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Protein

Guanine nucleotide-binding protein G(i) subunit alpha-1

Gene

GNAI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis (PubMed:17635935).By similarity3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi47 – 471MagnesiumCombined sources2 Publications
Binding sitei151 – 1511GTPCombined sources
Metal bindingi181 – 1811MagnesiumCombined sources2 Publications
Binding sitei326 – 3261GTP; via amide nitrogenCombined sources

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi43 – 486GTPCombined sources1 Publication
Nucleotide bindingi175 – 1817GTPCombined sources
Nucleotide bindingi200 – 2045GTP1 Publication
Nucleotide bindingi269 – 2724GTPCombined sources1 Publication

GO - Molecular functioni

GO - Biological processi

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

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-400042. Adrenaline,noradrenaline inhibits insulin secretion.
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-422356. Regulation of insulin secretion.
R-HSA-6814122. Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding.
SignaLinkiP63096.
SIGNORiP63096.

Names & Taxonomyi

Protein namesi
Recommended name:
Guanine nucleotide-binding protein G(i) subunit alpha-1
Alternative name(s):
Adenylate cyclase-inhibiting G alpha protein
Gene namesi
Name:GNAI1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:4384. GNAI1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm 1 Publication
  • Cell membrane 1 Publication; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome 1 Publication
  • Membrane By similarity; Lipid-anchor By similarity

  • Note: Localizes in the centrosomes of interphase and mitotic cells, but not in centrosomes during cytokinesis. Detected at the cleavage furrow or the midbody (PubMed:17635935). Localized at the plasma membrane throughout mitosis. Colocalizes with RIC8A and RGS14 at the plasma membrane (By similarity).By similarity1 Publication

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • heterotrimeric G-protein complex Source: ProtInc
  • lysosomal membrane Source: UniProtKB
  • membrane raft Source: Ensembl
  • midbody Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi42 – 421G → R: Abolishes switch to an activated conformation and dissociation from beta and gamma subunits upon GTP binding. Abolishes interaction with RGS family members. 1 Publication
Mutagenesisi116 – 1161E → L: Enhances interaction (inactive GDP-bound) with RGS14. 2 Publications
Mutagenesisi147 – 1471Q → L: Enhances interaction (inactive GDP-bound) with RGS14. 2 Publications
Mutagenesisi245 – 2451E → L: Enhances interaction (inactive GDP-bound) with RGS14. 1 Publication

Organism-specific databases

PharmGKBiPA172.

Chemistry

ChEMBLiCHEMBL4741.

Polymorphism and mutation databases

BioMutaiGNAI1.
DMDMi52000964.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved2 Publications
Chaini2 – 354353Guanine nucleotide-binding protein G(i) subunit alpha-1PRO_0000203671Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine2 Publications
Lipidationi3 – 31S-palmitoyl cysteineBy similarity
Modified residuei178 – 1781ADP-ribosylarginine; by cholera toxinBy similarity
Modified residuei204 – 2041Deamidated glutamine; by Photorhabdus PAU_022301 Publication
Modified residuei351 – 3511ADP-ribosylcysteine; by pertussis toxinBy similarity

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

EPDiP63096.
MaxQBiP63096.
PaxDbiP63096.
PeptideAtlasiP63096.
PRIDEiP63096.

PTM databases

iPTMnetiP63096.
PhosphoSiteiP63096.
SwissPalmiP63096.

Expressioni

Gene expression databases

BgeeiENSG00000127955.
CleanExiHS_GNAI1.
ExpressionAtlasiP63096. baseline and differential.
GenevisibleiP63096. HS.

Organism-specific databases

HPAiCAB022449.

Interactioni

Subunit structurei

Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Identified in complex with the beta subunit GNB1 and the gamma subunit GNG1 (PubMed:22383884). Identified in complex with the beta subunit GNB1 and the gamma subunit GNG2 (PubMed:18434541). GTP binding causes dissociation of the heterotrimer, liberating the individual subunits so that they can interact with downstream effector proteins (PubMed:22383884). Interacts (GDP-bound form) with GPSM1; this inhibits guanine nucleotide exchange and GTP binding (By similarity). Interacts (GDP-bound form) with GPSM2 (via GoLoco domains); this inhibits guanine nucleotide exchange (PubMed:22952234). Interacts with RGS10; this strongly enhances GTP hydrolysis (PubMed:8774883, PubMed:18434541). Interacts with RGS1 and RGS16; this strongly enhances GTPase activity (PubMed:18434541). Interacts with RGS4 (PubMed:18434541). Interacts with RGS12 (PubMed:18434541). Interacts (via active GTP- or inactive GDP-bound forms) with RGS14 (via RGS and GoLoco domains) (PubMed:11976690, PubMed:18434541, PubMed:21115486, PubMed:22383884). Interacts with RGS3, RGS6, RGS7, RGS8, RGS17, RGS18 and RGS20 (in vitro) (PubMed:18434541). Interacts (GDP-bound form) with RIC8A (via C-terminus) (By similarity).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GPSM2P812743EBI-618639,EBI-618655
GPSM3Q9Y4H43EBI-618639,EBI-347538
NUMA1Q149804EBI-618639,EBI-521611
RGS17Q9UGC63EBI-618639,EBI-3918154

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109032. 75 interactions.
IntActiP63096. 30 interactions.
MINTiMINT-2913925.
STRINGi9606.ENSP00000343027.

Chemistry

BindingDBiP63096.

Structurei

Secondary structure

1
354
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi9 – 168Combined sources
Helixi20 – 234Combined sources
Helixi27 – 293Combined sources
Beta strandi31 – 4111Combined sources
Helixi46 – 5712Combined sources
Helixi63 – 675Combined sources
Helixi70 – 9122Combined sources
Helixi100 – 11314Combined sources
Beta strandi115 – 1173Combined sources
Helixi121 – 13212Combined sources
Helixi134 – 1407Combined sources
Helixi141 – 1455Combined sources
Helixi152 – 1576Combined sources
Helixi159 – 1624Combined sources
Beta strandi164 – 1663Combined sources
Helixi171 – 1755Combined sources
Beta strandi183 – 1919Combined sources
Beta strandi194 – 2018Combined sources
Helixi208 – 2158Combined sources
Beta strandi220 – 2267Combined sources
Helixi227 – 2293Combined sources
Beta strandi238 – 2414Combined sources
Helixi242 – 25413Combined sources
Helixi257 – 2593Combined sources
Beta strandi260 – 26910Combined sources
Helixi271 – 2777Combined sources
Turni278 – 2803Combined sources
Helixi283 – 2853Combined sources
Helixi296 – 30813Combined sources
Turni314 – 3163Combined sources
Beta strandi319 – 3235Combined sources
Helixi329 – 34618Combined sources
Helixi348 – 3503Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KJYX-ray2.70A/C30-354[»]
1Y3AX-ray2.50A/B/C/D26-354[»]
2G83X-ray2.80A/B33-345[»]
2GTPX-ray2.55A/B32-354[»]
2IK8X-ray2.71A/C31-354[»]
2OM2X-ray2.20A/C31-354[»]
2XNSX-ray3.41A/B30-354[»]
3ONWX-ray2.38A/B31-354[»]
3QE0X-ray3.00A/B/C33-354[»]
3QI2X-ray2.80A/B31-354[»]
3UMRX-ray2.24A1-354[»]
3UMSX-ray2.60A1-354[»]
4G5QX-ray2.90A/B/C/D25-354[»]
ProteinModelPortaliP63096.
SMRiP63096. Positions 5-348.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63096.

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.
InParanoidiP63096.
KOiK04630.
OMAiACEYIVN.
OrthoDBiEOG091G0VUT.
PhylomeDBiP63096.
TreeFamiTF300673.

Family and domain databases

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.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P63096-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV
60 70 80 90 100
KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMGR LKIDFGDSAR
110 120 130 140 150
ADDARQLFVL AGAAEEGFMT AELAGVIKRL WKDSGVQACF NRSREYQLND
160 170 180 190 200
SAAYYLNDLD RIAQPNYIPT QQDVLRTRVK TTGIVETHFT FKDLHFKMFD
210 220 230 240 250
VGGQRSERKK WIHCFEGVTA IIFCVALSDY DLVLAEDEEM NRMHESMKLF
260 270 280 290 300
DSICNNKWFT DTSIILFLNK KDLFEEKIKK SPLTICYPEY AGSNTYEEAA
310 320 330 340 350
AYIQCQFEDL NKRKDTKEIY THFTCATDTK NVQFVFDAVT DVIIKNNLKD

CGLF
Length:354
Mass (Da):40,361
Last modified:January 23, 2007 - v2
Checksum:i9F88311B46E62DE3
GO
Isoform 2 (identifier: P63096-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.

Show »
Length:302
Mass (Da):34,775
Checksum:iDA5ED62E61B790A9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti138 – 1381A → G in CAB43212 (PubMed:11230166).Curated
Sequence conflicti219 – 2191T → A in AAH26326 (PubMed:15489334).Curated
Sequence conflicti244 – 2441H → Y in AAV38580 (Ref. 4) Curated
Sequence conflicti249 – 2491L → M in AAV38580 (Ref. 4) Curated
Sequence conflicti288 – 2881P → Q in AAH26326 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5252Missing in isoform 2. 1 PublicationVSP_045215Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF493905 mRNA. Translation: AAM12619.1.
AF055013 mRNA. Translation: AAC09361.1.
AL049933 mRNA. Translation: CAB43212.2.
BT019775 mRNA. Translation: AAV38580.1.
AK292953 mRNA. Translation: BAF85642.1.
AK304442 mRNA. Translation: BAG65263.1.
AC004159 Genomic DNA. No translation available.
AC080066 Genomic DNA. No translation available.
CH471091 Genomic DNA. Translation: EAW77011.1.
BC026326 mRNA. Translation: AAH26326.1.
M20596, M20594, M20595 Genomic DNA. Translation: AAA35893.1.
M17219 mRNA. Translation: AAA52581.1.
CCDSiCCDS5595.1. [P63096-1]
CCDS59061.1. [P63096-2]
PIRiA28318. RGHUI1.
RefSeqiNP_001243343.1. NM_001256414.1. [P63096-2]
NP_002060.4. NM_002069.5. [P63096-1]
UniGeneiHs.134587.

Genome annotation databases

EnsembliENST00000351004; ENSP00000343027; ENSG00000127955. [P63096-1]
ENST00000457358; ENSP00000410572; ENSG00000127955. [P63096-2]
GeneIDi2770.
KEGGihsa:2770.
UCSCiuc003uhb.2. human. [P63096-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF493905 mRNA. Translation: AAM12619.1.
AF055013 mRNA. Translation: AAC09361.1.
AL049933 mRNA. Translation: CAB43212.2.
BT019775 mRNA. Translation: AAV38580.1.
AK292953 mRNA. Translation: BAF85642.1.
AK304442 mRNA. Translation: BAG65263.1.
AC004159 Genomic DNA. No translation available.
AC080066 Genomic DNA. No translation available.
CH471091 Genomic DNA. Translation: EAW77011.1.
BC026326 mRNA. Translation: AAH26326.1.
M20596, M20594, M20595 Genomic DNA. Translation: AAA35893.1.
M17219 mRNA. Translation: AAA52581.1.
CCDSiCCDS5595.1. [P63096-1]
CCDS59061.1. [P63096-2]
PIRiA28318. RGHUI1.
RefSeqiNP_001243343.1. NM_001256414.1. [P63096-2]
NP_002060.4. NM_002069.5. [P63096-1]
UniGeneiHs.134587.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KJYX-ray2.70A/C30-354[»]
1Y3AX-ray2.50A/B/C/D26-354[»]
2G83X-ray2.80A/B33-345[»]
2GTPX-ray2.55A/B32-354[»]
2IK8X-ray2.71A/C31-354[»]
2OM2X-ray2.20A/C31-354[»]
2XNSX-ray3.41A/B30-354[»]
3ONWX-ray2.38A/B31-354[»]
3QE0X-ray3.00A/B/C33-354[»]
3QI2X-ray2.80A/B31-354[»]
3UMRX-ray2.24A1-354[»]
3UMSX-ray2.60A1-354[»]
4G5QX-ray2.90A/B/C/D25-354[»]
ProteinModelPortaliP63096.
SMRiP63096. Positions 5-348.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109032. 75 interactions.
IntActiP63096. 30 interactions.
MINTiMINT-2913925.
STRINGi9606.ENSP00000343027.

Chemistry

BindingDBiP63096.
ChEMBLiCHEMBL4741.

PTM databases

iPTMnetiP63096.
PhosphoSiteiP63096.
SwissPalmiP63096.

Polymorphism and mutation databases

BioMutaiGNAI1.
DMDMi52000964.

Proteomic databases

EPDiP63096.
MaxQBiP63096.
PaxDbiP63096.
PeptideAtlasiP63096.
PRIDEiP63096.

Protocols and materials databases

DNASUi2770.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000351004; ENSP00000343027; ENSG00000127955. [P63096-1]
ENST00000457358; ENSP00000410572; ENSG00000127955. [P63096-2]
GeneIDi2770.
KEGGihsa:2770.
UCSCiuc003uhb.2. human. [P63096-1]

Organism-specific databases

CTDi2770.
GeneCardsiGNAI1.
HGNCiHGNC:4384. GNAI1.
HPAiCAB022449.
MIMi139310. gene.
neXtProtiNX_P63096.
PharmGKBiPA172.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0082. Eukaryota.
ENOG410XNVQ. LUCA.
GeneTreeiENSGT00760000118851.
HOGENOMiHOG000038730.
HOVERGENiHBG063184.
InParanoidiP63096.
KOiK04630.
OMAiACEYIVN.
OrthoDBiEOG091G0VUT.
PhylomeDBiP63096.
TreeFamiTF300673.

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-400042. Adrenaline,noradrenaline inhibits insulin secretion.
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-422356. Regulation of insulin secretion.
R-HSA-6814122. Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding.
SignaLinkiP63096.
SIGNORiP63096.

Miscellaneous databases

ChiTaRSiGNAI1. human.
EvolutionaryTraceiP63096.
GeneWikiiGNAI1.
GenomeRNAii2770.
PROiP63096.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127955.
CleanExiHS_GNAI1.
ExpressionAtlasiP63096. baseline and differential.
GenevisibleiP63096. HS.

Family and domain databases

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 nameiGNAI1_HUMAN
AccessioniPrimary (citable) accession number: P63096
Secondary accession number(s): A8KA88
, B4E2V1, C9J3A4, P04898, P11015, P31871, Q5U074, Q8TAN5, Q9UGA4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 143 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.