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Protein

Corticoliberin

Gene

CRH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  1. hormone activity Source: ProtInc
  2. neuropeptide hormone activity Source: ProtInc
  3. receptor binding Source: ProtInc

GO - Biological processi

  1. adrenal gland development Source: Ensembl
  2. associative learning Source: Ensembl
  3. cellular response to cocaine Source: Ensembl
  4. cellular response to dexamethasone stimulus Source: Ensembl
  5. diterpenoid metabolic process Source: Ensembl
  6. feeding behavior Source: Ensembl
  7. female pregnancy Source: UniProtKB
  8. glucocorticoid biosynthetic process Source: Ensembl
  9. hormone-mediated apoptotic signaling pathway Source: Ensembl
  10. hypothalamus development Source: Ensembl
  11. inflammatory response Source: UniProtKB
  12. ion homeostasis Source: Ensembl
  13. learning or memory Source: ProtInc
  14. locomotory exploration behavior Source: Ensembl
  15. long-term memory Source: Ensembl
  16. long-term synaptic potentiation Source: Ensembl
  17. lung development Source: Ensembl
  18. negative regulation of blood pressure Source: Ensembl
  19. negative regulation of cell death Source: Ensembl
  20. negative regulation of circadian sleep/wake cycle, REM sleep Source: BHF-UCL
  21. negative regulation of epinephrine secretion Source: Ensembl
  22. negative regulation of gene expression Source: Ensembl
  23. negative regulation of glucagon secretion Source: Ensembl
  24. negative regulation of luteinizing hormone secretion Source: Ensembl
  25. negative regulation of norepinephrine secretion Source: Ensembl
  26. parturition Source: ProtInc
  27. positive regulation of behavioral fear response Source: Ensembl
  28. positive regulation of calcium ion import Source: Ensembl
  29. positive regulation of cAMP biosynthetic process Source: Ensembl
  30. positive regulation of cell death Source: Ensembl
  31. positive regulation of cell proliferation Source: Ensembl
  32. positive regulation of circadian sleep/wake cycle, wakefulness Source: BHF-UCL
  33. positive regulation of corticosterone secretion Source: Ensembl
  34. positive regulation of corticotropin secretion Source: Ensembl
  35. positive regulation of cortisol secretion Source: BHF-UCL
  36. positive regulation of digestive system process Source: Ensembl
  37. positive regulation of gene expression Source: Ensembl
  38. positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
  39. positive regulation of protein phosphorylation Source: Ensembl
  40. regulation of N-methyl-D-aspartate selective glutamate receptor activity Source: UniProtKB
  41. regulation of serotonin secretion Source: Ensembl
  42. response to corticosterone Source: Ensembl
  43. response to drug Source: Ensembl
  44. response to electrical stimulus Source: Ensembl
  45. response to estrogen Source: Ensembl
  46. response to ethanol Source: Ensembl
  47. response to ether Source: Ensembl
  48. response to immobilization stress Source: Ensembl
  49. response to pain Source: Ensembl
  50. signal transduction Source: ProtInc
  51. synaptic transmission Source: ProtInc
  52. synaptic transmission, dopaminergic Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hormone

Enzyme and pathway databases

ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Corticoliberin
Alternative name(s):
Corticotropin-releasing factor
Short name:
CRF
Corticotropin-releasing hormone
Gene namesi
Name:CRH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:2355. CRH.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. extracellular region Source: Reactome
  3. extracellular space Source: UniProtKB
  4. perikaryon Source: Ensembl
  5. varicosity Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi183 – 1831Q → A: Strongly reduced affinity for CRFR1. 1 Publication
Mutagenesisi187 – 1871N → A: No effect on affinity for CRFR1. 1 Publication
Mutagenesisi188 – 1881R → A: Strongly reduced affinity for CRFR1. 1 Publication
Mutagenesisi190 – 1901L → A: Strongly reduced affinity for CRFR1. 1 Publication
Mutagenesisi191 – 1911M → A: Strongly reduced affinity for CRFR1. 1 Publication
Mutagenesisi192 – 1921E → A: No effect on affinity for CRFR1. 1 Publication

Organism-specific databases

MIMi122560. gene+phenotype.
Orphaneti98784. Autosomal dominant nocturnal frontal lobe epilepsy.
PharmGKBiPA119.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424CuratedAdd
BLAST
Propeptidei25 – 1531291 PublicationPRO_0000006212Add
BLAST
Peptidei154 – 19441CorticoliberinPRO_0000006213Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei194 – 1941Isoleucine amide1 Publication

Keywords - PTMi

Amidation, Cleavage on pair of basic residues

Proteomic databases

PaxDbiP06850.
PRIDEiP06850.

Expressioni

Gene expression databases

BgeeiP06850.
CleanExiHS_CRH.
GenevestigatoriP06850.

Organism-specific databases

HPAiCAB010885.

Interactioni

Subunit structurei

Interacts (via C-terminus) with CRFR1 (via N-terminal extracellular domain).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CRHR1P349982EBI-3870390,EBI-3870393

Protein-protein interaction databases

BioGridi107782. 5 interactions.
IntActiP06850. 1 interaction.
STRINGi9606.ENSP00000276571.

Structurei

Secondary structure

1
196
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi180 – 19314Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3EHTX-ray3.40B180-194[»]
3EHUX-ray1.96C/D175-194[»]
ProteinModelPortaliP06850.
SMRiP06850. Positions 154-194.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06850.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG38852.
GeneTreeiENSGT00510000048573.
HOGENOMiHOG000004762.
HOVERGENiHBG001951.
InParanoidiP06850.
KOiK05256.
OMAiSALGGHQ.
OrthoDBiEOG7NSB43.
PhylomeDBiP06850.
TreeFamiTF332956.

Family and domain databases

InterProiIPR018446. Corticotropin-releasing_fac_CS.
IPR000187. Corticotropin-releasing_factor.
IPR003620. Urocortin_CRF.
[Graphical view]
PANTHERiPTHR15035. PTHR15035. 1 hit.
PfamiPF00473. CRF. 1 hit.
[Graphical view]
PRINTSiPR01612. CRFFAMILY.
SMARTiSM00039. CRF. 1 hit.
[Graphical view]
PROSITEiPS00511. CRF. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P06850-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLPLLVSAG VLLVALLPCP PCRALLSRGP VPGARQAPQH PQPLDFFQPP
60 70 80 90 100
PQSEQPQQPQ ARPVLLRMGE EYFLRLGNLN KSPAAPLSPA SSLLAGGSGS
110 120 130 140 150
RPSPEQATAN FFRVLLQQLL LPRRSLDSPA ALAERGARNA LGGHQEAPER
160 170 180 190
ERRSEEPPIS LDLTFHLLRE VLEMARAEQL AQQAHSNRKL MEIIGK
Length:196
Mass (Da):21,422
Last modified:December 31, 1987 - v1
Checksum:i0CCDFF05BE364E92
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6188.1.
PIRiA30327.
RefSeqiNP_000747.1. NM_000756.2.
UniGeneiHs.75294.

Genome annotation databases

EnsembliENST00000276571; ENSP00000276571; ENSG00000147571.
GeneIDi1392.
KEGGihsa:1392.
UCSCiuc003xvy.2. human.

Polymorphism databases

DMDMi117445.

Cross-referencesi

Web resourcesi

Wikipedia

Corticotropin-releasing hormone entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6188.1.
PIRiA30327.
RefSeqiNP_000747.1. NM_000756.2.
UniGeneiHs.75294.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3EHTX-ray3.40B180-194[»]
3EHUX-ray1.96C/D175-194[»]
ProteinModelPortaliP06850.
SMRiP06850. Positions 154-194.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107782. 5 interactions.
IntActiP06850. 1 interaction.
STRINGi9606.ENSP00000276571.

Chemistry

DrugBankiDB01285. Corticotropin.

Polymorphism databases

DMDMi117445.

Proteomic databases

PaxDbiP06850.
PRIDEiP06850.

Protocols and materials databases

DNASUi1392.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000276571; ENSP00000276571; ENSG00000147571.
GeneIDi1392.
KEGGihsa:1392.
UCSCiuc003xvy.2. human.

Organism-specific databases

CTDi1392.
GeneCardsiGC08M067088.
GeneReviewsiCRH.
HGNCiHGNC:2355. CRH.
HPAiCAB010885.
MIMi122560. gene+phenotype.
neXtProtiNX_P06850.
Orphaneti98784. Autosomal dominant nocturnal frontal lobe epilepsy.
PharmGKBiPA119.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG38852.
GeneTreeiENSGT00510000048573.
HOGENOMiHOG000004762.
HOVERGENiHBG001951.
InParanoidiP06850.
KOiK05256.
OMAiSALGGHQ.
OrthoDBiEOG7NSB43.
PhylomeDBiP06850.
TreeFamiTF332956.

Enzyme and pathway databases

ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

EvolutionaryTraceiP06850.
GeneWikiiCorticotropin-releasing_hormone.
GenomeRNAii1392.
NextBioi5695.
PROiP06850.
SOURCEiSearch...

Gene expression databases

BgeeiP06850.
CleanExiHS_CRH.
GenevestigatoriP06850.

Family and domain databases

InterProiIPR018446. Corticotropin-releasing_fac_CS.
IPR000187. Corticotropin-releasing_factor.
IPR003620. Urocortin_CRF.
[Graphical view]
PANTHERiPTHR15035. PTHR15035. 1 hit.
PfamiPF00473. CRF. 1 hit.
[Graphical view]
PRINTSiPR01612. CRFFAMILY.
SMARTiSM00039. CRF. 1 hit.
[Graphical view]
PROSITEiPS00511. CRF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], AMIDATION AT ILE-194.
  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(1988) [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 (APR-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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  5. 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(2003) [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(1987) [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(1992) [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(2007) [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.

Entry informationi

Entry nameiCRF_HUMAN
AccessioniPrimary (citable) accession number: P06850
Secondary accession number(s): B3KQS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 31, 1987
Last sequence update: December 31, 1987
Last modified: February 3, 2015
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.