GNB5A_DANRE
ID GNB5A_DANRE Reviewed; 355 AA.
AC A1L271;
DT 10-MAY-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Guanine nucleotide-binding protein subunit beta-5a;
GN Name=gnb5a {ECO:0000312|ZFIN:ZDB-GENE-070112-342}; ORFNames=zgc:158678;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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).
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 (By similarity). Along with gnb5b, plays an important role in
CC neuronal signaling, including in the parasympathetic, but not
CC sympathetic, control of heart rate (PubMed:27523599).
CC {ECO:0000250|UniProtKB:O14775, ECO:0000269|PubMed:27523599,
CC ECO:0000305}.
CC -!- SUBUNIT: May interact with RGS9; this interaction stabilizes both
CC proteins and increases RGS9 GTPase-activating protein (GAP) activity,
CC hence accelerating the deactivation of D(2) dopamine receptor-mediated
CC signaling. {ECO:0000250|UniProtKB:O14775}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P62881}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype; due to the redundancy with
CC gnb5b. Simultaneous knockout of gnb5a and gnb5b results in no striking
CC dysmorphologic features, but the larvae show impaired swimming
CC activity, remain small, and generally die 7-14 days post fertilization
CC (dpf), most likely as a result of their inability to feed.
CC {ECO:0000269|PubMed:27523599}.
CC -!- SIMILARITY: Belongs to the WD repeat G protein beta family.
CC {ECO:0000305}.
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DR EMBL; AL954697; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC129375; AAI29376.1; -; mRNA.
DR RefSeq; NP_001073650.1; NM_001080181.1.
DR AlphaFoldDB; A1L271; -.
DR SMR; A1L271; -.
DR STRING; 7955.ENSDARP00000011435; -.
DR PaxDb; A1L271; -.
DR PeptideAtlas; A1L271; -.
DR Ensembl; ENSDART00000168016; ENSDARP00000140306; ENSDARG00000099685.
DR GeneID; 562813; -.
DR KEGG; dre:562813; -.
DR CTD; 562813; -.
DR ZFIN; ZDB-GENE-070112-342; gnb5a.
DR eggNOG; KOG0286; Eukaryota.
DR GeneTree; ENSGT01000000214413; -.
DR HOGENOM; CLU_000288_57_34_1; -.
DR InParanoid; A1L271; -.
DR OMA; CVELMAT; -.
DR OrthoDB; 704786at2759; -.
DR PhylomeDB; A1L271; -.
DR TreeFam; TF106149; -.
DR Reactome; R-DRE-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-DRE-202040; G-protein activation.
DR Reactome; R-DRE-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR Reactome; R-DRE-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-DRE-392170; ADP signalling through P2Y purinoceptor 12.
DR Reactome; R-DRE-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-DRE-392851; Prostacyclin signalling through prostacyclin receptor.
DR Reactome; R-DRE-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-DRE-4086398; Ca2+ pathway.
DR Reactome; R-DRE-416476; G alpha (q) signalling events.
DR Reactome; R-DRE-416482; G alpha (12/13) signalling events.
DR Reactome; R-DRE-418217; G beta:gamma signalling through PLC beta.
DR Reactome; R-DRE-418555; G alpha (s) signalling events.
DR Reactome; R-DRE-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-DRE-418594; G alpha (i) signalling events.
DR Reactome; R-DRE-418597; G alpha (z) signalling events.
DR Reactome; R-DRE-420092; Glucagon-type ligand receptors.
DR Reactome; R-DRE-428930; Thromboxane signalling through TP receptor.
DR Reactome; R-DRE-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-DRE-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-DRE-500657; Presynaptic function of Kainate receptors.
DR Reactome; R-DRE-6814122; Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding.
DR Reactome; R-DRE-8964315; G beta:gamma signalling through BTK.
DR Reactome; R-DRE-8964616; G beta:gamma signalling through CDC42.
DR Reactome; R-DRE-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-DRE-9634597; GPER1 signaling.
DR Reactome; R-DRE-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR PRO; PR:A1L271; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 25.
DR Bgee; ENSDARG00000099685; Expressed in brain and 9 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IBA:GO_Central.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0060047; P:heart contraction; IGI:ZFIN.
DR GO; GO:0007634; P:optokinetic behavior; IGI:ZFIN.
DR GO; GO:0036269; P:swimming behavior; IGI:ZFIN.
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; 4.
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 2: Evidence at transcript level;
KW Membrane; Reference proteome; Repeat; Transducer; WD repeat.
FT CHAIN 1..355
FT /note="Guanine nucleotide-binding protein subunit beta-5a"
FT /id="PRO_0000439759"
FT REPEAT 63..102
FT /note="WD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 105..144
FT /note="WD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 153..194
FT /note="WD 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 195..238
FT /note="WD 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 239..278
FT /note="WD 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 280..322
FT /note="WD 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 325..355
FT /note="WD 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 355 AA; 38831 MW; E8F6D9BC9912D8C1 CRC64;
MAAQEEPAQP GDSLATLKSE SDTLKSKLEE ERAKLHDVEL HQVAEKIEAL GQFVMKTRRT
LKGHGNKVLC MDWCKDKRRI VSSSQDGKVI VWDAFTTNKE HAVTMPCTWV MACAYAPSGC
AVACGGLDNK CSVYPLSLDK NENLAAKKKS VAMHTNYLSA CCFTNSDMQI LTSSGDGTCA
LWDVESGQML QSFHGHAADV LCLDLAPSET GNTFVSGGCD KKACVWDMRT GQCVQSFESH
DSDINSVRYY PSGDAFASGS DDATCRLYDL RADREVAIYS KESIIFGASS VDFSLSGRLL
FGGYNDYTIN VWDVLKGARV SILFGHENRV STLRVSPDGT AFCSGSWDHT LRIWA
