GPHA2_HUMAN
ID GPHA2_HUMAN Reviewed; 129 AA.
AC Q96T91; Q52LE2;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Glycoprotein hormone alpha-2;
DE AltName: Full=Putative secreted protein Zsig51;
DE AltName: Full=Thyrostimulin subunit alpha;
DE Flags: Precursor;
GN Name=GPHA2; Synonyms=GPA2, ZSIG51;
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].
RA Ching A., Gilbert T., Lok S., Sheppard P., Webster P., O'Hara P.J.;
RT "A novel cysteine knot protein expressed in pancreatic acinar cells.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP FUNCTION, SUBUNIT, INTERACTION WITH TSHR, AND 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 [4]
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).
CC -!- FUNCTION: Functions as a heterodimeric glycoprotein hormone with GPHB5
CC able to bind and activate the thyroid-stimulating hormone receptor
CC (TSHR), leading to increased cAMP production (PubMed:12045258). Plays a
CC central role in controlling thyroid cell metabolism (PubMed:12045258).
CC {ECO:0000269|PubMed:12045258}.
CC -!- SUBUNIT: Heterodimer with GPHB5; this heterodimer interacts with
CC thyroid-stimulating hormone receptor (TSHR), and hence stimulates cAMP
CC production. {ECO:0000269|PubMed:12045258}.
CC -!- INTERACTION:
CC Q96T91; Q86YW7: GPHB5; NbExp=3; IntAct=EBI-11659696, EBI-11659720;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Found in a variety of tissues.
CC {ECO:0000269|PubMed:12089349}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:12045258}.
CC -!- SIMILARITY: Belongs to the glycoprotein hormones subunit alpha family.
CC {ECO:0000305}.
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DR EMBL; AF260739; AAK51638.1; -; mRNA.
DR EMBL; BC093960; AAH93960.1; -; mRNA.
DR EMBL; BC093962; AAH93962.1; -; mRNA.
DR EMBL; BC101523; AAI01524.1; -; mRNA.
DR CCDS; CCDS8086.1; -.
DR RefSeq; NP_570125.1; NM_130769.3.
DR RefSeq; XP_011543077.1; XM_011544775.2.
DR RefSeq; XP_011543078.1; XM_011544776.2.
DR AlphaFoldDB; Q96T91; -.
DR BioGRID; 128064; 76.
DR IntAct; Q96T91; 19.
DR STRING; 9606.ENSP00000279168; -.
DR GlyGen; Q96T91; 2 sites.
DR BioMuta; GPHA2; -.
DR DMDM; 48474600; -.
DR MassIVE; Q96T91; -.
DR PaxDb; Q96T91; -.
DR PeptideAtlas; Q96T91; -.
DR PRIDE; Q96T91; -.
DR Antibodypedia; 65614; 40 antibodies from 9 providers.
DR DNASU; 170589; -.
DR Ensembl; ENST00000279168.7; ENSP00000279168.2; ENSG00000149735.7.
DR Ensembl; ENST00000533257.1; ENSP00000432918.1; ENSG00000149735.7.
DR GeneID; 170589; -.
DR KEGG; hsa:170589; -.
DR MANE-Select; ENST00000279168.7; ENSP00000279168.2; NM_130769.4; NP_570125.1.
DR UCSC; uc001oca.3; human.
DR CTD; 170589; -.
DR DisGeNET; 170589; -.
DR GeneCards; GPHA2; -.
DR HGNC; HGNC:18054; GPHA2.
DR HPA; ENSG00000149735; Tissue enriched (pancreas).
DR MIM; 609651; gene.
DR neXtProt; NX_Q96T91; -.
DR OpenTargets; ENSG00000149735; -.
DR PharmGKB; PA28839; -.
DR VEuPathDB; HostDB:ENSG00000149735; -.
DR eggNOG; ENOG502S2RQ; Eukaryota.
DR GeneTree; ENSGT00390000009379; -.
DR HOGENOM; CLU_134026_1_0_1; -.
DR InParanoid; Q96T91; -.
DR OMA; ISQCCTI; -.
DR OrthoDB; 1435006at2759; -.
DR PhylomeDB; Q96T91; -.
DR TreeFam; TF332313; -.
DR PathwayCommons; Q96T91; -.
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; Q96T91; -.
DR SIGNOR; Q96T91; -.
DR BioGRID-ORCS; 170589; 8 hits in 1056 CRISPR screens.
DR ChiTaRS; GPHA2; human.
DR GeneWiki; GPHA2; -.
DR GenomeRNAi; 170589; -.
DR Pharos; Q96T91; Tbio.
DR PRO; PR:Q96T91; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96T91; protein.
DR Bgee; ENSG00000149735; Expressed in oocyte and 135 other tissues.
DR ExpressionAtlas; Q96T91; baseline and differential.
DR Genevisible; Q96T91; HS.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0051427; F:hormone receptor binding; IBA:GO_Central.
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:0007166; P:cell surface receptor signaling pathway; IMP:UniProtKB.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR004133; DAN.
DR InterPro; IPR000476; Glyco_hormone.
DR Pfam; PF03045; DAN; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS01225; CTCK_2; 1.
DR PROSITE; PS50277; GLYCO_HORMONE_ALPHA_3; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Hormone; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..129
FT /note="Glycoprotein hormone alpha-2"
FT /id="PRO_0000011672"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 48..103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 57..119
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 61..121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
SQ SEQUENCE 129 AA; 14163 MW; 6E924AF7BE8D7A70 CRC64;
MPMASPQTLV LYLLVLAVTE AWGQEAVIPG CHLHPFNVTV RSDRQGTCQG SHVAQACVGH
CESSAFPSRY SVLVASGYRH NITSVSQCCT ISGLKKVKVQ LQCVGSRREE LEIFTARACQ
CDMCRLSRY
