P08754 (GNAI3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
G(i) alpha-3

Gene names

Name:

GNAI3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	354 AA.
Sequence status	Complete.
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. G(k) is the stimulatory G protein of receptor-regulated K+ channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division. Ref.10
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 (via active GTP- or inactive GDP-bound form) with RGS14 By similarity.
Subcellular location	Cytoplasm. Cell membrane. Cytoplasm › cytoskeleton › centrosome. Note: Localizes in the centrosomes of interphase and mitotic cells. Detected at the cleavage furrow and/or the midbody. Ref.10
Involvement in disease	Auriculocondylar syndrome 1 (ARCND1) [MIM:602483]: An autosomal dominant craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12
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
Disease	Disease mutation
Ligand	GTP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Transducer
PTM	ADP-ribosylation Lipoprotein Myristate Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Traceable author statement. Source: Reactome cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from direct assay Ref.10. Source: UniProtKB negative regulation of adenylate cyclase activity Traceable author statement PubMed 7608168. Source: ProtInc platelet activation Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome transport Non-traceable author statement Ref.4. Source: ProtInc vesicle fusion Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara centrosome Inferred from direct assay Ref.10. Source: UniProtKB cytoplasm Inferred from direct assay Ref.10. Source: UniProtKB heterotrimeric G-protein complex Inferred from Biological aspect of Ancestor. Source: RefGenome membrane raft Inferred from electronic annotation. Source: Compara midbody Inferred from direct assay Ref.10. Source: UniProtKB zymogen granule Inferred from electronic annotation. Source: Compara
Molecular_function	G-protein beta/gamma-subunit complex binding Inferred from Biological aspect of Ancestor. Source: RefGenome G-protein coupled serotonin 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 metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW signal transducer activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 354

354

Guanine nucleotide-binding protein G(k) subunit alpha

PRO_0000203692

Regions

Nucleotide binding

40 – 47

8

GTP By similarity

Nucleotide binding

175 – 181

7

GTP By similarity

Nucleotide binding

200 – 204

5

GTP By similarity

Nucleotide binding

269 – 272

4

GTP By similarity

Sites

Metal binding

47

1

Magnesium By similarity

Metal binding

181

1

Magnesium By similarity

Binding site

326

1

GTP; via amide nitrogen By similarity

Amino acid modifications

Modified residue

178

1

ADP-ribosylarginine; by cholera toxin By similarity

Modified residue

351

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

Natural variant

40

1

G → R in ARCND1. Ref.12

VAR_068558

Experimental info

Sequence conflict

21

1

R → C no nucleotide entry Ref.9

Secondary structure

1

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354

Helix Strand Turn

Details...

Beta strand

34 – 39

6

Helix

46 – 57

12

Helix

63 – 68

6

Helix

70 – 91

22

Helix

100 – 110

11

Turn

111 – 116

6

Helix

121 – 131

11

Helix

134 – 141

8

Helix

142 – 145

4

Helix

152 – 157

6

Helix

159 – 162

4

Helix

171 – 175

5

Beta strand

183 – 191

9

Beta strand

194 – 201

8

Helix

205 – 214

10

Beta strand

219 – 226

8

Helix

227 – 231

5

Beta strand

237 – 241

5

Helix

242 – 254

13

Helix

257 – 259

3

Beta strand

262 – 269

8

Helix

271 – 278

8

Helix

283 – 285

3

Helix

296 – 308

13

Turn

314 – 316

3

Beta strand

319 – 323

5

Helix

329 – 346

18

Sequences

	Sequence		Length	Mass (Da)
	P08754 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: EAB6B4DD3646BC01	FASTA	354	40,532
	10 20 30 40 50 60 MGCTLSAEDK AAVERSKMID RNLREDGEKA AKEVKLLLLG AGESGKSTIV KQMKIIHEDG 70 80 90 100 110 120 YSEDECKQYK VVVYSNTIQS IIAIIRAMGR LKIDFGEAAR ADDARQLFVL AGSAEEGVMT 130 140 150 160 170 180 PELAGVIKRL WRDGGVQACF SRSREYQLND SASYYLNDLD RISQSNYIPT QQDVLRTRVK 190 200 210 220 230 240 TTGIVETHFT FKDLYFKMFD VGGQRSERKK WIHCFEGVTA IIFCVALSDY DLVLAEDEEM 250 260 270 280 290 300 NRMHESMKLF DSICNNKWFT ETSIILFLNK KDLFEEKIKR SPLTICYPEY TGSNTYEEAA 310 320 330 340 350 AYIQCQFEDL NRRKDTKEIY THFTCATDTK NVQFVFDAVT DVIIKNNLKE CGLY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a new human G protein. Evidence for two Gi alpha-like protein families." Didsbury J.R., Snyderman R. FEBS Lett. 219:259-263(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Alpha i-3 cDNA encodes the alpha subunit of Gk, the stimulatory G protein of receptor-regulated K+ channels." Codina J., Olate J., Abramowitz J., Mattera R., Cook R.G., Birnbaumer L. J. Biol. Chem. 263:6746-6750(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Identification of cDNA encoding an additional alpha subunit of a human GTP-binding protein: expression of three alpha i subtypes in human tissues and cell lines." Kim S., Ang S.L., Bloch D.B., Bloch K.D., Kawahara Y., Tolman C., Lee R., Seidman J.G., Neer E.J. Proc. Natl. Acad. Sci. U.S.A. 85:4153-4157(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"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].
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[9]	"The human genome encodes at least three non-allelic G proteins with alpha i-type subunits." Suki W.N., Abramowitz J., Mattera R., Codina J., Birnbaumer L. FEBS Lett. 220:187-192(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-354.
[10]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome." Rieder M.J., Green G.E., Park S.S., Stamper B.D., Gordon C.T., Johnson J.M., Cunniff C.M., Smith J.D., Emery S.B., Lyonnet S., Amiel J., Holder M., Heggie A.A., Bamshad M.J., Nickerson D.A., Cox T.C., Hing A.V., Horst J.A., Cunningham M.L. Am. J. Hum. Genet. 90:907-914(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARCND1 ARG-40.
[13]	Erratum Rieder M.J., Green G.E., Park S.S., Stamper B.D., Gordon C.T., Johnson J.M., Cunniff C.M., Smith J.D., Emery S.B., Lyonnet S., Amiel J., Holder M., Heggie A.A., Bamshad M.J., Nickerson D.A., Cox T.C., Hing A.V., Horst J.A., Cunningham M.L. Am. J. Hum. Genet. 90:1116-1116(2012)
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M27543 mRNA. Translation: AAA52579.1.
J03005 mRNA. Translation: AAA52557.1.
M20604 , M20597, M20598, M20599, M20600, M20601, M20602, M20603 Genomic DNA. Translation: AAA35895.1.
J03198 mRNA. Translation: AAA35896.1.
J03238 mRNA. Translation: AAA35939.1.
AF493907 mRNA. Translation: AAM12621.1.
BT019974 mRNA. Translation: AAV38777.1.
BC025285 mRNA. Translation: AAH25285.1.

IPI

IPI00220578.

PIR

RGHUI3. S02348.

RefSeq

NP_006487.1. NM_006496.3.

UniGene

Hs.73799.
Hs.741171.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IHB	X-ray	2.71	A	32-354	[»]
2ODE	X-ray	1.90	A/C	4-350	[»]
2V4Z	X-ray	2.80	A	4-350	[»]
4G5O	X-ray	2.90	A/B/C/D	25-354	[»]
4G5R	X-ray	3.48	A/B/C/D	25-354	[»]
4G5S	X-ray	3.62	A/B/C/D	25-354	[»]

ProteinModelPortal

P08754.

ModBase

Search...

Protein-protein interaction databases

IntAct

P08754. 21 interactions.

MINT

MINT-1146232.

STRING

9606.ENSP00000358867.

PTM databases

PhosphoSite

P08754.

Polymorphism databases

DMDM

120996.

Proteomic databases

PaxDb

P08754.

PeptideAtlas

P08754.

PRIDE

P08754.

Protocols and materials databases

DNASU

2773.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369851; ENSP00000358867; ENSG00000065135.

GeneID

2773.

KEGG

hsa:2773.

UCSC

uc001dxz.2. human.

Organism-specific databases

CTD

2773.

GeneCards

GC01P110091.

HGNC

HGNC:4387. GNAI3.

HPA

CAB022099.

MIM

139370. gene.
602483. phenotype.

neXtProt

NX_P08754.

Orphanet

137888. Auriculo-condylar syndrome.

PharmGKB

PA173.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG322962.

HOGENOM

HOG000038730.

HOVERGEN

HBG063184.

InParanoid

P08754.

KO

K04630.

OMA

RISQTNY.

OrthoDB

EOG4WDDC1.

PhylomeDB

P08754.

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.

Reactome

REACT_111102. Signal Transduction.
REACT_13685. Neuronal System.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P08754.

Bgee

P08754.

CleanEx

HS_GNAI3.

Genevestigator

P08754.

GermOnline

ENSG00000065135. Homo sapiens.

Family and domain databases

Gene3D

1.10.400.10. 1 hit.

InterPro

IPR001408. Gprotein_alpha_I.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
[Graphical view]

PANTHER

PTHR10218. PTHR10218. 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

BindingDB

P08754.

ChEMBL

CHEMBL4221.

ChiTaRS

GNAI3. human.

EvolutionaryTrace

P08754.

GenomeRNAi

2773.

NextBio

10906.

SOURCE

Search...

Entry information

Entry name

GNAI3_HUMAN

Accession

Primary (citable) accession number: P08754
Secondary accession number(s): P17539

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 155 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.