GBB4_HUMAN
ID GBB4_HUMAN Reviewed; 340 AA.
AC Q9HAV0; B3KMH5; D3DNR8;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Guanine nucleotide-binding protein subunit beta-4;
DE AltName: Full=Transducin beta chain 4;
GN Name=GNB4;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11842130; DOI=10.1152/physiolgenomics.00085.2001;
RA Ruiz-Velasco V., Ikeda S.R., Puhl H.L. III;
RT "Cloning, tissue distribution, and functional expression of the human G
RT protein beta 4-subunit.";
RL Physiol. Genomics 8:41-50(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix;
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 [5]
RP PROTEIN SEQUENCE OF 2-15 AND 58-78, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RA Bienvenut W.V., Quadroni M.;
RL Submitted (JUL-2005) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP TISSUE SPECIFICITY, VARIANTS CMTDIF ASP-53 AND GLU-89, AND CHARACTERIZATION
RP OF VARIANTS CMTDIF ASP-53 AND GLU-89.
RX PubMed=23434117; DOI=10.1016/j.ajhg.2013.01.014;
RA Soong B.W., Huang Y.H., Tsai P.C., Huang C.C., Pan H.C., Lu Y.C.,
RA Chien H.J., Liu T.T., Chang M.H., Lin K.P., Tu P.H., Kao L.S., Lee Y.C.;
RT "Exome sequencing identifies GNB4 mutations as a cause of dominant
RT intermediate Charcot-Marie-Tooth disease.";
RL Am. J. Hum. Genet. 92:422-430(2013).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved
CC as a modulator or transducer in various transmembrane signaling
CC systems. The beta and gamma chains are required for the GTPase
CC activity, for replacement of GDP by GTP, and for G protein-effector
CC interaction.
CC -!- SUBUNIT: G proteins are composed of 3 units, alpha, beta and gamma.
CC -!- INTERACTION:
CC Q9HAV0; P55212: CASP6; NbExp=3; IntAct=EBI-358539, EBI-718729;
CC Q9HAV0; P13473-2: LAMP2; NbExp=3; IntAct=EBI-358539, EBI-21591415;
CC Q9HAV0; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-358539, EBI-2623095;
CC -!- TISSUE SPECIFICITY: Strongly expressed in lung and placenta, whereas it
CC is weakly expressed in brain and heart. Abundantly expressed in the
CC axons and Schwann cells of peripheral nerves.
CC {ECO:0000269|PubMed:11842130, ECO:0000269|PubMed:23434117}.
CC -!- DISEASE: Charcot-Marie-Tooth disease, dominant, intermediate type, F
CC (CMTDIF) [MIM:615185]: A form of Charcot-Marie-Tooth disease, a
CC disorder of the peripheral nervous system, characterized by progressive
CC weakness and atrophy, initially of the peroneal muscles and later of
CC the distal muscles of the arms. CMTDIF is characterized by onset around
CC adolescence of slowly progressive distal muscle atrophy and weakness
CC affecting the upper and lower limbs and resulting in steppage gait.
CC There is distal sensory impairment with decreased reflexes. Nerve
CC conduction velocities are variable, ranging from the demyelinating to
CC the axonal range. {ECO:0000269|PubMed:23434117}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the WD repeat G protein beta family.
CC {ECO:0000305}.
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DR EMBL; AF300648; AAG18442.1; -; mRNA.
DR EMBL; AK001890; BAG50987.1; -; mRNA.
DR EMBL; CH471052; EAW78403.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78404.1; -; Genomic_DNA.
DR EMBL; BC000873; AAH00873.1; -; mRNA.
DR CCDS; CCDS3230.1; -.
DR RefSeq; NP_067642.1; NM_021629.3.
DR RefSeq; XP_005247749.1; XM_005247692.2.
DR RefSeq; XP_006713784.1; XM_006713721.2.
DR AlphaFoldDB; Q9HAV0; -.
DR SMR; Q9HAV0; -.
DR BioGRID; 121887; 113.
DR CORUM; Q9HAV0; -.
DR IntAct; Q9HAV0; 52.
DR MINT; Q9HAV0; -.
DR STRING; 9606.ENSP00000232564; -.
DR GlyGen; Q9HAV0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9HAV0; -.
DR PhosphoSitePlus; Q9HAV0; -.
DR SwissPalm; Q9HAV0; -.
DR BioMuta; GNB4; -.
DR DMDM; 22256759; -.
DR OGP; Q9HAV0; -.
DR EPD; Q9HAV0; -.
DR jPOST; Q9HAV0; -.
DR MassIVE; Q9HAV0; -.
DR MaxQB; Q9HAV0; -.
DR PaxDb; Q9HAV0; -.
DR PeptideAtlas; Q9HAV0; -.
DR PRIDE; Q9HAV0; -.
DR ProteomicsDB; 81444; -.
DR Antibodypedia; 18788; 171 antibodies from 25 providers.
DR DNASU; 59345; -.
DR Ensembl; ENST00000232564.8; ENSP00000232564.3; ENSG00000114450.11.
DR Ensembl; ENST00000674862.1; ENSP00000502628.1; ENSG00000114450.11.
DR Ensembl; ENST00000676128.1; ENSP00000501882.1; ENSG00000114450.11.
DR GeneID; 59345; -.
DR KEGG; hsa:59345; -.
DR MANE-Select; ENST00000232564.8; ENSP00000232564.3; NM_021629.4; NP_067642.1.
DR UCSC; uc003fjv.5; human.
DR CTD; 59345; -.
DR DisGeNET; 59345; -.
DR GeneCards; GNB4; -.
DR GeneReviews; GNB4; -.
DR HGNC; HGNC:20731; GNB4.
DR HPA; ENSG00000114450; Low tissue specificity.
DR MalaCards; GNB4; -.
DR MIM; 610863; gene.
DR MIM; 615185; phenotype.
DR neXtProt; NX_Q9HAV0; -.
DR OpenTargets; ENSG00000114450; -.
DR Orphanet; 352670; Autosomal dominant intermediate Charcot-Marie-Tooth disease type F.
DR PharmGKB; PA134864200; -.
DR VEuPathDB; HostDB:ENSG00000114450; -.
DR eggNOG; KOG0286; Eukaryota.
DR GeneTree; ENSGT01000000214413; -.
DR HOGENOM; CLU_000288_57_34_1; -.
DR InParanoid; Q9HAV0; -.
DR OMA; GDTNCAL; -.
DR OrthoDB; 704786at2759; -.
DR PhylomeDB; Q9HAV0; -.
DR TreeFam; TF106149; -.
DR PathwayCommons; Q9HAV0; -.
DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-HSA-163359; Glucagon signaling in metabolic regulation.
DR Reactome; R-HSA-202040; G-protein activation.
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; Q9HAV0; -.
DR BioGRID-ORCS; 59345; 9 hits in 1078 CRISPR screens.
DR ChiTaRS; GNB4; human.
DR GeneWiki; GNB4; -.
DR GenomeRNAi; 59345; -.
DR Pharos; Q9HAV0; Tbio.
DR PRO; PR:Q9HAV0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9HAV0; protein.
DR Bgee; ENSG00000114450; Expressed in upper arm skin and 194 other tissues.
DR ExpressionAtlas; Q9HAV0; baseline and differential.
DR Genevisible; Q9HAV0; HS.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0021762; P:substantia nigra development; HEP: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; 7.
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 Acetylation; Charcot-Marie-Tooth disease; Direct protein sequencing;
KW Disease variant; Neurodegeneration; Neuropathy; Phosphoprotein;
KW Reference proteome; Repeat; Transducer; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.5"
FT CHAIN 2..340
FT /note="Guanine nucleotide-binding protein subunit beta-4"
FT /id="PRO_0000127702"
FT REPEAT 53..92
FT /note="WD 1"
FT REPEAT 95..134
FT /note="WD 2"
FT REPEAT 141..179
FT /note="WD 3"
FT REPEAT 182..221
FT /note="WD 4"
FT REPEAT 224..263
FT /note="WD 5"
FT REPEAT 268..307
FT /note="WD 6"
FT REPEAT 310..339
FT /note="WD 7"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.5"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62873"
FT MOD_RES 266
FT /note="Phosphohistidine"
FT /evidence="ECO:0000250|UniProtKB:P62871"
FT VARIANT 53
FT /note="G -> D (in CMTDIF; the mutant protein has impaired
FT bradykinin-induced G-protein-coupled receptor intracellular
FT signaling compared to the wild-type protein;
FT dbSNP:rs387907340)"
FT /evidence="ECO:0000269|PubMed:23434117"
FT /id="VAR_069908"
FT VARIANT 89
FT /note="K -> E (in CMTDIF; the mutant protein has impaired
FT bradykinin-induced G-protein-coupled receptor intracellular
FT signaling compared to the wild-type protein;
FT dbSNP:rs387907341)"
FT /evidence="ECO:0000269|PubMed:23434117"
FT /id="VAR_069909"
SQ SEQUENCE 340 AA; 37567 MW; EDF085155A1EDC89 CRC64;
MSELEQLRQE AEQLRNQIQD ARKACNDATL VQITSNMDSV GRIQMRTRRT LRGHLAKIYA
MHWGYDSRLL VSASQDGKLI IWDSYTTNKM HAIPLRSSWV MTCAYAPSGN YVACGGLDNI
CSIYNLKTRE GNVRVSRELP GHTGYLSCCR FLDDSQIVTS SGDTTCALWD IETAQQTTTF
TGHSGDVMSL SLSPDMRTFV SGACDASSKL WDIRDGMCRQ SFTGHVSDIN AVSFFPNGYA
FATGSDDATC RLFDLRADQE LLLYSHDNII CGITSVAFSK SGRLLLAGYD DFNCNVWDTL
KGDRAGVLAG HDNRVSCLGV TDDGMAVATG SWDSFLRIWN
