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Protein

Guanine nucleotide-binding protein G(k) subunit alpha

Gene

GNAI3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:8774883, PubMed:18434541, PubMed:19478087). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K+ channels (PubMed:2535845). 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 (PubMed:17635935).4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi47MagnesiumCombined sources1 Publication1
Metal bindingi181MagnesiumCombined sources1 Publication1
Binding sitei326GTP; via amide nitrogenCombined sources1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi43 – 48GTPCombined sources6
Nucleotide bindingi150 – 151GTPCombined sources2
Nucleotide bindingi175 – 181GTPCombined sources7
Nucleotide bindingi200 – 204GTPCombined sources1 Publication5
Nucleotide bindingi269 – 272GTPCombined sources4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransducer
Biological processCell cycle, Cell division
LigandGTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-112043 PLC beta mediated events
R-HSA-170670 Adenylate cyclase inhibitory pathway
R-HSA-202040 G-protein activation
R-HSA-392170 ADP signalling through P2Y purinoceptor 12
R-HSA-418555 G alpha (s) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-6814122 Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
SignaLinkiP08754
SIGNORiP08754

Names & Taxonomyi

Protein namesi
Recommended name:
Guanine nucleotide-binding protein G(k) subunit alpha1 Publication
Alternative name(s):
G(i) alpha-3
Gene namesi
Name:GNAI3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000065135.8
HGNCiHGNC:4387 GNAI3
MIMi139370 gene
neXtProtiNX_P08754

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Auriculocondylar syndrome 1 (ARCND1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:602483
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06855840G → R in ARCND1. 1 PublicationCorresponds to variant dbSNP:rs387907178EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2773
MalaCardsiGNAI3
MIMi602483 phenotype
OpenTargetsiENSG00000065135
Orphaneti137888 Auriculocondylar syndrome
PharmGKBiPA173

Chemistry databases

ChEMBLiCHEMBL4221

Polymorphism and mutation databases

BioMutaiGNAI3
DMDMi120996

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00002036922 – 354Guanine nucleotide-binding protein G(k) subunit alphaAdd BLAST353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Lipidationi3S-palmitoyl cysteineBy similarity1
Modified residuei178ADP-ribosylarginine; by cholera toxinBy similarity1
Modified residuei204Deamidated glutamine; by Photorhabdus PAU_022301 Publication1
Modified residuei351ADP-ribosylcysteine; by pertussis toxinBy similarity1

Post-translational modificationi

(Microbial infection) Deamidated at Gln-204 by Photorhabdus asymbiotica toxin PAU_02230, blocking GTP hydrolysis of heterotrimeric GNAQ or GNA11 and G-alphai (GNAI1, GNAI2 or GNAI3) proteins, thereby activating RhoA.1 Publication

Keywords - PTMi

ADP-ribosylation, Lipoprotein, Myristate, Palmitate

Proteomic databases

EPDiP08754
PaxDbiP08754
PeptideAtlasiP08754
PRIDEiP08754
ProteomicsDBi52164

PTM databases

iPTMnetiP08754
PhosphoSitePlusiP08754
SwissPalmiP08754

Expressioni

Gene expression databases

BgeeiENSG00000065135
CleanExiHS_GNAI3
GenevisibleiP08754 HS

Organism-specific databases

HPAiCAB022099
HPA042141

Interactioni

Subunit structurei

Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha subunit contains the guanine nucleotide binding site. GTP binding causes dissociation of the heterotrimer, liberating the individual subunits so that they can interact with downstream effector proteins. Interacts with GPSM1 (By similarity). Interacts (GDP-bound form) with GPSM2 (via GoLoco domains) (PubMed:22952234). Does not interact with RGS2 (PubMed:19478087). Interacts with RGS8 and RGS10; this strongly enhances the intrinsic GTPase activity (PubMed:8774883, PubMed:18434541). Interacts with RGS16; this strongly enhances the intrinsic GTPase activity (PubMed:19478087). Interacts with RGS12 (By similarity). Interacts (via active GTP- or inactive GDP-bound form) with RGS14 (By similarity).By similarityCurated3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109035, 99 interactors
IntActiP08754, 39 interactors
MINTiP08754
STRINGi9606.ENSP00000358867

Chemistry databases

BindingDBiP08754

Structurei

Secondary structure

1354
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi34 – 39Combined sources6
Helixi46 – 57Combined sources12
Helixi63 – 68Combined sources6
Helixi70 – 91Combined sources22
Helixi100 – 110Combined sources11
Turni111 – 116Combined sources6
Helixi121 – 131Combined sources11
Helixi134 – 141Combined sources8
Helixi142 – 145Combined sources4
Helixi152 – 157Combined sources6
Helixi159 – 162Combined sources4
Helixi171 – 175Combined sources5
Beta strandi183 – 191Combined sources9
Beta strandi194 – 201Combined sources8
Helixi205 – 214Combined sources10
Beta strandi219 – 226Combined sources8
Helixi227 – 231Combined sources5
Beta strandi237 – 241Combined sources5
Helixi242 – 254Combined sources13
Helixi257 – 259Combined sources3
Beta strandi262 – 269Combined sources8
Helixi271 – 278Combined sources8
Helixi283 – 285Combined sources3
Helixi296 – 308Combined sources13
Turni314 – 316Combined sources3
Beta strandi319 – 323Combined sources5
Helixi329 – 346Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP08754
SMRiP08754
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08754

Family & Domainsi

Sequence similaritiesi

Belongs to the G-alpha family. G(i/o/t/z) subfamily.Curated

Phylogenomic databases

eggNOGiKOG0082 Eukaryota
ENOG410XNVQ LUCA
GeneTreeiENSGT00760000118851
HOGENOMiHOG000038730
HOVERGENiHBG063184
InParanoidiP08754
KOiK04630
OMAiMRIIHDV
OrthoDBiEOG091G0VUT
PhylomeDBiP08754
TreeFamiTF300673

Family and domain databases

CDDicd00066 G-alpha, 1 hit
Gene3Di1.10.400.10, 1 hit
InterProiView protein in InterPro
IPR001408 Gprotein_alpha_I
IPR001019 Gprotein_alpha_su
IPR011025 GproteinA_insert
IPR027417 P-loop_NTPase
PANTHERiPTHR10218 PTHR10218, 1 hit
PfamiView protein in Pfam
PF00503 G-alpha, 1 hit
PRINTSiPR00318 GPROTEINA
PR00441 GPROTEINAI
SMARTiView protein in SMART
SM00275 G_alpha, 1 hit
SUPFAMiSSF47895 SSF47895, 1 hit
SSF52540 SSF52540, 2 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08754-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCTLSAEDK AAVERSKMID RNLREDGEKA AKEVKLLLLG AGESGKSTIV
60 70 80 90 100
KQMKIIHEDG YSEDECKQYK VVVYSNTIQS IIAIIRAMGR LKIDFGEAAR
110 120 130 140 150
ADDARQLFVL AGSAEEGVMT PELAGVIKRL WRDGGVQACF SRSREYQLND
160 170 180 190 200
SASYYLNDLD RISQSNYIPT QQDVLRTRVK TTGIVETHFT FKDLYFKMFD
210 220 230 240 250
VGGQRSERKK WIHCFEGVTA IIFCVALSDY DLVLAEDEEM NRMHESMKLF
260 270 280 290 300
DSICNNKWFT ETSIILFLNK KDLFEEKIKR SPLTICYPEY TGSNTYEEAA
310 320 330 340 350
AYIQCQFEDL NRRKDTKEIY THFTCATDTK NVQFVFDAVT DVIIKNNLKE

CGLY
Length:354
Mass (Da):40,532
Last modified:January 23, 2007 - v3
Checksum:iEAB6B4DD3646BC01
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21R → C no nucleotide entry (PubMed:2440724).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06855840G → R in ARCND1. 1 PublicationCorresponds to variant dbSNP:rs387907178EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
BT019973 mRNA Translation: AAV38776.1
BT019974 mRNA Translation: AAV38777.1
AK312252 mRNA Translation: BAG35184.1
CH471122 Genomic DNA Translation: EAW56393.1
BC025285 mRNA Translation: AAH25285.1
CCDSiCCDS802.1
PIRiS02348 RGHUI3
RefSeqiNP_006487.1, NM_006496.3
UniGeneiHs.73799
Hs.741171

Genome annotation databases

EnsembliENST00000369851; ENSP00000358867; ENSG00000065135
GeneIDi2773
KEGGihsa:2773
UCSCiuc001dxz.4 human

Similar proteinsi

Entry informationi

Entry nameiGNAI3_HUMAN
AccessioniPrimary (citable) accession number: P08754
Secondary accession number(s): P17539, Q5TZX1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 210 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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