ID   UCN1_HUMAN              Reviewed;         124 AA.
AC   P55089; Q6FG64;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   24-JAN-2024, entry version 165.
DE   RecName: Full=Urocortin;
DE   Flags: Precursor;
GN   Name=UCN;
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], AND FUNCTION.
RC   TISSUE=Placenta;
RX   PubMed=8612563; DOI=10.1210/endo.137.5.8612563;
RA   Donaldson C.J., Sutton S.W., Perrin M.H., Corrigan A.Z., Lewis K.A.,
RA   Rivier J.E., Vaughan J.M., Vale W.W.;
RT   "Cloning and characterization of human urocortin.";
RL   Endocrinology 137:2167-2170(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9628819; DOI=10.1006/geno.1998.5292;
RA   Zhao L., Donaldson C.J., Smith G.W., Vale W.W.;
RT   "The structures of the mouse and human urocortin genes (Ucn and UCN).";
RL   Genomics 50:23-33(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA   Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA   LaBaer J.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [5]
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   [6]
RP   TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=10690896; DOI=10.1210/jcem.85.2.6381;
RA   Slominski A., Roloff B., Curry J., Dahiya M., Szczesniewski A.,
RA   Wortsman J.;
RT   "The skin produces urocortin.";
RL   J. Clin. Endocrinol. Metab. 85:815-823(2000).
RN   [7]
RP   TISSUE SPECIFICITY, AND ASSOCIATION WITH INFLAMMATION IN ULCERATIVE
RP   COLITIS.
RX   PubMed=15531481; DOI=10.1210/jc.2004-0195;
RA   Saruta M., Takahashi K., Suzuki T., Torii A., Kawakami M., Sasano H.;
RT   "Urocortin 1 in colonic mucosa in patients with ulcerative colitis.";
RL   J. Clin. Endocrinol. Metab. 89:5352-5361(2004).
RN   [8]
RP   STRUCTURE BY NMR OF 83-122.
RX   PubMed=18052377; DOI=10.1021/ja0760933;
RA   Grace C.R.R., Perrin M.H., Cantle J.P., Vale W.W., Rivier J.E., Riek R.;
RT   "Common and divergent structural features of a series of corticotropin
RT   releasing factor-related peptides.";
RL   J. Am. Chem. Soc. 129:16102-16114(2007).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 107-122 IN COMPLEX WITH CRHR2,
RP   MUTAGENESIS OF ARG-116; ILE-118; PHE-119 AND VAL-122, AND INTERACTION WITH
RP   CRHR2 AND CRHR1.
RX   PubMed=20966082; DOI=10.1074/jbc.m110.186072;
RA   Pal K., Swaminathan K., Xu H.E., Pioszak A.A.;
RT   "Structural basis for hormone recognition by the Human CRFR2{alpha} G
RT   protein-coupled receptor.";
RL   J. Biol. Chem. 285:40351-40361(2010).
CC   -!- FUNCTION: Acts in vitro to stimulate the secretion of
CC       adrenocorticotropic hormone (ACTH) (PubMed:8612563). Binds with high
CC       affinity to CRF receptor types 1, 2-alpha, and 2-beta (PubMed:8612563).
CC       Plays a role in the establishment of normal hearing thresholds (By
CC       similarity). Reduces food intake and regulates ghrelin levels in
CC       gastric body and plasma (By similarity). {ECO:0000250|UniProtKB:P55090,
CC       ECO:0000250|UniProtKB:P81615, ECO:0000269|PubMed:8612563}.
CC   -!- SUBUNIT: Interacts with CRHR1 and CRHR2 (via their N-terminal
CC       extracellular domain). {ECO:0000269|PubMed:20966082}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Keratinocytes in epidermis and the outer and inner
CC       root sheaths of hair follicles, epithelium of sebaceous and sweat
CC       glands, erector pili muscle, cutaneous blood vessel walls, cutaneous
CC       nerves and dermal mononuclear cells (PubMed:10690896). Detected in
CC       plasma cells in the lamia propria in colon mucosa (PubMed:15531481) (at
CC       protein level). Expressed in pituitary and adrenal glands
CC       (PubMed:10690896). Detected in plasma cells in the lamia propria in
CC       colon mucosa (PubMed:15531481). {ECO:0000269|PubMed:10690896,
CC       ECO:0000269|PubMed:15531481}.
CC   -!- MISCELLANEOUS: Positive correlation between increased expression in
CC       colonic lamina propria and severity of inflammation in patients with
CC       ulcerative colitis. {ECO:0000269|PubMed:15531481}.
CC   -!- SIMILARITY: Belongs to the sauvagine/corticotropin-releasing
CC       factor/urotensin I family. {ECO:0000305}.
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DR   EMBL; AF038633; AAC24204.1; -; Genomic_DNA.
DR   EMBL; CR542244; CAG47040.1; -; mRNA.
DR   EMBL; AC013413; AAY24297.1; -; Genomic_DNA.
DR   EMBL; BC104470; AAI04471.1; -; mRNA.
DR   EMBL; BC104471; AAI04472.1; -; mRNA.
DR   CCDS; CCDS1747.1; -.
DR   RefSeq; NP_003344.1; NM_003353.3.
DR   PDB; 2RMF; NMR; -; A=83-122.
DR   PDB; 3N96; X-ray; 2.75 A; E/F/G/H=107-122.
DR   PDB; 6PB0; EM; 3.00 A; U=83-122.
DR   PDB; 6PB1; EM; 2.80 A; U=83-122.
DR   PDB; 7TRY; EM; 3.70 A; U=83-122.
DR   PDB; 7TS0; EM; 2.80 A; U=83-122.
DR   PDBsum; 2RMF; -.
DR   PDBsum; 3N96; -.
DR   PDBsum; 6PB0; -.
DR   PDBsum; 6PB1; -.
DR   PDBsum; 7TRY; -.
DR   PDBsum; 7TS0; -.
DR   AlphaFoldDB; P55089; -.
DR   EMDB; EMD-20284; -.
DR   EMDB; EMD-20285; -.
DR   EMDB; EMD-26103; -.
DR   EMDB; EMD-26104; -.
DR   SMR; P55089; -.
DR   BioGRID; 113196; 5.
DR   IntAct; P55089; 2.
DR   STRING; 9606.ENSP00000296099; -.
DR   BioMuta; UCN; -.
DR   DMDM; 1718059; -.
DR   MassIVE; P55089; -.
DR   PaxDb; 9606-ENSP00000296099; -.
DR   PeptideAtlas; P55089; -.
DR   ProteomicsDB; 56790; -.
DR   Antibodypedia; 4400; 246 antibodies from 31 providers.
DR   DNASU; 7349; -.
DR   Ensembl; ENST00000296099.2; ENSP00000296099.2; ENSG00000163794.6.
DR   GeneID; 7349; -.
DR   KEGG; hsa:7349; -.
DR   MANE-Select; ENST00000296099.2; ENSP00000296099.2; NM_003353.4; NP_003344.1.
DR   UCSC; uc002rjp.2; human.
DR   AGR; HGNC:12516; -.
DR   CTD; 7349; -.
DR   DisGeNET; 7349; -.
DR   GeneCards; UCN; -.
DR   HGNC; HGNC:12516; UCN.
DR   HPA; ENSG00000163794; Tissue enhanced (brain).
DR   MalaCards; UCN; -.
DR   MIM; 600945; gene.
DR   neXtProt; NX_P55089; -.
DR   OpenTargets; ENSG00000163794; -.
DR   PharmGKB; PA37163; -.
DR   VEuPathDB; HostDB:ENSG00000163794; -.
DR   eggNOG; ENOG502S63E; Eukaryota.
DR   GeneTree; ENSGT00940000154473; -.
DR   HOGENOM; CLU_138901_0_0_1; -.
DR   InParanoid; P55089; -.
DR   OMA; QNRIVFD; -.
DR   PhylomeDB; P55089; -.
DR   TreeFam; TF332956; -.
DR   PathwayCommons; P55089; -.
DR   Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR   Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR   SignaLink; P55089; -.
DR   SIGNOR; P55089; -.
DR   BioGRID-ORCS; 7349; 28 hits in 1143 CRISPR screens.
DR   EvolutionaryTrace; P55089; -.
DR   GeneWiki; Urocortin; -.
DR   GenomeRNAi; 7349; -.
DR   Pharos; P55089; Tbio.
DR   PRO; PR:P55089; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P55089; Protein.
DR   Bgee; ENSG00000163794; Expressed in middle temporal gyrus and 96 other cell types or tissues.
DR   GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR   GO; GO:0043196; C:varicosity; IEA:Ensembl.
DR   GO; GO:0051430; F:corticotropin-releasing hormone receptor 1 binding; IEA:Ensembl.
DR   GO; GO:0051431; F:corticotropin-releasing hormone receptor 2 binding; IEA:Ensembl.
DR   GO; GO:0046811; F:histone deacetylase inhibitor activity; IEA:Ensembl.
DR   GO; GO:0005184; F:neuropeptide hormone activity; TAS:ProtInc.
DR   GO; GO:0009060; P:aerobic respiration; IEA:Ensembl.
DR   GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR   GO; GO:0042756; P:drinking behavior; IEA:Ensembl.
DR   GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0032099; P:negative regulation of appetite; IEA:Ensembl.
DR   GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
DR   GO; GO:0045792; P:negative regulation of cell size; IEA:Ensembl.
DR   GO; GO:2000252; P:negative regulation of feeding behavior; IBA:GO_Central.
DR   GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR   GO; GO:0046888; P:negative regulation of hormone secretion; IEA:Ensembl.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IEA:Ensembl.
DR   GO; GO:2000987; P:positive regulation of behavioral fear response; IEA:Ensembl.
DR   GO; GO:0090280; P:positive regulation of calcium ion import; IEA:Ensembl.
DR   GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IEA:Ensembl.
DR   GO; GO:0060452; P:positive regulation of cardiac muscle contraction; IEA:Ensembl.
DR   GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
DR   GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IEA:Ensembl.
DR   GO; GO:0051461; P:positive regulation of corticotropin secretion; IDA:UniProtKB.
DR   GO; GO:0045740; P:positive regulation of DNA replication; IEA:Ensembl.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0045727; P:positive regulation of translation; IEA:Ensembl.
DR   GO; GO:0043117; P:positive regulation of vascular permeability; IEA:Ensembl.
DR   GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR   GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl.
DR   GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR   GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR   GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR   GO; GO:0048265; P:response to pain; IEA:Ensembl.
DR   GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR   GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR   GO; GO:0001964; P:startle response; IEA:Ensembl.
DR   GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR   Gene3D; 6.10.250.1920; -; 1.
DR   InterPro; IPR018446; Corticotropin-releasing_fac_CS.
DR   InterPro; IPR000187; CRF.
DR   InterPro; IPR003620; Urocortin_CRF.
DR   PANTHER; PTHR15035; CORTICOLIBERIN/UROCORTIN; 1.
DR   PANTHER; PTHR15035:SF11; UROCORTIN; 1.
DR   Pfam; PF00473; CRF; 1.
DR   PRINTS; PR01612; CRFFAMILY.
DR   SMART; SM00039; CRF; 1.
DR   PROSITE; PS00511; CRF; 1.
DR   Genevisible; P55089; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Cleavage on pair of basic residues; Hearing;
KW   Hormone; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   PROPEP          26..82
FT                   /id="PRO_0000006233"
FT   PEPTIDE         83..122
FT                   /note="Urocortin"
FT                   /id="PRO_0000006234"
FT   REGION          23..46
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         122
FT                   /note="Valine amide"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         116
FT                   /note="R->A: Reduced affinity for CRHR1."
FT                   /evidence="ECO:0000269|PubMed:20966082"
FT   MUTAGEN         118
FT                   /note="I->A: Reduced affinity for CRHR2."
FT                   /evidence="ECO:0000269|PubMed:20966082"
FT   MUTAGEN         119
FT                   /note="F->A: Strongly reduced affinity for CRHR2."
FT                   /evidence="ECO:0000269|PubMed:20966082"
FT   MUTAGEN         122
FT                   /note="V->A: Reduced affinity for CRHR2."
FT                   /evidence="ECO:0000269|PubMed:20966082"
FT   HELIX           108..121
FT                   /evidence="ECO:0007829|PDB:3N96"
SQ   SEQUENCE   124 AA;  13458 MW;  4F765DA75DDD4A5E CRC64;
     MRQAGRAALL AALLLLVQLC PGSSQRSPEA AGVQDPSLRW SPGARNQGGG ARALLLLLAE
     RFPRRAGPGR LGLGTAGERP RRDNPSLSID LTFHLLRTLL ELARTQSQRE RAEQNRIIFD
     SVGK
//