ID TRH_HUMAN Reviewed; 242 AA.
AC P20396; B2R8R1; Q2TB83;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 27-MAR-2024, entry version 188.
DE RecName: Full=Pro-thyrotropin-releasing hormone;
DE Short=Pro-TRH;
DE AltName: Full=Prothyroliberin;
DE Contains:
DE RecName: Full=Thyrotropin-releasing hormone;
DE Short=TRH;
DE AltName: Full=Protirelin;
DE AltName: Full=TSH-releasing factor;
DE AltName: Full=Thyroliberin;
DE AltName: Full=Thyrotropin-releasing factor;
DE Short=TRF;
DE Flags: Precursor;
GN Name=TRH;
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 [GENOMIC DNA / MRNA].
RX PubMed=2126343; DOI=10.1210/mend-4-4-551;
RA Yamada M., Radovick S., Wondisford F.E., Nakayama Y., Weintraub B.D.,
RA Wilber J.F.;
RT "Cloning and structure of human genomic DNA and hypothalamic cDNA encoding
RT human prepro thyrotropin-releasing hormone.";
RL Mol. Endocrinol. 4:551-556(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Subthalamic nucleus;
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=Lung;
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 FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19825978; DOI=10.1096/fj.08-126417;
RA Gaspar E., Hardenbicker C., Bodo E., Wenzel B., Ramot Y., Funk W.,
RA Kromminga A., Paus R.;
RT "Thyrotropin releasing hormone (TRH): a new player in human hair-growth
RT control.";
RL FASEB J. 24:393-403(2010).
CC -!- FUNCTION: As a component of the hypothalamic-pituitary-thyroid axis, it
CC controls the secretion of thyroid-stimulating hormone (TSH) and is
CC involved in thyroid hormone synthesis regulation. It also operates as
CC modulator of hair growth. It promotes hair-shaft elongation, prolongs
CC the hair cycle growth phase (anagen) and antagonizes its termination
CC (catagen) by TGFB2. It stimulates proliferation and inhibits apoptosis
CC of hair matrix keratinocytes. {ECO:0000269|PubMed:19825978}.
CC -!- INTERACTION:
CC P20396; Q6PIL6: KCNIP4; NbExp=3; IntAct=EBI-12813975, EBI-1051469;
CC P20396; P80188: LCN2; NbExp=3; IntAct=EBI-12813975, EBI-11911016;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Hypothalamus. Expressed in the hair follicle
CC epithelium (at protein level). {ECO:0000269|PubMed:19825978}.
CC -!- SIMILARITY: Belongs to the TRH family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Thyrotropin-releasing hormone entry;
CC URL="https://en.wikipedia.org/wiki/Thyrotropin-releasing_hormone";
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DR EMBL; M63582; AAA36480.1; -; Genomic_DNA.
DR EMBL; M63581; AAA36480.1; JOINED; Genomic_DNA.
DR EMBL; AK313473; BAG36258.1; -; mRNA.
DR EMBL; CH471052; EAW79229.1; -; Genomic_DNA.
DR EMBL; BC069375; AAH69375.1; -; mRNA.
DR EMBL; BC074888; AAH74888.1; -; mRNA.
DR EMBL; BC074889; AAH74889.1; -; mRNA.
DR EMBL; BC110515; AAI10516.1; -; mRNA.
DR EMBL; BC110516; AAI10517.1; -; mRNA.
DR CCDS; CCDS3066.1; -.
DR PIR; A34550; RHHUT.
DR RefSeq; NP_009048.1; NM_007117.4.
DR AlphaFoldDB; P20396; -.
DR BioGRID; 113051; 2.
DR IntAct; P20396; 2.
DR STRING; 9606.ENSP00000303452; -.
DR BindingDB; P20396; -.
DR iPTMnet; P20396; -.
DR PhosphoSitePlus; P20396; -.
DR BioMuta; TRH; -.
DR DMDM; 135841; -.
DR MassIVE; P20396; -.
DR PaxDb; 9606-ENSP00000303452; -.
DR PeptideAtlas; P20396; -.
DR ProteomicsDB; 53760; -.
DR Antibodypedia; 33301; 181 antibodies from 26 providers.
DR DNASU; 7200; -.
DR Ensembl; ENST00000302649.4; ENSP00000303452.3; ENSG00000170893.4.
DR GeneID; 7200; -.
DR KEGG; hsa:7200; -.
DR MANE-Select; ENST00000302649.4; ENSP00000303452.3; NM_007117.5; NP_009048.1.
DR UCSC; uc003enc.5; human.
DR AGR; HGNC:12298; -.
DR CTD; 7200; -.
DR DisGeNET; 7200; -.
DR GeneCards; TRH; -.
DR HGNC; HGNC:12298; TRH.
DR HPA; ENSG00000170893; Group enriched (brain, cervix, endometrium, retina).
DR MalaCards; TRH; -.
DR MIM; 613879; gene.
DR neXtProt; NX_P20396; -.
DR OpenTargets; ENSG00000170893; -.
DR Orphanet; 238670; Isolated thyrotropin-releasing hormone deficiency.
DR PharmGKB; PA36978; -.
DR VEuPathDB; HostDB:ENSG00000170893; -.
DR eggNOG; ENOG502RWH0; Eukaryota.
DR GeneTree; ENSGT00390000016951; -.
DR InParanoid; P20396; -.
DR OMA; HPGKRFT; -.
DR OrthoDB; 5356148at2759; -.
DR PhylomeDB; P20396; -.
DR TreeFam; TF332073; -.
DR PathwayCommons; P20396; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P20396; -.
DR SIGNOR; P20396; -.
DR BioGRID-ORCS; 7200; 10 hits in 1149 CRISPR screens.
DR GenomeRNAi; 7200; -.
DR Pharos; P20396; Tbio.
DR PRO; PR:P20396; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P20396; Protein.
DR Bgee; ENSG00000170893; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 112 other cell types or tissues.
DR ExpressionAtlas; P20396; baseline and differential.
DR Genevisible; P20396; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0008437; F:thyrotropin-releasing hormone activity; IBA:GO_Central.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0042755; P:eating behavior; IBA:GO_Central.
DR GO; GO:0001692; P:histamine metabolic process; IBA:GO_Central.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:InterPro.
DR GO; GO:0014050; P:negative regulation of glutamate secretion; IBA:GO_Central.
DR GO; GO:0014054; P:positive regulation of gamma-aminobutyric acid secretion; IBA:GO_Central.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR008857; TRH.
DR PANTHER; PTHR17530; PRO-THYROTROPIN-RELEASING HORMONE; 1.
DR PANTHER; PTHR17530:SF2; PRO-THYROTROPIN-RELEASING HORMONE; 1.
DR Pfam; PF05438; TRH; 1.
DR PIRSF; PIRSF001795; TRH; 1.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Hormone; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..242
FT /note="Pro-thyrotropin-releasing hormone"
FT /id="PRO_0000022509"
FT PEPTIDE 84..86
FT /note="Thyrotropin-releasing hormone"
FT /id="PRO_0000022510"
FT PEPTIDE 114..116
FT /note="Thyrotropin-releasing hormone"
FT /id="PRO_0000022511"
FT PEPTIDE 135..137
FT /note="Thyrotropin-releasing hormone"
FT /id="PRO_0000022512"
FT PEPTIDE 152..154
FT /note="Thyrotropin-releasing hormone"
FT /id="PRO_0000022513"
FT PEPTIDE 186..188
FT /note="Thyrotropin-releasing hormone"
FT /id="PRO_0000022514"
FT PEPTIDE 227..229
FT /note="Thyrotropin-releasing hormone"
FT /id="PRO_0000022515"
FT REGION 63..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 220..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..80
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 105..135
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 86
FT /note="Proline amide"
FT /evidence="ECO:0000250"
FT MOD_RES 116
FT /note="Proline amide"
FT /evidence="ECO:0000250"
FT MOD_RES 137
FT /note="Proline amide"
FT /evidence="ECO:0000250"
FT MOD_RES 154
FT /note="Proline amide"
FT /evidence="ECO:0000250"
FT MOD_RES 188
FT /note="Proline amide"
FT /evidence="ECO:0000250"
FT MOD_RES 229
FT /note="Proline amide"
FT /evidence="ECO:0000250"
FT VARIANT 8
FT /note="L -> V (in dbSNP:rs5658)"
FT /id="VAR_014787"
SQ SEQUENCE 242 AA; 27404 MW; 8C0F9D915B32F29F CRC64;
MPGPWLLLAL ALTLNLTGVP GGRAQPEAAQ QEAVTAAEHP GLDDFLRQVE RLLFLRENIQ
RLQGDQGEHS ASQIFQSDWL SKRQHPGKRE EEEEEGVEEE EEEEGGAVGP HKRQHPGRRE
DEASWSVDVT QHKRQHPGRR SPWLAYAVPK RQHPGRRLAD PKAQRSWEEE EEEEEREEDL
MPEKRQHPGK RALGGPCGPQ GAYGQAGLLL GLLDDLSRSQ GAEEKRQHPG RRAAWVREPL
EE
//
