger AW (February 2000). "Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin". British Journal of Cancer. 82 (3): 683–90. doi:10.1054/bjoc.1999.0981. PMC 2363329. PMID 10682683.
• Lessor TJ, Yoo JY, Xia X, Woodford N, Hamburger AW (June 2000). "Ectopic expression of the ErbB-3 binding protein ebp1 inhibits growth and induces differentiation of human breast cancer cell lines". Journal of Cellular Physiology. 183 (3): 321–9. doi:10.1002/(SICI)1097-4652(200006)183:3<321::AID-JCP4>3.0.CO;2-O. PMID 10797306.
• Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW (May 2001). "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation". Journal of Cellular Physiology. 187 (2): 209–17. doi:10.1002/jcp.1075. PMID 11268000.
• Lessor TJ, Hamburger AW (April 2001). "Regulation of the ErbB3 binding protein Ebp1 by protein kinase C". Molecular and Cellular Endocrinology. 175 (1–2): 185–91. doi:10.1016/S0303-7207(01)00387-2. PMID 11325528.
• Xia X, Lessor TJ, Zhang Y, Woodford N, Hamburger AW (November 2001). "Analysis of the expression pattern of Ebp1, an ErbB-3-binding protein". Biochemical and Biophysical Research Communications. 289 (1): 240–4. doi:10.1006/bbrc.2001.5942. PMID 11708806.
• Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI (January 2002). "Directed proteomic analysis of the human nucleolus". Current Biology. 12 (1): 1–11. doi:10.1016/S0960-9822(01)00650-9. PMID 11790298.
• Zhang Y, Fondell JD, Wang Q, Xia X, Cheng A, Lu ML, Hamburger AW (August 2002). "Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1". Oncogene. 21 (36): 5609–18. doi:10.1038/sj.onc.1205638. PMID 12165860.
• Scherl A, Couté Y, Déon C, Callé A, Kindbeiter K, Sanchez JC, Greco A, Hochstrasser D, Diaz JJ (November 2002). "Functional proteomic analysis of human nucleolus". Molecular Biology of the Cell. 13 (11): 4100–9. doi:10.1091/mbc.E02-05-0271. PMC 133617. PMID 12429849.
• Zhang Y, Woodford N, Xia X, Hamburger AW (April 2003). "Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases". Nucleic Acids Research. 31 (8): 2168–77. doi:10.1093/nar/gkg318. PMC 153746. PMID 12682367.
• Squatrito M, Mancino M, Donzelli M, Areces LB, Draetta GF (May 2004). "EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes". Oncogene. 23 (25): 4454–65. doi:10.1038/sj.onc.1207579. PMID 15064750.
• Zhang Y, Hamburger AW (June 2004). "Heregulin regulates the ability of the ErbB3-binding protein Ebp1 to bind E2F promoter elements and repress E2F-mediated transcription". The Journal of Biological Chemistry. 279 (25): 26126–33. doi:10.1074/jbc.M314305200. PMID 15073182.
• Lehner B, Sanderson CM (July 2004). "A protein interaction framework for human mRNA degradation". Genome Research. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
• Zhang Y, Hamburger AW (January 2005). "Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signalling". British Journal of Cancer. 92 (1): 140–6. doi:10.1038/sj.bjc.6602257. PMC 2361729. PMID 15583694.