GPS2 (gene)

G protein pathway suppressor 2
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2L5G​
Identifiers
Symbols	GPS2 ; AMF-1
External IDs	OMIM: 601935 MGI: 1891751 HomoloGene: 49599 GeneCards: GPS2 Gene
Gene ontology Molecular function • transcription corepressor activity • GTPase inhibitor activity • protein binding Cellular component • nucleoplasm • transcriptional repressor complex Biological process • negative regulation of transcription from RNA polymerase II promoter • inactivation of MAPK activity • chromatin organization • cell cycle • JNK cascade • negative regulation of GTPase activity • negative regulation of JNK cascade Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2874	56310
Ensembl	ENSG00000132522	ENSMUSG00000023170
UniProt	Q13227	Q921N8
RefSeq (mRNA)	NM_004489	NM_019726
RefSeq (protein)	NP_004480	NP_062700
Location (UCSC)	Chr 17: 7.31 – 7.32 Mb	Chr 11: 69.91 – 69.92 Mb
PubMed search

G protein pathway suppressor 2 is a protein that in humans is encoded by the GPS2 gene.^[1][2]

Function

This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function.^[2]

Interactions

GPS2 (gene) has been shown to interact with:

• C21orf7,^[3]
• Cyclin A1,^[4]
• EP300,^[5]
• HDAC3,^[6]
• NCOR1,^[6][7][8]
• P53,^[9] and
• TBL1X.^[6]

References

1. Spain BH, Bowdish KS, Pacal AR, Staub SF, Koo D, Chang CY, Xie W, Colicelli J (Dec 1996). "Two human cDNAs, including a homolog of Arabidopsis FUS6 (COP11), suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction in yeast and mammalian cells". Molecular and Cellular Biology 16 (12): 6698–706. doi:10.1128/mcb.16.12.6698. PMC 231672. PMID 8943324.
2. "Entrez Gene: GPS2 G protein pathway suppressor 2".
3. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
4. Diederichs S, Bäumer N, Ji P, Metzelder SK, Idos GE, Cauvet T, Wang W, Möller M, Pierschalski S, Gromoll J, Schrader MG, Koeffler HP, Berdel WE, Serve H, Müller-Tidow C (Aug 2004). "Identification of interaction partners and substrates of the cyclin A1-CDK2 complex". The Journal of Biological Chemistry 279 (32): 33727–41. doi:10.1074/jbc.M401708200. PMID 15159402.
5. Peng YC, Breiding DE, Sverdrup F, Richard J, Androphy EJ (Jul 2000). "AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins". Journal of Virology 74 (13): 5872–9. doi:10.1128/jvi.74.13.5872-5879.2000. PMC 112082. PMID 10846067.
6. Zhang J, Kalkum M, Chait BT, Roeder RG (Mar 2002). "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2". Molecular Cell 9 (3): 611–23. doi:10.1016/s1097-2765(02)00468-9. PMID 11931768.
7. Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (Sep 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Molecular Cell 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. PMID 14527417.
8. Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J (Mar 2003). "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". The EMBO Journal 22 (6): 1336–46. doi:10.1093/emboj/cdg120. PMC 151047. PMID 12628926.
9. Peng YC, Kuo F, Breiding DE, Wang YF, Mansur CP, Androphy EJ (Sep 2001). "AMF1 (GPS2) modulates p53 transactivation". Molecular and Cellular Biology 21 (17): 5913–24. doi:10.1128/mcb.21.17.5913-5924.2001. PMC 87310. PMID 11486030.

Further reading

• Jin DY, Teramoto H, Giam CZ, Chun RF, Gutkind JS, Jeang KT (Oct 1997). "A human suppressor of c-Jun N-terminal kinase 1 activation by tumor necrosis factor alpha". The Journal of Biological Chemistry 272 (41): 25816–23. doi:10.1074/jbc.272.41.25816. PMID 9325311.
• Peng YC, Breiding DE, Sverdrup F, Richard J, Androphy EJ (Jul 2000). "AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins". Journal of Virology 74 (13): 5872–9. doi:10.1128/JVI.74.13.5872-5879.2000. PMC 112082. PMID 10846067.
• Degenhardt YY, Silverstein SJ (Jan 2001). "Gps2, a protein partner for human papillomavirus E6 proteins". Journal of Virology 75 (1): 151–60. doi:10.1128/JVI.75.1.151-160.2001. PMC 113908. PMID 11119584.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (Apr 2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research 8 (2): 85–95. doi:10.1093/dnares/8.2.85. PMID 11347906.
• Peng YC, Kuo F, Breiding DE, Wang YF, Mansur CP, Androphy EJ (Sep 2001). "AMF1 (GPS2) modulates p53 transactivation". Molecular and Cellular Biology 21 (17): 5913–24. doi:10.1128/MCB.21.17.5913-5924.2001. PMC 87310. PMID 11486030.
• Zhang J, Kalkum M, Chait BT, Roeder RG (Mar 2002). "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2". Molecular Cell 9 (3): 611–23. doi:10.1016/S1097-2765(02)00468-9. PMID 11931768.
• Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, Wong J (Mar 2003). "Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1". The EMBO Journal 22 (6): 1336–46. doi:10.1093/emboj/cdg120. PMC 151047. PMID 12628926.
• Yoon HG, Chan DW, Reynolds AB, Qin J, Wong J (Sep 2003). "N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso". Molecular Cell 12 (3): 723–34. doi:10.1016/j.molcel.2003.08.008. PMID 14527417.
• Diederichs S, Bäumer N, Ji P, Metzelder SK, Idos GE, Cauvet T, Wang W, Möller M, Pierschalski S, Gromoll J, Schrader MG, Koeffler HP, Berdel WE, Serve H, Müller-Tidow C (Aug 2004). "Identification of interaction partners and substrates of the cyclin A1-CDK2 complex". The Journal of Biological Chemistry 279 (32): 33727–41. doi:10.1074/jbc.M401708200. PMID 15159402.
• Lee TH, Yi W, Griswold MD, Zhu F, Her C (Jan 2006). "Formation of hMSH4-hMSH5 heterocomplex is a prerequisite for subsequent GPS2 recruitment". DNA Repair 5 (1): 32–42. doi:10.1016/j.dnarep.2005.07.004. PMID 16122992.
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (Sep 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
• Sanyal S, Båvner A, Haroniti A, Nilsson LM, Lundåsen T, Rehnmark S, Witt MR, Einarsson C, Talianidis I, Gustafsson JA, Treuter E (Oct 2007). "Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis". Proceedings of the National Academy of Sciences of the United States of America 104 (40): 15665–70. doi:10.1073/pnas.0706736104. PMC 2000397. PMID 17895379.