Full text data of GNAI2
GNAI2
(GNAI2B)
[Confidence: high (present in two of the MS resources)]
Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein)
Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein)
Comments
Isoform P04899-4 was detected.
Isoform P04899-4 was detected.
UniProt
P04899
ID GNAI2_HUMAN Reviewed; 355 AA.
AC P04899; B4DYA0; Q6B6N3; Q8IZ71;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 161.
DE RecName: Full=Guanine nucleotide-binding protein G(i) subunit alpha-2;
DE AltName: Full=Adenylate cyclase-inhibiting G alpha protein;
GN Name=GNAI2; Synonyms=GNAI2B;
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] (ISOFORM 1).
RX PubMed=3100330; DOI=10.1016/0014-5793(87)81428-X;
RA Didsbury J.R., Ho Y.-S., Snyderman R.;
RT "Human Gi protein alpha-subunit: deduction of amino acid structure
RT from a cloned cDNA.";
RL FEBS Lett. 211:160-164(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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;
RA Itoh H., Toyama R., Kozasa T., Tsukamoto T., Matsuoka M., Kaziro Y.;
RT "Presence of three distinct molecular species of Gi protein alpha
RT subunit. Structure of rat cDNAs and human genomic DNAs.";
RL J. Biol. Chem. 263:6656-6664(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SGI2), AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=17550964; DOI=10.1242/jcs.005611;
RA Lopez-Aranda M.F., Acevedo M.J., Gutierrez A., Koulen P., Khan Z.U.;
RT "Role of a Galphai2 protein splice variant in the formation of an
RT intracellular dopamine D2 receptor pool.";
RL J. Cell Sci. 120:2171-2178(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, and Mammary gland;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-39.
RX PubMed=2837412; DOI=10.1016/0014-5793(88)80764-6;
RA Weinstein L.S., Spiegel A.M., Carter A.D.;
RT "Cloning and characterization of the human gene for the alpha-subunit
RT of Gi2, a GTP-binding signal transduction protein.";
RL FEBS Lett. 232:333-340(1988).
RN [11]
RP INTERACTION WITH UNC5B.
RX PubMed=12359238; DOI=10.1016/S0006-291X(02)02277-5;
RA Komatsuzaki K., Dalvin S., Kinane T.B.;
RT "Modulation of G(ialpha(2)) signaling by the axonal guidance molecule
RT UNC5H2.";
RL Biochem. Biophys. Res. Commun. 297:898-905(2002).
RN [12]
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
RT midbody: implication for their role in cell division.";
RL J. Cell Biol. 178:245-255(2007).
RN [13]
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. The G(i) proteins are involved in hormonal
CC regulation of adenylate cyclase: they inhibit the cyclase in
CC response to beta-adrenergic stimuli. May play a role in cell
CC division.
CC -!- FUNCTION: Isoform sGi2: Regulates the cell surface density of
CC dopamine receptors DRD2 by sequestrating them as an intracellular
CC pool.
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 GPSM1. Interacts with RGS12 and RGS14 (By
CC similarity). Interacts with UNC5B.
CC -!- INTERACTION:
CC Q99750:MDFI; NbExp=2; IntAct=EBI-353997, EBI-724076;
CC P14598:NCF1; NbExp=2; IntAct=EBI-353997, EBI-395044;
CC P19878:NCF2; NbExp=4; IntAct=EBI-353997, EBI-489611;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome. Cell membrane.
CC Note=Localizes in the centrosomes of interphase and mitotic cells.
CC Detected at the cleavage furrow and/or the midbody.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P04899-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04899-2; Sequence=VSP_017497;
CC Name=3;
CC IsoId=P04899-3; Sequence=VSP_043473;
CC Note=No experimental confirmation available;
CC Name=sGi2; Synonyms=sGalphai2;
CC IsoId=P04899-4; Sequence=VSP_043903;
CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
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DR EMBL; X04828; CAA28512.1; -; mRNA.
DR EMBL; J03004; AAA52556.1; ALT_SEQ; mRNA.
DR EMBL; M20593; AAA35894.1; -; Genomic_DNA.
DR EMBL; M20586; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20587; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20588; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20589; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20590; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20591; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20592; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; AY677118; AAT78421.1; -; mRNA.
DR EMBL; AF493906; AAM12620.1; -; mRNA.
DR EMBL; AK302330; BAG63662.1; -; mRNA.
DR EMBL; AC002077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U73166; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U73169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65056.1; -; Genomic_DNA.
DR EMBL; BC012138; AAH12138.1; -; mRNA.
DR EMBL; BC016995; AAH16995.1; -; mRNA.
DR EMBL; X07854; CAA30703.1; -; Genomic_DNA.
DR PIR; S02319; RGHUI2.
DR RefSeq; NP_001159897.1; NM_001166425.1.
DR RefSeq; NP_001269547.1; NM_001282618.1.
DR RefSeq; NP_001269548.1; NM_001282619.1.
DR RefSeq; NP_002061.1; NM_002070.3.
DR RefSeq; XP_005265124.1; XM_005265067.1.
DR UniGene; Hs.77269; -.
DR ProteinModelPortal; P04899; -.
DR SMR; P04899; 5-354.
DR DIP; DIP-602N; -.
DR IntAct; P04899; 21.
DR MINT; MINT-7901704; -.
DR STRING; 9606.ENSP00000312999; -.
DR PhosphoSite; P04899; -.
DR DMDM; 121023; -.
DR PaxDb; P04899; -.
DR PRIDE; P04899; -.
DR DNASU; 2771; -.
DR Ensembl; ENST00000266027; ENSP00000266027; ENSG00000114353.
DR Ensembl; ENST00000313601; ENSP00000312999; ENSG00000114353.
DR Ensembl; ENST00000451956; ENSP00000406369; ENSG00000114353.
DR Ensembl; ENST00000574925; ENSP00000460235; ENSG00000263156.
DR Ensembl; ENST00000576852; ENSP00000460226; ENSG00000263156.
DR GeneID; 2771; -.
DR KEGG; hsa:2771; -.
DR UCSC; uc003cyq.1; human.
DR CTD; 2771; -.
DR GeneCards; GC03P050263; -.
DR H-InvDB; HIX0003320; -.
DR HGNC; HGNC:4385; GNAI2.
DR HPA; HPA007704; -.
DR MIM; 139360; gene.
DR neXtProt; NX_P04899; -.
DR PharmGKB; PA24347; -.
DR eggNOG; NOG322962; -.
DR HOGENOM; HOG000038730; -.
DR HOVERGEN; HBG063184; -.
DR InParanoid; P04899; -.
DR KO; K04630; -.
DR OMA; EYAGANK; -.
DR PhylomeDB; P04899; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; P04899; -.
DR ChiTaRS; GNAI2; human.
DR GeneWiki; GNAI2; -.
DR GenomeRNAi; 2771; -.
DR NextBio; 10900; -.
DR PRO; PR:P04899; -.
DR ArrayExpress; P04899; -.
DR Bgee; P04899; -.
DR CleanEx; HS_GNAI2; -.
DR Genevestigator; P04899; -.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:RefGenome.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:RefGenome.
DR GO; GO:0001664; F:G-protein coupled receptor 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:0000186; P:activation of MAPKK activity; IEA:Ensembl.
DR GO; GO:0001973; P:adenosine receptor signaling pathway; IBA:RefGenome.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IMP:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0007213; P:G-protein coupled acetylcholine receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IBA:RefGenome.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IEA:Ensembl.
DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:0050805; P:negative regulation of synaptic transmission; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; TAS:ProtInc.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR Gene3D; 1.10.400.10; -; 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; 2.
PE 1: Evidence at protein level;
KW ADP-ribosylation; Alternative splicing; Cell cycle; Cell division;
KW Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton;
KW GTP-binding; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Myristate; Nucleotide-binding; Palmitate; Reference proteome;
KW Transducer.
FT INIT_MET 1 1 Removed (Probable).
FT CHAIN 2 355 Guanine nucleotide-binding protein G(i)
FT subunit alpha-2.
FT /FTId=PRO_0000203679.
FT NP_BIND 40 47 GTP (By similarity).
FT NP_BIND 176 182 GTP (By similarity).
FT NP_BIND 201 205 GTP (By similarity).
FT NP_BIND 270 273 GTP (By similarity).
FT METAL 47 47 Magnesium (By similarity).
FT METAL 182 182 Magnesium (By similarity).
FT BINDING 327 327 GTP; via amide nitrogen (By similarity).
FT MOD_RES 179 179 ADP-ribosylarginine; by cholera toxin (By
FT similarity).
FT MOD_RES 352 352 ADP-ribosylcysteine; by pertussis toxin
FT (By similarity).
FT LIPID 2 2 N-myristoyl glycine (Probable).
FT LIPID 3 3 S-palmitoyl cysteine (By similarity).
FT VAR_SEQ 1 39 MGCTVSAEDKAAAERSKMIDKNLREDGEKAAREVKLLLL
FT -> MEYAGHLPASSAQGTILACTSCT (in isoform
FT 2).
FT /FTId=VSP_017497.
FT VAR_SEQ 1 39 MGCTVSAEDKAAAERSKMIDKNLREDGEKAAREVKLLLL
FT -> MR (in isoform 3).
FT /FTId=VSP_043473.
FT VAR_SEQ 332 355 NVQFVFDAVTDVIIKNNLKDCGLF -> SRKLFRETYLKLS
FT GPDQHPHPSPAPAPPLSSDSVP (in isoform sGi2).
FT /FTId=VSP_043903.
SQ SEQUENCE 355 AA; 40451 MW; BE6D6FF720CF3DCC CRC64;
MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEDG
YSEEECRQYR AVVYSNTIQS IMAIVKAMGN LQIDFADPSR ADDARQLFAL SCTAEEQGVL
PDDLSGVIRR LWADHGVQAC FGRSREYQLN DSAAYYLNDL ERIAQSDYIP TQQDVLRTRV
KTTGIVETHF TFKDLHFKMF DVGGQRSERK KWIHCFEGVT AIIFCVALSA YDLVLAEDEE
MNRMHESMKL FDSICNNKWF TDTSIILFLN KKDLFEEKIT HSPLTICFPE YTGANKYDEA
ASYIQSKFED LNKRKDTKEI YTHFTCATDT KNVQFVFDAV TDVIIKNNLK DCGLF
//
ID GNAI2_HUMAN Reviewed; 355 AA.
AC P04899; B4DYA0; Q6B6N3; Q8IZ71;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 161.
DE RecName: Full=Guanine nucleotide-binding protein G(i) subunit alpha-2;
DE AltName: Full=Adenylate cyclase-inhibiting G alpha protein;
GN Name=GNAI2; Synonyms=GNAI2B;
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] (ISOFORM 1).
RX PubMed=3100330; DOI=10.1016/0014-5793(87)81428-X;
RA Didsbury J.R., Ho Y.-S., Snyderman R.;
RT "Human Gi protein alpha-subunit: deduction of amino acid structure
RT from a cloned cDNA.";
RL FEBS Lett. 211:160-164(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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;
RA Itoh H., Toyama R., Kozasa T., Tsukamoto T., Matsuoka M., Kaziro Y.;
RT "Presence of three distinct molecular species of Gi protein alpha
RT subunit. Structure of rat cDNAs and human genomic DNAs.";
RL J. Biol. Chem. 263:6656-6664(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SGI2), AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=17550964; DOI=10.1242/jcs.005611;
RA Lopez-Aranda M.F., Acevedo M.J., Gutierrez A., Koulen P., Khan Z.U.;
RT "Role of a Galphai2 protein splice variant in the formation of an
RT intracellular dopamine D2 receptor pool.";
RL J. Cell Sci. 120:2171-2178(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, and Mammary gland;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-39.
RX PubMed=2837412; DOI=10.1016/0014-5793(88)80764-6;
RA Weinstein L.S., Spiegel A.M., Carter A.D.;
RT "Cloning and characterization of the human gene for the alpha-subunit
RT of Gi2, a GTP-binding signal transduction protein.";
RL FEBS Lett. 232:333-340(1988).
RN [11]
RP INTERACTION WITH UNC5B.
RX PubMed=12359238; DOI=10.1016/S0006-291X(02)02277-5;
RA Komatsuzaki K., Dalvin S., Kinane T.B.;
RT "Modulation of G(ialpha(2)) signaling by the axonal guidance molecule
RT UNC5H2.";
RL Biochem. Biophys. Res. Commun. 297:898-905(2002).
RN [12]
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
RT midbody: implication for their role in cell division.";
RL J. Cell Biol. 178:245-255(2007).
RN [13]
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. The G(i) proteins are involved in hormonal
CC regulation of adenylate cyclase: they inhibit the cyclase in
CC response to beta-adrenergic stimuli. May play a role in cell
CC division.
CC -!- FUNCTION: Isoform sGi2: Regulates the cell surface density of
CC dopamine receptors DRD2 by sequestrating them as an intracellular
CC pool.
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 GPSM1. Interacts with RGS12 and RGS14 (By
CC similarity). Interacts with UNC5B.
CC -!- INTERACTION:
CC Q99750:MDFI; NbExp=2; IntAct=EBI-353997, EBI-724076;
CC P14598:NCF1; NbExp=2; IntAct=EBI-353997, EBI-395044;
CC P19878:NCF2; NbExp=4; IntAct=EBI-353997, EBI-489611;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome. Cell membrane.
CC Note=Localizes in the centrosomes of interphase and mitotic cells.
CC Detected at the cleavage furrow and/or the midbody.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P04899-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04899-2; Sequence=VSP_017497;
CC Name=3;
CC IsoId=P04899-3; Sequence=VSP_043473;
CC Note=No experimental confirmation available;
CC Name=sGi2; Synonyms=sGalphai2;
CC IsoId=P04899-4; Sequence=VSP_043903;
CC -!- SIMILARITY: Belongs to the G-alpha family. G(i/o/t/z) subfamily.
CC -----------------------------------------------------------------------
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DR EMBL; X04828; CAA28512.1; -; mRNA.
DR EMBL; J03004; AAA52556.1; ALT_SEQ; mRNA.
DR EMBL; M20593; AAA35894.1; -; Genomic_DNA.
DR EMBL; M20586; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20587; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20588; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20589; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20590; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20591; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; M20592; AAA35894.1; JOINED; Genomic_DNA.
DR EMBL; AY677118; AAT78421.1; -; mRNA.
DR EMBL; AF493906; AAM12620.1; -; mRNA.
DR EMBL; AK302330; BAG63662.1; -; mRNA.
DR EMBL; AC002077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U73166; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U73169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW65056.1; -; Genomic_DNA.
DR EMBL; BC012138; AAH12138.1; -; mRNA.
DR EMBL; BC016995; AAH16995.1; -; mRNA.
DR EMBL; X07854; CAA30703.1; -; Genomic_DNA.
DR PIR; S02319; RGHUI2.
DR RefSeq; NP_001159897.1; NM_001166425.1.
DR RefSeq; NP_001269547.1; NM_001282618.1.
DR RefSeq; NP_001269548.1; NM_001282619.1.
DR RefSeq; NP_002061.1; NM_002070.3.
DR RefSeq; XP_005265124.1; XM_005265067.1.
DR UniGene; Hs.77269; -.
DR ProteinModelPortal; P04899; -.
DR SMR; P04899; 5-354.
DR DIP; DIP-602N; -.
DR IntAct; P04899; 21.
DR MINT; MINT-7901704; -.
DR STRING; 9606.ENSP00000312999; -.
DR PhosphoSite; P04899; -.
DR DMDM; 121023; -.
DR PaxDb; P04899; -.
DR PRIDE; P04899; -.
DR DNASU; 2771; -.
DR Ensembl; ENST00000266027; ENSP00000266027; ENSG00000114353.
DR Ensembl; ENST00000313601; ENSP00000312999; ENSG00000114353.
DR Ensembl; ENST00000451956; ENSP00000406369; ENSG00000114353.
DR Ensembl; ENST00000574925; ENSP00000460235; ENSG00000263156.
DR Ensembl; ENST00000576852; ENSP00000460226; ENSG00000263156.
DR GeneID; 2771; -.
DR KEGG; hsa:2771; -.
DR UCSC; uc003cyq.1; human.
DR CTD; 2771; -.
DR GeneCards; GC03P050263; -.
DR H-InvDB; HIX0003320; -.
DR HGNC; HGNC:4385; GNAI2.
DR HPA; HPA007704; -.
DR MIM; 139360; gene.
DR neXtProt; NX_P04899; -.
DR PharmGKB; PA24347; -.
DR eggNOG; NOG322962; -.
DR HOGENOM; HOG000038730; -.
DR HOVERGEN; HBG063184; -.
DR InParanoid; P04899; -.
DR KO; K04630; -.
DR OMA; EYAGANK; -.
DR PhylomeDB; P04899; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; P04899; -.
DR ChiTaRS; GNAI2; human.
DR GeneWiki; GNAI2; -.
DR GenomeRNAi; 2771; -.
DR NextBio; 10900; -.
DR PRO; PR:P04899; -.
DR ArrayExpress; P04899; -.
DR Bgee; P04899; -.
DR CleanEx; HS_GNAI2; -.
DR Genevestigator; P04899; -.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:RefGenome.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:RefGenome.
DR GO; GO:0001664; F:G-protein coupled receptor 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:0000186; P:activation of MAPKK activity; IEA:Ensembl.
DR GO; GO:0001973; P:adenosine receptor signaling pathway; IBA:RefGenome.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IMP:UniProtKB.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0007213; P:G-protein coupled acetylcholine receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IBA:RefGenome.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IEA:Ensembl.
DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; TAS:ProtInc.
DR GO; GO:0050805; P:negative regulation of synaptic transmission; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; TAS:ProtInc.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR Gene3D; 1.10.400.10; -; 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; 2.
PE 1: Evidence at protein level;
KW ADP-ribosylation; Alternative splicing; Cell cycle; Cell division;
KW Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton;
KW GTP-binding; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Myristate; Nucleotide-binding; Palmitate; Reference proteome;
KW Transducer.
FT INIT_MET 1 1 Removed (Probable).
FT CHAIN 2 355 Guanine nucleotide-binding protein G(i)
FT subunit alpha-2.
FT /FTId=PRO_0000203679.
FT NP_BIND 40 47 GTP (By similarity).
FT NP_BIND 176 182 GTP (By similarity).
FT NP_BIND 201 205 GTP (By similarity).
FT NP_BIND 270 273 GTP (By similarity).
FT METAL 47 47 Magnesium (By similarity).
FT METAL 182 182 Magnesium (By similarity).
FT BINDING 327 327 GTP; via amide nitrogen (By similarity).
FT MOD_RES 179 179 ADP-ribosylarginine; by cholera toxin (By
FT similarity).
FT MOD_RES 352 352 ADP-ribosylcysteine; by pertussis toxin
FT (By similarity).
FT LIPID 2 2 N-myristoyl glycine (Probable).
FT LIPID 3 3 S-palmitoyl cysteine (By similarity).
FT VAR_SEQ 1 39 MGCTVSAEDKAAAERSKMIDKNLREDGEKAAREVKLLLL
FT -> MEYAGHLPASSAQGTILACTSCT (in isoform
FT 2).
FT /FTId=VSP_017497.
FT VAR_SEQ 1 39 MGCTVSAEDKAAAERSKMIDKNLREDGEKAAREVKLLLL
FT -> MR (in isoform 3).
FT /FTId=VSP_043473.
FT VAR_SEQ 332 355 NVQFVFDAVTDVIIKNNLKDCGLF -> SRKLFRETYLKLS
FT GPDQHPHPSPAPAPPLSSDSVP (in isoform sGi2).
FT /FTId=VSP_043903.
SQ SEQUENCE 355 AA; 40451 MW; BE6D6FF720CF3DCC CRC64;
MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEDG
YSEEECRQYR AVVYSNTIQS IMAIVKAMGN LQIDFADPSR ADDARQLFAL SCTAEEQGVL
PDDLSGVIRR LWADHGVQAC FGRSREYQLN DSAAYYLNDL ERIAQSDYIP TQQDVLRTRV
KTTGIVETHF TFKDLHFKMF DVGGQRSERK KWIHCFEGVT AIIFCVALSA YDLVLAEDEE
MNRMHESMKL FDSICNNKWF TDTSIILFLN KKDLFEEKIT HSPLTICFPE YTGANKYDEA
ASYIQSKFED LNKRKDTKEI YTHFTCATDT KNVQFVFDAV TDVIIKNNLK DCGLF
//
MIM
139360
*RECORD*
*FIELD* NO
139360
*FIELD* TI
*139360 GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-INHIBITING ACTIVITY POLYPEPTIDE
2; GNAI2
read more;;G PROTEIN, ALPHA-INHIBITING 2B; GNAI2B
*FIELD* TX
CLONING
Magovcevic et al. (1992) isolated a cDNA for the GNAI2 gene from a human
T-cell library.
Itoh et al. (1988) demonstrated 3 distinct human G-alpha inhibitory
proteins. Southern blot analysis indicated that a single copy of each
gene is present in the haploid human genome.
GENE STRUCTURE
Itoh et al. (1988) determined that the GNAI2 and GNAI3 (139380) genes
contain 8 coding exons and possess identical exon-intron organization.
MAPPING
Sparkes et al. (1987, 1987) and Blatt et al. (1988) used a cDNA probe
with a mouse/human somatic cell hybrid panel to assign the alpha-2
inhibitory polypeptide to chromosome 3 in man and chromosome 9 in mouse.
Blatt et al. (1988) also assigned the GNAI2 gene to chromosome 3 by
hybridization of cDNA clones with DNA from human-mouse somatic cell
hybrids. Magovcevic et al. (1992) mapped the GNAI2 gene to 3p21 by
chromosomal in situ hybridization. A related sequence, GNAI2L (139180),
was mapped by the same method to 12p13-p12. The assignment to chromosome
3 was supported by PCR amplification of GNAI2-specific sequences in a
human/rodent somatic cell hybrid containing only human chromosome 3.
Wilkie et al. (1992) assigned the corresponding gene to mouse chromosome
9.
GENE FUNCTION
Hermouet et al. (1991) demonstrated that activating and inactivating
mutations of the GNAI2 gene have opposite effects on proliferation of
NIH 3T3 cells.
Jiang et al. (2011) found that microRNA-138 (MIR138; see 613394) was
downregulated in tongue squamous cell carcinoma (TSCC) compared with
normal tissue. Using microarray-based differential expression analysis
on human TSCC cells transfected with an MIR138 mimic or a control mimic,
followed by bioinformatic analysis, Jiang et al. (2011) identified GNAI2
and 4 other genes as high-confidence candidate targets of MIR138. They
observed a reverse correlation between MIR138 and GNAI2 levels in a TSCC
cell line panel and identified 2 MIR138 target sequences in the 3-prime
UTR of GNAI2 mRNA. Reporter gene assays confirmed that both putative
target sequences were inhibited by MIR138. Knockdown of MIR138 in TSCC
cells enhanced the expression of GNAI2 at the mRNA and protein levels.
In contrast, transfection of MIR138 or an MIR138 mimic reduced GNAI2
mRNA and protein expression, which was associated with reduced cell
proliferation and enhanced apoptosis.
MOLECULAR GENETICS
Since somatic mutations in some growth hormone-secreting pituitary
tumors convert the gene for the alpha polypeptide chain of G(s) into a
putative oncogene, referred to as GSP (139320), Lyons et al. (1990)
considered the likelihood that similar mutations would activate other G
proteins. They found mutations of the GNAI2 gene that replaced
arginine-179 with either cysteine or histidine in tumors of the adrenal
cortex and endocrine tumors of the ovary. They referred to this mutant
GNAI2 gene as the GIP2 oncogene. Williamson et al. (1995) studied 32
adrenocorticotrophin hormone-secreting pituitary adenomas for the
presence of GSP and GIP mutations. GSP mutations were demonstrated in 2
tumors at codon 227 (139320.0012) and a GIP mutation was identified in 1
tumor at codon 179 (139360.0003).
Idiopathic ventricular tachycardia is a generic term that describes the
various forms of ventricular arrhythmias that occur in patients without
structural heart disease and in the absence of the long QT syndrome.
Many of these tachycardias are focal in origin, localize to the right
ventricular outflow tracts, terminate in response to beta-blockers,
verapamil, vagal maneuvers, and adenosine, and are thought to result
from cAMP-mediated triggered activity. Lerman et al. (1998) prepared DNA
from biopsy samples obtained from myocardial tissue from a patient with
adenosine-insensitive idiopathic ventricular tachycardia arising from
the right ventricular outflow tracts. Genomic sequences of the GNAI2B
gene showed a point mutation (phe200 to leu; 139360.0004) in the
GTP-binding domain of the inhibitory G protein, as identified in a
biopsy sample from the arrhythmogenic focus. This mutation was shown to
increase intracellular cAMP concentration and inhibit suppression of
cAMP by adenosine. No mutations were detected in the GNAI2B gene from
myocardial tissue sampled from regions remote from the origin of
tachycardia, or from peripheral lymphocytes. The findings suggested that
somatic cell mutations in the cAMP-dependent signal transduction pathway
occurring during myocardial development may be responsible for some
forms of idiopathic ventricular tachycardia.
ANIMAL MODEL
Rudolph et al. (1995) generated mice deficient in the G protein subunit
alpha-i2 by homologous recombination in embryonic stem cells. The
deficient mice displayed growth retardation and developed a lethal
diffuse colitis with clinical and histopathologic features closely
resembling ulcerative colitis (see 266600) in humans, including the
development of adenocarcinoma of the colon. Before clinical symptoms,
the mice showed profound alterations in thymocyte maturation and
function. Elevated immunoglobulin levels, particularly IgG in the large
bowel, were observed. Bowel disease developed even when mice were raised
in a specific-pathogen-free facility.
*FIELD* AV
.0001
ADRENAL CORTICAL TUMOR, SOMATIC
GRANULOSA CELL TUMOR, SOMATIC, INCLUDED;;
THECOMA, SOMATIC, INCLUDED
GNAI2, ARG179CYS
In 3 of 11 tumors of the adrenal cortex and in 3 of 10 endocrine tumors
of the ovary, Lyons et al. (1990) found mutations that replaced
arginine-179 with either cysteine or histidine. Two of the ovarian
tumors were granulosa cell tumors and 1 was a thecoma.
.0002
ADRENAL CORTICAL TUMOR, SOMATIC
GRANULOSA CELL TUMOR, SOMATIC, INCLUDED;;
THECOMA, SOMATIC, INCLUDED
GNAI2, ARG179HIS
See 139360.0001.
.0003
PITUITARY ADENOMA, ACTH-SECRETING, SOMATIC
GNAI2, ARG179GLY
In an adrenocorticotrophic hormone-secreting pituitary adenoma,
Williamson et al. (1995) found a CGC-to-GGC change in codon 179 of the
GNAI2 gene converting arginine to glycine.
.0004
VENTRICULAR TACHYCARDIA, SOMATIC
GNAI2, PHE200LEU
Lerman et al. (1998) found a somatic mutation of the GNAI2 gene in
myocardial DNA biopsied from the arrhythmogenic focus in the right
ventricular outflow tract of a 58-year-old man with idiopathic
ventricular tachycardia (192605). The man developed sustained
monomorphic ventricular tachycardia during an intense argument. The
tachycardia was associated with chest pain, dyspnea, diaphoresis, and a
systolic blood pressure of 60 mm Hg. The cycle length of tachycardia was
240 ms. Emergency medical services restored sinus rhythm with an
electric shock. The resting ECG was normal, as was an echocardiogram.
Cardiac catheterization demonstrated normal coronary anatomy and normal
left ventricular function. There was no family history of ventricular
tachycardia or sudden cardiac death. The mutation in this patient was a
change of codon 200 from TTT (phe) to TTA (leu).
*FIELD* RF
1. Blatt, C.; Eversole-Cire, P.; Cohn, V. H.; Zollman, S.; Fournier,
R. E. K.; Mohandas, L. T.; Nesbitt, M.; Lugo, T.; Jones, D. T.; Reed,
R. R.; Weiner, L. P.; Sparkes, R. S.; Simon, M. I.: Chromosomal localization
of genes encoding guanine nucleotide-binding protein subunits in mouse
and human. Proc. Nat. Acad. Sci. 85: 7642-7646, 1988.
2. Hermouet, S.; Merendino, J. J., Jr.; Gutkind, J. S.; Spiegel, A.
M.: Activating and inactivating mutations of the alpha subunit of
G(i2) protein have opposite effects on proliferation of NIH 3T3 cells. Proc.
Nat. Acad. Sci. 88: 10455-10459, 1991.
3. Itoh, H.; Toyama, R.; Kozasa, T.; Tsukamoto, T.; Matsuoka, M.;
Kaziro, Y.: Presence of three distinct molecular species of G(i)
protein alpha subunit: structure of rat cDNAs and human genomic DNAs. J.
Biol. Chem. 263: 6656-6664, 1988.
4. Jiang, L.; Dai, Y.; Liu, X.; Wang, C.; Wang, A.; Chen, Z.; Heidbreder,
C. E.; Kolokythas, A.; Zhou, X.: Identification and experimental
validation of G protein alpha inhibiting activity polypeptide 2 (GNAI2)
as a microRNA-138 target in tongue squamous cell carcinoma. Hum.
Genet. 129: 189-197, 2011.
5. Lerman, B. B.; Dong, B.; Stein, K. M.; Markowitz, S. M.; Linden,
J.; Catanzaro, D. F.: Right ventricular outflow tract tachycardia
due to a somatic cell mutation in G protein subunit-alpha-i2. J.
Clin. Invest. 101: 2862-2868, 1998.
6. Lyons, J.; Landis, C. A.; Harsh, G.; Vallar, L.; Grunewald, K.;
Feichtinger, H.; Duh, Q.-Y.; Clark, O. H.; Kawasaki, E.; Bourne, H.
R.; McCormick, F.: Two G protein oncogenes in human endocrine tumors. Science 249:
655-659, 1990.
7. Magovcevic, I.; Ang, S.-L.; Seidman, J. G.; Tolman, C. J.; Neer,
E. J.; Morton, C. C.: Regional localization of the human G protein
alpha(i2) (GNAI2) gene: assignment to 3p21 and a related sequence
(GNAI2L) to 12p12-p13. Genomics 12: 125-129, 1992.
8. Rudolph, U.; Finegold, M. J.; Rich, S. S.; Harriman, G. R.; Srinivasan,
Y.; Brabet, P.; Boulay, G.; Bradley, A.; Birnbaumer, L.: Ulcerative
colitis and adenocarcinoma of the colon in G alpha(i2)-deficient mice. Nature
Genet. 10: 143-150, 1995.
9. Sparkes, R. S.; Cohn, V. H.; Cire-Eversole, P.; Blatt, C.; Amatruda,
T. T.; Weiner, L. P.; Nesbitt, M.; Reed, R. R.; Lochrie, M. A.; Fournier,
R. E. K.; Simon, M. I.: Mapping of genes encoding the subunits of
guanine nucleotide-binding proteins (G-proteins) in the mouse. (Abstract) Cytogenet.
Cell Genet. 46: 696 only, 1987.
10. Sparkes, R. S.; Cohn, V. H.; Mohandas, T.; Zollman, S.; Cire-Eversole,
P.; Amatruda, T. T.; Reed, R. R.; Lochrie, M. A.; Simon, M. I.: Mapping
of genes encoding the subunits of guanine nucleotide-binding protein
(G-proteins) in humans. (Abstract) Cytogenet. Cell Genet. 46: 696
only, 1987.
11. Wilkie, T. M.; Gilbert, D. J.; Olsen, A. S.; Chen, X.-N.; Amatruda,
T. T.; Korenberg, J. R.; Trask, B. J.; de Jong, P.; Reed, R. R.; Simon,
M. I.; Jenkins, N. A.; Copeland, N. G.: Evolution of the mammalian
G protein alpha subunit multigene family. Nature Genet. 1: 85-91,
1992.
12. Williamson, E. A.; Ince, P. G.; Harrison, D.; Kendall-Taylor,
P.; Harris, P. E.: G-protein mutations in human pituitary adrenocorticotrophic
hormone-secreting adenomas. Europ. J. Clin. Invest. 25: 128-131,
1995.
*FIELD* CN
Patricia A. Hartz - updated: 4/21/2011
Victor A. McKusick - updated: 7/13/1998
*FIELD* CD
Victor A. McKusick: 9/22/1987
*FIELD* ED
carol: 09/13/2013
mgross: 4/21/2011
carol: 7/15/2009
terry: 3/4/2009
carol: 8/15/2008
carol: 8/14/2008
carol: 7/17/1998
terry: 7/13/1998
carol: 7/2/1998
psherman: 6/16/1998
mark: 6/14/1997
mark: 1/8/1996
mark: 7/25/1995
carol: 2/17/1995
carol: 5/19/1992
supermim: 3/16/1992
carol: 1/27/1992
carol: 1/6/1992
*RECORD*
*FIELD* NO
139360
*FIELD* TI
*139360 GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-INHIBITING ACTIVITY POLYPEPTIDE
2; GNAI2
read more;;G PROTEIN, ALPHA-INHIBITING 2B; GNAI2B
*FIELD* TX
CLONING
Magovcevic et al. (1992) isolated a cDNA for the GNAI2 gene from a human
T-cell library.
Itoh et al. (1988) demonstrated 3 distinct human G-alpha inhibitory
proteins. Southern blot analysis indicated that a single copy of each
gene is present in the haploid human genome.
GENE STRUCTURE
Itoh et al. (1988) determined that the GNAI2 and GNAI3 (139380) genes
contain 8 coding exons and possess identical exon-intron organization.
MAPPING
Sparkes et al. (1987, 1987) and Blatt et al. (1988) used a cDNA probe
with a mouse/human somatic cell hybrid panel to assign the alpha-2
inhibitory polypeptide to chromosome 3 in man and chromosome 9 in mouse.
Blatt et al. (1988) also assigned the GNAI2 gene to chromosome 3 by
hybridization of cDNA clones with DNA from human-mouse somatic cell
hybrids. Magovcevic et al. (1992) mapped the GNAI2 gene to 3p21 by
chromosomal in situ hybridization. A related sequence, GNAI2L (139180),
was mapped by the same method to 12p13-p12. The assignment to chromosome
3 was supported by PCR amplification of GNAI2-specific sequences in a
human/rodent somatic cell hybrid containing only human chromosome 3.
Wilkie et al. (1992) assigned the corresponding gene to mouse chromosome
9.
GENE FUNCTION
Hermouet et al. (1991) demonstrated that activating and inactivating
mutations of the GNAI2 gene have opposite effects on proliferation of
NIH 3T3 cells.
Jiang et al. (2011) found that microRNA-138 (MIR138; see 613394) was
downregulated in tongue squamous cell carcinoma (TSCC) compared with
normal tissue. Using microarray-based differential expression analysis
on human TSCC cells transfected with an MIR138 mimic or a control mimic,
followed by bioinformatic analysis, Jiang et al. (2011) identified GNAI2
and 4 other genes as high-confidence candidate targets of MIR138. They
observed a reverse correlation between MIR138 and GNAI2 levels in a TSCC
cell line panel and identified 2 MIR138 target sequences in the 3-prime
UTR of GNAI2 mRNA. Reporter gene assays confirmed that both putative
target sequences were inhibited by MIR138. Knockdown of MIR138 in TSCC
cells enhanced the expression of GNAI2 at the mRNA and protein levels.
In contrast, transfection of MIR138 or an MIR138 mimic reduced GNAI2
mRNA and protein expression, which was associated with reduced cell
proliferation and enhanced apoptosis.
MOLECULAR GENETICS
Since somatic mutations in some growth hormone-secreting pituitary
tumors convert the gene for the alpha polypeptide chain of G(s) into a
putative oncogene, referred to as GSP (139320), Lyons et al. (1990)
considered the likelihood that similar mutations would activate other G
proteins. They found mutations of the GNAI2 gene that replaced
arginine-179 with either cysteine or histidine in tumors of the adrenal
cortex and endocrine tumors of the ovary. They referred to this mutant
GNAI2 gene as the GIP2 oncogene. Williamson et al. (1995) studied 32
adrenocorticotrophin hormone-secreting pituitary adenomas for the
presence of GSP and GIP mutations. GSP mutations were demonstrated in 2
tumors at codon 227 (139320.0012) and a GIP mutation was identified in 1
tumor at codon 179 (139360.0003).
Idiopathic ventricular tachycardia is a generic term that describes the
various forms of ventricular arrhythmias that occur in patients without
structural heart disease and in the absence of the long QT syndrome.
Many of these tachycardias are focal in origin, localize to the right
ventricular outflow tracts, terminate in response to beta-blockers,
verapamil, vagal maneuvers, and adenosine, and are thought to result
from cAMP-mediated triggered activity. Lerman et al. (1998) prepared DNA
from biopsy samples obtained from myocardial tissue from a patient with
adenosine-insensitive idiopathic ventricular tachycardia arising from
the right ventricular outflow tracts. Genomic sequences of the GNAI2B
gene showed a point mutation (phe200 to leu; 139360.0004) in the
GTP-binding domain of the inhibitory G protein, as identified in a
biopsy sample from the arrhythmogenic focus. This mutation was shown to
increase intracellular cAMP concentration and inhibit suppression of
cAMP by adenosine. No mutations were detected in the GNAI2B gene from
myocardial tissue sampled from regions remote from the origin of
tachycardia, or from peripheral lymphocytes. The findings suggested that
somatic cell mutations in the cAMP-dependent signal transduction pathway
occurring during myocardial development may be responsible for some
forms of idiopathic ventricular tachycardia.
ANIMAL MODEL
Rudolph et al. (1995) generated mice deficient in the G protein subunit
alpha-i2 by homologous recombination in embryonic stem cells. The
deficient mice displayed growth retardation and developed a lethal
diffuse colitis with clinical and histopathologic features closely
resembling ulcerative colitis (see 266600) in humans, including the
development of adenocarcinoma of the colon. Before clinical symptoms,
the mice showed profound alterations in thymocyte maturation and
function. Elevated immunoglobulin levels, particularly IgG in the large
bowel, were observed. Bowel disease developed even when mice were raised
in a specific-pathogen-free facility.
*FIELD* AV
.0001
ADRENAL CORTICAL TUMOR, SOMATIC
GRANULOSA CELL TUMOR, SOMATIC, INCLUDED;;
THECOMA, SOMATIC, INCLUDED
GNAI2, ARG179CYS
In 3 of 11 tumors of the adrenal cortex and in 3 of 10 endocrine tumors
of the ovary, Lyons et al. (1990) found mutations that replaced
arginine-179 with either cysteine or histidine. Two of the ovarian
tumors were granulosa cell tumors and 1 was a thecoma.
.0002
ADRENAL CORTICAL TUMOR, SOMATIC
GRANULOSA CELL TUMOR, SOMATIC, INCLUDED;;
THECOMA, SOMATIC, INCLUDED
GNAI2, ARG179HIS
See 139360.0001.
.0003
PITUITARY ADENOMA, ACTH-SECRETING, SOMATIC
GNAI2, ARG179GLY
In an adrenocorticotrophic hormone-secreting pituitary adenoma,
Williamson et al. (1995) found a CGC-to-GGC change in codon 179 of the
GNAI2 gene converting arginine to glycine.
.0004
VENTRICULAR TACHYCARDIA, SOMATIC
GNAI2, PHE200LEU
Lerman et al. (1998) found a somatic mutation of the GNAI2 gene in
myocardial DNA biopsied from the arrhythmogenic focus in the right
ventricular outflow tract of a 58-year-old man with idiopathic
ventricular tachycardia (192605). The man developed sustained
monomorphic ventricular tachycardia during an intense argument. The
tachycardia was associated with chest pain, dyspnea, diaphoresis, and a
systolic blood pressure of 60 mm Hg. The cycle length of tachycardia was
240 ms. Emergency medical services restored sinus rhythm with an
electric shock. The resting ECG was normal, as was an echocardiogram.
Cardiac catheterization demonstrated normal coronary anatomy and normal
left ventricular function. There was no family history of ventricular
tachycardia or sudden cardiac death. The mutation in this patient was a
change of codon 200 from TTT (phe) to TTA (leu).
*FIELD* RF
1. Blatt, C.; Eversole-Cire, P.; Cohn, V. H.; Zollman, S.; Fournier,
R. E. K.; Mohandas, L. T.; Nesbitt, M.; Lugo, T.; Jones, D. T.; Reed,
R. R.; Weiner, L. P.; Sparkes, R. S.; Simon, M. I.: Chromosomal localization
of genes encoding guanine nucleotide-binding protein subunits in mouse
and human. Proc. Nat. Acad. Sci. 85: 7642-7646, 1988.
2. Hermouet, S.; Merendino, J. J., Jr.; Gutkind, J. S.; Spiegel, A.
M.: Activating and inactivating mutations of the alpha subunit of
G(i2) protein have opposite effects on proliferation of NIH 3T3 cells. Proc.
Nat. Acad. Sci. 88: 10455-10459, 1991.
3. Itoh, H.; Toyama, R.; Kozasa, T.; Tsukamoto, T.; Matsuoka, M.;
Kaziro, Y.: Presence of three distinct molecular species of G(i)
protein alpha subunit: structure of rat cDNAs and human genomic DNAs. J.
Biol. Chem. 263: 6656-6664, 1988.
4. Jiang, L.; Dai, Y.; Liu, X.; Wang, C.; Wang, A.; Chen, Z.; Heidbreder,
C. E.; Kolokythas, A.; Zhou, X.: Identification and experimental
validation of G protein alpha inhibiting activity polypeptide 2 (GNAI2)
as a microRNA-138 target in tongue squamous cell carcinoma. Hum.
Genet. 129: 189-197, 2011.
5. Lerman, B. B.; Dong, B.; Stein, K. M.; Markowitz, S. M.; Linden,
J.; Catanzaro, D. F.: Right ventricular outflow tract tachycardia
due to a somatic cell mutation in G protein subunit-alpha-i2. J.
Clin. Invest. 101: 2862-2868, 1998.
6. Lyons, J.; Landis, C. A.; Harsh, G.; Vallar, L.; Grunewald, K.;
Feichtinger, H.; Duh, Q.-Y.; Clark, O. H.; Kawasaki, E.; Bourne, H.
R.; McCormick, F.: Two G protein oncogenes in human endocrine tumors. Science 249:
655-659, 1990.
7. Magovcevic, I.; Ang, S.-L.; Seidman, J. G.; Tolman, C. J.; Neer,
E. J.; Morton, C. C.: Regional localization of the human G protein
alpha(i2) (GNAI2) gene: assignment to 3p21 and a related sequence
(GNAI2L) to 12p12-p13. Genomics 12: 125-129, 1992.
8. Rudolph, U.; Finegold, M. J.; Rich, S. S.; Harriman, G. R.; Srinivasan,
Y.; Brabet, P.; Boulay, G.; Bradley, A.; Birnbaumer, L.: Ulcerative
colitis and adenocarcinoma of the colon in G alpha(i2)-deficient mice. Nature
Genet. 10: 143-150, 1995.
9. Sparkes, R. S.; Cohn, V. H.; Cire-Eversole, P.; Blatt, C.; Amatruda,
T. T.; Weiner, L. P.; Nesbitt, M.; Reed, R. R.; Lochrie, M. A.; Fournier,
R. E. K.; Simon, M. I.: Mapping of genes encoding the subunits of
guanine nucleotide-binding proteins (G-proteins) in the mouse. (Abstract) Cytogenet.
Cell Genet. 46: 696 only, 1987.
10. Sparkes, R. S.; Cohn, V. H.; Mohandas, T.; Zollman, S.; Cire-Eversole,
P.; Amatruda, T. T.; Reed, R. R.; Lochrie, M. A.; Simon, M. I.: Mapping
of genes encoding the subunits of guanine nucleotide-binding protein
(G-proteins) in humans. (Abstract) Cytogenet. Cell Genet. 46: 696
only, 1987.
11. Wilkie, T. M.; Gilbert, D. J.; Olsen, A. S.; Chen, X.-N.; Amatruda,
T. T.; Korenberg, J. R.; Trask, B. J.; de Jong, P.; Reed, R. R.; Simon,
M. I.; Jenkins, N. A.; Copeland, N. G.: Evolution of the mammalian
G protein alpha subunit multigene family. Nature Genet. 1: 85-91,
1992.
12. Williamson, E. A.; Ince, P. G.; Harrison, D.; Kendall-Taylor,
P.; Harris, P. E.: G-protein mutations in human pituitary adrenocorticotrophic
hormone-secreting adenomas. Europ. J. Clin. Invest. 25: 128-131,
1995.
*FIELD* CN
Patricia A. Hartz - updated: 4/21/2011
Victor A. McKusick - updated: 7/13/1998
*FIELD* CD
Victor A. McKusick: 9/22/1987
*FIELD* ED
carol: 09/13/2013
mgross: 4/21/2011
carol: 7/15/2009
terry: 3/4/2009
carol: 8/15/2008
carol: 8/14/2008
carol: 7/17/1998
terry: 7/13/1998
carol: 7/2/1998
psherman: 6/16/1998
mark: 6/14/1997
mark: 1/8/1996
mark: 7/25/1995
carol: 2/17/1995
carol: 5/19/1992
supermim: 3/16/1992
carol: 1/27/1992
carol: 1/6/1992