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Protein

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

Gene

GNAI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi47MagnesiumCombined sources2 Publications1
Binding sitei151GTPCombined sources1
Metal bindingi181MagnesiumCombined sources2 Publications1
Binding sitei326GTP; via amide nitrogenCombined sources1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi43 – 48GTPCombined sources1 Publication6
Nucleotide bindingi175 – 181GTPCombined sources7
Nucleotide bindingi200 – 204GTP1 Publication5
Nucleotide bindingi269 – 272GTPCombined sources1 Publication4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransducer
Biological processCell cycle, Cell division, Mitosis, Transport
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-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

EuPathDBiHostDB:ENSG00000127955.15
HGNCiHGNC:4384 GNAI1
MIMi139310 gene
neXtProtiNX_P63096

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, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42G → R: Abolishes switch to an activated conformation and dissociation from beta and gamma subunits upon GTP binding. Abolishes interaction with RGS family members. 1 Publication1
Mutagenesisi116E → L: Enhances interaction (inactive GDP-bound) with RGS14. 2 Publications1
Mutagenesisi147Q → L: Enhances interaction (inactive GDP-bound) with RGS14. 2 Publications1
Mutagenesisi245E → L: Enhances interaction (inactive GDP-bound) with RGS14. 1 Publication1

Organism-specific databases

DisGeNETi2770
OpenTargetsiENSG00000127955
PharmGKBiPA172

Chemistry databases

ChEMBLiCHEMBL4741
DrugBankiDB04315 Guanosine-5'-Diphosphate
DB04444 Tetrafluoroaluminate Ion

Polymorphism and mutation databases

BioMutaiGNAI1
DMDMi52000964

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00002036712 – 354Guanine nucleotide-binding protein G(i) subunit alpha-1Add BLAST353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine2 Publications1
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

Myristoylation at Gly-2 is required for membrane anchoring before palmitoylation.By similarity
Palmitoylation at Cys-3 varies with membrane lipid composition.By similarity
(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
ProteomicsDBi57475

PTM databases

iPTMnetiP63096
PhosphoSitePlusiP63096
SwissPalmiP63096

Expressioni

Gene expression databases

BgeeiENSG00000127955
CleanExiHS_GNAI1
ExpressionAtlasiP63096 baseline and differential
GenevisibleiP63096 HS

Organism-specific databases

HPAiCAB022449
HPA042141

Interactioni

Subunit structurei

Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (PubMed:26766442). 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 similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109032, 78 interactors
CORUMiP63096
ELMiP63096
IntActiP63096, 34 interactors
MINTiP63096
STRINGi9606.ENSP00000343027

Chemistry databases

BindingDBiP63096

Structurei

Secondary structure

1354
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 16Combined sources8
Helixi20 – 23Combined sources4
Helixi27 – 29Combined sources3
Beta strandi31 – 41Combined sources11
Helixi46 – 57Combined sources12
Helixi63 – 67Combined sources5
Helixi70 – 91Combined sources22
Helixi100 – 113Combined sources14
Beta strandi115 – 117Combined sources3
Helixi121 – 132Combined sources12
Helixi134 – 140Combined sources7
Helixi141 – 145Combined sources5
Helixi152 – 157Combined sources6
Helixi159 – 162Combined sources4
Beta strandi164 – 166Combined sources3
Helixi171 – 175Combined sources5
Beta strandi183 – 191Combined sources9
Beta strandi194 – 201Combined sources8
Helixi208 – 215Combined sources8
Beta strandi220 – 226Combined sources7
Helixi227 – 229Combined sources3
Beta strandi238 – 241Combined sources4
Helixi242 – 254Combined sources13
Helixi257 – 259Combined sources3
Beta strandi260 – 269Combined sources10
Helixi271 – 277Combined sources7
Turni278 – 280Combined sources3
Helixi283 – 285Combined sources3
Helixi296 – 308Combined sources13
Turni314 – 316Combined sources3
Beta strandi319 – 323Combined sources5
Helixi329 – 346Combined sources18
Helixi348 – 350Combined sources3

3D structure databases

ProteinModelPortaliP63096
SMRiP63096
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
OMAiRIAQTSY
OrthoDBiEOG091G0VUT
PhylomeDBiP63096
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

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)DescriptionActionsGraphical viewLength
Sequence conflicti138A → G in CAB43212 (PubMed:11230166).Curated1
Sequence conflicti219T → A in AAH26326 (PubMed:15489334).Curated1
Sequence conflicti244H → Y in AAV38580 (Ref. 4) Curated1
Sequence conflicti249L → M in AAV38580 (Ref. 4) Curated1
Sequence conflicti288P → Q in AAH26326 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0452151 – 52Missing in isoform 2. 1 PublicationAdd BLAST52

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

Similar proteinsi

Entry informationi

Entry nameiGNAI1_HUMAN
AccessioniPrimary (citable) accession number: P63096
Secondary accession number(s): A8KA88
, B4E2V1, C9J3A4, P04898, P11015, P31871, Q5U074, Q8TAN5, Q9UGA4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 159 of the entry and version 2 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, 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

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