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   10-FEB-2021, entry version 177.
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   SMR; Q9HAV0; -.
DR   BioGRID; 121887; 86.
DR   CORUM; Q9HAV0; -.
DR   IntAct; Q9HAV0; 48.
DR   STRING; 9606.ENSP00000232564; -.
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; 159 antibodies.
DR   DNASU; 59345; -.
DR   Ensembl; ENST00000232564; ENSP00000232564; ENSG00000114450.
DR   Ensembl; ENST00000674862; ENSP00000502628; ENSG00000114450.
DR   Ensembl; ENST00000676128; ENSP00000501882; ENSG00000114450.
DR   GeneID; 59345; -.
DR   KEGG; hsa:59345; -.
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:ENSG00000114450.9; -.
DR   eggNOG; KOG0286; Eukaryota.
DR   GeneTree; ENSGT01000000214605; -.
DR   HOGENOM; CLU_000288_57_34_1; -.
DR   InParanoid; Q9HAV0; -.
DR   OMA; AQWDIET; -.
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-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; 4 hits in 874 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 223 other tissues.
DR   ExpressionAtlas; Q9HAV0; baseline and differential.
DR   Genevisible; Q9HAV0; HS.
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:0031682; F:G-protein gamma-subunit binding; IBA:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:MGI.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0006457; P:protein folding; TAS:Reactome.
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; IPR017986; WD40_repeat_dom.
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
//