UCN3_HUMAN
ID UCN3_HUMAN Reviewed; 161 AA.
AC Q969E3; Q496H2; Q5SR91;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Urocortin-3;
DE AltName: Full=Stresscopin;
DE AltName: Full=Urocortin III;
DE Short=Ucn III;
DE Flags: Precursor;
GN Name=UCN3; Synonyms=SPC;
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], SYNTHESIS OF UCN III, AND VARIANT
RP GLY-91.
RX PubMed=11416224; DOI=10.1073/pnas.121165198;
RA Lewis K., Li C., Perrin M.H., Blount A., Kunitake K., Donaldson C.,
RA Vaughan J., Reyes T.M., Gulyas J., Fischer W., Bilezikjian L., Rivier J.,
RA Sawchenko P.E., Vale W.W.;
RT "Identification of urocortin III, an additional member of the
RT corticotropin-releasing factor (CRF) family with high affinity for the CRF2
RT receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7570-7575(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-91.
RX PubMed=11329063; DOI=10.1038/87936;
RA Hsu S.Y., Hsueh A.J.W.;
RT "Human stresscopin and stresscopin-related peptide are selective ligands
RT for the type 2 corticotropin-releasing hormone receptor.";
RL Nat. Med. 7:605-611(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-91.
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 STRUCTURE BY NMR OF 120-157.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 142-157 IN COMPLEX WITH CRHR2.
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: Suppresses food intake, delays gastric emptying and decreases
CC heat-induced edema. Might represent an endogenous ligand for
CC maintaining homeostasis after stress.
CC -!- SUBUNIT: Binds with high affinity to CRF receptors 2-alpha and 2-beta.
CC {ECO:0000269|PubMed:20966082}.
CC -!- INTERACTION:
CC Q969E3; Q13324-1: CRHR2; NbExp=2; IntAct=EBI-26585468, EBI-26585317;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the sauvagine/corticotropin-releasing
CC factor/urotensin I family. {ECO:0000305}.
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DR EMBL; AF361943; AAK67317.1; -; Genomic_DNA.
DR EMBL; AY026949; AAK11729.1; -; mRNA.
DR EMBL; AL683826; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069530; AAH69530.1; -; mRNA.
DR EMBL; BC100867; AAI00868.1; -; mRNA.
DR EMBL; BC100868; AAI00869.1; -; mRNA.
DR EMBL; BC100869; AAI00870.1; -; mRNA.
DR EMBL; BC100870; AAI00871.1; -; mRNA.
DR CCDS; CCDS7065.1; -.
DR RefSeq; NP_444277.2; NM_053049.3.
DR PDB; 2RMH; NMR; -; A=120-157.
DR PDB; 3N93; X-ray; 2.50 A; C=142-157.
DR PDBsum; 2RMH; -.
DR PDBsum; 3N93; -.
DR AlphaFoldDB; Q969E3; -.
DR SMR; Q969E3; -.
DR BioGRID; 125284; 23.
DR IntAct; Q969E3; 2.
DR STRING; 9606.ENSP00000369798; -.
DR iPTMnet; Q969E3; -.
DR PhosphoSitePlus; Q969E3; -.
DR BioMuta; UCN3; -.
DR DMDM; 296452853; -.
DR MassIVE; Q969E3; -.
DR PaxDb; Q969E3; -.
DR PeptideAtlas; Q969E3; -.
DR PRIDE; Q969E3; -.
DR ProteomicsDB; 75743; -.
DR Antibodypedia; 24078; 165 antibodies from 27 providers.
DR DNASU; 114131; -.
DR Ensembl; ENST00000380433.5; ENSP00000369798.3; ENSG00000178473.7.
DR GeneID; 114131; -.
DR KEGG; hsa:114131; -.
DR MANE-Select; ENST00000380433.5; ENSP00000369798.3; NM_053049.4; NP_444277.2.
DR UCSC; uc001ihx.2; human.
DR CTD; 114131; -.
DR DisGeNET; 114131; -.
DR GeneCards; UCN3; -.
DR HGNC; HGNC:17781; UCN3.
DR HPA; ENSG00000178473; Tissue enhanced (intestine, pancreas, stomach).
DR MIM; 605901; gene.
DR neXtProt; NX_Q969E3; -.
DR OpenTargets; ENSG00000178473; -.
DR PharmGKB; PA130413153; -.
DR VEuPathDB; HostDB:ENSG00000178473; -.
DR eggNOG; ENOG502S1WZ; Eukaryota.
DR GeneTree; ENSGT00940000160568; -.
DR HOGENOM; CLU_1767442_0_0_1; -.
DR InParanoid; Q969E3; -.
DR OMA; KFYKAKP; -.
DR OrthoDB; 1568003at2759; -.
DR PhylomeDB; Q969E3; -.
DR TreeFam; TF330723; -.
DR PathwayCommons; Q969E3; -.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR SignaLink; Q969E3; -.
DR BioGRID-ORCS; 114131; 8 hits in 1064 CRISPR screens.
DR ChiTaRS; UCN3; human.
DR EvolutionaryTrace; Q969E3; -.
DR GeneWiki; UCN3; -.
DR GenomeRNAi; 114131; -.
DR Pharos; Q969E3; Tbio.
DR PRO; PR:Q969E3; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q969E3; protein.
DR Bgee; ENSG00000178473; Expressed in islet of Langerhans and 50 other tissues.
DR Genevisible; Q969E3; HS.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0043196; C:varicosity; IEA:Ensembl.
DR GO; GO:0051431; F:corticotropin-releasing hormone receptor 2 binding; IEA:InterPro.
DR GO; GO:0051429; F:corticotropin-releasing hormone receptor binding; IPI:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0031669; P:cellular response to nutrient levels; IBA:GO_Central.
DR GO; GO:0007586; P:digestion; IEA:InterPro.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0045838; P:positive regulation of membrane potential; IEA:Ensembl.
DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR InterPro; IPR000187; CRF.
DR InterPro; IPR024270; Urocortin_II/III.
DR PANTHER; PTHR17575; PTHR17575; 1.
DR Pfam; PF00473; CRF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Hormone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..118
FT /id="PRO_0000006245"
FT CHAIN 120..157
FT /note="Urocortin-3"
FT /id="PRO_0000006246"
FT REGION 64..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..81
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Isoleucine amide"
FT /evidence="ECO:0000255"
FT VARIANT 77
FT /note="E -> K (in dbSNP:rs12768730)"
FT /id="VAR_060410"
FT VARIANT 91
FT /note="R -> G (in dbSNP:rs10904481)"
FT /evidence="ECO:0000269|PubMed:11329063,
FT ECO:0000269|PubMed:11416224, ECO:0000269|PubMed:15489334"
FT /id="VAR_060411"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:2RMH"
FT HELIX 143..156
FT /evidence="ECO:0007829|PDB:3N93"
SQ SEQUENCE 161 AA; 17961 MW; B83B3D8D30879911 CRC64;
MLMPVHFLLL LLLLLGGPRT GLPHKFYKAK PIFSCLNTAL SEAEKGQWED ASLLSKRSFH
YLRSRDASSG EEEEGKEKKT FPISGARGGA RGTRYRYVSQ AQPRGKPRQD TAKSPHRTKF
TLSLDVPTNI MNLLFNIAKA KNLRAQAAAN AHLMAQIGRK K
