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P06850 (CRF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Corticoliberin
Alternative name(s):
Corticotropin-releasing factor
Short name=CRF
Corticotropin-releasing hormone
Gene names
Name:CRH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length196 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This hormone from hypothalamus regulates the release of corticotropin from pituitary gland.

Subunit structure

Interacts (via C-terminus) with CRFR1 (via N-terminal extracellular domain). Ref.9

Subcellular location

Secreted.

Sequence similarities

Belongs to the sauvagine/corticotropin-releasing factor/urotensin I family.

Ontologies

Keywords
   Cellular componentSecreted
   DomainSignal
   Molecular functionHormone
   PTMAmidation
Cleavage on pair of basic residues
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadrenal gland development

Inferred from electronic annotation. Source: Ensembl

associative learning

Inferred from electronic annotation. Source: Ensembl

cellular response to cocaine

Inferred from electronic annotation. Source: Ensembl

cellular response to dexamethasone stimulus

Inferred from electronic annotation. Source: Ensembl

diterpenoid metabolic process

Inferred from electronic annotation. Source: Ensembl

feeding behavior

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from direct assay PubMed 18559919. Source: UniProtKB

ferulate metabolic process

Inferred from electronic annotation. Source: Ensembl

glucocorticoid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

hormone-mediated apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

hypothalamus development

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Inferred from direct assay PubMed 18559919. Source: UniProtKB

ion homeostasis

Inferred from electronic annotation. Source: Ensembl

learning or memory

Traceable author statement PubMed 7477348. Source: ProtInc

locomotory exploration behavior

Inferred from electronic annotation. Source: Ensembl

long-term memory

Inferred from electronic annotation. Source: Ensembl

long-term synaptic potentiation

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from electronic annotation. Source: Ensembl

negative regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell death

Inferred from electronic annotation. Source: Ensembl

negative regulation of circadian sleep/wake cycle, REM sleep

Non-traceable author statement PubMed 18329818. Source: BHF-UCL

negative regulation of epinephrine secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

negative regulation of glucagon secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of luteinizing hormone secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of norepinephrine secretion

Inferred from electronic annotation. Source: Ensembl

parturition

Traceable author statement PubMed 7585095. Source: ProtInc

positive regulation of behavioral fear response

Inferred from electronic annotation. Source: Ensembl

positive regulation of cAMP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of calcium ion import

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell death

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of circadian sleep/wake cycle, wakefulness

Non-traceable author statement PubMed 18329818. Source: BHF-UCL

positive regulation of corticosterone secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of corticotropin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of cortisol secretion

Inferred from direct assay PubMed 18329818. Source: BHF-UCL

positive regulation of digestive system process

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of N-methyl-D-aspartate selective glutamate receptor activity

Inferred from direct assay PubMed 12895416. Source: UniProtKB

regulation of serotonin secretion

Inferred from electronic annotation. Source: Ensembl

response to corticosterone

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to ether

Inferred from electronic annotation. Source: Ensembl

response to immobilization stress

Inferred from electronic annotation. Source: Ensembl

response to pain

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement PubMed 7867564. Source: ProtInc

synaptic transmission

Traceable author statement PubMed 7477348. Source: ProtInc

synaptic transmission, dopaminergic

Inferred from direct assay PubMed 12895416. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 18559919. Source: UniProtKB

perikaryon

Inferred from electronic annotation. Source: Ensembl

varicosity

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionhormone activity

Traceable author statement PubMed 7585095. Source: ProtInc

neuropeptide hormone activity

Traceable author statement PubMed 7867564. Source: ProtInc

receptor binding

Traceable author statement PubMed 7477348. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CRHR1P349982EBI-3870390,EBI-3870393

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Probable
Propeptide25 – 153129
PRO_0000006212
Peptide154 – 19441Corticoliberin
PRO_0000006213

Amino acid modifications

Modified residue1941Isoleucine amide

Experimental info

Mutagenesis1831Q → A: Strongly reduced affinity for CRFR1. Ref.9
Mutagenesis1871N → A: No effect on affinity for CRFR1. Ref.9
Mutagenesis1881R → A: Strongly reduced affinity for CRFR1. Ref.9
Mutagenesis1901L → A: Strongly reduced affinity for CRFR1. Ref.9
Mutagenesis1911M → A: Strongly reduced affinity for CRFR1. Ref.9
Mutagenesis1921E → A: No effect on affinity for CRFR1. Ref.9

Secondary structure

... 196
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06850 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 0CCDFF05BE364E92

FASTA19621,422
        10         20         30         40         50         60 
MRLPLLVSAG VLLVALLPCP PCRALLSRGP VPGARQAPQH PQPLDFFQPP PQSEQPQQPQ 

        70         80         90        100        110        120 
ARPVLLRMGE EYFLRLGNLN KSPAAPLSPA SSLLAGGSGS RPSPEQATAN FFRVLLQQLL 

       130        140        150        160        170        180 
LPRRSLDSPA ALAERGARNA LGGHQEAPER ERRSEEPPIS LDLTFHLLRE VLEMARAEQL 

       190 
AQQAHSNRKL MEIIGK 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene."
Shibahara S., Morimoto Y., Furutani Y., Notake M., Takahashi H., Shimizu S., Horikawa S., Numa S.
EMBO J. 2:775-779(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Preprocorticotropin releasing hormone: cDNA sequence and in vitro processing."
Robinson B.G., D'Angio L.A. Jr., Pasieka K.B., Majzoub J.A.
Mol. Cell. Endocrinol. 61:175-180(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
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.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
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. expand/collapse author list , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[5]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. expand/collapse author list , 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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Isolation and characterization of a corticotropin-releasing hormone-like peptide from human placenta."
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.
J. Clin. Endocrinol. Metab. 67:768-773(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 154-186.
[8]"Solution structure of human corticotropin releasing factor by 1H NMR and distance geometry with restrained molecular dynamics."
Romier C., Bernassau J.-M., Cambillau C., Darbon H.
Protein Eng. 6:149-156(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 154-194.
[9]"Molecular recognition of corticotropin-releasing factor by its G-protein-coupled receptor CRFR1."
Pioszak A.A., Parker N.R., Suino-Powell K., Xu H.E.
J. Biol. Chem. 283:32900-32912(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 175-194 IN COMPLEX WITH CRFR1, SUBUNIT, MUTAGENESIS OF GLN-183; ASN-187; ARG-188; LEU-190; MET-191 AND GLU-192.
+Additional computationally mapped references.

Web resources

Wikipedia

Corticotropin-releasing hormone entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
V00571 Genomic DNA. Translation: CAA23834.1.
BT007453 mRNA. Translation: AAP36121.1.
AK075431 mRNA. Translation: BAG52136.1.
CH471068 Genomic DNA. Translation: EAW86897.1.
BC002599 mRNA. Translation: AAH02599.1.
BC011031 mRNA. Translation: AAH11031.1.
PIRA30327.
RefSeqNP_000747.1. NM_000756.2.
UniGeneHs.75294.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3EHTX-ray3.40B180-194[»]
3EHUX-ray1.96C/D175-194[»]
ProteinModelPortalP06850.
SMRP06850. Positions 154-194.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107782. 4 interactions.
IntActP06850. 1 interaction.
STRING9606.ENSP00000276571.

Chemistry

DrugBankDB01285. Corticotropin.

Polymorphism databases

DMDM117445.

Proteomic databases

PaxDbP06850.
PRIDEP06850.

Protocols and materials databases

DNASU1392.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000276571; ENSP00000276571; ENSG00000147571.
GeneID1392.
KEGGhsa:1392.
UCSCuc003xvy.2. human.

Organism-specific databases

CTD1392.
GeneCardsGC08M067088.
HGNCHGNC:2355. CRH.
HPACAB010885.
MIM122560. gene+phenotype.
neXtProtNX_P06850.
PharmGKBPA119.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG38852.
HOGENOMHOG000004762.
HOVERGENHBG001951.
InParanoidP06850.
KOK05256.
OMASALGGHQ.
OrthoDBEOG7NSB43.
PhylomeDBP06850.
TreeFamTF332956.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP06850.
CleanExHS_CRH.
GenevestigatorP06850.

Family and domain databases

InterProIPR018446. Corticotropin-releasing_fac_CS.
IPR000187. Corticotropin-releasing_factor.
IPR003620. Urocortin_CRF.
[Graphical view]
PANTHERPTHR15035. PTHR15035. 1 hit.
PfamPF00473. CRF. 1 hit.
[Graphical view]
PRINTSPR01612. CRFFAMILY.
SMARTSM00039. CRF. 1 hit.
[Graphical view]
PROSITEPS00511. CRF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP06850.
GeneWikiCorticotropin-releasing_hormone.
GenomeRNAi1392.
NextBio5695.
PROP06850.
SOURCESearch...

Entry information

Entry nameCRF_HUMAN
AccessionPrimary (citable) accession number: P06850
Secondary accession number(s): B3KQS4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: April 16, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM