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P08754 (GNAI3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Guanine nucleotide-binding protein G(k) subunit alpha
Alternative name(s):
G(i) alpha-3
Gene names
Name:GNAI3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length354 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. 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 processCell cycle
Cell division
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
   DiseaseDisease mutation
   LigandGTP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionTransducer
   PTMADP-ribosylation
Lipoprotein
Myristate
Palmitate
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Traceable author statement. Source: Reactome

blood coagulation

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: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

centrosome

Inferred from direct assay Ref.10. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.10. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337. Source: UniProt

extrinsic component of cytoplasmic side of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

heterotrimeric G-protein complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

midbody

Inferred from direct assay Ref.10. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.10. Source: UniProtKB

zymogen granule

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionG-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 354353Guanine nucleotide-binding protein G(k) subunit alpha
PRO_0000203692

Regions

Nucleotide binding40 – 478GTP By similarity
Nucleotide binding175 – 1817GTP By similarity
Nucleotide binding200 – 2045GTP By similarity
Nucleotide binding269 – 2724GTP By similarity

Sites

Metal binding471Magnesium By similarity
Metal binding1811Magnesium By similarity
Binding site3261GTP; via amide nitrogen By similarity

Amino acid modifications

Modified residue1781ADP-ribosylarginine; by cholera toxin By similarity
Modified residue3511ADP-ribosylcysteine; by pertussis toxin By similarity
Lipidation21N-myristoyl glycine By similarity
Lipidation31S-palmitoyl cysteine By similarity

Natural variations

Natural variant401G → R in ARCND1. Ref.12
VAR_068558

Experimental info

Sequence conflict211R → C no nucleotide entry Ref.9

Secondary structure

................................................... 354
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08754 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: EAB6B4DD3646BC01

FASTA35440,532
        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 

« Hide

References

« Hide '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 expand/collapse EMBL AC list , 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.
PIRRGHUI3. S02348.
RefSeqNP_006487.1. NM_006496.3.
UniGeneHs.73799.
Hs.741171.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IHBX-ray2.71A32-354[»]
2ODEX-ray1.90A/C4-350[»]
2V4ZX-ray2.80A4-350[»]
4G5OX-ray2.90A/B/C/D25-354[»]
4G5RX-ray3.48A/B/C/D25-354[»]
4G5SX-ray3.62A/B/C/D25-354[»]
ProteinModelPortalP08754.
SMRP08754. Positions 5-348.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109035. 59 interactions.
IntActP08754. 21 interactions.
MINTMINT-1146232.
STRING9606.ENSP00000358867.

Chemistry

BindingDBP08754.
ChEMBLCHEMBL4221.

PTM databases

PhosphoSiteP08754.

Polymorphism databases

DMDM120996.

Proteomic databases

PaxDbP08754.
PeptideAtlasP08754.
PRIDEP08754.

Protocols and materials databases

DNASU2773.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369851; ENSP00000358867; ENSG00000065135.
GeneID2773.
KEGGhsa:2773.
UCSCuc001dxz.3. human.

Organism-specific databases

CTD2773.
GeneCardsGC01P110091.
HGNCHGNC:4387. GNAI3.
HPACAB022099.
MIM139370. gene.
602483. phenotype.
neXtProtNX_P08754.
Orphanet137888. Auriculocondylar syndrome.
PharmGKBPA173.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322962.
HOGENOMHOG000038730.
HOVERGENHBG063184.
InParanoidP08754.
KOK04630.
OMAGEAARAX.
OrthoDBEOG72C50B.
PhylomeDBP08754.
TreeFamTF300673.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_13685. Neuronal System.
REACT_604. Hemostasis.
SignaLinkP08754.

Gene expression databases

ArrayExpressP08754.
BgeeP08754.
CleanExHS_GNAI3.
GenevestigatorP08754.

Family and domain databases

Gene3D1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProIPR001408. Gprotein_alpha_I.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10218. PTHR10218. 1 hit.
PfamPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSPR00318. GPROTEINA.
PR00441. GPROTEINAI.
SMARTSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.
ProtoNetSearch...

Other

ChiTaRSGNAI3. human.
EvolutionaryTraceP08754.
GeneWikiGNAI3.
GenomeRNAi2773.
NextBio10906.
PROP08754.
SOURCESearch...

Entry information

Entry nameGNAI3_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM