P06850 (CRF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Corticoliberin

Alternative name(s):
Corticotropin-releasing factor
Short name=CRF
Corticotropin-releasing hormone

Gene names

Name:

CRH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	196 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Domain	Signal
Molecular function	Hormone
PTM	Amidation Cleavage on pair of basic residues
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adrenal gland development Inferred from electronic annotation. Source: Compara associative learning Inferred from electronic annotation. Source: Compara cellular response to cocaine Inferred from electronic annotation. Source: Compara cellular response to dexamethasone stimulus Inferred from electronic annotation. Source: Compara diterpenoid metabolic process Inferred from electronic annotation. Source: Compara feeding behavior Inferred from electronic annotation. Source: Compara female pregnancy Inferred from direct assay PubMed 18559919. Source: UniProtKB ferulate metabolic process Inferred from electronic annotation. Source: Compara glucocorticoid biosynthetic process Inferred from electronic annotation. Source: Compara hormone-mediated apoptotic signaling pathway Inferred from electronic annotation. Source: Compara hypothalamus development Inferred from electronic annotation. Source: Compara inflammatory response Inferred from direct assay PubMed 18559919. Source: UniProtKB ion homeostasis Inferred from electronic annotation. Source: Compara learning or memory Traceable author statement PubMed 7477348. Source: ProtInc locomotory exploration behavior Inferred from electronic annotation. Source: Compara long-term memory Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara negative regulation of blood pressure Inferred from electronic annotation. Source: Compara negative regulation of cell death Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of gene expression Inferred from electronic annotation. Source: Compara negative regulation of glucagon secretion Inferred from electronic annotation. Source: Compara negative regulation of luteinizing hormone secretion Inferred from electronic annotation. Source: Compara negative regulation of norepinephrine secretion Inferred from electronic annotation. Source: Compara parturition Traceable author statement PubMed 7585095. Source: ProtInc positive regulation of behavioral fear response Inferred from electronic annotation. Source: Compara positive regulation of cAMP biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of calcium ion import Inferred from electronic annotation. Source: Compara positive regulation of cell death Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of corticotropin secretion Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara positive regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara 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: Compara response to corticosterone stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to estrogen stimulus Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to ether Inferred from electronic annotation. Source: Compara response to immobilization stress Inferred from electronic annotation. Source: Compara response to pain Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement PubMed 7867564. Source: ProtInc synaptic transmission, dopaminergic Inferred from direct assay PubMed 12895416. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 18559919. Source: UniProtKB perikaryon Inferred from electronic annotation. Source: Compara varicosity Inferred from electronic annotation. Source: Compara
Molecular_function	neuropeptide hormone activity Traceable author statement PubMed 7867564. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRHR1	P34998	2	EBI-3870390,EBI-3870393

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Probable

Propeptide

25 – 153

129

PRO_0000006212

Peptide

154 – 194

41

Corticoliberin

PRO_0000006213

Amino acid modifications

Modified residue

194

1

Isoleucine amide

Experimental info

Mutagenesis

183

1

Q → A: Strongly reduced affinity for CRFR1. Ref.9

Mutagenesis

187

1

N → A: No effect on affinity for CRFR1. Ref.9

Mutagenesis

188

1

R → A: Strongly reduced affinity for CRFR1. Ref.9

Mutagenesis

190

1

L → A: Strongly reduced affinity for CRFR1. Ref.9

Mutagenesis

191

1

M → A: Strongly reduced affinity for CRFR1. Ref.9

Mutagenesis

192

1

E → A: No effect on affinity for CRFR1. Ref.9

Secondary structure

1

.

.

.

196

Helix Strand Turn

Details...

Helix

180 – 193

14

Sequences

	Sequence		Length	Mass (Da)
	P06850 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 0CCDFF05BE364E92	FASTA	196	21,422
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00027839.

PIR

A30327.

RefSeq

NP_000747.1. NM_000756.2.

UniGene

Hs.75294.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EHT	X-ray	3.40	B	180-194	[»]
3EHU	X-ray	1.96	C/D	175-194	[»]

ProteinModelPortal

P06850.

ModBase

Search...

Protein-protein interaction databases

IntAct

P06850. 1 interaction.

STRING

9606.ENSP00000276571.

Polymorphism databases

DMDM

117445.

Proteomic databases

PaxDb

P06850.

PRIDE

P06850.

Protocols and materials databases

DNASU

1392.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000276571; ENSP00000276571; ENSG00000147571.

GeneID

1392.

KEGG

hsa:1392.

UCSC

uc003xvy.2. human.

Organism-specific databases

CTD

1392.

GeneCards

GC08M067088.

HGNC

HGNC:2355. CRH.

HPA

CAB010885.

MIM

122560. gene+phenotype.

neXtProt

NX_P06850.

PharmGKB

PA119.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG38852.

HOGENOM

HOG000004762.

HOVERGEN

HBG001951.

InParanoid

P06850.

KO

K05256.

OMA

AANFFRV.

OrthoDB

EOG4P2Q3Q.

PhylomeDB

P06850.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

Bgee

P06850.

CleanEx

HS_CRH.

Genevestigator

P06850.

GermOnline

ENSG00000147571. Homo sapiens.

Family and domain databases

InterPro

IPR018446. Corticotropin-releasing_fac_CS.
IPR000187. Corticotropin-releasing_factor.
IPR003620. Urocortin_CRF.
[Graphical view]

PANTHER

PTHR15035. PTHR15035. 1 hit.

Pfam

PF00473. CRF. 1 hit.
[Graphical view]

PRINTS

PR01612. CRFFAMILY.

SMART

SM00039. CRF. 1 hit.
[Graphical view]

PROSITE

PS00511. CRF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01285. Corticotropin.

EvolutionaryTrace

P06850.

GenomeRNAi

1392.

NextBio

5695.

SOURCE

Search...

Entry information

Entry name

CRF_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.