ID   CRF_HUMAN               Reviewed;         196 AA.
AC   P06850; B3KQS4;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1988, sequence version 1.
DT   25-JAN-2012, entry version 119.
DE   RecName: Full=Corticoliberin;
DE   AltName: Full=Corticotropin-releasing factor;
DE            Short=CRF;
DE   AltName: Full=Corticotropin-releasing hormone;
DE   Flags: Precursor;
GN   Name=CRH;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=84057755; PubMed=6605851;
RA   Shibahara S., Morimoto Y., Furutani Y., Notake M., Takahashi H.,
RA   Shimizu S., Horikawa S., Numa S.;
RT   "Isolation and sequence analysis of the human corticotropin-releasing
RT   factor precursor gene.";
RL   EMBO J. 2:775-779(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=89137721; PubMed=2783917; DOI=10.1016/0303-7207(89)90128-7;
RA   Robinson B.G., D'Angio L.A. Jr., Pasieka K.B., Majzoub J.A.;
RT   "Preprocorticotropin releasing hormone: cDNA sequence and in vitro
RT   processing.";
RL   Mol. Cell. Endocrinol. 61:175-180(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT   vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
RX   PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA   Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA   Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA   Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA   Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA   Isogai T.;
RT   "Signal sequence and keyword trap in silico for selection of full-
RT   length human cDNAs encoding secretion or membrane proteins from oligo-
RT   capped cDNA libraries.";
RL   DNA Res. 12:117-126(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   PROTEIN SEQUENCE OF 154-186.
RX   MEDLINE=88331316; PubMed=3262120;
RA   Sasaki A., Tempst P., Liotta A.S., Margioris A.N., Hood L.E.,
RA   Kent S.B., Sato S., Shinkawa O., Yoshinaga K., Krieger D.T.;
RT   "Isolation and characterization of a corticotropin-releasing hormone-
RT   like peptide from human placenta.";
RL   J. Clin. Endocrinol. Metab. 67:768-773(1988).
RN   [8]
RP   STRUCTURE BY NMR OF 154-194.
RX   MEDLINE=93234434; PubMed=8386360; DOI=10.1093/protein/6.2.149;
RA   Romier C., Bernassau J.-M., Cambillau C., Darbon H.;
RT   "Solution structure of human corticotropin releasing factor by 1H NMR
RT   and distance geometry with restrained molecular dynamics.";
RL   Protein Eng. 6:149-156(1993).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 175-194 IN COMPLEX WITH
RP   CRFR1, SUBUNIT, AND MUTAGENESIS OF GLN-183; ASN-187; ARG-188; LEU-190;
RP   MET-191 AND GLU-192.
RX   PubMed=18801728; DOI=10.1074/jbc.M805749200;
RA   Pioszak A.A., Parker N.R., Suino-Powell K., Xu H.E.;
RT   "Molecular recognition of corticotropin-releasing factor by its G-
RT   protein-coupled receptor CRFR1.";
RL   J. Biol. Chem. 283:32900-32912(2008).
CC   -!- FUNCTION: This hormone from hypothalamus regulates the release of
CC       corticotropin from pituitary gland.
CC   -!- SUBUNIT: Interacts (via C-terminus) with CRFR1 (via N-terminal
CC       extracellular domain).
CC   -!- INTERACTION:
CC       P34998:CRHR1; NbExp=2; IntAct=EBI-3870390, EBI-3870393;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the sauvagine/corticotropin-releasing
CC       factor/urotensin I family.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Corticotropin-releasing hormone
CC       entry;
CC       URL="http://en.wikipedia.org/wiki/Corticotropin-releasing_hormone";
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DR   EMBL; V00571; CAA23834.1; -; Genomic_DNA.
DR   EMBL; BT007453; AAP36121.1; -; mRNA.
DR   EMBL; AK075431; BAG52136.1; -; mRNA.
DR   EMBL; CH471068; EAW86897.1; -; Genomic_DNA.
DR   EMBL; BC002599; AAH02599.1; -; mRNA.
DR   EMBL; BC011031; AAH11031.1; -; mRNA.
DR   IPI; IPI00027839; -.
DR   PIR; A30327; A30327.
DR   RefSeq; NP_000747.1; NM_000756.2.
DR   UniGene; Hs.75294; -.
DR   PDB; 3EHT; X-ray; 3.40 A; B=180-194.
DR   PDB; 3EHU; X-ray; 1.96 A; C/D=175-194.
DR   PDBsum; 3EHT; -.
DR   PDBsum; 3EHU; -.
DR   ProteinModelPortal; P06850; -.
DR   SMR; P06850; 154-194.
DR   IntAct; P06850; 1.
DR   STRING; P06850; -.
DR   DMDM; 117445; -.
DR   PRIDE; P06850; -.
DR   Ensembl; ENST00000276571; ENSP00000276571; ENSG00000147571.
DR   GeneID; 1392; -.
DR   KEGG; hsa:1392; -.
DR   UCSC; uc003xvy.1; human.
DR   CTD; 1392; -.
DR   GeneCards; GC08M067138; -.
DR   H-InvDB; HIX0007552; -.
DR   HGNC; HGNC:2355; CRH.
DR   HPA; CAB010885; -.
DR   MIM; 122560; gene+phenotype.
DR   neXtProt; NX_P06850; -.
DR   PharmGKB; PA119; -.
DR   eggNOG; prNOG21212; -.
DR   GeneTree; ENSGT00510000048573; -.
DR   HOGENOM; HBG715743; -.
DR   HOVERGEN; HBG001951; -.
DR   InParanoid; P06850; -.
DR   OMA; AANFFRV; -.
DR   OrthoDB; EOG4P2Q3Q; -.
DR   PhylomeDB; P06850; -.
DR   Reactome; REACT_111102; Signal Transduction.
DR   DrugBank; DB01285; Corticotropin.
DR   NextBio; 5695; -.
DR   ArrayExpress; P06850; -.
DR   Bgee; P06850; -.
DR   CleanEx; HS_CRH; -.
DR   Genevestigator; P06850; -.
DR   GermOnline; ENSG00000147571; Homo sapiens.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005625; C:soluble fraction; TAS:ProtInc.
DR   GO; GO:0005184; F:neuropeptide hormone activity; TAS:ProtInc.
DR   GO; GO:0007565; P:female pregnancy; TAS:ProtInc.
DR   GO; GO:0042322; P:negative regulation of circadian sleep/wake cycle, REM sleep; NAS:BHF-UCL.
DR   GO; GO:0007567; P:parturition; TAS:ProtInc.
DR   GO; GO:0010841; P:positive regulation of circadian sleep/wake cycle, wakefulness; NAS:BHF-UCL.
DR   GO; GO:0051464; P:positive regulation of cortisol secretion; IDA:BHF-UCL.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
DR   InterPro; IPR018446; Corticotropin-releasing_fac_CS.
DR   InterPro; IPR000187; Corticotropin-releasing_factor.
DR   InterPro; IPR003620; Urocortin_CRF.
DR   KO; K05256; -.
DR   PANTHER; PTHR15035; Urocortin_CRF; 1.
DR   Pfam; PF00473; CRF; 1.
DR   PRINTS; PR01612; CRFFAMILY.
DR   SMART; SM00039; CRF; 1.
DR   PROSITE; PS00511; CRF; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amidation; Cleavage on pair of basic residues;
KW   Complete proteome; Direct protein sequencing; Hormone;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     24       Probable.
FT   PROPEP       25    153
FT                                /FTId=PRO_0000006212.
FT   PEPTIDE     154    194       Corticoliberin.
FT                                /FTId=PRO_0000006213.
FT   MOD_RES     194    194       Isoleucine amide.
FT   MUTAGEN     183    183       Q->A: Strongly reduced affinity for
FT                                CRFR1.
FT   MUTAGEN     187    187       N->A: No effect on affinity for CRFR1.
FT   MUTAGEN     188    188       R->A: Strongly reduced affinity for
FT                                CRFR1.
FT   MUTAGEN     190    190       L->A: Strongly reduced affinity for
FT                                CRFR1.
FT   MUTAGEN     191    191       M->A: Strongly reduced affinity for
FT                                CRFR1.
FT   MUTAGEN     192    192       E->A: No effect on affinity for CRFR1.
FT   HELIX       180    193
SQ   SEQUENCE   196 AA;  21422 MW;  0CCDFF05BE364E92 CRC64;
     MRLPLLVSAG VLLVALLPCP PCRALLSRGP VPGARQAPQH PQPLDFFQPP PQSEQPQQPQ
     ARPVLLRMGE EYFLRLGNLN KSPAAPLSPA SSLLAGGSGS RPSPEQATAN FFRVLLQQLL
     LPRRSLDSPA ALAERGARNA LGGHQEAPER ERRSEEPPIS LDLTFHLLRE VLEMARAEQL
     AQQAHSNRKL MEIIGK
//