GNB5_HUMAN
ID GNB5_HUMAN Reviewed; 395 AA.
AC O14775; B2RBR5; Q9HAU9; Q9UFT3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Guanine nucleotide-binding protein subunit beta-5;
DE AltName: Full=Gbeta5;
DE AltName: Full=Transducin beta chain 5;
GN Name=GNB5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=9606987; DOI=10.1016/s0167-4889(98)00017-2;
RA Jones P.G., Lombardi S.J., Cockett M.I.;
RT "Cloning and tissue distribution of the human G protein beta 5 cDNA.";
RL Biochim. Biophys. Acta 1402:288-291(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH RGS6 AND RGS7.
RX PubMed=10521509; DOI=10.1074/jbc.274.43.31087;
RA Posner B.A., Gilman A.G., Harris B.A.;
RT "Regulators of G protein signaling 6 and 7. Purification of complexes with
RT gbeta5 and assessment of their effects on g protein-mediated signaling
RT pathways.";
RL J. Biol. Chem. 274:31087-31093(1999).
RN [7]
RP INTERACTION WITH RGS6 AND RGS7.
RX PubMed=10339615; DOI=10.1073/pnas.96.11.6489;
RA Snow B.E., Betts L., Mangion J., Sondek J., Siderovski D.P.;
RT "Fidelity of G protein beta-subunit association by the G protein gamma-
RT subunit-like domains of RGS6, RGS7, and RGS11.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6489-6494(1999).
RN [8]
RP INVOLVEMENT IN IDDCA, INVOLVEMENT IN LADCI, AND VARIANT LADCI LEU-123.
RX PubMed=27523599; DOI=10.1016/j.ajhg.2016.06.025;
RA Lodder E.M., De Nittis P., Koopman C.D., Wiszniewski W.,
RA Moura de Souza C.F., Lahrouchi N., Guex N., Napolioni V., Tessadori F.,
RA Beekman L., Nannenberg E.A., Boualla L., Blom N.A., de Graaff W.,
RA Kamermans M., Cocciadiferro D., Malerba N., Mandriani B., Akdemir Z.H.,
RA Fish R.J., Eldomery M.K., Ratbi I., Wilde A.A., de Boer T., Simonds W.F.,
RA Neerman-Arbez M., Sutton V.R., Kok F., Lupski J.R., Reymond A.,
RA Bezzina C.R., Bakkers J., Merla G.;
RT "GNB5 mutations cause an autosomal-recessive multisystem syndrome with
RT sinus bradycardia and cognitive disability.";
RL Am. J. Hum. Genet. 99:704-710(2016).
RN [9]
RP INVOLVEMENT IN LADCI, VARIANT LADCI LEU-123, FUNCTION, AND CHARACTERIZATION
RP OF VARIANT LADCI LEU-123.
RX PubMed=27677260; DOI=10.1186/s13059-016-1061-6;
RA Shamseldin H.E., Masuho I., Alenizi A., Alyamani S., Patil D.N.,
RA Ibrahim N., Martemyanov K.A., Alkuraya F.S.;
RT "GNB5 mutation causes a novel neuropsychiatric disorder featuring attention
RT deficit hyperactivity disorder, severely impaired language development and
RT normal cognition.";
RL Genome Biol. 17:R195.1-R195.9(2016).
CC -!- FUNCTION: Enhances GTPase-activating protein (GAP) activity of
CC regulator of G protein signaling (RGS) proteins, hence involved in the
CC termination of the signaling initiated by the G protein coupled
CC receptors (GPCRs) by accelerating the GTP hydrolysis on the G-alpha
CC subunits, thereby promoting their inactivation (Probable). Increases
CC RGS9 GTPase-activating protein (GAP) activity, hence contributes to the
CC deactivation of G protein signaling initiated by D(2) dopamine
CC receptors (PubMed:27677260). May play an important role in neuronal
CC signaling, including in the parasympathetic, but not sympathetic,
CC control of heart rate (By similarity). {ECO:0000250|UniProtKB:A1L271,
CC ECO:0000269|PubMed:27677260, ECO:0000305}.
CC -!- SUBUNIT: Component of a complex composed of RGS9 (isoform RGS9-1), GNB5
CC and RGS9BP; within this complex, the presence of GNB5 stabilizes both
CC itself and RGS9 and increases RGS9 GTPase-activating protein (GAP)
CC activity (By similarity) (PubMed:27677260). Interacts with RGS6 and
CC RGS7 (PubMed:10339615, PubMed:10521509). {ECO:0000250|UniProtKB:P62881,
CC ECO:0000269|PubMed:10339615, ECO:0000269|PubMed:10521509,
CC ECO:0000269|PubMed:27677260}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P62881}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long, Beta-5L;
CC IsoId=O14775-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14775-2; Sequence=VSP_008765;
CC Name=3;
CC IsoId=O14775-3; Sequence=VSP_008765, VSP_039101;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9606987}.
CC -!- DISEASE: Intellectual developmental disorder with cardiac arrhythmia
CC (IDDCA) [MIM:617173]: An autosomal recessive multisystem disorder
CC characterized by delayed psychomotor development, severe intellectual
CC disability with poor or absent speech, and bradycardia and/or cardiac
CC sinus arrhythmias. Additional features include visual abnormalities,
CC seizures, hypotonia, and gastric reflux. {ECO:0000269|PubMed:27523599}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Language delay and attention deficit-hyperactivity
CC disorder/cognitive impairment with or without cardiac arrhythmia
CC (LADCI) [MIM:617182]: An autosomal recessive neurodevelopmental
CC disorder characterized by speech impairment and variable expressivity
CC of attention deficit hyperactivity disorder. Some patients manifest
CC developmental and motor delay, hypotonia, and sinus-node dysfunction.
CC {ECO:0000269|PubMed:27523599, ECO:0000269|PubMed:27677260}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the WD repeat G protein beta family.
CC {ECO:0000305}.
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DR EMBL; AF017656; AAC63826.1; -; mRNA.
DR EMBL; AL117471; CAB55946.1; -; mRNA.
DR EMBL; AF501885; AAM15921.1; -; mRNA.
DR EMBL; AF300650; AAG18444.1; -; mRNA.
DR EMBL; AK314775; BAG37312.1; -; mRNA.
DR EMBL; BC013997; AAH13997.1; -; mRNA.
DR CCDS; CCDS10149.1; -. [O14775-1]
DR CCDS; CCDS45261.1; -. [O14775-2]
DR PIR; T17256; T17256.
DR RefSeq; NP_006569.1; NM_006578.3. [O14775-2]
DR RefSeq; NP_057278.2; NM_016194.3. [O14775-1]
DR PDB; 7EWP; EM; 4.30 A; D=1-395.
DR PDB; 7EWR; EM; 4.70 A; D/F=1-395.
DR PDBsum; 7EWP; -.
DR PDBsum; 7EWR; -.
DR AlphaFoldDB; O14775; -.
DR SMR; O14775; -.
DR BioGRID; 115920; 44.
DR CORUM; O14775; -.
DR IntAct; O14775; 36.
DR MINT; O14775; -.
DR STRING; 9606.ENSP00000261837; -.
DR iPTMnet; O14775; -.
DR PhosphoSitePlus; O14775; -.
DR BioMuta; GNB5; -.
DR EPD; O14775; -.
DR jPOST; O14775; -.
DR MassIVE; O14775; -.
DR MaxQB; O14775; -.
DR PaxDb; O14775; -.
DR PeptideAtlas; O14775; -.
DR PRIDE; O14775; -.
DR ProteomicsDB; 48226; -. [O14775-1]
DR ProteomicsDB; 48227; -. [O14775-2]
DR ProteomicsDB; 48228; -. [O14775-3]
DR Antibodypedia; 24930; 309 antibodies from 32 providers.
DR DNASU; 10681; -.
DR Ensembl; ENST00000261837.12; ENSP00000261837.7; ENSG00000069966.19. [O14775-1]
DR Ensembl; ENST00000358784.11; ENSP00000351635.7; ENSG00000069966.19. [O14775-2]
DR Ensembl; ENST00000396335.8; ENSP00000379626.4; ENSG00000069966.19. [O14775-3]
DR GeneID; 10681; -.
DR KEGG; hsa:10681; -.
DR MANE-Select; ENST00000261837.12; ENSP00000261837.7; NM_016194.4; NP_057278.2.
DR UCSC; uc002abr.2; human. [O14775-1]
DR CTD; 10681; -.
DR DisGeNET; 10681; -.
DR GeneCards; GNB5; -.
DR GeneReviews; GNB5; -.
DR HGNC; HGNC:4401; GNB5.
DR HPA; ENSG00000069966; Tissue enhanced (retina).
DR MalaCards; GNB5; -.
DR MIM; 604447; gene.
DR MIM; 617173; phenotype.
DR MIM; 617182; phenotype.
DR neXtProt; NX_O14775; -.
DR OpenTargets; ENSG00000069966; -.
DR Orphanet; 542306; GNB5-related intellectual disability-cardiac arrhythmia syndrome.
DR PharmGKB; PA28780; -.
DR VEuPathDB; HostDB:ENSG00000069966; -.
DR eggNOG; KOG0286; Eukaryota.
DR GeneTree; ENSGT01000000214413; -.
DR HOGENOM; CLU_000288_57_34_1; -.
DR InParanoid; O14775; -.
DR OMA; WVMACSY; -.
DR PhylomeDB; O14775; -.
DR TreeFam; TF106149; -.
DR PathwayCommons; O14775; -.
DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-HSA-202040; G-protein activation.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade. [O14775-1]
DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-HSA-392170; ADP signalling through P2Y purinoceptor 12.
DR Reactome; R-HSA-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-HSA-392851; Prostacyclin signalling through prostacyclin receptor.
DR Reactome; R-HSA-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-418217; G beta:gamma signalling through PLC beta.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR Reactome; R-HSA-428930; Thromboxane signalling through TP receptor.
DR Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-HSA-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-HSA-500657; Presynaptic function of Kainate receptors.
DR Reactome; R-HSA-6814122; Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding.
DR Reactome; R-HSA-8964315; G beta:gamma signalling through BTK.
DR Reactome; R-HSA-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9634597; GPER1 signaling.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR Reactome; R-HSA-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR SignaLink; O14775; -.
DR SIGNOR; O14775; -.
DR BioGRID-ORCS; 10681; 7 hits in 1075 CRISPR screens.
DR ChiTaRS; GNB5; human.
DR GeneWiki; GNB5; -.
DR GenomeRNAi; 10681; -.
DR Pharos; O14775; Tbio.
DR PRO; PR:O14775; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; O14775; protein.
DR Bgee; ENSG00000069966; Expressed in middle temporal gyrus and 194 other tissues.
DR ExpressionAtlas; O14775; baseline and differential.
DR Genevisible; O14775; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:1902773; C:GTPase activator complex; TAS:UniProtKB.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0098793; C:presynapse; IEA:Ensembl.
DR GO; GO:0051087; F:chaperone binding; IPI:UniProtKB.
DR GO; GO:0031682; F:G-protein gamma-subunit binding; IPI:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; NAS:UniProtKB.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IBA:GO_Central.
DR GO; GO:1990603; P:dark adaptation; IEA:Ensembl.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0036367; P:light adaption; IEA:Ensembl.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR001632; Gprotein_B.
DR InterPro; IPR016346; Guanine_nucleotide-bd_bsu.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR19850; PTHR19850; 1.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00319; GPROTEINB.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 3.
DR PROSITE; PS50082; WD_REPEATS_2; 6.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant;
KW Intellectual disability; Membrane; Reference proteome; Repeat; Transducer;
KW WD repeat.
FT CHAIN 1..395
FT /note="Guanine nucleotide-binding protein subunit beta-5"
FT /id="PRO_0000127705"
FT REPEAT 103..142
FT /note="WD 1"
FT REPEAT 145..184
FT /note="WD 2"
FT REPEAT 193..234
FT /note="WD 3"
FT REPEAT 236..278
FT /note="WD 4"
FT REPEAT 279..318
FT /note="WD 5"
FT REPEAT 320..362
FT /note="WD 6"
FT REPEAT 365..394
FT /note="WD 7"
FT VAR_SEQ 1..42
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9606987, ECO:0000303|Ref.3"
FT /id="VSP_008765"
FT VAR_SEQ 140..209
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11230166"
FT /id="VSP_039101"
FT VARIANT 123
FT /note="S -> L (in LADCI; severe, but incomplete loss of
FT activation of RGS9 GTPase activator activity, affecting the
FT deactivation of D(2) dopamine receptor-mediated signaling;
FT decreased stability; decreased RGS9 stabilization;
FT dbSNP:rs761399728)"
FT /evidence="ECO:0000269|PubMed:27523599,
FT ECO:0000269|PubMed:27677260"
FT /id="VAR_077994"
FT VARIANT 213
FT /note="A -> V (in dbSNP:rs34637551)"
FT /id="VAR_049270"
FT CONFLICT 223
FT /note="D -> G (in Ref. 4; BAG37312)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 395 AA; 43566 MW; E001B07FCFA587AD CRC64;
MCDQTFLVNV FGSCDKCFKQ RALRPVFKKS QQLSYCSTCA EIMATEGLHE NETLASLKSE
AESLKGKLEE ERAKLHDVEL HQVAERVEAL GQFVMKTRRT LKGHGNKVLC MDWCKDKRRI
VSSSQDGKVI VWDSFTTNKE HAVTMPCTWV MACAYAPSGC AIACGGLDNK CSVYPLTFDK
NENMAAKKKS VAMHTNYLSA CSFTNSDMQI LTASGDGTCA LWDVESGQLL QSFHGHGADV
LCLDLAPSET GNTFVSGGCD KKAMVWDMRS GQCVQAFETH ESDINSVRYY PSGDAFASGS
DDATCRLYDL RADREVAIYS KESIIFGASS VDFSLSGRLL FAGYNDYTIN VWDVLKGSRV
SILFGHENRV STLRVSPDGT AFCSGSWDHT LRVWA
