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   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.
DR   Genevisible; P20396; HS.
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
//