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Urocortin

 UCN1_HUMAN              Reviewed;         124 AA.
P55089; Q6FG64;
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 1.
25-OCT-2017, entry version 132.
RecName: Full=Urocortin;
Flags: Precursor;
Name=UCN;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
TISSUE=Placenta;
PubMed=8612563; DOI=10.1210/endo.137.5.8612563;
Donaldson C.J., Sutton S.W., Perrin M.H., Corrigan A.Z., Lewis K.A.,
Rivier J.E., Vaughan J.M., Vale W.W.;
"Cloning and characterization of human urocortin.";
Endocrinology 137:2167-2170(1996).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=9628819; DOI=10.1006/geno.1998.5292;
Zhao L., Donaldson C.J., Smith G.W., Vale W.W.;
"The structures of the mouse and human urocortin genes (Ucn and
UCN).";
Genomics 50:23-33(1998).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
Korn B., Zuo D., Hu Y., LaBaer J.;
"Cloning of human full open reading frames in Gateway(TM) system entry
vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15815621; DOI=10.1038/nature03466;
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2
and 4.";
Nature 434:724-731(2005).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS SPECTROMETRY.
PubMed=10690896; DOI=10.1210/jcem.85.2.6381;
Slominski A., Roloff B., Curry J., Dahiya M., Szczesniewski A.,
Wortsman J.;
"The skin produces urocortin.";
J. Clin. Endocrinol. Metab. 85:815-823(2000).
[7]
TISSUE SPECIFICITY, AND ASSOCIATION WITH INFLAMMATION IN ULCERATIVE
COLITIS.
PubMed=15531481; DOI=10.1210/jc.2004-0195;
Saruta M., Takahashi K., Suzuki T., Torii A., Kawakami M., Sasano H.;
"Urocortin 1 in colonic mucosa in patients with ulcerative colitis.";
J. Clin. Endocrinol. Metab. 89:5352-5361(2004).
[8]
STRUCTURE BY NMR OF 83-122.
PubMed=18052377; DOI=10.1021/ja0760933;
Grace C.R.R., Perrin M.H., Cantle J.P., Vale W.W., Rivier J.E.,
Riek R.;
"Common and divergent structural features of a series of corticotropin
releasing factor-related peptides.";
J. Am. Chem. Soc. 129:16102-16114(2007).
[9]
X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 107-122 IN COMPLEX WITH
CRHR2, MUTAGENESIS OF ARG-116; ILE-118; PHE-119 AND VAL-122, AND
INTERACTION WITH CRHR2 AND CRHR1.
PubMed=20966082; DOI=10.1074/jbc.M110.186072;
Pal K., Swaminathan K., Xu H.E., Pioszak A.A.;
"Structural basis for hormone recognition by the Human CRFR2{alpha} G
protein-coupled receptor.";
J. Biol. Chem. 285:40351-40361(2010).
-!- FUNCTION: Acts in vitro to stimulate the secretion of
adrenocorticotropic hormone (ACTH) (PubMed:8612563). Binds with
high affinity to CRF receptor types 1, 2-alpha, and 2-beta
(PubMed:8612563). Plays a role in the establishment of normal
hearing thresholds (By similarity). Reduces food intake and
regulates ghrelin levels in gastric body and plasma (By
similarity). {ECO:0000250|UniProtKB:P55090,
ECO:0000250|UniProtKB:P81615, ECO:0000269|PubMed:8612563}.
-!- SUBUNIT: Interacts with CRHR1 and CRHR2 (via their N-terminal
extracellular domain). {ECO:0000269|PubMed:20966082}.
-!- SUBCELLULAR LOCATION: Secreted.
-!- TISSUE SPECIFICITY: Keratinocytes in epidermis and the outer and
inner root sheaths of hair follicles, epithelium of sebaceous and
sweat glands, erector pili muscle, cutaneous blood vessel walls,
cutaneous nerves and dermal mononuclear cells (PubMed:10690896).
Detected in plasma cells in the lamia propria in colon mucosa
(PubMed:15531481) (at protein level). Expressed in pituitary and
adrenal glands (PubMed:10690896). Detected in plasma cells in the
lamia propria in colon mucosa (PubMed:15531481).
{ECO:0000269|PubMed:10690896, ECO:0000269|PubMed:15531481}.
-!- MISCELLANEOUS: Positive correlation between increased expression
in colonic lamina propria and severity of inflammation in patients
with ulcerative colitis. {ECO:0000269|PubMed:15531481}.
-!- SIMILARITY: Belongs to the sauvagine/corticotropin-releasing
factor/urotensin I family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AF038633; AAC24204.1; -; Genomic_DNA.
EMBL; CR542244; CAG47040.1; -; mRNA.
EMBL; AC013413; AAY24297.1; -; Genomic_DNA.
EMBL; BC104470; AAI04471.1; -; mRNA.
EMBL; BC104471; AAI04472.1; -; mRNA.
CCDS; CCDS1747.1; -.
RefSeq; NP_003344.1; NM_003353.3.
UniGene; Hs.534363; -.
PDB; 2RMF; NMR; -; A=83-122.
PDB; 3N96; X-ray; 2.75 A; E/F/G/H=107-122.
PDBsum; 2RMF; -.
PDBsum; 3N96; -.
ProteinModelPortal; P55089; -.
SMR; P55089; -.
BioGrid; 113196; 4.
STRING; 9606.ENSP00000296099; -.
BioMuta; UCN; -.
DMDM; 1718059; -.
PaxDb; P55089; -.
PeptideAtlas; P55089; -.
PRIDE; P55089; -.
DNASU; 7349; -.
Ensembl; ENST00000296099; ENSP00000296099; ENSG00000163794.
GeneID; 7349; -.
KEGG; hsa:7349; -.
UCSC; uc002rjp.2; human.
CTD; 7349; -.
DisGeNET; 7349; -.
EuPathDB; HostDB:ENSG00000163794.6; -.
GeneCards; UCN; -.
HGNC; HGNC:12516; UCN.
HPA; CAB010911; -.
MIM; 600945; gene.
neXtProt; NX_P55089; -.
OpenTargets; ENSG00000163794; -.
PharmGKB; PA37163; -.
eggNOG; ENOG410J8KZ; Eukaryota.
eggNOG; ENOG410Y0J4; LUCA.
GeneTree; ENSGT00510000049284; -.
HOGENOM; HOG000121779; -.
HOVERGEN; HBG036241; -.
InParanoid; P55089; -.
OMA; LRWSPGA; -.
PhylomeDB; P55089; -.
TreeFam; TF332956; -.
Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin.
SIGNOR; P55089; -.
EvolutionaryTrace; P55089; -.
GeneWiki; Urocortin; -.
GenomeRNAi; 7349; -.
PRO; PR:P55089; -.
Proteomes; UP000005640; Chromosome 2.
Bgee; ENSG00000163794; -.
CleanEx; HS_UCN; -.
Genevisible; P55089; HS.
GO; GO:0043679; C:axon terminus; IEA:Ensembl.
GO; GO:0030425; C:dendrite; IEA:Ensembl.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0043204; C:perikaryon; IEA:Ensembl.
GO; GO:0043196; C:varicosity; IEA:Ensembl.
GO; GO:0051430; F:corticotropin-releasing hormone receptor 1 binding; IEA:Ensembl.
GO; GO:0051431; F:corticotropin-releasing hormone receptor 2 binding; IEA:Ensembl.
GO; GO:0046811; F:histone deacetylase inhibitor activity; IEA:Ensembl.
GO; GO:0005184; F:neuropeptide hormone activity; TAS:ProtInc.
GO; GO:0034199; P:activation of protein kinase A activity; IEA:Ensembl.
GO; GO:0009060; P:aerobic respiration; IEA:Ensembl.
GO; GO:0008306; P:associative learning; IEA:Ensembl.
GO; GO:0042756; P:drinking behavior; IEA:Ensembl.
GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:ProtInc.
GO; GO:0035483; P:gastric emptying; IEA:Ensembl.
GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
GO; GO:0032099; P:negative regulation of appetite; IEA:Ensembl.
GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
GO; GO:0045792; P:negative regulation of cell size; IEA:Ensembl.
GO; GO:2000252; P:negative regulation of feeding behavior; IBA:GO_Central.
GO; GO:0060455; P:negative regulation of gastric acid secretion; IEA:Ensembl.
GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
GO; GO:0046888; P:negative regulation of hormone secretion; IEA:Ensembl.
GO; GO:0060547; P:negative regulation of necrotic cell death; IEA:Ensembl.
GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
GO; GO:0007218; P:neuropeptide signaling pathway; IEA:Ensembl.
GO; GO:0030157; P:pancreatic juice secretion; IEA:Ensembl.
GO; GO:2000987; P:positive regulation of behavioral fear response; IEA:Ensembl.
GO; GO:0097755; P:positive regulation of blood vessel diameter; IEA:Ensembl.
GO; GO:0090280; P:positive regulation of calcium ion import; IEA:Ensembl.
GO; GO:0030819; P:positive regulation of cAMP biosynthetic process; IEA:Ensembl.
GO; GO:0060452; P:positive regulation of cardiac muscle contraction; IEA:Ensembl.
GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IEA:Ensembl.
GO; GO:0051461; P:positive regulation of corticotropin secretion; IEA:Ensembl.
GO; GO:0045740; P:positive regulation of DNA replication; IEA:Ensembl.
GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0045727; P:positive regulation of translation; IEA:Ensembl.
GO; GO:0043117; P:positive regulation of vascular permeability; IEA:Ensembl.
GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl.
GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
GO; GO:0048265; P:response to pain; IEA:Ensembl.
GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
GO; GO:0035176; P:social behavior; IEA:Ensembl.
GO; GO:0001964; P:startle response; IEA:Ensembl.
InterPro; IPR018446; Corticotropin-releasing_fac_CS.
InterPro; IPR000187; CRF.
InterPro; IPR003620; Urocortin_CRF.
PANTHER; PTHR15035; PTHR15035; 1.
Pfam; PF00473; CRF; 1.
PRINTS; PR01612; CRFFAMILY.
SMART; SM00039; CRF; 1.
PROSITE; PS00511; CRF; 1.
1: Evidence at protein level;
3D-structure; Amidation; Cleavage on pair of basic residues;
Complete proteome; Hearing; Hormone; Reference proteome; Secreted;
Signal.
SIGNAL 1 25 {ECO:0000255}.
PROPEP 26 82
/FTId=PRO_0000006233.
PEPTIDE 83 122 Urocortin.
/FTId=PRO_0000006234.
MOD_RES 122 122 Valine amide. {ECO:0000250}.
MUTAGEN 116 116 R->A: Reduced affinity for CRHR1.
{ECO:0000269|PubMed:20966082}.
MUTAGEN 118 118 I->A: Reduced affinity for CRHR2.
{ECO:0000269|PubMed:20966082}.
MUTAGEN 119 119 F->A: Strongly reduced affinity for
CRHR2. {ECO:0000269|PubMed:20966082}.
MUTAGEN 122 122 V->A: Reduced affinity for CRHR2.
{ECO:0000269|PubMed:20966082}.
HELIX 108 121 {ECO:0000244|PDB:3N96}.
SEQUENCE 124 AA; 13458 MW; 4F765DA75DDD4A5E CRC64;
MRQAGRAALL AALLLLVQLC PGSSQRSPEA AGVQDPSLRW SPGARNQGGG ARALLLLLAE
RFPRRAGPGR LGLGTAGERP RRDNPSLSID LTFHLLRTLL ELARTQSQRE RAEQNRIIFD
SVGK


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