Full text data of GNA13
GNA13
[Confidence: high (present in two of the MS resources)]
Guanine nucleotide-binding protein subunit alpha-13; G alpha-13; G-protein subunit alpha-13
Guanine nucleotide-binding protein subunit alpha-13; G alpha-13; G-protein subunit alpha-13
hRBCD
IPI00290928
IPI00290928 Guanine nucleotide-binding protein, alpha-13 subunit Guanine nucleotide-binding protein, alpha-13 subunit membrane n/a n/a n/a n/a 1 n/a n/a n/a 8 n/a n/a n/a n/a n/a 2 n/a 2 2 n/a n/a inner surface of plasma membrane n/a found at its expected molecular weight found at molecular weight
IPI00290928 Guanine nucleotide-binding protein, alpha-13 subunit Guanine nucleotide-binding protein, alpha-13 subunit membrane n/a n/a n/a n/a 1 n/a n/a n/a 8 n/a n/a n/a n/a n/a 2 n/a 2 2 n/a n/a inner surface of plasma membrane n/a found at its expected molecular weight found at molecular weight
UniProt
Q14344
ID GNA13_HUMAN Reviewed; 377 AA.
AC Q14344; B2R977; Q8TD70;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 31-OCT-2003, sequence version 2.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Guanine nucleotide-binding protein subunit alpha-13;
DE Short=G alpha-13;
DE Short=G-protein subunit alpha-13;
GN Name=GNA13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-221.
RC TISSUE=Thymus;
RX PubMed=7791744; DOI=10.1007/BF00926739;
RA Kabouridis P.S., Waters S.T., Escobar S., Stanners J., Tsoukas C.D.;
RT "Expression of GTP-binding protein alpha subunits in human
RT thymocytes.";
RL Mol. Cell. Biochem. 144:45-51(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Melanoma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PALMITOYLATION AT CYS-14 AND CYS-18, AND MUTAGENESIS OF CYS-14 AND
RP CYS-18.
RX PubMed=10747909; DOI=10.1074/jbc.M000415200;
RA Bhattacharyya R., Wedegaertner P.B.;
RT "Galpha 13 requires palmitoylation for plasma membrane localization,
RT Rho-dependent signaling, and promotion of p115-RhoGEF membrane
RT binding.";
RL J. Biol. Chem. 275:14992-14999(2000).
RN [7]
RP PHOSPHORYLATION AT THR-203, AND MUTAGENESIS OF THR-203.
RX PubMed=12399457; DOI=10.1074/jbc.M209219200;
RA Manganello J.M., Huang J.-S., Kozasa T., Voyno-Yasenetskaya T.A.,
RA Le Breton G.C.;
RT "PKA-mediated phosphorylation of Galpha 13 switch I region alters the
RT Galpha beta gamma 13-GPCR complex and inhibits Rho activation.";
RL J. Biol. Chem. 278:124-130(2003).
RN [8]
RP INTERACTION WITH HAX1.
RX PubMed=15339924; DOI=10.1074/jbc.M408836200;
RA Radhika V., Onesime D., Ha J.H., Dhanasekaran N.;
RT "Galpha13 stimulates cell migration through cortactin-interacting
RT protein Hax-1.";
RL J. Biol. Chem. 279:49406-49413(2004).
RN [9]
RP INTERACTION WITH UBXD5.
RX PubMed=16202387; DOI=10.1016/j.bbrc.2005.09.097;
RA Tateiwa K., Katoh H., Negishi M.;
RT "Socius, a novel binding partner of Galpha12/13, promotes the
RT Galpha12-induced RhoA activation.";
RL Biochem. Biophys. Res. Commun. 337:615-620(2005).
RN [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are
CC involved as modulators or transducers in various transmembrane
CC signaling systems.
CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and
CC gamma. The alpha chain contains the guanine nucleotide binding
CC site. Interacts with UBXD5. Interacts with HAX1. Interacts (when
CC active) with PPP5C (via TPR repeats); activates PPP5C phosphatase
CC activity and translocates PPP5C to the cell membrane.
CC -!- INTERACTION:
CC Q92888:ARHGEF1; NbExp=3; IntAct=EBI-465387, EBI-465400;
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor. Melanosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV.
CC -!- PTM: Palmitoylation is critical for proper membrane localization
CC and signaling.
CC -!- PTM: Phosphorylation on Thr-203 by PKA destabilizes the
CC heterotrimer of alpha, beta and gamma, and inhibits Rho
CC activation.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(12) subfamily.
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DR EMBL; L22075; AAA74235.1; -; mRNA.
DR EMBL; AF493902; AAM12616.1; -; mRNA.
DR EMBL; AK313672; BAG36424.1; -; mRNA.
DR EMBL; CH471099; EAW88993.1; -; Genomic_DNA.
DR EMBL; BC036756; AAH36756.1; -; mRNA.
DR PIR; I57490; I57490.
DR RefSeq; NP_006563.2; NM_006572.5.
DR UniGene; Hs.515018; -.
DR ProteinModelPortal; Q14344; -.
DR SMR; Q14344; 47-369.
DR IntAct; Q14344; 2.
DR MINT; MINT-85993; -.
DR STRING; 9606.ENSP00000400717; -.
DR PhosphoSite; Q14344; -.
DR DMDM; 38258936; -.
DR PaxDb; Q14344; -.
DR PeptideAtlas; Q14344; -.
DR PRIDE; Q14344; -.
DR DNASU; 10672; -.
DR Ensembl; ENST00000439174; ENSP00000400717; ENSG00000120063.
DR GeneID; 10672; -.
DR KEGG; hsa:10672; -.
DR UCSC; uc002jfc.3; human.
DR CTD; 10672; -.
DR GeneCards; GC17M063005; -.
DR HGNC; HGNC:4381; GNA13.
DR HPA; HPA010087; -.
DR MIM; 604406; gene.
DR neXtProt; NX_Q14344; -.
DR PharmGKB; PA28766; -.
DR eggNOG; NOG279688; -.
DR HOGENOM; HOG000038729; -.
DR HOVERGEN; HBG063184; -.
DR InParanoid; Q14344; -.
DR KO; K04639; -.
DR OMA; CFPGCVL; -.
DR OrthoDB; EOG7HF1JF; -.
DR PhylomeDB; Q14344; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; Q14344; -.
DR ChiTaRS; GNA13; human.
DR GeneWiki; GNA13; -.
DR GenomeRNAi; 10672; -.
DR NextBio; 40583; -.
DR PRO; PR:Q14344; -.
DR ArrayExpress; Q14344; -.
DR Bgee; Q14344; -.
DR CleanEx; HS_GNA13; -.
DR Genevestigator; Q14344; -.
DR GO; GO:0031526; C:brush border membrane; IBA:RefGenome.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:RefGenome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031752; F:D5 dopamine receptor binding; IBA:RefGenome.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:RefGenome.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IBA:RefGenome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004871; F:signal transducer activity; IBA:RefGenome.
DR GO; GO:0031702; F:type 1 angiotensin receptor binding; IBA:RefGenome.
DR GO; GO:0031584; P:activation of phospholipase D activity; IBA:RefGenome.
DR GO; GO:0007189; P:adenylate cyclase-activating G-protein coupled receptor signaling pathway; IBA:RefGenome.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0006928; P:cellular component movement; TAS:ProtInc.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IEA:Ensembl.
DR GO; GO:0001569; P:patterning of blood vessels; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl.
DR GO; GO:0008360; P:regulation of cell shape; IEA:Ensembl.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:RefGenome.
DR Gene3D; 1.10.400.10; -; 1.
DR InterPro; IPR000469; Gprotein_alpha_12.
DR InterPro; IPR001019; Gprotein_alpha_su.
DR InterPro; IPR011025; GproteinA_insert.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10218; PTHR10218; 1.
DR Pfam; PF00503; G-alpha; 1.
DR PRINTS; PR00318; GPROTEINA.
DR PRINTS; PR00440; GPROTEINA12.
DR SMART; SM00275; G_alpha; 1.
DR SUPFAM; SSF47895; SSF47895; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
PE 1: Evidence at protein level;
KW Complete proteome; GTP-binding; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Palmitate; Phosphoprotein;
KW Polymorphism; Reference proteome; Transducer.
FT CHAIN 1 377 Guanine nucleotide-binding protein
FT subunit alpha-13.
FT /FTId=PRO_0000203773.
FT NP_BIND 55 62 GTP (By similarity).
FT NP_BIND 197 203 GTP (By similarity).
FT NP_BIND 222 226 GTP (By similarity).
FT NP_BIND 291 294 GTP (By similarity).
FT METAL 62 62 Magnesium (By similarity).
FT METAL 203 203 Magnesium (By similarity).
FT BINDING 349 349 GTP; via amide nitrogen (By similarity).
FT MOD_RES 203 203 Phosphothreonine; by PKA.
FT LIPID 14 14 S-palmitoyl cysteine.
FT LIPID 18 18 S-palmitoyl cysteine.
FT VARIANT 221 221 V -> L (in dbSNP:rs1062597).
FT /FTId=VAR_017160.
FT MUTAGEN 14 14 C->S: Fails to localize to plasma
FT membranes and failed to activate Rho-
FT dependent serum response factor-mediated
FT transcription and actin stress fiber
FT formation.
FT MUTAGEN 18 18 C->S: Fails to localize to plasma
FT membranes and failed to activate Rho-
FT dependent serum response factor-mediated
FT transcription and actin stress fiber
FT formation.
FT MUTAGEN 203 203 T->A: Abolishes phosphorylation by PKA;
FT disrupts heterotrimer stability.
SQ SEQUENCE 377 AA; 44050 MW; 929B7B6473C54F2E CRC64;
MADFLPSRSV LSVCFPGCLL TSGEAEQQRK SKEIDKCLSR EKTYVKRLVK ILLLGAGESG
KSTFLKQMRI IHGQDFDQRA REEFRPTIYS NVIKGMRVLV DAREKLHIPW GDNSNQQHGD
KMMSFDTRAP MAAQGMVETR VFLQYLPAIR ALWADSGIQN AYDRRREFQL GESVKYFLDN
LDKLGEPDYI PSQQDILLAR RPTKGIHEYD FEIKNVPFKM VDVGGQRSER KRWFECFDSV
TSILFLVSSS EFDQVLMEDR LTNRLTESLN IFETIVNNRV FSNVSIILFL NKTDLLEEKV
QIVSIKDYFL EFEGDPHCLR DVQKFLVECF RNKRRDQQQK PLYHHFTTAI NTENIRLVFR
DVKDTILHDN LKQLMLQ
//
ID GNA13_HUMAN Reviewed; 377 AA.
AC Q14344; B2R977; Q8TD70;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 31-OCT-2003, sequence version 2.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Guanine nucleotide-binding protein subunit alpha-13;
DE Short=G alpha-13;
DE Short=G-protein subunit alpha-13;
GN Name=GNA13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-221.
RC TISSUE=Thymus;
RX PubMed=7791744; DOI=10.1007/BF00926739;
RA Kabouridis P.S., Waters S.T., Escobar S., Stanners J., Tsoukas C.D.;
RT "Expression of GTP-binding protein alpha subunits in human
RT thymocytes.";
RL Mol. Cell. Biochem. 144:45-51(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Melanoma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PALMITOYLATION AT CYS-14 AND CYS-18, AND MUTAGENESIS OF CYS-14 AND
RP CYS-18.
RX PubMed=10747909; DOI=10.1074/jbc.M000415200;
RA Bhattacharyya R., Wedegaertner P.B.;
RT "Galpha 13 requires palmitoylation for plasma membrane localization,
RT Rho-dependent signaling, and promotion of p115-RhoGEF membrane
RT binding.";
RL J. Biol. Chem. 275:14992-14999(2000).
RN [7]
RP PHOSPHORYLATION AT THR-203, AND MUTAGENESIS OF THR-203.
RX PubMed=12399457; DOI=10.1074/jbc.M209219200;
RA Manganello J.M., Huang J.-S., Kozasa T., Voyno-Yasenetskaya T.A.,
RA Le Breton G.C.;
RT "PKA-mediated phosphorylation of Galpha 13 switch I region alters the
RT Galpha beta gamma 13-GPCR complex and inhibits Rho activation.";
RL J. Biol. Chem. 278:124-130(2003).
RN [8]
RP INTERACTION WITH HAX1.
RX PubMed=15339924; DOI=10.1074/jbc.M408836200;
RA Radhika V., Onesime D., Ha J.H., Dhanasekaran N.;
RT "Galpha13 stimulates cell migration through cortactin-interacting
RT protein Hax-1.";
RL J. Biol. Chem. 279:49406-49413(2004).
RN [9]
RP INTERACTION WITH UBXD5.
RX PubMed=16202387; DOI=10.1016/j.bbrc.2005.09.097;
RA Tateiwa K., Katoh H., Negishi M.;
RT "Socius, a novel binding partner of Galpha12/13, promotes the
RT Galpha12-induced RhoA activation.";
RL Biochem. Biophys. Res. Commun. 337:615-620(2005).
RN [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are
CC involved as modulators or transducers in various transmembrane
CC signaling systems.
CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and
CC gamma. The alpha chain contains the guanine nucleotide binding
CC site. Interacts with UBXD5. Interacts with HAX1. Interacts (when
CC active) with PPP5C (via TPR repeats); activates PPP5C phosphatase
CC activity and translocates PPP5C to the cell membrane.
CC -!- INTERACTION:
CC Q92888:ARHGEF1; NbExp=3; IntAct=EBI-465387, EBI-465400;
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor. Melanosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV.
CC -!- PTM: Palmitoylation is critical for proper membrane localization
CC and signaling.
CC -!- PTM: Phosphorylation on Thr-203 by PKA destabilizes the
CC heterotrimer of alpha, beta and gamma, and inhibits Rho
CC activation.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(12) subfamily.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; L22075; AAA74235.1; -; mRNA.
DR EMBL; AF493902; AAM12616.1; -; mRNA.
DR EMBL; AK313672; BAG36424.1; -; mRNA.
DR EMBL; CH471099; EAW88993.1; -; Genomic_DNA.
DR EMBL; BC036756; AAH36756.1; -; mRNA.
DR PIR; I57490; I57490.
DR RefSeq; NP_006563.2; NM_006572.5.
DR UniGene; Hs.515018; -.
DR ProteinModelPortal; Q14344; -.
DR SMR; Q14344; 47-369.
DR IntAct; Q14344; 2.
DR MINT; MINT-85993; -.
DR STRING; 9606.ENSP00000400717; -.
DR PhosphoSite; Q14344; -.
DR DMDM; 38258936; -.
DR PaxDb; Q14344; -.
DR PeptideAtlas; Q14344; -.
DR PRIDE; Q14344; -.
DR DNASU; 10672; -.
DR Ensembl; ENST00000439174; ENSP00000400717; ENSG00000120063.
DR GeneID; 10672; -.
DR KEGG; hsa:10672; -.
DR UCSC; uc002jfc.3; human.
DR CTD; 10672; -.
DR GeneCards; GC17M063005; -.
DR HGNC; HGNC:4381; GNA13.
DR HPA; HPA010087; -.
DR MIM; 604406; gene.
DR neXtProt; NX_Q14344; -.
DR PharmGKB; PA28766; -.
DR eggNOG; NOG279688; -.
DR HOGENOM; HOG000038729; -.
DR HOVERGEN; HBG063184; -.
DR InParanoid; Q14344; -.
DR KO; K04639; -.
DR OMA; CFPGCVL; -.
DR OrthoDB; EOG7HF1JF; -.
DR PhylomeDB; Q14344; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; Q14344; -.
DR ChiTaRS; GNA13; human.
DR GeneWiki; GNA13; -.
DR GenomeRNAi; 10672; -.
DR NextBio; 40583; -.
DR PRO; PR:Q14344; -.
DR ArrayExpress; Q14344; -.
DR Bgee; Q14344; -.
DR CleanEx; HS_GNA13; -.
DR Genevestigator; Q14344; -.
DR GO; GO:0031526; C:brush border membrane; IBA:RefGenome.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:RefGenome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031752; F:D5 dopamine receptor binding; IBA:RefGenome.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:RefGenome.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IBA:RefGenome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004871; F:signal transducer activity; IBA:RefGenome.
DR GO; GO:0031702; F:type 1 angiotensin receptor binding; IBA:RefGenome.
DR GO; GO:0031584; P:activation of phospholipase D activity; IBA:RefGenome.
DR GO; GO:0007189; P:adenylate cyclase-activating G-protein coupled receptor signaling pathway; IBA:RefGenome.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0006928; P:cellular component movement; TAS:ProtInc.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IEA:Ensembl.
DR GO; GO:0001569; P:patterning of blood vessels; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl.
DR GO; GO:0008360; P:regulation of cell shape; IEA:Ensembl.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:RefGenome.
DR Gene3D; 1.10.400.10; -; 1.
DR InterPro; IPR000469; Gprotein_alpha_12.
DR InterPro; IPR001019; Gprotein_alpha_su.
DR InterPro; IPR011025; GproteinA_insert.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10218; PTHR10218; 1.
DR Pfam; PF00503; G-alpha; 1.
DR PRINTS; PR00318; GPROTEINA.
DR PRINTS; PR00440; GPROTEINA12.
DR SMART; SM00275; G_alpha; 1.
DR SUPFAM; SSF47895; SSF47895; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
PE 1: Evidence at protein level;
KW Complete proteome; GTP-binding; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Palmitate; Phosphoprotein;
KW Polymorphism; Reference proteome; Transducer.
FT CHAIN 1 377 Guanine nucleotide-binding protein
FT subunit alpha-13.
FT /FTId=PRO_0000203773.
FT NP_BIND 55 62 GTP (By similarity).
FT NP_BIND 197 203 GTP (By similarity).
FT NP_BIND 222 226 GTP (By similarity).
FT NP_BIND 291 294 GTP (By similarity).
FT METAL 62 62 Magnesium (By similarity).
FT METAL 203 203 Magnesium (By similarity).
FT BINDING 349 349 GTP; via amide nitrogen (By similarity).
FT MOD_RES 203 203 Phosphothreonine; by PKA.
FT LIPID 14 14 S-palmitoyl cysteine.
FT LIPID 18 18 S-palmitoyl cysteine.
FT VARIANT 221 221 V -> L (in dbSNP:rs1062597).
FT /FTId=VAR_017160.
FT MUTAGEN 14 14 C->S: Fails to localize to plasma
FT membranes and failed to activate Rho-
FT dependent serum response factor-mediated
FT transcription and actin stress fiber
FT formation.
FT MUTAGEN 18 18 C->S: Fails to localize to plasma
FT membranes and failed to activate Rho-
FT dependent serum response factor-mediated
FT transcription and actin stress fiber
FT formation.
FT MUTAGEN 203 203 T->A: Abolishes phosphorylation by PKA;
FT disrupts heterotrimer stability.
SQ SEQUENCE 377 AA; 44050 MW; 929B7B6473C54F2E CRC64;
MADFLPSRSV LSVCFPGCLL TSGEAEQQRK SKEIDKCLSR EKTYVKRLVK ILLLGAGESG
KSTFLKQMRI IHGQDFDQRA REEFRPTIYS NVIKGMRVLV DAREKLHIPW GDNSNQQHGD
KMMSFDTRAP MAAQGMVETR VFLQYLPAIR ALWADSGIQN AYDRRREFQL GESVKYFLDN
LDKLGEPDYI PSQQDILLAR RPTKGIHEYD FEIKNVPFKM VDVGGQRSER KRWFECFDSV
TSILFLVSSS EFDQVLMEDR LTNRLTESLN IFETIVNNRV FSNVSIILFL NKTDLLEEKV
QIVSIKDYFL EFEGDPHCLR DVQKFLVECF RNKRRDQQQK PLYHHFTTAI NTENIRLVFR
DVKDTILHDN LKQLMLQ
//
MIM
604406
*RECORD*
*FIELD* NO
604406
*FIELD* TI
*604406 GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-13; GNA13
;;G-ALPHA-13
*FIELD* TX
read moreFor background information on G proteins, see 600874.
CLONING
Kabouridis et al. (1995) cloned human thymocyte cDNAs corresponding to
the full-length coding sequence of G-alpha-13. The GNA13 cDNA encodes a
deduced 377-amino acid protein that is 97% homologous to the mouse Gna13
protein. It contains the highly conserved motifs found in all G protein
alpha subunits that are thought to be directly involved in the
interaction with the guanine nucleotide. Northern blot analysis revealed
that GNA13 is expressed as a major 4.8-kb and a minor 5.3-kb transcript
in Jurkat and HPB-ALL leukemic T-cell lines.
GENE FUNCTION
Moers et al. (2003) showed that lack of G-alpha-13, but not G-alpha-12
(604394), severely reduced the potency of thrombin (176930), thromboxane
A2, and collagen to induce platelet shape changes and aggregation in
vitro. These defects were accompanied by a reduced activation of RhoA
(165390) and inability to form stable platelet thrombi under high shear
stress ex vivo. G-alpha-13 deficiency in platelets resulted in a severe
defect of primary hemostasis and complete protection against arterial
thrombosis in vivo. Moers et al. (2003) concluded that G13-mediated
signaling processes are required for normal hemostasis and thrombosis.
Radhika et al. (2004) presented evidence that mammalian Gna13 associates
with intracellular Hax1 (605998), a cortactin (164765)-interacting
protein, and that Hax1 promotes Gna13-mediated cell migration. Gna13 and
Hax1 existed in a complex with Rac (see 602048) and cortactin in
transfected cells, and coexpression of Hax1 enhanced Gna13-mediated Rac
activity while inhibiting Rho activity, both of which can promote cell
movement.
Shan et al. (2006) showed that Gna13 was essential for receptor tyrosine
kinase-induced migration of mouse fibroblasts and endothelial cells.
Gna13 activity in cell migration was retained in a C-terminal mutant
that was defective in coupling to G protein-coupled receptors,
suggesting that the migration function is independent of receptor
signaling.
G-alpha-q (GNAQ; 600998)-coupled receptors, such as alpha-1-adrenergic
(see ADRA1A; 104221), angiotensin (106165), and endothelin (see ENDRA;
131243) receptors, play key roles in cardiac physiology. These receptors
also interact with G-alpha-12 and G-alpha-13. Using photoaffinity
labeling and immunoprecipitation, Kilts et al. (2007) showed that these
receptors differentially activated cardiac G-alpha-12 and G-alpha-13 in
membranes of human right arial appendages. Endothelin receptors
activated only G-alpha-12, whereas angiotensin receptors activated only
G-alpha-13. Alpha-1-adrenergic receptors activated neither G-alpha-12
nor G-alpha-13.
Using mice lacking G-alpha subunits specifically in smooth muscle cells,
Wirth et al. (2008) found that G-alpha-q and G-alpha-11 (GNA11; 139313)
were required for maintenance of basal blood pressure and for
development of salt-induced hypertension. In contrast, lack of
G-alpha-12 and G-alpha-13 and their effector, Larg (ARHGEF12; 604763),
did not alter normal blood pressure regulation, but blocked development
of salt-induced hypertension.
Gong et al. (2010) found that the heterotrimeric guanine
nucleotide-binding protein G-alpha-13 directly binds to the integrin
beta-3 (173470) cytoplasmic domain and that G-alpha-13-integrin
interaction is promoted by ligand binding to the integrin alpha-IIb
(607759)-beta-3 and by GTP loading of G-alpha-13. Interference of
G-alpha-13 expression or a myristoylated fragment of G-alpha-13 that
inhibited interaction of alpha-IIb-beta-3 with G-alpha-13 diminished
activation of protein kinase c-Src (124095) and stimulated the small
guanosine triphosphatase RhoA (165390), consequently inhibiting cell
spreading and accelerating cell retraction. Gong et al. (2010) concluded
that integrins are noncanonical G-alpha-13-coupled receptors that
provide a mechanism for dynamic regulation of RhoA.
Shen et al. (2013) demonstrated that G-alpha-13 and talin (186745) bind
to mutually exclusive but distinct sites within the integrin beta-3
cytoplasmic domain in opposing waves. The first talin-binding wave
mediates inside-out signaling and also ligand-induced integrin
activation, but is not required for outside-in signaling. Integrin
ligation induces transient talin dissociation and G-alpha-13 binding to
an EXE motif (in which X denotes any residue), which selectively
mediates outside-in signaling and platelet spreading. The second
talin-binding wave is associated with clot retraction. An
EXE-motif-based inhibitor of G-alpha-13-integrin interaction selectively
abolishes outside-in signaling without affecting integrin ligation, and
suppresses occlusive arterial thrombosis without affecting bleeding
time. Shen et al. (2013) concluded that they discovered a mechanism for
the directional switch of integrin signaling and, on the basis of this
mechanism, designed a potent antithrombotic drug that does not cause
bleeding.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the GNA13
gene to chromosome 17 (TMAP RH18264).
ANIMAL MODEL
Offermanns et al. (1997) showed that disruption of the Gna13 gene in
mice impaired the ability of endothelial cells to develop into an
organized vascular system, resulting in intrauterine death. Furthermore,
embryonic fibroblasts lacking a functional Gna13 gene showed greatly
impaired migratory responses to thrombin. The results demonstrated that
GNA13 participates in the regulation of cell movement in response to
specific ligands, and in developmental angiogenesis.
Ruppel et al. (2005) found that Gna13 was expressed throughout the
mesenchyme of developing mouse embryos, with strong staining in vascular
endothelial cells and dorsal neural tube. Gna13-knockout embryos died
between embryonic days 9.5 and 11.5 and were pale, with pericardial
swelling, and variable bleeding into cavities and tissues.
Endothelial-specific Gna13-knockout embryos showed a somewhat less
severe phenotype. Targeted reintroduction of Gna13 into the endothelium
of Gna13-null embryos prevented vascular defects, and embryos survived
several days beyond transgene-negative embryos, but they developed a
second phenotype characterized by exencephaly and hemorrhage within the
head mesenchyme.
*FIELD* RF
1. Gong, H.; Shen, B.; Flevaris, P.; Chow, C.; Lam, S. C.-T.; Voyno-Yasenetskaya,
T. A.; Kozasa, T.; Du, X.: G protein subunit G-alpha-13 binds to
integrin alphaIIb-beta-3 and mediates integrin 'outside-in' signaling. Science 327:
340-343, 2010.
2. Kabouridis, P. S.; Waters, S. T.; Escobar, S.; Stanners, J.; Tsoukas,
C. D.: Expression of GTP-binding protein alpha subunits in human
thymocytes. Molec. Cell. Biochem. 144: 45-51, 1995.
3. Kilts, J. D.; Lin, S. S.; Lowe, J. E.; Kwatra, M. M.: Selective
activation of human atrial G-alpha-12 and G-alpha-13 by G-alpha-q-coupled
angiotensin and endothelin receptors. J. Cardiovasc. Pharm. 50:
299-303, 2007.
4. Moers, A.; Nieswandt, B.; Massberg, S.; Wettschureck, N.; Gruner,
S.; Konrad, I.; Schulte, V.; Aktas, B.; Gratacap, M.-P.; Simon, M.
I.; Gawaz, M.; Offermanns, S.: G(13) is an essential mediator of
platelet activation in hemostasis and thrombosis. Nature Med. 9:
1418-1422, 2003.
5. Offermanns, S.; Mancino, V.; Revel, J.-P.; Simon, M. I.: Vascular
system defects and impaired cell chemokinesis as a result of G-alpha-13
deficiency. Science 275: 533-536, 1997.
6. Radhika, V.; Onesime, D.; Ha, J. H.; Dhanasekaran, N.: G-alpha-13
stimulates cell migration through cortactin-interacting protein Hax-1. J.
Biol. Chem. 279: 49406-49413, 2004.
7. Ruppel, K. M.; Willison, D.; Kataoka, H.; Wang, A.; Zheng, Y.-W.;
Cornelissen, I.; Yin, L.; Xu, S. M.; Coughlin, S. R.: Essential role
for G-alpha-13 in endothelial cells during embryonic development. Proc.
Nat. Acad. Sci. 102: 8281-8286, 2005.
8. Shan, D.; Chen, L.; Wang, D.; Tan, Y.-C.; Gu, J. L.; Huang, X.-Y.
: The G protein G-alpha-13 is required for growth factor-induced cell
migration. Dev. Cell 10: 707-718, 2006.
9. Shen, B.; Zhao, X.; O'Brien, K. A.; Stojanovic-Terpo, A.; Delaney,
M. K.; Kim, K.; Cho, J.; Lam, S. C.-T.; Du, X.: A directional switch
of integrin signalling and a new anti-thrombotic strategy. Nature 503:
131-135, 2013.
10. Wirth, A.; Benyo, Z.; Lukasova, M.; Leutgeb, B.; Wettschureck,
N.; Gorbey, S.; Orsy, P.; Horvath, B.; Maser-Gluth, C.; Greiner, E.;
Lemmer, B.; Schutz, G.; Gutkind, J. S.; Offermanns, S.: G-12-G-13-LARG-mediated
signaling in vascular smooth muscle is required for salt-induced hypertension. Nature
Med. 14: 64-68, 2008. Note: Erratum: Nature Med. 14: 222 only, 2008.
*FIELD* CN
Ada Hamosh - updated: 11/20/2013
Ada Hamosh - updated: 2/1/2010
Patricia A. Hartz - updated: 3/6/2008
Patricia A. Hartz - updated: 7/11/2006
Patricia A. Hartz - updated: 7/19/2005
Ada Hamosh - updated: 10/29/2003
*FIELD* CD
Paul J. Converse: 1/5/2000
*FIELD* ED
alopez: 11/21/2013
alopez: 11/20/2013
terry: 8/6/2012
alopez: 2/2/2010
terry: 2/1/2010
mgross: 3/6/2008
mgross: 7/11/2006
terry: 7/11/2006
wwang: 8/4/2005
wwang: 7/29/2005
terry: 7/19/2005
alopez: 11/7/2003
alopez: 10/30/2003
terry: 10/29/2003
carol: 3/13/2000
carol: 1/6/2000
carol: 1/5/2000
*RECORD*
*FIELD* NO
604406
*FIELD* TI
*604406 GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-13; GNA13
;;G-ALPHA-13
*FIELD* TX
read moreFor background information on G proteins, see 600874.
CLONING
Kabouridis et al. (1995) cloned human thymocyte cDNAs corresponding to
the full-length coding sequence of G-alpha-13. The GNA13 cDNA encodes a
deduced 377-amino acid protein that is 97% homologous to the mouse Gna13
protein. It contains the highly conserved motifs found in all G protein
alpha subunits that are thought to be directly involved in the
interaction with the guanine nucleotide. Northern blot analysis revealed
that GNA13 is expressed as a major 4.8-kb and a minor 5.3-kb transcript
in Jurkat and HPB-ALL leukemic T-cell lines.
GENE FUNCTION
Moers et al. (2003) showed that lack of G-alpha-13, but not G-alpha-12
(604394), severely reduced the potency of thrombin (176930), thromboxane
A2, and collagen to induce platelet shape changes and aggregation in
vitro. These defects were accompanied by a reduced activation of RhoA
(165390) and inability to form stable platelet thrombi under high shear
stress ex vivo. G-alpha-13 deficiency in platelets resulted in a severe
defect of primary hemostasis and complete protection against arterial
thrombosis in vivo. Moers et al. (2003) concluded that G13-mediated
signaling processes are required for normal hemostasis and thrombosis.
Radhika et al. (2004) presented evidence that mammalian Gna13 associates
with intracellular Hax1 (605998), a cortactin (164765)-interacting
protein, and that Hax1 promotes Gna13-mediated cell migration. Gna13 and
Hax1 existed in a complex with Rac (see 602048) and cortactin in
transfected cells, and coexpression of Hax1 enhanced Gna13-mediated Rac
activity while inhibiting Rho activity, both of which can promote cell
movement.
Shan et al. (2006) showed that Gna13 was essential for receptor tyrosine
kinase-induced migration of mouse fibroblasts and endothelial cells.
Gna13 activity in cell migration was retained in a C-terminal mutant
that was defective in coupling to G protein-coupled receptors,
suggesting that the migration function is independent of receptor
signaling.
G-alpha-q (GNAQ; 600998)-coupled receptors, such as alpha-1-adrenergic
(see ADRA1A; 104221), angiotensin (106165), and endothelin (see ENDRA;
131243) receptors, play key roles in cardiac physiology. These receptors
also interact with G-alpha-12 and G-alpha-13. Using photoaffinity
labeling and immunoprecipitation, Kilts et al. (2007) showed that these
receptors differentially activated cardiac G-alpha-12 and G-alpha-13 in
membranes of human right arial appendages. Endothelin receptors
activated only G-alpha-12, whereas angiotensin receptors activated only
G-alpha-13. Alpha-1-adrenergic receptors activated neither G-alpha-12
nor G-alpha-13.
Using mice lacking G-alpha subunits specifically in smooth muscle cells,
Wirth et al. (2008) found that G-alpha-q and G-alpha-11 (GNA11; 139313)
were required for maintenance of basal blood pressure and for
development of salt-induced hypertension. In contrast, lack of
G-alpha-12 and G-alpha-13 and their effector, Larg (ARHGEF12; 604763),
did not alter normal blood pressure regulation, but blocked development
of salt-induced hypertension.
Gong et al. (2010) found that the heterotrimeric guanine
nucleotide-binding protein G-alpha-13 directly binds to the integrin
beta-3 (173470) cytoplasmic domain and that G-alpha-13-integrin
interaction is promoted by ligand binding to the integrin alpha-IIb
(607759)-beta-3 and by GTP loading of G-alpha-13. Interference of
G-alpha-13 expression or a myristoylated fragment of G-alpha-13 that
inhibited interaction of alpha-IIb-beta-3 with G-alpha-13 diminished
activation of protein kinase c-Src (124095) and stimulated the small
guanosine triphosphatase RhoA (165390), consequently inhibiting cell
spreading and accelerating cell retraction. Gong et al. (2010) concluded
that integrins are noncanonical G-alpha-13-coupled receptors that
provide a mechanism for dynamic regulation of RhoA.
Shen et al. (2013) demonstrated that G-alpha-13 and talin (186745) bind
to mutually exclusive but distinct sites within the integrin beta-3
cytoplasmic domain in opposing waves. The first talin-binding wave
mediates inside-out signaling and also ligand-induced integrin
activation, but is not required for outside-in signaling. Integrin
ligation induces transient talin dissociation and G-alpha-13 binding to
an EXE motif (in which X denotes any residue), which selectively
mediates outside-in signaling and platelet spreading. The second
talin-binding wave is associated with clot retraction. An
EXE-motif-based inhibitor of G-alpha-13-integrin interaction selectively
abolishes outside-in signaling without affecting integrin ligation, and
suppresses occlusive arterial thrombosis without affecting bleeding
time. Shen et al. (2013) concluded that they discovered a mechanism for
the directional switch of integrin signaling and, on the basis of this
mechanism, designed a potent antithrombotic drug that does not cause
bleeding.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the GNA13
gene to chromosome 17 (TMAP RH18264).
ANIMAL MODEL
Offermanns et al. (1997) showed that disruption of the Gna13 gene in
mice impaired the ability of endothelial cells to develop into an
organized vascular system, resulting in intrauterine death. Furthermore,
embryonic fibroblasts lacking a functional Gna13 gene showed greatly
impaired migratory responses to thrombin. The results demonstrated that
GNA13 participates in the regulation of cell movement in response to
specific ligands, and in developmental angiogenesis.
Ruppel et al. (2005) found that Gna13 was expressed throughout the
mesenchyme of developing mouse embryos, with strong staining in vascular
endothelial cells and dorsal neural tube. Gna13-knockout embryos died
between embryonic days 9.5 and 11.5 and were pale, with pericardial
swelling, and variable bleeding into cavities and tissues.
Endothelial-specific Gna13-knockout embryos showed a somewhat less
severe phenotype. Targeted reintroduction of Gna13 into the endothelium
of Gna13-null embryos prevented vascular defects, and embryos survived
several days beyond transgene-negative embryos, but they developed a
second phenotype characterized by exencephaly and hemorrhage within the
head mesenchyme.
*FIELD* RF
1. Gong, H.; Shen, B.; Flevaris, P.; Chow, C.; Lam, S. C.-T.; Voyno-Yasenetskaya,
T. A.; Kozasa, T.; Du, X.: G protein subunit G-alpha-13 binds to
integrin alphaIIb-beta-3 and mediates integrin 'outside-in' signaling. Science 327:
340-343, 2010.
2. Kabouridis, P. S.; Waters, S. T.; Escobar, S.; Stanners, J.; Tsoukas,
C. D.: Expression of GTP-binding protein alpha subunits in human
thymocytes. Molec. Cell. Biochem. 144: 45-51, 1995.
3. Kilts, J. D.; Lin, S. S.; Lowe, J. E.; Kwatra, M. M.: Selective
activation of human atrial G-alpha-12 and G-alpha-13 by G-alpha-q-coupled
angiotensin and endothelin receptors. J. Cardiovasc. Pharm. 50:
299-303, 2007.
4. Moers, A.; Nieswandt, B.; Massberg, S.; Wettschureck, N.; Gruner,
S.; Konrad, I.; Schulte, V.; Aktas, B.; Gratacap, M.-P.; Simon, M.
I.; Gawaz, M.; Offermanns, S.: G(13) is an essential mediator of
platelet activation in hemostasis and thrombosis. Nature Med. 9:
1418-1422, 2003.
5. Offermanns, S.; Mancino, V.; Revel, J.-P.; Simon, M. I.: Vascular
system defects and impaired cell chemokinesis as a result of G-alpha-13
deficiency. Science 275: 533-536, 1997.
6. Radhika, V.; Onesime, D.; Ha, J. H.; Dhanasekaran, N.: G-alpha-13
stimulates cell migration through cortactin-interacting protein Hax-1. J.
Biol. Chem. 279: 49406-49413, 2004.
7. Ruppel, K. M.; Willison, D.; Kataoka, H.; Wang, A.; Zheng, Y.-W.;
Cornelissen, I.; Yin, L.; Xu, S. M.; Coughlin, S. R.: Essential role
for G-alpha-13 in endothelial cells during embryonic development. Proc.
Nat. Acad. Sci. 102: 8281-8286, 2005.
8. Shan, D.; Chen, L.; Wang, D.; Tan, Y.-C.; Gu, J. L.; Huang, X.-Y.
: The G protein G-alpha-13 is required for growth factor-induced cell
migration. Dev. Cell 10: 707-718, 2006.
9. Shen, B.; Zhao, X.; O'Brien, K. A.; Stojanovic-Terpo, A.; Delaney,
M. K.; Kim, K.; Cho, J.; Lam, S. C.-T.; Du, X.: A directional switch
of integrin signalling and a new anti-thrombotic strategy. Nature 503:
131-135, 2013.
10. Wirth, A.; Benyo, Z.; Lukasova, M.; Leutgeb, B.; Wettschureck,
N.; Gorbey, S.; Orsy, P.; Horvath, B.; Maser-Gluth, C.; Greiner, E.;
Lemmer, B.; Schutz, G.; Gutkind, J. S.; Offermanns, S.: G-12-G-13-LARG-mediated
signaling in vascular smooth muscle is required for salt-induced hypertension. Nature
Med. 14: 64-68, 2008. Note: Erratum: Nature Med. 14: 222 only, 2008.
*FIELD* CN
Ada Hamosh - updated: 11/20/2013
Ada Hamosh - updated: 2/1/2010
Patricia A. Hartz - updated: 3/6/2008
Patricia A. Hartz - updated: 7/11/2006
Patricia A. Hartz - updated: 7/19/2005
Ada Hamosh - updated: 10/29/2003
*FIELD* CD
Paul J. Converse: 1/5/2000
*FIELD* ED
alopez: 11/21/2013
alopez: 11/20/2013
terry: 8/6/2012
alopez: 2/2/2010
terry: 2/1/2010
mgross: 3/6/2008
mgross: 7/11/2006
terry: 7/11/2006
wwang: 8/4/2005
wwang: 7/29/2005
terry: 7/19/2005
alopez: 11/7/2003
alopez: 10/30/2003
terry: 10/29/2003
carol: 3/13/2000
carol: 1/6/2000
carol: 1/5/2000