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Corticoliberin (Corticotropin-releasing factor) (CRF) (Corticotropin-releasing hormone)

 CRF_HUMAN               Reviewed;         196 AA.
P06850; B3KQS4;
01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
01-JAN-1988, sequence version 1.
22-NOV-2017, entry version 174.
RecName: Full=Corticoliberin;
AltName: Full=Corticotropin-releasing factor;
Short=CRF;
AltName: Full=Corticotropin-releasing hormone;
Flags: Precursor;
Name=CRH;
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 AMIDATION AT ILE-194.
PubMed=6605851;
Shibahara S., Morimoto Y., Furutani Y., Notake M., Takahashi H.,
Shimizu S., Horikawa S., Numa S.;
"Isolation and sequence analysis of the human corticotropin-releasing
factor precursor gene.";
EMBO J. 2:775-779(1983).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
PubMed=2783917; DOI=10.1016/0303-7207(89)90128-7;
Robinson B.G., D'Angio L.A. Jr., Pasieka K.B., Majzoub J.A.;
"Preprocorticotropin releasing hormone: cDNA sequence and in vitro
processing.";
Mol. Cell. Endocrinol. 61:175-180(1989).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor
vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Placenta;
PubMed=16303743; DOI=10.1093/dnares/12.2.117;
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
Isogai T.;
"Signal sequence and keyword trap in silico for selection of full-
length human cDNAs encoding secretion or membrane proteins from oligo-
capped cDNA libraries.";
DNA Res. 12:117-126(2005).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
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).
[7]
PROTEIN SEQUENCE OF 154-186, AND TISSUE SPECIFICITY.
PubMed=3262120; DOI=10.1210/jcem-67-4-768;
Sasaki A., Tempst P., Liotta A.S., Margioris A.N., Hood L.E.,
Kent S.B., Sato S., Shinkawa O., Yoshinaga K., Krieger D.T.;
"Isolation and characterization of a corticotropin-releasing hormone-
like peptide from human placenta.";
J. Clin. Endocrinol. Metab. 67:768-773(1988).
[8]
STRUCTURE BY NMR OF 154-194.
PubMed=8386360; DOI=10.1093/protein/6.2.149;
Romier C., Bernassau J.-M., Cambillau C., Darbon H.;
"Solution structure of human corticotropin releasing factor by 1H NMR
and distance geometry with restrained molecular dynamics.";
Protein Eng. 6:149-156(1993).
[9]
X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 175-194 IN COMPLEX WITH
CRFR1, SUBUNIT, AND MUTAGENESIS OF GLN-183; ASN-187; ARG-188; LEU-190;
MET-191 AND GLU-192.
PubMed=18801728; DOI=10.1074/jbc.M805749200;
Pioszak A.A., Parker N.R., Suino-Powell K., Xu H.E.;
"Molecular recognition of corticotropin-releasing factor by its G-
protein-coupled receptor CRFR1.";
J. Biol. Chem. 283:32900-32912(2008).
[10]
VARIANT ARG-30, AND CHARACTERIZATION OF VARIANT ARG-30.
PubMed=23593457; DOI=10.1371/journal.pone.0061306;
Sansoni V., Forcella M., Mozzi A., Fusi P., Ambrosini R.,
Ferini-Strambi L., Combi R.;
"Functional characterization of a CRH missense mutation identified in
an ADNFLE family.";
PLoS ONE 8:E61306-E61306(2013).
-!- FUNCTION: Hormone regulating the release of corticotropin from
pituitary gland (By similarity). Induces NLRP6 in intestinal
epithelial cells, hence may influence gut microbiota profile (By
similarity). {ECO:0000250|UniProtKB:P06296,
ECO:0000250|UniProtKB:Q8CIT0}.
-!- SUBUNIT: Interacts (via C-terminus) with CRFR1 (via N-terminal
extracellular domain). {ECO:0000269|PubMed:18801728}.
-!- INTERACTION:
P34998:CRHR1; NbExp=2; IntAct=EBI-3870390, EBI-3870393;
Q15323:KRT31; NbExp=3; IntAct=EBI-3870390, EBI-948001;
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P06296}.
-!- TISSUE SPECIFICITY: Produced by the hypothalamus and placenta.
{ECO:0000269|PubMed:2783917, ECO:0000269|PubMed:3262120}.
-!- SIMILARITY: Belongs to the sauvagine/corticotropin-releasing
factor/urotensin I family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Wikipedia; Note=Corticotropin-releasing hormone
entry;
URL="https://en.wikipedia.org/wiki/Corticotropin-releasing_hormone";
-----------------------------------------------------------------------
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EMBL; V00571; CAA23834.1; -; Genomic_DNA.
EMBL; BT007453; AAP36121.1; -; mRNA.
EMBL; AK075431; BAG52136.1; -; mRNA.
EMBL; CH471068; EAW86897.1; -; Genomic_DNA.
EMBL; BC002599; AAH02599.1; -; mRNA.
EMBL; BC011031; AAH11031.1; -; mRNA.
CCDS; CCDS6188.1; -.
PIR; A30327; A30327.
RefSeq; NP_000747.1; NM_000756.3.
RefSeq; XP_016868579.1; XM_017013090.1.
RefSeq; XP_016868580.1; XM_017013091.1.
RefSeq; XP_016868581.1; XM_017013092.1.
RefSeq; XP_016868582.1; XM_017013093.1.
UniGene; Hs.75294; -.
PDB; 1GO9; NMR; -; A=154-194.
PDB; 1GOE; NMR; -; A=154-194.
PDB; 3EHT; X-ray; 3.40 A; B=180-194.
PDB; 3EHU; X-ray; 1.96 A; C/D=175-194.
PDBsum; 1GO9; -.
PDBsum; 1GOE; -.
PDBsum; 3EHT; -.
PDBsum; 3EHU; -.
ProteinModelPortal; P06850; -.
SMR; P06850; -.
BioGrid; 107782; 7.
IntAct; P06850; 9.
STRING; 9606.ENSP00000276571; -.
DrugBank; DB02952; Alpha-Aminoisobutyric Acid.
DrugBank; DB01285; Corticotropin.
DrugBank; DB02556; D-Phenylalanine.
iPTMnet; P06850; -.
PhosphoSitePlus; P06850; -.
BioMuta; CRH; -.
DMDM; 117445; -.
PaxDb; P06850; -.
PeptideAtlas; P06850; -.
PRIDE; P06850; -.
TopDownProteomics; P06850; -.
DNASU; 1392; -.
Ensembl; ENST00000276571; ENSP00000276571; ENSG00000147571.
GeneID; 1392; -.
KEGG; hsa:1392; -.
UCSC; uc003xvy.3; human.
CTD; 1392; -.
DisGeNET; 1392; -.
EuPathDB; HostDB:ENSG00000147571.4; -.
GeneCards; CRH; -.
GeneReviews; CRH; -.
HGNC; HGNC:2355; CRH.
HPA; CAB010885; -.
HPA; HPA046846; -.
HPA; HPA062111; -.
MalaCards; CRH; -.
MIM; 122560; gene+phenotype.
neXtProt; NX_P06850; -.
OpenTargets; ENSG00000147571; -.
Orphanet; 98784; Autosomal dominant nocturnal frontal lobe epilepsy.
PharmGKB; PA119; -.
eggNOG; ENOG410IWZK; Eukaryota.
eggNOG; ENOG4111ZIN; LUCA.
GeneTree; ENSGT00510000048573; -.
HOGENOM; HOG000004762; -.
HOVERGEN; HBG001951; -.
InParanoid; P06850; -.
KO; K05256; -.
OMA; YFIRLGN; -.
OrthoDB; EOG091G0QDI; -.
PhylomeDB; P06850; -.
TreeFam; TF332956; -.
Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
Reactome; R-HSA-418555; G alpha (s) signalling events.
SIGNOR; P06850; -.
EvolutionaryTrace; P06850; -.
GeneWiki; Corticotropin-releasing_hormone; -.
GenomeRNAi; 1392; -.
PRO; PR:P06850; -.
Proteomes; UP000005640; Chromosome 8.
Bgee; ENSG00000147571; -.
CleanEx; HS_CRH; -.
ExpressionAtlas; P06850; baseline and differential.
Genevisible; P06850; HS.
GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
GO; GO:0043204; C:perikaryon; IEA:Ensembl.
GO; GO:0043196; C:varicosity; IEA:Ensembl.
GO; GO:0017045; F:corticotropin-releasing hormone activity; IBA:GO_Central.
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:0005179; F:hormone activity; TAS:ProtInc.
GO; GO:0005184; F:neuropeptide hormone activity; TAS:ProtInc.
GO; GO:0005102; F:receptor binding; TAS:ProtInc.
GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
GO; GO:0008306; P:associative learning; IEA:Ensembl.
GO; GO:0071314; P:cellular response to cocaine; IEA:Ensembl.
GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
GO; GO:0016101; P:diterpenoid metabolic process; IEA:Ensembl.
GO; GO:0007565; P:female pregnancy; IDA:UniProtKB.
GO; GO:0006704; P:glucocorticoid biosynthetic process; IEA:Ensembl.
GO; GO:0008628; P:hormone-mediated apoptotic signaling pathway; IEA:Ensembl.
GO; GO:0021854; P:hypothalamus development; IEA:Ensembl.
GO; GO:0006954; P:inflammatory response; IDA:UniProtKB.
GO; GO:0050801; P:ion homeostasis; IEA:Ensembl.
GO; GO:0007611; P:learning or memory; TAS:ProtInc.
GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
GO; GO:0030324; P:lung development; IEA:Ensembl.
GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
GO; GO:0060548; P:negative regulation of cell death; IEA:Ensembl.
GO; GO:0042322; P:negative regulation of circadian sleep/wake cycle, REM sleep; NAS:BHF-UCL.
GO; GO:0032811; P:negative regulation of epinephrine secretion; IBA:GO_Central.
GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
GO; GO:0070093; P:negative regulation of glucagon secretion; IBA:GO_Central.
GO; GO:0033685; P:negative regulation of luteinizing hormone secretion; IEA:Ensembl.
GO; GO:0010700; P:negative regulation of norepinephrine secretion; IEA:Ensembl.
GO; GO:0007567; P:parturition; TAS:ProtInc.
GO; GO:2000987; P:positive regulation of behavioral fear response; 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:0010942; P:positive regulation of cell death; IEA:Ensembl.
GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
GO; GO:0010841; P:positive regulation of circadian sleep/wake cycle, wakefulness; NAS:BHF-UCL.
GO; GO:2000854; P:positive regulation of corticosterone secretion; IEA:Ensembl.
GO; GO:0051461; P:positive regulation of corticotropin secretion; IEA:Ensembl.
GO; GO:0051464; P:positive regulation of cortisol secretion; IDA:BHF-UCL.
GO; GO:0060456; P:positive regulation of digestive system process; IEA:Ensembl.
GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl.
GO; GO:2000310; P:regulation of NMDA receptor activity; IDA:UniProtKB.
GO; GO:0014062; P:regulation of serotonin secretion; IEA:Ensembl.
GO; GO:0051412; P:response to corticosterone; IEA:Ensembl.
GO; GO:0042493; P:response to drug; IEA:Ensembl.
GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
GO; GO:0045472; P:response to ether; IEA:Ensembl.
GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
GO; GO:0048265; P:response to pain; IEA:Ensembl.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
GO; GO:0001963; P:synaptic transmission, dopaminergic; IDA:UniProtKB.
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; Direct protein sequencing; Hormone; Polymorphism;
Reference proteome; Secreted; Signal.
SIGNAL 1 24 {ECO:0000305}.
PROPEP 25 153 {ECO:0000269|PubMed:3262120}.
/FTId=PRO_0000006212.
PEPTIDE 154 194 Corticoliberin.
/FTId=PRO_0000006213.
MOD_RES 194 194 Isoleucine amide.
{ECO:0000269|PubMed:6605851}.
VARIANT 30 30 P -> R (found in patients with autosomal
dominant nocturnal frontal lobe epilepsy;
unknown pathological significance;
results in decreased protein levels;
decreased protein secretion;
dbSNP:rs748404250).
{ECO:0000269|PubMed:23593457}.
/FTId=VAR_075504.
MUTAGEN 183 183 Q->A: Strongly reduced affinity for
CRFR1. {ECO:0000269|PubMed:18801728}.
MUTAGEN 187 187 N->A: No effect on affinity for CRFR1.
{ECO:0000269|PubMed:18801728}.
MUTAGEN 188 188 R->A: Strongly reduced affinity for
CRFR1. {ECO:0000269|PubMed:18801728}.
MUTAGEN 190 190 L->A: Strongly reduced affinity for
CRFR1. {ECO:0000269|PubMed:18801728}.
MUTAGEN 191 191 M->A: Strongly reduced affinity for
CRFR1. {ECO:0000269|PubMed:18801728}.
MUTAGEN 192 192 E->A: No effect on affinity for CRFR1.
{ECO:0000269|PubMed:18801728}.
HELIX 159 171 {ECO:0000244|PDB:1GO9}.
HELIX 173 193 {ECO:0000244|PDB:1GO9}.
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


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