RGS2

RGS2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2AF0, 2V4Z, 4EKC, 4EKD
Identifikatori
Aliasi	RGS2
Vanjski ID-jevi	OMIM: 600861 MGI: 1098271 HomoloGene: 2192 GeneCards: RGS2
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	192,812,275 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	143,879,899 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0005097, GO:0005099, GO:0005100 GTPase activator activity; • calmodulin binding; • GO:0001948, GO:0016582 vezivanje za proteine; • G-protein alpha-subunit binding; • beta-tubulin binding; • GO:0006184 GTPase activity;
Ćelijska komponenta	• membrana; • Jedarce; • mitohondrija; • neuron projection; • cytoplasmic side of plasma membrane; • jedro; • citoplazma; • ćelijska membrana; • citosol;
Biološki proces	• negative regulation of cAMP-mediated signaling; • regulation of G protein-coupled receptor signaling pathway; • negative regulation of cardiac muscle hypertrophy; • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity; • negative regulation of MAP kinase activity; • positive regulation of cardiac muscle contraction; • Spermatogeneza; • brown fat cell differentiation; • positive regulation of microtubule polymerization; • relaxation of vascular associated smooth muscle; • ćelijski ciklus; • negative regulation of signal transduction; • negative regulation of G protein-coupled receptor signaling pathway; • relaxation of cardiac muscle; • regulation of translation; • negative regulation of phospholipase activity; • negative regulation of adenylate cyclase-inhibiting adrenergic receptor signaling pathway involved in heart process; • response to amphetamine; • brain development; • positive regulation of neuron projection development; • negative regulation of translation; • Ovulacija; • response to ethanol; • maternal process involved in female pregnancy; • negative regulation of cell growth involved in cardiac muscle cell development; • negative regulation of glycine import across plasma membrane; • G protein-coupled receptor signaling pathway;
	Izvori:Amigo / QuickGO
Ortolozi
	5997
	19735
	ENSG00000116741
	ENSMUSG00000026360
	P41220
	O08849
	NM_002923
	NM_009061
	NP_002914; NP_002914.1
	NP_033087
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Regulator G-proteinske signalizacije 2 jest protein koji je kod ljudi kodiran genom RGS2 sa hromosoma 1.^[5]^[6] Dio je velike porodice RGS-proteina koja kontrolira signalzaciju, putem G-protein spregnutih receptora (GPCR).

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 211 aminokiselina, a molekulska težina 24 382 Da.^[7]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MQSAMFLAVQ	HDCRPMDKSA	GSGHKSEEKR	EKMKRTLLKD	WKTRLSYFLQ
NSSTPGKPKT	GKKSKQQAFI	KPSPEEAQLW	SEAFDELLAS	KYGLAAFRAF
LKSEFCEENI	EFWLACEDFK	KTKSPQKLSS	KARKIYTDFI	EKEAPKEINI
DFQTKTLIAQ	NIQEATSGCF	TTAQKRVYSL	MENNSYPRFL	ESEFYQDLCK
KPQITTEPHA	T

Funkcija

Smatra se da RGS2 ima zaštitne efekte protiv hipertrofije miokarda, kao i pretkomorskih aritmija.^[8]^[9] Povećan stimulacija Gs povezanih β1-adrenergičnih receptor i Gq]] povezanih α1-adrenergičnih receptora u srcu može dovesti do hipertrofije srca.^[8] U slučaju hipertrofije posredovane Gq proteinskim receptorom (GqPCR), Gαq će aktivirati unutarćelijske afektore fosfolipaza Cβ i rho guaninski faktor razmjene nukleotida da stimulira ćelijske procese koji dovode do hipertrofije kardiomiocita.^[8]^[10] RGS2 funkcionira kao protein koji aktivira GTP-azu (GAP) koja djeluje na povećanje prirodne GTPazne aktivnosti podjedinice Gα.^[8]^[10] Povećanjem GTPazne aktivnosti Gα podjedinice, RGS2 promovira GTP hidrolizu nazad u GDP, pretvarajući tako podjedinicu Gα nazad u njeno neaktivno stanje i smanjujući njenu signalnu sposobnost.^[10] I GsPCR i GqPCR aktivacija mogu doprinijeti srčanoj hipertrofiji putem aktivacije MAP-kinaza. Pokazalo se da RGS2 smanjuje fosforilaciju tih MAP-kinaza i stoga smanjuje njihovu aktivaciju kao odgovor na Gαs-signalizaciju.^[8]

U slučaju hipertrofije posredovane GsPCR, glavni mehanizam kojim signalizacija doprinosi hipertrofiji je putem podjedinice Gβγ; Gαs signalizacija sama po sebi nije dovoljna.^[11] Ipak, pokazalo se da RGS2 inhibira Gs posredovanu hipertrofiju. Mehanizam kako RGS2 reguliše povećanu Gβγ signalizaciju nije dobro shvaćen, osim činjenice da nije povezan sa GAP funkcijom RGS2a.^[11] Nedostatak RGS2 je povezan sa povećanom hipertrofijom srca kod miševa.^[8] Srca s nedostatkom RGS2 izgledaju normalno, sve dok se ne suoče s povećanim opterećenjem, na koje spremno reagiraju pojačanim signalom Gαq i hipertrofijom.^[8]^[11]

Interakcije

Pokazalo se da RGS2 interraguje sa PRKG1^[12] i ADCY5.^[13]

Reference

{{reflist|refs=

^[8]

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^[10]

^[14]

Dopunska literatura

Siderovski DP, Blum S, Forsdyke RE, Forsdyke DR (1991). "A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes". DNA Cell Biol. 9 (8): 579–87. doi:10.1089/dna.1990.9.579. PMID 1702972.
Wu HK, Heng HH, Shi XM, et al. (1995). "Differential expression of a basic helix-loop-helix phosphoprotein gene, G0S8, in acute leukemia and localization to human chromosome 1q31". Leukemia. 9 (8): 1291–8. PMID 7643615.
Druey KM, Blumer KJ, Kang VH, Kehrl JH (1996). "Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family". Nature. 379 (6567): 742–6. Bibcode:1996Natur.379..742D. doi:10.1038/379742a0. PMID 8602223. S2CID 4362632.
Siderovski DP, Hessel A, Chung S, et al. (1996). "A new family of regulators of G-protein-coupled receptors?". Curr. Biol. 6 (2): 211–2. doi:10.1016/S0960-9822(02)00454-2. PMID 8673468. S2CID 17214806.
Heximer SP, Cristillo AD, Forsdyke DR (1997). "Comparison of mRNA expression of two regulators of G-protein signaling, RGS1/BL34/1R20 and RGS2/G0S8, in cultured human blood mononuclear cells". DNA Cell Biol. 16 (5): 589–98. doi:10.1089/dna.1997.16.589. PMID 9174164.
Heximer SP, Watson N, Linder ME, et al. (1998). "RGS2/G0S8 is a selective inhibitor of Gqalpha function". Proc. Natl. Acad. Sci. U.S.A. 94 (26): 14389–93. doi:10.1073/pnas.94.26.14389. PMC 24991. PMID 9405622.
Tseng CC, Zhang XY (1998). "Role of regulator of G protein signaling in desensitization of the glucose-dependent insulinotropic peptide receptor". Endocrinology. 139 (11): 4470–5. doi:10.1210/en.139.11.4470. PMID 9794454.
Beadling C, Druey KM, Richter G, et al. (1999). "Regulators of G protein signaling exhibit distinct patterns of gene expression and target G protein specificity in human lymphocytes". J. Immunol. 162 (5): 2677–82. PMID 10072511.
Popov SG, Krishna UM, Falck JR, Wilkie TM (2000). "Ca2+/Calmodulin reverses phosphatidylinositol 3,4, 5-trisphosphate-dependent inhibition of regulators of G protein-signaling GTPase-activating protein activity". J. Biol. Chem. 275 (25): 18962–8. doi:10.1074/jbc.M001128200. PMID 10747990.
Zheng B, Chen D, Farquhar MG (2000). "MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16". Proc. Natl. Acad. Sci. U.S.A. 97 (8): 3999–4004. Bibcode:2000PNAS...97.3999Z. doi:10.1073/pnas.97.8.3999. PMC 18131. PMID 10760272.
Chatterjee TK, Fisher RA (2000). "Cytoplasmic, nuclear, and golgi localization of RGS proteins. Evidence for N-terminal and RGS domain sequences as intracellular targeting motifs". J. Biol. Chem. 275 (31): 24013–21. doi:10.1074/jbc.M002082200. PMID 10791963.
Sullivan BM, Harrison-Lavoie KJ, Marshansky V, et al. (2000). "RGS4 and RGS2 bind coatomer and inhibit COPI association with Golgi membranes and intracellular transport". Mol. Biol. Cell. 11 (9): 3155–68. doi:10.1091/mbc.11.9.3155. PMC 14982. PMID 10982407.
Cunningham ML, Waldo GL, Hollinger S, et al. (2001). "Protein kinase C phosphorylates RGS2 and modulates its capacity for negative regulation of Galpha 11 signaling". J. Biol. Chem. 276 (8): 5438–44. doi:10.1074/jbc.M007699200. PMID 11063746.
Heximer SP, Lim H, Bernard JL, Blumer KJ (2001). "Mechanisms governing subcellular localization and function of human RGS2". J. Biol. Chem. 276 (17): 14195–203. doi:10.1074/jbc.M009942200. PMID 11278586.
Mittmann C, Schüler C, Chung CH, et al. (2001). "Evidence for a short form of RGS3 preferentially expressed in the human heart". Naunyn Schmiedebergs Arch. Pharmacol. 363 (4): 456–63. doi:10.1007/s002100000376. PMID 11330340. S2CID 36657400.
Mittmann C, Chung CH, Höppner G, et al. (2002). "Expression of ten RGS proteins in human myocardium: functional characterization of an upregulation of RGS4 in heart failure". Cardiovasc. Res. 55 (4): 778–86. doi:10.1016/S0008-6363(02)00459-5. PMID 12176127.
Nlend MC, Bookman RJ, Conner GE, Salathe M (2002). "Regulator of G-protein signaling protein 2 modulates purinergic calcium and ciliary beat frequency responses in airway epithelia". Am. J. Respir. Cell Mol. Biol. 27 (4): 436–45. doi:10.1165/rcmb.2002-0012oc. PMID 12356577.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Cho H, Harrison K, Schwartz O, Kehrl JH (2003). "The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling". Biochem. J. 371 (Pt 3): 973–80. doi:10.1042/BJ20021769. PMC 1223344. PMID 12564955.

Vanjski linkovi

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000116741 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026360 - Ensembl, maj 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.
^ Siderovski DP, Heximer SP, Forsdyke DR (Jun 1994). "A human gene encoding a putative basic helix-loop-helix phosphoprotein whose mRNA increases rapidly in cycloheximide-treated blood mononuclear cells". DNA Cell Biol. 13 (2): 125–47. doi:10.1089/dna.1994.13.125. PMID 8179820.
^ "RGS2 regulator of G-protein signaling 2, 24kDa".
^ "UniProt, P41220" (jezik: engleski). Pristupljeno 17. 12. 2021.
^ ^a ^b ^c ^d ^e ^f ^g ^h Nunn C, Zou MX, Sobiesiak AJ, Roy AA, Kirshenbaum LA, Chidiac P (august 2010). "RGS2 inhibits beta-adrenergic receptor-induced cardiomyocyte hypertrophy". Cell. Signal. 22 (8): 1231–9. doi:10.1016/j.cellsig.2010.03.015. PMID 20362664.
^ ^a ^b Tuomi JM, Chidiac P, Jones DL (februar 2010). "Evidence for enhanced M3 muscarinic receptor function and sensitivity to atrial arrhythmia in the RGS2-deficient mouse". Am. J. Physiol. Heart Circ. Physiol. 298 (2): H554–61. doi:10.1152/ajpheart.00779.2009. PMID 19966055.
^ ^a ^b ^c ^d Park-Windhol C, Zhang P, Zhu M, Su J, Chaves L, Maldonado AE, King ME, Rickey L, Cullen D, Mende U (2012). "Gq/11-mediated signaling and hypertrophy in mice with cardiac-specific transgenic expression of regulator of G-protein signaling 2". PLOS ONE. 7 (7): e40048. Bibcode:2012PLoSO...740048P. doi:10.1371/journal.pone.0040048. PMC 3388988. PMID 22802950.
^ ^a ^b ^c Vidal M, Wieland T, Lohse MJ, Lorenz K (novembar 2012). "β-Adrenergic receptor stimulation causes cardiac hypertrophy via a Gβγ/Erk-dependent pathway". Cardiovasc. Res. 96 (2): 255–64. doi:10.1093/cvr/cvs249. PMID 22843704.
^ Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, Kaltenbronn KM, Blumer KJ, Siderovski DP, Zhu Y, Mendelsohn ME, Tang M, Wang G (decembar 2003). "Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure". Nat. Med. 9 (12): 1506–12. doi:10.1038/nm958. PMID 14608379. S2CID 20331752.
^ Salim S, Sinnarajah S, Kehrl JH, Dessauer CW (maj 2003). "Identification of RGS2 and type V adenylyl cyclase interaction sites". J. Biol. Chem. 278 (18): 15842–9. doi:10.1074/jbc.M210663200. PMID 12604604.
^ Wieland T, Lutz S, Chidiac P (april 2007). "Regulators of G protein signalling: a spotlight on emerging functions in the cardiovascular system". Curr Opin Pharmacol. 7 (2): 201–7. doi:10.1016/j.coph.2006.11.007. PMID 17276730.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000116741 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026360 - Ensembl, maj 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.

[pmid8179820-5] Siderovski DP, Heximer SP, Forsdyke DR (Jun 1994). "A human gene encoding a putative basic helix-loop-helix phosphoprotein whose mRNA increases rapidly in cycloheximide-treated blood mononuclear cells". DNA Cell Biol. 13 (2): 125–47. doi:10.1089/dna.1994.13.125. PMID 8179820.

[6] "RGS2 regulator of G-protein signaling 2, 24kDa".

[UniProt-7] "UniProt, P41220" (jezik: engleski). Pristupljeno 17. 12. 2021.

[Nunn_2010-8] ^ ^a ^b ^c ^d ^e ^f ^g ^h Nunn C, Zou MX, Sobiesiak AJ, Roy AA, Kirshenbaum LA, Chidiac P (august 2010). "RGS2 inhibits beta-adrenergic receptor-induced cardiomyocyte hypertrophy". Cell. Signal. 22 (8): 1231–9. doi:10.1016/j.cellsig.2010.03.015. PMID 20362664.

[Tuomi_2010-9] Tuomi JM, Chidiac P, Jones DL (februar 2010). "Evidence for enhanced M3 muscarinic receptor function and sensitivity to atrial arrhythmia in the RGS2-deficient mouse". Am. J. Physiol. Heart Circ. Physiol. 298 (2): H554–61. doi:10.1152/ajpheart.00779.2009. PMID 19966055.

[Park-Windhol_2012-10] Park-Windhol C, Zhang P, Zhu M, Su J, Chaves L, Maldonado AE, King ME, Rickey L, Cullen D, Mende U (2012). "Gq/11-mediated signaling and hypertrophy in mice with cardiac-specific transgenic expression of regulator of G-protein signaling 2". PLOS ONE. 7 (7): e40048. Bibcode:2012PLoSO...740048P. doi:10.1371/journal.pone.0040048. PMC 3388988. PMID 22802950.

[Vidal_2012-11] Vidal M, Wieland T, Lohse MJ, Lorenz K (novembar 2012). "β-Adrenergic receptor stimulation causes cardiac hypertrophy via a Gβγ/Erk-dependent pathway". Cardiovasc. Res. 96 (2): 255–64. doi:10.1093/cvr/cvs249. PMID 22843704.

[pmid14608379-12] Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, Kaltenbronn KM, Blumer KJ, Siderovski DP, Zhu Y, Mendelsohn ME, Tang M, Wang G (decembar 2003). "Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure". Nat. Med. 9 (12): 1506–12. doi:10.1038/nm958. PMID 14608379. S2CID 20331752.

[pmid12604604-13] Salim S, Sinnarajah S, Kehrl JH, Dessauer CW (maj 2003). "Identification of RGS2 and type V adenylyl cyclase interaction sites". J. Biol. Chem. 278 (18): 15842–9. doi:10.1074/jbc.M210663200. PMID 12604604.

[Wieland_2007-14] Wieland T, Lutz S, Chidiac P (april 2007). "Regulators of G protein signalling: a spotlight on emerging functions in the cardiovascular system". Curr Opin Pharmacol. 7 (2): 201–7. doi:10.1016/j.coph.2006.11.007. PMID 17276730.

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