P04899 (GNAI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Guanine nucleotide-binding protein G(i) subunit alpha-2

Alternative name(s):
Adenylate cyclase-inhibiting G alpha protein

Gene names

Name:	GNAI2
Synonyms:	GNAI2B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	355 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division. Ref.9
Subunit structure	G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with GPSM1. Interacts with RGS12 and RGS14 By similarity. Interacts with UNC5B. Ref.7
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton › centrosome. Cell membrane. Note: Localizes in the centrosomes of interphase and mitotic cells. Detected at the cleavage furrow and/or the midbody. Ref.9
Sequence similarities	Belongs to the G-alpha family. G(i/o/t/z) subfamily.

Ontologies

Keywords
Biological process	Cell cycle Cell division
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing
Ligand	GTP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Transducer
PTM	ADP-ribosylation Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	adenosine receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from mutant phenotype Ref.9. Source: UniProtKB gamma-aminobutyric acid signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome inhibition of adenylate cyclase activity by G-protein signaling pathway Traceable author statement. Source: Reactome negative regulation of calcium ion transport via voltage-gated calcium channel activity Inferred from Biological aspect of Ancestor. Source: RefGenome platelet activation Traceable author statement. Source: Reactome response to nutrient Traceable author statement. Source: ProtInc synaptic transmission Traceable author statement. Source: Reactome
Cellular component	centrosome Inferred from direct assay Ref.9. Source: UniProtKB heterotrimeric G-protein complex Inferred from Biological aspect of Ancestor. Source: RefGenome midbody Inferred from direct assay Ref.9. Source: UniProtKB
Molecular function	G-protein beta/gamma-subunit complex binding Inferred from Biological aspect of Ancestor. Source: RefGenome G-protein coupled receptor binding Inferred from Biological aspect of Ancestor. Source: RefGenome GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Inferred from Biological aspect of Ancestor. Source: RefGenome guanyl-nucleotide exchange factor activity Traceable author statement. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol phospholipase C activity Traceable author statement. Source: Reactome signal transducer activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDFI	Q99750	2	EBI-353997,EBI-724076

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P04899-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P04899-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: MGCTVSAEDKAAAERSKMIDKNLREDGEKAAREVKLLLL → MEYAGHLPASSAQGTILACTSCT

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 355	354	Guanine nucleotide-binding protein G(i) subunit alpha-2		PRO_0000203679
Regions
	Nucleotide binding	40 – 47	8	GTP By similarity
	Nucleotide binding	176 – 182	7	GTP By similarity
	Nucleotide binding	201 – 205	5	GTP By similarity
	Nucleotide binding	270 – 273	4	GTP By similarity
Sites
	Metal binding	47	1	Magnesium By similarity
	Metal binding	182	1	Magnesium By similarity
	Binding site	327	1	GTP; via amide nitrogen By similarity
Amino acid modifications
	Modified residue	69	1	Phosphotyrosine Ref.8
	Modified residue	179	1	ADP-ribosylarginine; by cholera toxin By similarity
	Modified residue	352	1	ADP-ribosylcysteine; by pertussis toxin By similarity
	Lipidation	2	1	N-myristoyl glycine By similarity
	Lipidation	3	1	S-palmitoyl cysteine By similarity
Natural variations
	Alternative sequence	1 – 39	39	MGCTV…KLLLL → MEYAGHLPASSAQGTILACT SCT in isoform 2.		VSP_017497

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: BE6D6FF720CF3DCC	FASTA	355	40,451
	10 20 30 40 50 60 MGCTVSAEDK AAAERSKMID KNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEDG 70 80 90 100 110 120 YSEEECRQYR AVVYSNTIQS IMAIVKAMGN LQIDFADPSR ADDARQLFAL SCTAEEQGVL 130 140 150 160 170 180 PDDLSGVIRR LWADHGVQAC FGRSREYQLN DSAAYYLNDL ERIAQSDYIP TQQDVLRTRV 190 200 210 220 230 240 KTTGIVETHF TFKDLHFKMF DVGGQRSERK KWIHCFEGVT AIIFCVALSA YDLVLAEDEE 250 260 270 280 290 300 MNRMHESMKL FDSICNNKWF TDTSIILFLN KKDLFEEKIT HSPLTICFPE YTGANKYDEA 310 320 330 340 350 ASYIQSKFED LNKRKDTKEI YTHFTCATDT KNVQFVFDAV TDVIIKNNLK DCGLF
	Isoform 2 [UniParc]. Checksum: F14AB734881535C5	FASTA	339	38,473
	10 20 30 40 50 60 MEYAGHLPAS SAQGTILACT SCTGAGESGK STIVKQMKII HEDGYSEEEC RQYRAVVYSN 70 80 90 100 110 120 TIQSIMAIVK AMGNLQIDFA DPSRADDARQ LFALSCTAEE QGVLPDDLSG VIRRLWADHG 130 140 150 160 170 180 VQACFGRSRE YQLNDSAAYY LNDLERIAQS DYIPTQQDVL RTRVKTTGIV ETHFTFKDLH 190 200 210 220 230 240 FKMFDVGGQR SERKKWIHCF EGVTAIIFCV ALSAYDLVLA EDEEMNRMHE SMKLFDSICN 250 260 270 280 290 300 NKWFTDTSII LFLNKKDLFE EKITHSPLTI CFPEYTGANK YDEAASYIQS KFEDLNKRKD 310 320 330 TKEIYTHFTC ATDTKNVQFV FDAVTDVIIK NNLKDCGLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human Gi protein alpha-subunit: deduction of amino acid structure from a cloned cDNA." Didsbury J.R., Ho Y.-S., Snyderman R. FEBS Lett. 211:160-164(1987) [PubMed: 3100330] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"A small multigene family encodes Gi signal-transduction proteins." Beals C.R., Wilson C.B., Perlmutter R.M. Proc. Natl. Acad. Sci. U.S.A. 84:7886-7890(1987) [PubMed: 3120178] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Presence of three distinct molecular species of Gi protein alpha subunit. Structure of rat cDNAs and human genomic DNAs." Itoh H., Toyama R., Kozasa T., Tsukamoto T., Matsuoka M., Kaziro Y. J. Biol. Chem. 263:6656-6664(1988) [PubMed: 2834384] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Kidney and Mammary gland.
[6]	"Cloning and characterization of the human gene for the alpha-subunit of Gi2, a GTP-binding signal transduction protein." Weinstein L.S., Spiegel A.M., Carter A.D. FEBS Lett. 232:333-340(1988) [PubMed: 2837412] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-39.
[7]	"Modulation of G(ialpha(2)) signaling by the axonal guidance molecule UNC5H2." Komatsuzaki K., Dalvin S., Kinane T.B. Biochem. Biophys. Res. Commun. 297:898-905(2002) [PubMed: 12359238] [Abstract] Cited for: INTERACTION WITH UNC5B.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-69, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[9]	"Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division." Cho H., Kehrl J.H. J. Cell Biol. 178:245-255(2007) [PubMed: 17635935] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04828 mRNA. Translation: CAA28512.1. J03004 mRNA. Translation: AAA52556.1. Sequence problems. M20593 , M20586, M20587, M20588, M20589, M20590, M20591, M20592 Genomic DNA. Translation: AAA35894.1. AF493906 mRNA. Translation: AAM12620.1. BC012138 mRNA. Translation: AAH12138.1. BC016995 mRNA. Translation: AAH16995.1. X07854 Genomic DNA. Translation: CAA30703.1.
IPI	IPI00217906. IPI00748145.
PIR	RGHUI2. S02319.
RefSeq	NP_002061.1. NM_002070.2.
UniGene	Hs.77269.
3D structure databases
ProteinModelPortal	P04899.
SMR	P04899. Positions 5-354.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-602N.
IntAct	P04899. 18 interactions.
MINT	MINT-139884.
STRING	P04899.
PTM databases
PhosphoSite	P04899.
Polymorphism databases
DMDM	121023.
Proteomic databases
PRIDE	P04899.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000313601; ENSP00000312999; ENSG00000114353.
GeneID	2771.
KEGG	hsa:2771.
UCSC	uc003cyo.1. human. uc003cyq.1. human.
Organism-specific databases
CTD	2771.
GeneCards	GC03P050263.
H-InvDB	HIX0003320.
HGNC	HGNC:4385. GNAI2.
HPA	HPA007704.
MIM	139360. gene.
neXtProt	NX_P04899.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04726.
HOVERGEN	HBG063184.
InParanoid	P04899.
OMA	VIRRLWS.
OrthoDB	EOG4WDDC1.
PhylomeDB	P04899.
Enzyme and pathway databases
Pathway_Interaction_DB	endothelinpathway. Endothelins. hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins. lysophospholipid_pathway. LPA receptor mediated events. er_nongenomic_pathway. Plasma membrane estrogen receptor signaling. s1p_s1p1_pathway. S1P1 pathway. s1p_s1p2_pathway. S1P2 pathway. s1p_s1p3_pathway. S1P3 pathway. s1p_s1p4_pathway. S1P4 pathway. s1p_s1p5_pathway. S1P5 pathway. s1p_meta_pathway. Sphingosine 1-phosphate (S1P) pathway. txa2pathway. Thromboxane A2 receptor signaling.
Reactome	REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_13685. Neuronal System. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P04899.
Bgee	P04899.
CleanEx	HS_GNAI2.
Genevestigator	P04899.
GermOnline	ENSG00000114353. Homo sapiens.
Family and domain databases
InterPro	IPR001408. Gprotein_alpha_I. IPR001019. Gprotein_alpha_su. IPR011025. GproteinA_insert. [Graphical view]
Gene3D	G3DSA:1.10.400.10. GproteinA_insert. 1 hit.
KO	K04630.
PANTHER	PTHR10218. Gprotein_alph_bd. 1 hit.
Pfam	PF00503. G-alpha. 1 hit. [Graphical view]
PRINTS	PR00318. GPROTEINA. PR00441. GPROTEINAI.
SMART	SM00275. G_alpha. 1 hit. [Graphical view]
SUPFAM	SSF47895. Transducn_insert. 1 hit.
ProtoNet	Search...
Other
NextBio	10900.
SOURCE	Search...

Entry information

Entry name

GNAI2_HUMAN

Accession

Primary (citable) accession number: P04899
Secondary accession number(s): Q8IZ71

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.