GPHB5_HUMAN
ID GPHB5_HUMAN Reviewed; 130 AA.
AC Q86YW7; Q6NTD0; Q8NFW2;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Glycoprotein hormone beta-5;
DE AltName: Full=Thyrostimulin subunit beta;
DE Flags: Precursor;
GN Name=GPHB5; Synonyms=GPB5, ZLUT1;
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], FUNCTION, SUBUNIT, INTERACTION WITH TSHR, AND
RP GLYCOSYLATION.
RX PubMed=12045258; DOI=10.1172/jci14340;
RA Nakabayashi K., Matsumi H., Bhalla A., Bae J., Mosselman S., Hsu S.Y.,
RA Hsueh A.J.W.;
RT "Thyrostimulin, a heterodimer of two new human glycoprotein hormone
RT subunits, activates the thyroid-stimulating hormone receptor.";
RL J. Clin. Invest. 109:1445-1452(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Holloway J.L., O'Hogan S.L., Tackett M., Taft D., Thayer E.C., Webster P.;
RT "A novel glycoprotein hormone beta subunit.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 TISSUE SPECIFICITY.
RX PubMed=12089349; DOI=10.1210/mend.16.7.0871;
RA Hsu S.Y., Nakabayashi K., Bhalla A.;
RT "Evolution of glycoprotein hormone subunit genes in bilateral metazoa:
RT identification of two novel human glycoprotein hormone subunit family
RT genes, GPA2 and GPB5.";
RL Mol. Endocrinol. 16:1538-1551(2002).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16210345; DOI=10.1210/me.2005-0270;
RA Okada S.L., Ellsworth J.L., Durnam D.M., Haugen H.S., Holloway J.L.,
RA Kelley M.L., Lewis K.E., Ren H., Sheppard P.O., Storey H.M., Waggie K.S.,
RA Wolf A.C., Yao L.Y., Webster P.J.;
RT "A glycoprotein hormone expressed in corticotrophs exhibits unique binding
RT properties on thyroid-stimulating hormone receptor.";
RL Mol. Endocrinol. 20:414-425(2006).
CC -!- FUNCTION: Functions as a heterodimeric glycoprotein hormone with GPHA2
CC able to bind and activate the thyroid-stimulating hormone receptor
CC (TSHR), leading to increased cAMP production. Plays a central role in
CC controlling thyroid cell metabolism. {ECO:0000269|PubMed:12045258,
CC ECO:0000269|PubMed:16210345}.
CC -!- SUBUNIT: Heterodimer with GPHA2; this heterodimer interacts with
CC thyroid-stimulating hormone receptor (TSHR), and hence stimulates cAMP
CC production. {ECO:0000269|PubMed:12045258}.
CC -!- INTERACTION:
CC Q86YW7; P60508: ERVFRD-1; NbExp=3; IntAct=EBI-11659720, EBI-17973325;
CC Q86YW7; A8MTA8-2: FAM166B; NbExp=3; IntAct=EBI-11659720, EBI-12160437;
CC Q86YW7; Q96T91: GPHA2; NbExp=3; IntAct=EBI-11659720, EBI-11659696;
CC Q86YW7; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-11659720, EBI-10171774;
CC Q86YW7; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-11659720, EBI-17280858;
CC Q86YW7; Q8N6K0: TEX29; NbExp=3; IntAct=EBI-11659720, EBI-19027521;
CC Q86YW7; P55061: TMBIM6; NbExp=3; IntAct=EBI-11659720, EBI-1045825;
CC Q86YW7; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-11659720, EBI-11724423;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and at low levels in
CC pituitary. Also found in retina, testis and skin but not in pancreas,
CC parotid, kidney, stomach, liver, colon, small intestine, thyroid, brain
CC or adrenal gland. In pituitary, colocalizes with ACTH, suggesting that
CC it is located in corticotrophs. {ECO:0000269|PubMed:12089349,
CC ECO:0000269|PubMed:16210345}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12045258}.
CC -!- SIMILARITY: Belongs to the glycoprotein hormones subunit beta family.
CC {ECO:0000305}.
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DR EMBL; AF403430; AAM53261.1; -; mRNA.
DR EMBL; AF467770; AAO33390.1; -; mRNA.
DR EMBL; AL118555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069113; AAH69113.1; -; mRNA.
DR CCDS; CCDS73643.1; -.
DR RefSeq; NP_660154.3; NM_145171.3.
DR AlphaFoldDB; Q86YW7; -.
DR SMR; Q86YW7; -.
DR BioGRID; 125802; 6.
DR IntAct; Q86YW7; 9.
DR STRING; 9606.ENSP00000478993; -.
DR GlyGen; Q86YW7; 1 site.
DR BioMuta; GPHB5; -.
DR DMDM; 48474403; -.
DR PRIDE; Q86YW7; -.
DR Antibodypedia; 73167; 63 antibodies from 12 providers.
DR DNASU; 122876; -.
DR Ensembl; ENST00000314140.2; ENSP00000479431.1; ENSG00000179600.4.
DR Ensembl; ENST00000621500.2; ENSP00000478993.1; ENSG00000179600.4.
DR GeneID; 122876; -.
DR KEGG; hsa:122876; -.
DR MANE-Select; ENST00000621500.2; ENSP00000478993.1; NM_145171.4; NP_660154.3.
DR UCSC; uc032bdx.1; human.
DR CTD; 122876; -.
DR DisGeNET; 122876; -.
DR GeneCards; GPHB5; -.
DR HGNC; HGNC:18055; GPHB5.
DR HPA; ENSG00000179600; Not detected.
DR MIM; 609652; gene.
DR neXtProt; NX_Q86YW7; -.
DR OpenTargets; ENSG00000179600; -.
DR PharmGKB; PA134872371; -.
DR VEuPathDB; HostDB:ENSG00000179600; -.
DR eggNOG; ENOG502RZ3V; Eukaryota.
DR GeneTree; ENSGT00730000111179; -.
DR HOGENOM; CLU_126319_2_1_1; -.
DR InParanoid; Q86YW7; -.
DR OMA; MAVRCDC; -.
DR OrthoDB; 1362225at2759; -.
DR PhylomeDB; Q86YW7; -.
DR PathwayCommons; Q86YW7; -.
DR Reactome; R-HSA-375281; Hormone ligand-binding receptors.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; Q86YW7; -.
DR BioGRID-ORCS; 122876; 8 hits in 186 CRISPR screens.
DR GeneWiki; GPHB5; -.
DR GenomeRNAi; 122876; -.
DR Pharos; Q86YW7; Tbio.
DR PRO; PR:Q86YW7; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q86YW7; protein.
DR Bgee; ENSG00000179600; Expressed in right hemisphere of cerebellum and 20 other tissues.
DR ExpressionAtlas; Q86YW7; baseline and differential.
DR Genevisible; Q86YW7; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0031531; F:thyrotropin-releasing hormone receptor binding; IMP:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0002155; P:regulation of thyroid hormone mediated signaling pathway; IBA:GO_Central.
DR CDD; cd00069; GHB_like; 1.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR006208; Glyco_hormone_CN.
DR InterPro; IPR001545; Gonadotropin_bsu.
DR PANTHER; PTHR11515; PTHR11515; 1.
DR Pfam; PF00007; Cys_knot; 1.
DR SMART; SM00068; GHB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Hormone; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..130
FT /note="Glycoprotein hormone beta-5"
FT /id="PRO_0000011761"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 36..84
FT /evidence="ECO:0000255"
FT DISULFID 50..99
FT /evidence="ECO:0000255"
FT DISULFID 60..115
FT /evidence="ECO:0000255"
FT DISULFID 64..117
FT /evidence="ECO:0000255"
FT DISULFID 120..127
FT /evidence="ECO:0000255"
FT CONFLICT 68
FT /note="E -> Q (in Ref. 1; AAM53261 and 4; AAH69113)"
FT /evidence="ECO:0000305"
FT CONFLICT 112..122
FT /note="AIRCDCGACST -> PSAVTAEPAPL (in Ref. 1; AAM53261)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 130 AA; 14232 MW; 2C6C3BC0AA6725B9 CRC64;
MKLAFLFLGP MALLLLAGYG CVLGASSGNL RTFVGCAVRE FTFLAKKPGC RGLRITTDAC
WGRCETWEKP ILEPPYIEAH HRVCTYNETK QVTVKLPNCA PGVDPFYTYP VAIRCDCGAC
STATTECETI
