GNAI3_HUMAN
ID GNAI3_HUMAN Reviewed; 354 AA.
AC P08754; P17539; Q5TZX1;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 238.
DE RecName: Full=Guanine nucleotide-binding protein G(i) subunit alpha-3;
DE AltName: Full=G(i) alpha-3;
GN Name=GNAI3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3109953; DOI=10.1016/0014-5793(87)81228-0;
RA Didsbury J.R., Snyderman R.;
RT "Molecular cloning of a new human G protein. Evidence for two Gi alpha-like
RT protein families.";
RL FEBS Lett. 219:259-263(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3120178; DOI=10.1073/pnas.84.22.7886;
RA Beals C.R., Wilson C.B., Perlmutter R.M.;
RT "A small multigene family encodes Gi signal-transduction proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7886-7890(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2834384; DOI=10.1016/s0021-9258(18)68692-2;
RA Itoh H., Toyama R., Kozasa T., Tsukamoto T., Matsuoka M., Kaziro Y.;
RT "Presence of three distinct molecular species of Gi protein alpha subunit.
RT Structure of rat cDNAs and human genomic DNAs.";
RL J. Biol. Chem. 263:6656-6664(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2452165; DOI=10.1016/s0021-9258(18)68706-x;
RA Codina J., Olate J., Abramowitz J., Mattera R., Cook R.G., Birnbaumer L.;
RT "Alpha i-3 cDNA encodes the alpha subunit of Gk, the stimulatory G protein
RT of receptor-regulated K+ channels.";
RL J. Biol. Chem. 263:6746-6750(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3132707; DOI=10.1073/pnas.85.12.4153;
RA Kim S., Ang S.L., Bloch D.B., Bloch K.D., Kawahara Y., Tolman C., Lee R.,
RA Seidman J.G., Neer E.J.;
RT "Identification of cDNA encoding an additional alpha subunit of a human
RT GTP-binding protein: expression of three alpha i subtypes in human tissues
RT and cell lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:4153-4157(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-354.
RX PubMed=2440724; DOI=10.1016/0014-5793(87)80900-6;
RA Suki W.N., Abramowitz J., Mattera R., Codina J., Birnbaumer L.;
RT "The human genome encodes at least three non-allelic G proteins with alpha
RT i-type subunits.";
RL FEBS Lett. 220:187-192(1987).
RN [12]
RP FUNCTION.
RX PubMed=2535845; DOI=10.1016/s0021-9258(17)31281-4;
RA Mattera R., Yatani A., Kirsch G.E., Graf R., Okabe K., Olate J., Codina J.,
RA Brown A.M., Birnbaumer L.;
RT "Recombinant alpha i-3 subunit of G protein activates Gk-gated K+
RT channels.";
RL J. Biol. Chem. 264:465-471(1989).
RN [13]
RP FUNCTION, AND INTERACTION WITH RGS10.
RX PubMed=8774883; DOI=10.1038/383175a0;
RA Hunt T.W., Fields T.A., Casey P.J., Peralta E.G.;
RT "RGS10 is a selective activator of G alpha i GTPase activity.";
RL Nature 383:175-177(1996).
RN [14]
RP FUNCTION, INTERACTION WITH RGS14, AND SUBCELLULAR LOCATION.
RX PubMed=16870394; DOI=10.1016/j.cellsig.2006.06.002;
RA Shu F.J., Ramineni S., Amyot W., Hepler J.R.;
RT "Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR
RT domain of RGS14 influence its dynamic subcellular localization.";
RL Cell. Signal. 19:163-176(2007).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17635935; DOI=10.1083/jcb.200604114;
RA Cho H., Kehrl J.H.;
RT "Localization of Gi alpha proteins in the centrosomes and at the midbody:
RT implication for their role in cell division.";
RL J. Cell Biol. 178:245-255(2007).
RN [16]
RP INTERACTION WITH CCDC88A.
RX PubMed=19211784; DOI=10.1073/pnas.0900294106;
RA Garcia-Marcos M., Ghosh P., Farquhar M.G.;
RT "GIV is a nonreceptor GEF for G alpha i with a unique motif that regulates
RT Akt signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3178-3183(2009).
RN [17]
RP IDENTIFICATION IN COMPLEX WITH CCDC88A AND EGFR.
RX PubMed=20462955; DOI=10.1091/mbc.e10-01-0028;
RA Ghosh P., Beas A.O., Bornheimer S.J., Garcia-Marcos M., Forry E.P.,
RA Johannson C., Ear J., Jung B.H., Cabrera B., Carethers J.M., Farquhar M.G.;
RT "A G{alpha}i-GIV molecular complex binds epidermal growth factor receptor
RT and determines whether cells migrate or proliferate.";
RL Mol. Biol. Cell 21:2338-2354(2010).
RN [18]
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., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP DEAMIDATION AT GLN-204 (MICROBIAL INFECTION).
RX PubMed=24141704; DOI=10.1038/nsmb.2688;
RA Jank T., Bogdanovic X., Wirth C., Haaf E., Spoerner M., Boehmer K.E.,
RA Steinemann M., Orth J.H., Kalbitzer H.R., Warscheid B., Hunte C.,
RA Aktories K.;
RT "A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation
RT of Gq and Gi proteins.";
RL Nat. Struct. Mol. Biol. 20:1273-1280(2013).
RN [20]
RP INTERACTION WITH CCDC88A AND INSR.
RX PubMed=25187647; DOI=10.1091/mbc.e14-05-0978;
RA Lin C., Ear J., Midde K., Lopez-Sanchez I., Aznar N., Garcia-Marcos M.,
RA Kufareva I., Abagyan R., Ghosh P.;
RT "Structural basis for activation of trimeric Gi proteins by multiple growth
RT factor receptors via GIV/Girdin.";
RL Mol. Biol. Cell 25:3654-3671(2014).
RN [21]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [22]
RP INTERACTION WITH CCDC88C, AND MUTAGENESIS OF TRP-211; PHE-215; LYS-248 AND
RP TRP-258.
RX PubMed=26126266; DOI=10.7554/elife.07091;
RA Aznar N., Midde K.K., Dunkel Y., Lopez-Sanchez I., Pavlova Y., Marivin A.,
RA Barbazan J., Murray F., Nitsche U., Janssen K.P., Willert K., Goel A.,
RA Abal M., Garcia-Marcos M., Ghosh P.;
RT "Daple is a novel non-receptor GEF required for trimeric G protein
RT activation in Wnt signaling.";
RL Elife 4:E07091-E07091(2015).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=27864364; DOI=10.1074/jbc.m116.764431;
RA Parag-Sharma K., Leyme A., DiGiacomo V., Marivin A., Broselid S.,
RA Garcia-Marcos M.;
RT "Membrane recruitment of the non-receptor protein GIV/Girdin (Galpha-
RT interacting, Vesicle-associated Protein/Girdin) is sufficient for
RT activating heterotrimeric G protein signaling.";
RL J. Biol. Chem. 291:27098-27111(2016).
RN [25]
RP INTERACTION WITH PLCD4, AND MUTAGENESIS OF LYS-35; LEU-36; LEU-37; LEU-39;
RP GLY-42; ILE-184; TRP-211; PHE-215; VAL-218; LEU-249; SER-252; ASN-256;
RP LYS-257; TRP-258 AND PHE-259.
RX PubMed=30194280; DOI=10.1074/jbc.ra118.003580;
RA Maziarz M., Broselid S., DiGiacomo V., Park J.C., Luebbers A.,
RA Garcia-Navarrete L., Blanco-Canosa J.B., Baillie G.S., Garcia-Marcos M.;
RT "A biochemical and genetic discovery pipeline identifies PLCdelta4b as a
RT nonreceptor activator of heterotrimeric G-proteins.";
RL J. Biol. Chem. 293:16964-16983(2018).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 4-350 IN COMPLEX WITH GDP AND
RP RGS10, FUNCTION, AND INTERACTION WITH RGS8 AND RGS10.
RX PubMed=18434541; DOI=10.1073/pnas.0801508105;
RA Soundararajan M., Willard F.S., Kimple A.J., Turnbull A.P., Ball L.J.,
RA Schoch G.A., Gileadi C., Fedorov O.Y., Dowler E.F., Higman V.A.,
RA Hutsell S.Q., Sundstroem M., Doyle D.A., Siderovski D.P.;
RT "Structural diversity in the RGS domain and its interaction with
RT heterotrimeric G protein alpha-subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:6457-6462(2008).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 4-350 IN COMPLEX WITH RGS2;
RP MAGNESIUM AND GDP, LACK OF INTERACTION WITH RGS2, INTERACTION WITH RGS16,
RP AND FUNCTION.
RX PubMed=19478087; DOI=10.1074/jbc.m109.024711;
RA Kimple A.J., Soundararajan M., Hutsell S.Q., Roos A.K., Urban D.J.,
RA Setola V., Temple B.R., Roth B.L., Knapp S., Willard F.S., Siderovski D.P.;
RT "Structural determinants of G-protein alpha subunit selectivity by
RT regulator of G-protein signaling 2 (RGS2).";
RL J. Biol. Chem. 284:19402-19411(2009).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 25-354 IN COMPLEX WITH GPSM2 AND
RP GDP, AND INTERACTION WITH GPSM2.
RX PubMed=22952234; DOI=10.1074/jbc.m112.391607;
RA Jia M., Li J., Zhu J., Wen W., Zhang M., Wang W.;
RT "Crystal structures of the scaffolding protein LGN reveal the general
RT mechanism by which GoLoco binding motifs inhibit the release of GDP from
RT Galphai.";
RL J. Biol. Chem. 287:36766-36776(2012).
RN [29]
RP VARIANT ARCND1 ARG-40.
RX PubMed=22560091; DOI=10.1016/j.ajhg.2012.04.002;
RA Rieder M.J., Green G.E., Park S.S., Stamper B.D., Gordon C.T.,
RA Johnson J.M., Cunniff C.M., Smith J.D., Emery S.B., Lyonnet S., Amiel J.,
RA Holder M., Heggie A.A., Bamshad M.J., Nickerson D.A., Cox T.C., Hing A.V.,
RA Horst J.A., Cunningham M.L.;
RT "A human homeotic transformation resulting from mutations in PLCB4 and
RT GNAI3 causes auriculocondylar syndrome.";
RL Am. J. Hum. Genet. 90:907-914(2012).
RN [30]
RP ERRATUM OF PUBMED:22560091.
RA Rieder M.J., Green G.E., Park S.S., Stamper B.D., Gordon C.T.,
RA Johnson J.M., Cunniff C.M., Smith J.D., Emery S.B., Lyonnet S., Amiel J.,
RA Holder M., Heggie A.A., Bamshad M.J., Nickerson D.A., Cox T.C., Hing A.V.,
RA Horst J.A., Cunningham M.L.;
RL Am. J. Hum. Genet. 90:1116-1116(2012).
CC -!- FUNCTION: Heterotrimeric guanine nucleotide-binding proteins (G
CC proteins) function as transducers downstream of G protein-coupled
CC receptors (GPCRs) in numerous signaling cascades. The alpha chain
CC contains the guanine nucleotide binding site and alternates between an
CC active, GTP-bound state and an inactive, GDP-bound state. Signaling by
CC an activated GPCR promotes GDP release and GTP binding. The alpha
CC subunit has a low GTPase activity that converts bound GTP to GDP,
CC thereby terminating the signal. Both GDP release and GTP hydrolysis are
CC modulated by numerous regulatory proteins (PubMed:8774883,
CC PubMed:18434541, PubMed:19478087). Signaling is mediated via effector
CC proteins, such as adenylate cyclase. Inhibits adenylate cyclase
CC activity, leading to decreased intracellular cAMP levels
CC (PubMed:19478087). Stimulates the activity of receptor-regulated K(+)
CC channels (PubMed:2535845). The active GTP-bound form prevents the
CC association of RGS14 with centrosomes and is required for the
CC translocation of RGS14 from the cytoplasm to the plasma membrane. May
CC play a role in cell division (PubMed:17635935).
CC {ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:18434541,
CC ECO:0000269|PubMed:2535845, ECO:0000269|PubMed:8774883}.
CC -!- SUBUNIT: Heterotrimeric G proteins are composed of 3 units; alpha, beta
CC and gamma. The alpha subunit contains the guanine nucleotide binding
CC site. GTP binding causes dissociation of the heterotrimer, liberating
CC the individual subunits so that they can interact with downstream
CC effector proteins. Forms a complex with CCDC88A/GIV and EGFR which
CC leads to enhanced EGFR signaling and triggering of cell migration;
CC ligand stimulation is required for recruitment of GNAI3 to the complex
CC (PubMed:20462955). Interacts (inactive GDP-bound form) with CCDC88A/GIV
CC (via GBA motif); the interaction leads to activation of GNAI3
CC (PubMed:19211784, PubMed:20462955). Interacts (inactive GDP-bound form)
CC with CCDC88C/DAPLE (via GBA motif); the interaction leads to activation
CC of GNAI3 (PubMed:26126266). Interacts (inactive GDP-bound form) with
CC NUCB1 (via GBA motif) and NUCB2 (via GBA motif); the interaction leads
CC to activation of GNAI3 (By similarity). Interacts (inactive GDP-bound
CC form) with PLCD4 (via GBA motif); the interaction leads to activation
CC of GNAI3 (PubMed:30194280). Interacts with INSR; the interaction is
CC probably mediated by CCDC88A/GIV (PubMed:25187647). Interacts with
CC GPSM1 (By similarity). Interacts (GDP-bound form) with GPSM2 (via
CC GoLoco domains) (PubMed:22952234). Does not interact with RGS2
CC (PubMed:19478087). Interacts with RGS8 and RGS10; this strongly
CC enhances the intrinsic GTPase activity (PubMed:8774883,
CC PubMed:18434541). Interacts with RGS16; this strongly enhances the
CC intrinsic GTPase activity (PubMed:19478087). Interacts with RGS12 (By
CC similarity). Interacts (via active GTP- or inactive GDP-bound form)
CC with RGS14 (By similarity). {ECO:0000250|UniProtKB:P08753,
CC ECO:0000250|UniProtKB:Q9DC51, ECO:0000269|PubMed:18434541,
CC ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:19478087,
CC ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:22952234,
CC ECO:0000269|PubMed:25187647, ECO:0000269|PubMed:26126266,
CC ECO:0000269|PubMed:30194280, ECO:0000305}.
CC -!- INTERACTION:
CC P08754; A0A0A0MR69: CCDC88C; NbExp=3; IntAct=EBI-357563, EBI-12954453;
CC P08754; P81274: GPSM2; NbExp=3; IntAct=EBI-357563, EBI-618655;
CC P08754; Q9Y4H4: GPSM3; NbExp=8; IntAct=EBI-357563, EBI-347538;
CC P08754; Q8IVA1: PCP2; NbExp=9; IntAct=EBI-357563, EBI-12250122;
CC P08754; Q9UPV7: PHF24; NbExp=3; IntAct=EBI-357563, EBI-17717171;
CC P08754; O43566: RGS14; NbExp=4; IntAct=EBI-357563, EBI-750603;
CC P08754; Q9UGC6: RGS17; NbExp=3; IntAct=EBI-357563, EBI-3918154;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17635935}. Cell
CC membrane {ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:27864364};
CC Lipid-anchor {ECO:0000305}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:17635935}.
CC Note=Localizes in the centrosomes of interphase and mitotic cells.
CC Detected at the cleavage furrow and/or the midbody.
CC {ECO:0000269|PubMed:17635935}.
CC -!- PTM: (Microbial infection) Deamidated at Gln-204 by Photorhabdus
CC asymbiotica toxin PAU_02230, blocking GTP hydrolysis of heterotrimeric
CC GNAQ or GNA11 and G-alphai (GNAI1, GNAI2 or GNAI3) proteins, thereby
CC activating RhoA. {ECO:0000269|PubMed:24141704}.
CC -!- DISEASE: Auriculocondylar syndrome 1 (ARCND1) [MIM:602483]: An
CC autosomal dominant craniofacial malformation syndrome characterized by
CC variable mandibular anomalies, including mild to severe micrognathia,
CC temporomandibular joint ankylosis, cleft palate, and a characteristic
CC ear malformation that consists of separation of the lobule from the
CC external ear, giving the appearance of a question mark (question-mark
CC ear). Other frequently described features include prominent cheeks,
CC cupped and posteriorly rotated ears, preauricular tags, and
CC microstomia. {ECO:0000269|PubMed:22560091}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M27543; AAA52579.1; -; mRNA.
DR EMBL; J03005; AAA52557.1; -; mRNA.
DR EMBL; M20604; AAA35895.1; -; Genomic_DNA.
DR EMBL; M20597; AAA35895.1; JOINED; Genomic_DNA.
DR EMBL; M20598; AAA35895.1; JOINED; Genomic_DNA.
DR EMBL; M20599; AAA35895.1; JOINED; Genomic_DNA.
DR EMBL; M20600; AAA35895.1; JOINED; Genomic_DNA.
DR EMBL; M20601; AAA35895.1; JOINED; Genomic_DNA.
DR EMBL; M20602; AAA35895.1; JOINED; Genomic_DNA.
DR EMBL; M20603; AAA35895.1; JOINED; Genomic_DNA.
DR EMBL; J03198; AAA35896.1; -; mRNA.
DR EMBL; J03238; AAA35939.1; -; mRNA.
DR EMBL; AF493907; AAM12621.1; -; mRNA.
DR EMBL; BT019973; AAV38776.1; -; mRNA.
DR EMBL; BT019974; AAV38777.1; -; mRNA.
DR EMBL; AK312252; BAG35184.1; -; mRNA.
DR EMBL; CH471122; EAW56393.1; -; Genomic_DNA.
DR EMBL; BC025285; AAH25285.1; -; mRNA.
DR CCDS; CCDS802.1; -.
DR PIR; S02348; RGHUI3.
DR RefSeq; NP_006487.1; NM_006496.3.
DR PDB; 2IHB; X-ray; 2.71 A; A=32-354.
DR PDB; 2ODE; X-ray; 1.90 A; A/C=4-350.
DR PDB; 2V4Z; X-ray; 2.80 A; A=4-350.
DR PDB; 4G5O; X-ray; 2.90 A; A/B/C/D=25-354.
DR PDB; 4G5R; X-ray; 3.48 A; A/B/C/D=25-354.
DR PDB; 4G5S; X-ray; 3.62 A; A/B/C/D=25-354.
DR PDB; 7E9H; EM; 4.00 A; A=1-354.
DR PDB; 7KH0; EM; 2.80 A; A=2-19.
DR PDB; 7RA3; EM; 3.24 A; A=1-19.
DR PDB; 7RGP; EM; 2.90 A; A=4-19.
DR PDB; 7T10; EM; 2.50 A; A=1-354.
DR PDB; 7T11; EM; 2.70 A; A=1-354.
DR PDBsum; 2IHB; -.
DR PDBsum; 2ODE; -.
DR PDBsum; 2V4Z; -.
DR PDBsum; 4G5O; -.
DR PDBsum; 4G5R; -.
DR PDBsum; 4G5S; -.
DR PDBsum; 7E9H; -.
DR PDBsum; 7KH0; -.
DR PDBsum; 7RA3; -.
DR PDBsum; 7RGP; -.
DR PDBsum; 7T10; -.
DR PDBsum; 7T11; -.
DR AlphaFoldDB; P08754; -.
DR BMRB; P08754; -.
DR SMR; P08754; -.
DR BioGRID; 109035; 188.
DR IntAct; P08754; 77.
DR MINT; P08754; -.
DR STRING; 9606.ENSP00000358867; -.
DR BindingDB; P08754; -.
DR ChEMBL; CHEMBL4221; -.
DR GlyGen; P08754; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P08754; -.
DR PhosphoSitePlus; P08754; -.
DR SwissPalm; P08754; -.
DR BioMuta; GNAI3; -.
DR DMDM; 120996; -.
DR CPTAC; CPTAC-1245; -.
DR CPTAC; CPTAC-1246; -.
DR EPD; P08754; -.
DR jPOST; P08754; -.
DR MassIVE; P08754; -.
DR PaxDb; P08754; -.
DR PeptideAtlas; P08754; -.
DR PRIDE; P08754; -.
DR ProteomicsDB; 52164; -.
DR Antibodypedia; 20068; 236 antibodies from 32 providers.
DR DNASU; 2773; -.
DR Ensembl; ENST00000369851.7; ENSP00000358867.4; ENSG00000065135.12.
DR GeneID; 2773; -.
DR KEGG; hsa:2773; -.
DR MANE-Select; ENST00000369851.7; ENSP00000358867.4; NM_006496.4; NP_006487.1.
DR UCSC; uc001dxz.4; human.
DR CTD; 2773; -.
DR DisGeNET; 2773; -.
DR GeneCards; GNAI3; -.
DR HGNC; HGNC:4387; GNAI3.
DR HPA; ENSG00000065135; Low tissue specificity.
DR MalaCards; GNAI3; -.
DR MIM; 139370; gene.
DR MIM; 602483; phenotype.
DR neXtProt; NX_P08754; -.
DR OpenTargets; ENSG00000065135; -.
DR Orphanet; 137888; Auriculocondylar syndrome.
DR PharmGKB; PA173; -.
DR VEuPathDB; HostDB:ENSG00000065135; -.
DR eggNOG; KOG0082; Eukaryota.
DR GeneTree; ENSGT00940000153567; -.
DR HOGENOM; CLU_014184_6_0_1; -.
DR InParanoid; P08754; -.
DR OMA; IETHFTF; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; P08754; -.
DR TreeFam; TF300673; -.
DR PathwayCommons; P08754; -.
DR Reactome; R-HSA-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-HSA-392170; ADP signalling through P2Y purinoceptor 12.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9634597; GPER1 signaling.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P08754; -.
DR SIGNOR; P08754; -.
DR BioGRID-ORCS; 2773; 14 hits in 1076 CRISPR screens.
DR ChiTaRS; GNAI3; human.
DR EvolutionaryTrace; P08754; -.
DR GeneWiki; GNAI3; -.
DR GenomeRNAi; 2773; -.
DR Pharos; P08754; Tbio.
DR PRO; PR:P08754; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P08754; protein.
DR Bgee; ENSG00000065135; Expressed in esophagus squamous epithelium and 207 other tissues.
DR Genevisible; P08754; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042588; C:zymogen granule; IEA:Ensembl.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0031821; F:G protein-coupled serotonin receptor binding; IEA:Ensembl.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:GO_Central.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0032794; F:GTPase activating protein binding; IEA:Ensembl.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IDA:UniProtKB.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0046039; P:GTP metabolic process; IDA:UniProtKB.
DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:UniProtKB.
DR GO; GO:0033864; P:positive regulation of NAD(P)H oxidase activity; IEA:Ensembl.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IEA:Ensembl.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0006906; P:vesicle fusion; IEA:Ensembl.
DR CDD; cd00066; G-alpha; 1.
DR Gene3D; 1.10.400.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR001408; Gprotein_alpha_I.
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; PR00441; GPROTEINAI.
DR SMART; SM00275; G_alpha; 1.
DR SUPFAM; SSF47895; SSF47895; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51882; G_ALPHA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Cell cycle; Cell division; Cell membrane;
KW Cytoplasm; Cytoskeleton; Disease variant; GTP-binding; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Myristate; Nucleotide-binding;
KW Palmitate; Reference proteome; Transducer.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..354
FT /note="Guanine nucleotide-binding protein G(i) subunit
FT alpha-3"
FT /id="PRO_0000203692"
FT DOMAIN 32..354
FT /note="G-alpha"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 35..48
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 173..181
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 196..205
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 265..272
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 324..329
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT BINDING 43..48
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0007744|PDB:2IHB, ECO:0007744|PDB:2ODE,
FT ECO:0007744|PDB:2V4Z, ECO:0007744|PDB:4G5O,
FT ECO:0007744|PDB:4G5R, ECO:0007744|PDB:4G5S"
FT BINDING 47
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:19478087,
FT ECO:0007744|PDB:2V4Z"
FT BINDING 150..151
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0007744|PDB:2V4Z, ECO:0007744|PDB:4G5O,
FT ECO:0007744|PDB:4G5R, ECO:0007744|PDB:4G5S"
FT BINDING 175..181
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0007744|PDB:2IHB, ECO:0007744|PDB:2ODE,
FT ECO:0007744|PDB:2V4Z, ECO:0007744|PDB:4G5O,
FT ECO:0007744|PDB:4G5R, ECO:0007744|PDB:4G5S"
FT BINDING 181
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:19478087,
FT ECO:0007744|PDB:2V4Z"
FT BINDING 200..204
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000305|PubMed:19478087,
FT ECO:0007744|PDB:2V4Z"
FT BINDING 269..272
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0007744|PDB:2IHB, ECO:0007744|PDB:2ODE,
FT ECO:0007744|PDB:2V4Z, ECO:0007744|PDB:4G5O,
FT ECO:0007744|PDB:4G5R, ECO:0007744|PDB:4G5S"
FT BINDING 326
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0007744|PDB:2IHB, ECO:0007744|PDB:2ODE,
FT ECO:0007744|PDB:2V4Z, ECO:0007744|PDB:4G5O,
FT ECO:0007744|PDB:4G5R"
FT MOD_RES 178
FT /note="ADP-ribosylarginine; by cholera toxin"
FT /evidence="ECO:0000250"
FT MOD_RES 204
FT /note="Deamidated glutamine; by Photorhabdus PAU_02230"
FT /evidence="ECO:0000269|PubMed:24141704"
FT MOD_RES 351
FT /note="ADP-ribosylcysteine; by pertussis toxin"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:25255805"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VARIANT 40
FT /note="G -> R (in ARCND1; dbSNP:rs387907178)"
FT /evidence="ECO:0000269|PubMed:22560091"
FT /id="VAR_068558"
FT MUTAGEN 35
FT /note="K->A: Decreased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 36
FT /note="L->A: Increased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 37
FT /note="L->A: No effect on binding to PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 39
FT /note="L->A: Decreased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 42
FT /note="G->R: Decreased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 184
FT /note="I->A: No effect on binding to PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 211
FT /note="W->A: Decreased affinity for CCDC88C and PLCD4."
FT /evidence="ECO:0000269|PubMed:26126266,
FT ECO:0000269|PubMed:30194280"
FT MUTAGEN 215
FT /note="F->A: Decreased affinity for CCDC88C and PLCD4."
FT /evidence="ECO:0000269|PubMed:26126266,
FT ECO:0000269|PubMed:30194280"
FT MUTAGEN 218
FT /note="V->A: No effect on binding to PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 248
FT /note="K->M: No effect on binding to CCDC88C."
FT /evidence="ECO:0000269|PubMed:26126266"
FT MUTAGEN 249
FT /note="L->H: Decreased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 249
FT /note="L->V: No effect on binding to PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 252
FT /note="S->A: Increased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 252
FT /note="S->D: Decreased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 256
FT /note="N->A: Decreased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 256
FT /note="N->E: Decreased affinity for PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 257
FT /note="K->A: No effect on binding to PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT MUTAGEN 258
FT /note="W->F: Increased affinity for PLCD4. No effect on
FT binding to CCDC88C."
FT /evidence="ECO:0000269|PubMed:26126266,
FT ECO:0000269|PubMed:30194280"
FT MUTAGEN 259
FT /note="F->A: No effect on binding to PLCD4."
FT /evidence="ECO:0000269|PubMed:30194280"
FT CONFLICT 21
FT /note="R -> C (in Ref. 11; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT HELIX 7..19
FT /evidence="ECO:0007829|PDB:7KH0"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 46..57
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 63..68
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 70..91
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 100..110
FT /evidence="ECO:0007829|PDB:2ODE"
FT TURN 111..116
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 121..131
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 134..141
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 152..157
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 159..162
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 171..175
FT /evidence="ECO:0007829|PDB:2ODE"
FT STRAND 183..191
FT /evidence="ECO:0007829|PDB:2ODE"
FT STRAND 194..201
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 205..214
FT /evidence="ECO:0007829|PDB:2ODE"
FT STRAND 219..226
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 227..231
FT /evidence="ECO:0007829|PDB:2ODE"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 242..254
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:2ODE"
FT STRAND 262..269
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 271..278
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 296..308
FT /evidence="ECO:0007829|PDB:2ODE"
FT TURN 314..316
FT /evidence="ECO:0007829|PDB:2ODE"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:2ODE"
FT HELIX 329..346
FT /evidence="ECO:0007829|PDB:2ODE"
SQ SEQUENCE 354 AA; 40532 MW; EAB6B4DD3646BC01 CRC64;
MGCTLSAEDK AAVERSKMID RNLREDGEKA AKEVKLLLLG AGESGKSTIV KQMKIIHEDG
YSEDECKQYK VVVYSNTIQS IIAIIRAMGR LKIDFGEAAR ADDARQLFVL AGSAEEGVMT
PELAGVIKRL WRDGGVQACF SRSREYQLND SASYYLNDLD RISQSNYIPT QQDVLRTRVK
TTGIVETHFT FKDLYFKMFD VGGQRSERKK WIHCFEGVTA IIFCVALSDY DLVLAEDEEM
NRMHESMKLF DSICNNKWFT ETSIILFLNK KDLFEEKIKR SPLTICYPEY TGSNTYEEAA
AYIQCQFEDL NRRKDTKEIY THFTCATDTK NVQFVFDAVT DVIIKNNLKE CGLY
