Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Guanine nucleotide-binding protein G(k) subunit alpha

Gene

GNAI3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • GDP binding Source: UniProtKB
  • G-protein beta/gamma-subunit complex binding Source: GO_Central
  • G-protein coupled receptor binding Source: GO_Central
  • GTPase activity Source: UniProtKB
  • GTP binding Source: Reactome
  • metal ion binding Source: UniProtKB-KW
  • signal transducer activity Source: GO_Central

GO - Biological processi

  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • cell division Source: UniProtKB
  • dopamine receptor signaling pathway Source: UniProtKB
  • GTP metabolic process Source: UniProtKB
  • negative regulation of adenylate cyclase activity Source: ProtInc
  • protein folding Source: Reactome
  • transport Source: ProtInc
  • vesicle fusion Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Transducer

Keywords - Biological processi

Cell cycle, Cell division

Keywords - Ligandi

GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000065135-MONOMER.
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

HGNCiHGNC:4387. GNAI3.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Cell membrane 1 Publication
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome 1 Publication
  • Membrane Curated; Lipid-anchor Curated

  • Note: Localizes in the centrosomes of interphase and mitotic cells. Detected at the cleavage furrow and/or the midbody.1 Publication

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: Ensembl
  • heterotrimeric G-protein complex Source: GO_Central
  • lysosomal membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • membrane raft Source: Ensembl
  • midbody Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • zymogen granule Source: Ensembl
Complete GO annotation...

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 rs387907178dbSNPEnsembl.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.

PTM databases

iPTMnetiP08754.
PhosphoSitePlusiP08754.
SwissPalmiP08754.

Expressioni

Gene expression databases

BgeeiENSG00000065135.
CleanExiHS_GNAI3.
GenevisibleiP08754. HS.

Organism-specific databases

HPAiCAB022099.

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

WithEntry#Exp.IntActNotes
GPSM3Q9Y4H45EBI-357563,EBI-347538
RGS14O435663EBI-357563,EBI-750603
RGS17Q9UGC63EBI-357563,EBI-3918154

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109035. 93 interactors.
IntActiP08754. 33 interactors.
MINTiMINT-1146232.
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.
OMAiTKEVYTH.
OrthoDBiEOG091G0VUT.
PhylomeDBiP08754.
TreeFamiTF300673.

Family and domain databases

CDDicd00066. G-alpha. 1 hit.
Gene3Di1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR001408. Gprotein_alpha_I.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 1 hit.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR00441. GPROTEINAI.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
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 rs387907178dbSNPEnsembl.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.

Cross-referencesi

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.

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...

Protein-protein interaction databases

BioGridi109035. 93 interactors.
IntActiP08754. 33 interactors.
MINTiMINT-1146232.
STRINGi9606.ENSP00000358867.

Chemistry databases

BindingDBiP08754.
ChEMBLiCHEMBL4221.

PTM databases

iPTMnetiP08754.
PhosphoSitePlusiP08754.
SwissPalmiP08754.

Polymorphism and mutation databases

BioMutaiGNAI3.
DMDMi120996.

Proteomic databases

EPDiP08754.
PaxDbiP08754.
PeptideAtlasiP08754.
PRIDEiP08754.

Protocols and materials databases

DNASUi2773.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2773.
DisGeNETi2773.
GeneCardsiGNAI3.
HGNCiHGNC:4387. GNAI3.
HPAiCAB022099.
MalaCardsiGNAI3.
MIMi139370. gene.
602483. phenotype.
neXtProtiNX_P08754.
OpenTargetsiENSG00000065135.
Orphaneti137888. Auriculocondylar syndrome.
PharmGKBiPA173.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000065135-MONOMER.
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.

Miscellaneous databases

ChiTaRSiGNAI3. human.
EvolutionaryTraceiP08754.
GeneWikiiGNAI3.
GenomeRNAii2773.
PROiP08754.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000065135.
CleanExiHS_GNAI3.
GenevisibleiP08754. HS.

Family and domain databases

CDDicd00066. G-alpha. 1 hit.
Gene3Di1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR001408. Gprotein_alpha_I.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 1 hit.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR00441. GPROTEINAI.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiGNAI3_HUMAN
AccessioniPrimary (citable) accession number: P08754
Secondary accession number(s): P17539, Q5TZX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 195 of the entry and version 3 of the sequence. [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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.