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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
{{Infobox_gene}}
'''Guanine nucleotide-binding protein subunit alpha-12''' is a [[protein]] that in humans is encoded by the ''GNA12'' [[gene]].<ref name="pmid8423800">{{cite journal | vauthors = Chan AM, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA | title = Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product | journal = Molecular and Cellular Biology | volume = 13 | issue = 2 | pages = 762–8 | date = February 1993 | pmid = 8423800 | pmc = 358958 | doi = 10.1128/mcb.13.2.762}}</ref><ref name="pmid16247467">{{cite journal | vauthors = Kumar RN, Shore SK, Dhanasekaran N | title = Neoplastic transformation by the gep oncogene, Galpha12, involves signaling by STAT3 | journal = Oncogene | volume = 25 | issue = 6 | pages = 899–906 | date = February 2006 | pmid = 16247467 | pmc = | doi = 10.1038/sj.onc.1209132 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GNA12 guanine nucleotide binding protein (G protein) alpha 12| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2768| accessdate = }}</ref>
'''Guanine nucleotide-binding protein subunit alpha-12''' is a [[protein]] that in humans is encoded by the ''GNA12'' [[gene]].<ref name="pmid8423800">{{cite journal | vauthors = Chan AM, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA | title = Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product | journal = Molecular and Cellular Biology | volume = 13 | issue = 2 | pages = 762–8 | date = February 1993 | pmid = 8423800 | pmc = 358958 | doi = 10.1128/mcb.13.2.762}}</ref><ref name="pmid16247467">{{cite journal | vauthors = Kumar RN, Shore SK, Dhanasekaran N | title = Neoplastic transformation by the gep oncogene, Galpha12, involves signaling by STAT3 | journal = Oncogene | volume = 25 | issue = 6 | pages = 899–906 | date = February 2006 | pmid = 16247467 | doi = 10.1038/sj.onc.1209132 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: GNA12 guanine nucleotide binding protein (G protein) alpha 12| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2768}}</ref>



== Interactions and functions ==
== Interactions and functions ==


The GNA12 gene encodes the G<sub>12</sub> [[G alpha subunit |G protein alpha subunit]]. Together with [[GNA13]], these two proteins comprise one of the four classes of [[heterotrimeric G protein]] alpha subunits.<ref name="pmid1905812">{{cite journal |vauthors=Strathmann MP, Simon MI | title = G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 13 | pages = 5582–6 | year = 1991 | pmid = 1905812 | doi = 10.1073/pnas.88.13.5582 | pmc = 51921 }}</ref> Heterotrimeric G proteins function in transducing [[hormone]] and [[neurotransmitter]] signals detected by cell surface [[G protein-coupled receptor]]s to [[signal transduction |intracellular signaling pathways]] to modulate cell functions. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to [[Guanosine triphosphate|GTP]] but inactive and associated with the [[G beta-gamma complex]] when bound to [[Guanosine diphosphate |GDP]].<ref name=“pmid3113327”>{{cite journal |last1=Gilman |first1=AG |date=1987 |title= G proteins: transducers of receptor-generated signals |url= |journal= Annual Review of Biochemistry |volume=56 |issue= |pages=615-649 |doi=10.1146/annurev.bi.56.070187.003151 |pmid=3113327 |access-date= }}</ref><ref name=“pmid7579038”>{{cite journal |last1=Rodbell |first1=M |date=1995 |title=Nobel Lecture: Signal transduction: Evolution of an idea |url= |journal=Bioscience Reports |volume=15 |issue=3 |pages=117-133 |doi=10.1007/bf01207453 |pmid=7579038 |access-date= }}</ref>
The GNA12 gene encodes the G<sub>12</sub> [[G alpha subunit|G protein alpha subunit]]. Together with [[GNA13]], these two proteins comprise one of the four classes of [[heterotrimeric G protein]] alpha subunits.<ref name="pmid1905812">{{cite journal |vauthors=Strathmann MP, Simon MI | title = G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 13 | pages = 5582–6 | year = 1991 | pmid = 1905812 | doi = 10.1073/pnas.88.13.5582 | pmc = 51921 | bibcode = 1991PNAS...88.5582S | doi-access = free }}</ref> Heterotrimeric G proteins function in transducing [[hormone]] and [[neurotransmitter]] signals detected by cell surface [[G protein-coupled receptor]]s to [[signal transduction|intracellular signaling pathways]] to modulate cell functions. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to [[Guanosine triphosphate|GTP]] but inactive and associated with the [[G beta-gamma complex]] when bound to [[Guanosine diphosphate|GDP]].<ref name="pmid3113327">{{cite journal |last1=Gilman |first1=AG |date=1987 |title= G proteins: transducers of receptor-generated signals |journal= Annual Review of Biochemistry |volume=56 |pages=615–649 |doi=10.1146/annurev.bi.56.070187.003151 |pmid=3113327 }}</ref><ref name="pmid7579038">{{cite journal |last1=Rodbell |first1=M |date=1995 |title=Nobel Lecture: Signal transduction: Evolution of an idea |journal=Bioscience Reports |volume=15 |issue=3 |pages=117–133 |doi=10.1007/bf01207453 |pmid=7579038 |s2cid=11025853 |pmc=1519115 }}</ref>


Active GTP-bound G<sub>12</sub> alpha subunit [[Protein-protein interaction|interacts]] with and activates [[ARHGEF1]],<ref name=pmid14634662>{{cite journal | vauthors = Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM | title = RGS16 inhibits signalling through the G alpha 13-Rho axis | journal = Nature Cell Biology | volume = 5 | issue = 12 | pages = 1095–103 | date = December 2003 | pmid = 14634662 | doi = 10.1038/ncb1065 | url = https://zenodo.org/record/1233351 }}</ref> [[ARHGEF11]],<ref name=”pmid10026210”>{{cite journal |last1=Fukuhara |first1=S |last2=Murga |first2=C |last3= Zohar |first3=M |last4=Igishi |first4=T |last5=Gutkind |first5=JS |date=1999-02-26 |title=A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho |url= |journal=Journal of Biological Chemistry |volume=274 |issue=9 |pages=5868-5879 |doi=10.1074/jbc.274.9.5868 |pmc= |access-date= }}</ref><ref name=”pmid10526156”>{{cite journal |last1=Rümenapp |first1=U |last2=Blomquist |first2=A |last3=Schwörer |first3=G |last4=Schablowski |first4=H |last5=Psoma |first5=A |last6=Jakobs |first6=KH |date=1999-10-15 |title=Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member |url= |journal= FEBS Letters |volume=459 |issue=3 |pages=313-318 |doi=10.1016/s0014-5793(99)01270-3 |pmc= |access-date= }}</ref> and [[ARHGEF12]].<ref name=pmid11094164>{{cite journal | vauthors = Fukuhara S, Chikumi H, Gutkind JS | title = Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho | journal = FEBS Letters | volume = 485 | issue = 2–3 | pages = 183–8 | date = November 2000 | pmid = 11094164 | doi = 10.1016/S0014-5793(00)02224-9 }}</ref><ref name=pmid12515866>{{cite journal | vauthors = Suzuki N, Nakamura S, Mano H, Kozasa T | title = Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 2 | pages = 733–8 | date = January 2003 | pmid = 12515866 | pmc = 141065 | doi = 10.1073/pnas.0234057100 }}</ref> These ARHGEF proteins function as [[guanine nucleotide exchange factor]]s for the [[Rho family of GTPases |Rho]] [[small GTPases]] to regulate the [[actin]] [[cytoskeleton]].<ref name="pmid8842523">{{cite journal |vauthors=Dhanasekaran N, Dermott JM | title = Signaling by the G12 class of G proteins | journal = Cell. Signal. | volume = 8 | issue = 4 | pages = 235–45 | year = 1996 | pmid = 8842523 | doi = 10.1016/0898-6568(96)00048-4 }}</ref>
Active GTP-bound G<sub>12</sub> alpha subunit [[Protein-protein interaction|interacts]] with and activates [[ARHGEF1]],<ref name=pmid14634662>{{cite journal | vauthors = Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM | title = RGS16 inhibits signalling through the G alpha 13-Rho axis | journal = Nature Cell Biology | volume = 5 | issue = 12 | pages = 1095–103 | date = December 2003 | pmid = 14634662 | doi = 10.1038/ncb1065 | s2cid = 6798899 | url = https://zenodo.org/record/1233351 }}</ref> [[ARHGEF11]],<ref name="pmid10026210">{{cite journal |last1=Fukuhara |first1=S |last2=Murga |first2=C |last3= Zohar |first3=M |last4=Igishi |first4=T |last5=Gutkind |first5=JS |date=1999-02-26 |title=A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho |journal=Journal of Biological Chemistry |volume=274 |issue=9 |pages=5868–5879 |doi=10.1074/jbc.274.9.5868 |pmid=10026210 |doi-access=free }}</ref><ref name="pmid10526156">{{cite journal |last1=Rümenapp |first1=U |last2=Blomquist |first2=A |last3=Schwörer |first3=G |last4=Schablowski |first4=H |last5=Psoma |first5=A |last6=Jakobs |first6=KH |date=1999-10-15 |title=Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member |journal= FEBS Letters |volume=459 |issue=3 |pages=313–318 |doi=10.1016/s0014-5793(99)01270-3 |pmid=10526156 |s2cid=8529412 }}</ref> and [[ARHGEF12]].<ref name=pmid11094164>{{cite journal | vauthors = Fukuhara S, Chikumi H, Gutkind JS | title = Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho | journal = FEBS Letters | volume = 485 | issue = 2–3 | pages = 183–8 | date = November 2000 | pmid = 11094164 | doi = 10.1016/S0014-5793(00)02224-9 | s2cid = 7300556 | doi-access = free }}</ref><ref name=pmid12515866>{{cite journal | vauthors = Suzuki N, Nakamura S, Mano H, Kozasa T | title = Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 2 | pages = 733–8 | date = January 2003 | pmid = 12515866 | pmc = 141065 | doi = 10.1073/pnas.0234057100 | bibcode = 2003PNAS..100..733S | doi-access = free }}</ref> These ARHGEF proteins function as [[guanine nucleotide exchange factor]]s for the [[Rho family of GTPases|Rho]] [[small GTPases]] to regulate the [[actin]] [[cytoskeleton]].<ref name="pmid8842523">{{cite journal |vauthors=Dhanasekaran N, Dermott JM | title = Signaling by the G12 class of G proteins | journal = Cell. Signal. | volume = 8 | issue = 4 | pages = 235–45 | year = 1996 | pmid = 8842523 | doi = 10.1016/0898-6568(96)00048-4 }}</ref>


GNA12 also interacts with [[PPP5C]],<ref name=pmid12176367>{{cite journal | vauthors = Yamaguchi Y, Katoh H, Mori K, Negishi M | title = Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity | journal = Current Biology | volume = 12 | issue = 15 | pages = 1353–8 | date = August 2002 | pmid = 12176367 | doi = 10.1016/S0960-9822(02)01034-5 }}</ref> [[HSP90]]<ref name=pmid11598136>{{cite journal | vauthors = Vaiskunaite R, Kozasa T, Voyno-Yasenetskaya TA | title = Interaction between the G alpha subunit of heterotrimeric G(12) protein and Hsp90 is required for G alpha(12) signaling | journal = The Journal of Biological Chemistry | volume = 276 | issue = 49 | pages = 46088–93 | date = December 2001 | pmid = 11598136 | doi = 10.1074/jbc.M108711200 }}</ref>, [[RIC8A |Resistance to inhibitors of cholinesterase-8A (Ric-8A)]] <ref name=pmid21771786>{{cite journal | vauthors = Wang L, Guo D, Xing B, Zhang JJ, Shu HB, Guo L, Huang XY | title = Resistance to inhibitors of cholinesterase-8A (Ric-8A) is critical for growth factor receptor-induced actin cytoskeletal reorganization | journal = The Journal of Biological Chemistry | volume = 286 | issue = 35 | pages = 31055–61 | date = September 2011 | pmid = 21771786 | doi = 10.1074/jbc.M111.253427 | pmc=3162464}}</ref> and [[TEC (gene)|TEC]].<ref name=pmid12515866/>
GNA12 also interacts with [[PPP5C]],<ref name=pmid12176367>{{cite journal | vauthors = Yamaguchi Y, Katoh H, Mori K, Negishi M | title = Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity | journal = Current Biology | volume = 12 | issue = 15 | pages = 1353–8 | date = August 2002 | pmid = 12176367 | doi = 10.1016/S0960-9822(02)01034-5 | s2cid = 11485795 | doi-access = free }}</ref> [[HSP90]],<ref name=pmid11598136>{{cite journal | vauthors = Vaiskunaite R, Kozasa T, Voyno-Yasenetskaya TA | title = Interaction between the G alpha subunit of heterotrimeric G(12) protein and Hsp90 is required for G alpha(12) signaling | journal = The Journal of Biological Chemistry | volume = 276 | issue = 49 | pages = 46088–93 | date = December 2001 | pmid = 11598136 | doi = 10.1074/jbc.M108711200 | doi-access = free }}</ref> [[RIC8A|Resistance to inhibitors of cholinesterase-8A (Ric-8A)]]<ref name=pmid21771786>{{cite journal | vauthors = Wang L, Guo D, Xing B, Zhang JJ, Shu HB, Guo L, Huang XY | title = Resistance to inhibitors of cholinesterase-8A (Ric-8A) is critical for growth factor receptor-induced actin cytoskeletal reorganization | journal = The Journal of Biological Chemistry | volume = 286 | issue = 35 | pages = 31055–61 | date = September 2011 | pmid = 21771786 | doi = 10.1074/jbc.M111.253427 | pmc=3162464| doi-access = free }}</ref> and [[TEC (gene)|TEC]].<ref name=pmid12515866/>


== See also ==
== See also ==
Line 26: Line 26:
== External links ==
== External links ==
* {{MeshName|GNA12+protein,+human}}
* {{MeshName|GNA12+protein,+human}}
* {{PDBe-KB2|P27600|Mouse Guanine nucleotide-binding protein subunit alpha-12 (GNA12)}}
* {{PDBe-KB2|P27600|Mouse Guanine nucleotide-binding protein subunit alpha-12 (GNA12)}}


{{PDB Gallery|geneid=2768}}
{{PDB Gallery|geneid=2768}}
{{Intracellular signaling peptides and proteins}}
{{Intracellular signaling peptides and proteins}}
{{GTPases}}
{{GTPases}}



{{gene-7-stub}}
{{gene-7-stub}}

Latest revision as of 22:45, 12 August 2023

GNA12
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGNA12, NNX3, RMP, gep, G protein subunit alpha 12, HG1M1
External IDsOMIM: 604394; MGI: 95767; HomoloGene: 22398; GeneCards: GNA12; OMA:GNA12 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2768

14673

Ensembl

ENSG00000146535

ENSMUSG00000000149

UniProt

Q03113

P27600

RefSeq (mRNA)

NM_001282440
NM_001282441
NM_001293092
NM_007353

NM_010302

RefSeq (protein)

NP_001269369
NP_001269370
NP_001280021
NP_031379

NP_034432

Location (UCSC)Chr 7: 2.73 – 2.84 MbChr 5: 140.74 – 140.82 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the GNA12 gene.[5][6][7]

Interactions and functions

[edit]

The GNA12 gene encodes the G12 G protein alpha subunit. Together with GNA13, these two proteins comprise one of the four classes of heterotrimeric G protein alpha subunits.[8] Heterotrimeric G proteins function in transducing hormone and neurotransmitter signals detected by cell surface G protein-coupled receptors to intracellular signaling pathways to modulate cell functions. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to GTP but inactive and associated with the G beta-gamma complex when bound to GDP.[9][10]

Active GTP-bound G12 alpha subunit interacts with and activates ARHGEF1,[11] ARHGEF11,[12][13] and ARHGEF12.[14][15] These ARHGEF proteins function as guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton.[16]

GNA12 also interacts with PPP5C,[17] HSP90,[18] Resistance to inhibitors of cholinesterase-8A (Ric-8A)[19] and TEC.[15]

See also

[edit]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000146535 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000149 – 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. ^ Chan AM, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA (February 1993). "Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product". Molecular and Cellular Biology. 13 (2): 762–8. doi:10.1128/mcb.13.2.762. PMC 358958. PMID 8423800.
  6. ^ Kumar RN, Shore SK, Dhanasekaran N (February 2006). "Neoplastic transformation by the gep oncogene, Galpha12, involves signaling by STAT3". Oncogene. 25 (6): 899–906. doi:10.1038/sj.onc.1209132. PMID 16247467.
  7. ^ "Entrez Gene: GNA12 guanine nucleotide binding protein (G protein) alpha 12".
  8. ^ Strathmann MP, Simon MI (1991). "G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits". Proc. Natl. Acad. Sci. U.S.A. 88 (13): 5582–6. Bibcode:1991PNAS...88.5582S. doi:10.1073/pnas.88.13.5582. PMC 51921. PMID 1905812.
  9. ^ Gilman, AG (1987). "G proteins: transducers of receptor-generated signals". Annual Review of Biochemistry. 56: 615–649. doi:10.1146/annurev.bi.56.070187.003151. PMID 3113327.
  10. ^ Rodbell, M (1995). "Nobel Lecture: Signal transduction: Evolution of an idea". Bioscience Reports. 15 (3): 117–133. doi:10.1007/bf01207453. PMC 1519115. PMID 7579038. S2CID 11025853.
  11. ^ Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM (December 2003). "RGS16 inhibits signalling through the G alpha 13-Rho axis". Nature Cell Biology. 5 (12): 1095–103. doi:10.1038/ncb1065. PMID 14634662. S2CID 6798899.
  12. ^ Fukuhara, S; Murga, C; Zohar, M; Igishi, T; Gutkind, JS (1999-02-26). "A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho". Journal of Biological Chemistry. 274 (9): 5868–5879. doi:10.1074/jbc.274.9.5868. PMID 10026210.
  13. ^ Rümenapp, U; Blomquist, A; Schwörer, G; Schablowski, H; Psoma, A; Jakobs, KH (1999-10-15). "Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member". FEBS Letters. 459 (3): 313–318. doi:10.1016/s0014-5793(99)01270-3. PMID 10526156. S2CID 8529412.
  14. ^ Fukuhara S, Chikumi H, Gutkind JS (November 2000). "Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho". FEBS Letters. 485 (2–3): 183–8. doi:10.1016/S0014-5793(00)02224-9. PMID 11094164. S2CID 7300556.
  15. ^ a b Suzuki N, Nakamura S, Mano H, Kozasa T (January 2003). "Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF". Proceedings of the National Academy of Sciences of the United States of America. 100 (2): 733–8. Bibcode:2003PNAS..100..733S. doi:10.1073/pnas.0234057100. PMC 141065. PMID 12515866.
  16. ^ Dhanasekaran N, Dermott JM (1996). "Signaling by the G12 class of G proteins". Cell. Signal. 8 (4): 235–45. doi:10.1016/0898-6568(96)00048-4. PMID 8842523.
  17. ^ Yamaguchi Y, Katoh H, Mori K, Negishi M (August 2002). "Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity". Current Biology. 12 (15): 1353–8. doi:10.1016/S0960-9822(02)01034-5. PMID 12176367. S2CID 11485795.
  18. ^ Vaiskunaite R, Kozasa T, Voyno-Yasenetskaya TA (December 2001). "Interaction between the G alpha subunit of heterotrimeric G(12) protein and Hsp90 is required for G alpha(12) signaling". The Journal of Biological Chemistry. 276 (49): 46088–93. doi:10.1074/jbc.M108711200. PMID 11598136.
  19. ^ Wang L, Guo D, Xing B, Zhang JJ, Shu HB, Guo L, Huang XY (September 2011). "Resistance to inhibitors of cholinesterase-8A (Ric-8A) is critical for growth factor receptor-induced actin cytoskeletal reorganization". The Journal of Biological Chemistry. 286 (35): 31055–61. doi:10.1074/jbc.M111.253427. PMC 3162464. PMID 21771786.
[edit]


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