{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P63096","secondaryAccessions":["A8KA88","B4E2V1","C9J3A4","P04898","P11015","P31871","Q5U074","Q8TAN5","Q9UGA4"],"uniProtkbId":"GNAI1_HUMAN","entryAudit":{"firstPublicDate":"1987-08-13","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"2007-01-23","entryVersion":204,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Guanine nucleotide-binding protein G(i) subunit alpha-1"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33762731"}],"value":"3.6.5.-"}]},"alternativeNames":[{"fullName":{"value":"Adenylate cyclase-inhibiting G alpha protein"}}]},"genes":[{"geneName":{"value":"GNAI1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P10824"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17635935"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18434541"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22327364"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33762731"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34239069"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35610220"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37935376"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37935377"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37963465"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38552625"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38918398"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40080544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8119955"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8774883"}],"value":"Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades (PubMed:18434541, PubMed:33762731, PubMed:34239069, PubMed:35610220, PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:38552625, PubMed:8774883, PubMed:38918398, PubMed:40080544). The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state (PubMed:18434541, PubMed:8774883). Signaling by an activated GPCR promotes GDP release and GTP binding (PubMed:18434541, PubMed:8774883). The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (PubMed:18434541, PubMed:8774883). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase: inhibits adenylate cyclase activity of ADCY1, ADCY5 and ADCY6, leading to decreased intracellular cAMP levels (PubMed:8119955). 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)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"GTP + H2O = GDP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:19669"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:37565"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:58189"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33762731"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:19670"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33762731"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P10824"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11976690"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16004878"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17264214"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18434541"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19211784"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21115486"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22383884"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22952234"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26126266"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26766442"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32126208"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32193322"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33762731"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34239069"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35217703"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35610220"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36064945"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37935376"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37935377"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37963465"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38552625"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38600377"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38776963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38918398"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"40080544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8774883"}],"value":"Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma (PubMed:33762731, PubMed:34239069, PubMed:35610220, PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:38552625). 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). Component of the TAS2R14-GNAI1 complex, consisting of TAS2R14, GNAI1, GNB1 and GNG2; within the complex interacts with TAS2R14; this complex plays a role in the perception of bitterness (PubMed:38600377, PubMed:38776963). 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:18434541, PubMed:8774883). 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); promoting GNAI1 folding and association with the plasma membrane (PubMed:32126208). Interacts (inactive GDP-bound form) with NUCB1 (via GBA motif); the interaction leads to activation of GNAI1 (By similarity). Interacts (inactive GDP-bound form) with CCDC88C/DAPLE (via GBA motif); the interaction leads to activation of GNAI1 (PubMed:26126266). Interacts (inactive GDP-bound form) with CCDC8A/GIV (via GBA motif) (PubMed:19211784). Interacts with GPR15 (PubMed:38918398). Interacts with FPR2 (PubMed:40080544). Component of a complex composed of FPR1 or FPR2 receptor and G(i) protein subunits GNAI1, GNB1 and GNG2; this complex is involved in innate recognition of N-formyl-methionyl peptides derived from invading microbes and host mitochondria as pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). Interacts with GCGR (PubMed:32193322)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35061538"}],"value":"(Microbial infection) Interacts with human cytomegalovirus (HHV-5) US27; this interaction this interaction does not lead to the catalytic activation of Gi complex and probably interferes with the chemokine-Gi signaling"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35061538"}],"value":"(Microbial infection) Interacts with human cytomegalovirus (HHV-5) US28; this interaction does not lead to the catalytic activation of Gi complex and probably interferes with the chemokine-Gi signaling"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"P62873","geneName":"GNB1","intActId":"EBI-357130"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"P63211","geneName":"GNGT1","intActId":"EBI-10220715"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"P81274","geneName":"GPSM2","intActId":"EBI-618655"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"Q9Y4H4","geneName":"GPSM3","intActId":"EBI-347538"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"Q14980","geneName":"NUMA1","intActId":"EBI-521611"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"Q8IVA1","geneName":"PCP2","intActId":"EBI-12250122"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"O43566","geneName":"RGS14","intActId":"EBI-750603"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"Q9UGC6","geneName":"RGS17","intActId":"EBI-3918154"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P63096","intActId":"EBI-618639"},"interactantTwo":{"uniProtKBAccession":"Q9NPQ8","geneName":"RIC8A","intActId":"EBI-717509"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17635935"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20213681"}],"value":"Associated to the plasma membrane via lipid-anchor (PubMed:20213681). 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 (PubMed:17635935)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12135370"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17635935"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26766442"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"12135370"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"12135370"}],"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P10824"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17635935"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17635935"}],"value":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","id":"SL-0048"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22327364"}],"value":"Cytoplasm, cell cortex","id":"SL-0138"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P63096-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["P63096-2"],"sequenceIds":["VSP_045215"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P10824"}],"value":"Myristoylation at Gly-2 is required for membrane anchoring before palmitoylation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P10824"}],"value":"Palmitoylation at Cys-3 varies with membrane lipid composition"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24141704"}],"value":"(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"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities","diseaseAccession":"DI-06412","acronym":"NEDHISB","description":"An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, delayed or absent speech, hypotonia, behavioral abnormalities, and epilepsy that ranges from self-limiting to intractable. More variable features include non-specific dysmorphic facial features, distal skeletal anomalies, and brain imaging abnormalities.","diseaseCrossReference":{"database":"MIM","id":"619854"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33473207"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34685729"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34819662"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the G-alpha family. G(i/o/t/z) subfamily"}],"commentType":"SIMILARITY"}],"features":[{"type":"Initiator methionine","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"Removed","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20213681"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25255805"}]},{"type":"Chain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":354,"modifier":"EXACT"}},"description":"Guanine nucleotide-binding protein G(i) subunit alpha-1","featureId":"PRO_0000203671"},{"type":"Domain","location":{"start":{"value":32,"modifier":"EXACT"},"end":{"value":354,"modifier":"EXACT"}},"description":"G-alpha","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01230"}]},{"type":"Region","location":{"start":{"value":35,"modifier":"EXACT"},"end":{"value":48,"modifier":"EXACT"}},"description":"G1 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