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P06850

- CRF_HUMAN

UniProt

P06850 - CRF_HUMAN

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Protein

Corticoliberin

Gene

CRH

Organism
Homo sapiens (Human)
Status
Reviewed - 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. ferulate metabolic process Source: Ensembl
  9. glucocorticoid biosynthetic process Source: Ensembl
  10. hormone-mediated apoptotic signaling pathway Source: Ensembl
  11. hypothalamus development Source: Ensembl
  12. inflammatory response Source: UniProtKB
  13. ion homeostasis Source: Ensembl
  14. learning or memory Source: ProtInc
  15. locomotory exploration behavior Source: Ensembl
  16. long-term memory Source: Ensembl
  17. long-term synaptic potentiation Source: Ensembl
  18. lung development Source: Ensembl
  19. negative regulation of blood pressure Source: Ensembl
  20. negative regulation of cell death Source: Ensembl
  21. negative regulation of circadian sleep/wake cycle, REM sleep Source: BHF-UCL
  22. negative regulation of epinephrine secretion Source: Ensembl
  23. negative regulation of gene expression Source: Ensembl
  24. negative regulation of glucagon secretion Source: Ensembl
  25. negative regulation of luteinizing hormone secretion Source: Ensembl
  26. negative regulation of norepinephrine secretion Source: Ensembl
  27. parturition Source: ProtInc
  28. positive regulation of behavioral fear response Source: Ensembl
  29. positive regulation of calcium ion import Source: Ensembl
  30. positive regulation of cAMP biosynthetic process Source: Ensembl
  31. positive regulation of cell death Source: Ensembl
  32. positive regulation of cell proliferation Source: Ensembl
  33. positive regulation of circadian sleep/wake cycle, wakefulness Source: BHF-UCL
  34. positive regulation of corticosterone secretion Source: Ensembl
  35. positive regulation of corticotropin secretion Source: Ensembl
  36. positive regulation of cortisol secretion Source: BHF-UCL
  37. positive regulation of digestive system process Source: Ensembl
  38. positive regulation of gene expression Source: Ensembl
  39. positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
  40. positive regulation of protein phosphorylation Source: Ensembl
  41. regulation of N-methyl-D-aspartate selective glutamate receptor activity Source: UniProtKB
  42. regulation of serotonin secretion Source: Ensembl
  43. response to corticosterone Source: Ensembl
  44. response to drug 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: 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. 4 interactions.
IntActiP06850. 1 interaction.
STRINGi9606.ENSP00000276571.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.
OMAiNICTAGN.
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:January 1, 1988 - v1
Checksum:i0CCDFF05BE364E92
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS6188.1.
PIRi A30327.
RefSeqi NP_000747.1. NM_000756.2.
UniGenei Hs.75294.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3EHT X-ray 3.40 B 180-194 [» ]
3EHU X-ray 1.96 C/D 175-194 [» ]
ProteinModelPortali P06850.
SMRi P06850. Positions 154-194.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107782. 4 interactions.
IntActi P06850. 1 interaction.
STRINGi 9606.ENSP00000276571.

Chemistry

DrugBanki DB01285. Corticotropin.

Polymorphism databases

DMDMi 117445.

Proteomic databases

PaxDbi P06850.
PRIDEi P06850.

Protocols and materials databases

DNASUi 1392.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000276571 ; ENSP00000276571 ; ENSG00000147571 .
GeneIDi 1392.
KEGGi hsa:1392.
UCSCi uc003xvy.2. human.

Organism-specific databases

CTDi 1392.
GeneCardsi GC08M067088.
GeneReviewsi CRH.
HGNCi HGNC:2355. CRH.
HPAi CAB010885.
MIMi 122560. gene+phenotype.
neXtProti NX_P06850.
Orphaneti 98784. Autosomal dominant nocturnal frontal lobe epilepsy.
PharmGKBi PA119.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG38852.
GeneTreei ENSGT00510000048573.
HOGENOMi HOG000004762.
HOVERGENi HBG001951.
InParanoidi P06850.
KOi K05256.
OMAi NICTAGN.
OrthoDBi EOG7NSB43.
PhylomeDBi P06850.
TreeFami TF332956.

Enzyme and pathway databases

Reactomei REACT_18372. Class B/2 (Secretin family receptors).
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

EvolutionaryTracei P06850.
GeneWikii Corticotropin-releasing_hormone.
GenomeRNAii 1392.
NextBioi 5695.
PROi P06850.
SOURCEi Search...

Gene expression databases

Bgeei P06850.
CleanExi HS_CRH.
Genevestigatori P06850.

Family and domain databases

InterProi IPR018446. Corticotropin-releasing_fac_CS.
IPR000187. Corticotropin-releasing_factor.
IPR003620. Urocortin_CRF.
[Graphical view ]
PANTHERi PTHR15035. PTHR15035. 1 hit.
Pfami PF00473. CRF. 1 hit.
[Graphical view ]
PRINTSi PR01612. CRFFAMILY.
SMARTi SM00039. CRF. 1 hit.
[Graphical view ]
PROSITEi PS00511. CRF. 1 hit.
[Graphical view ]
ProtoNeti Search...

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(1983) [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(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. 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.

Entry informationi

Entry nameiCRF_HUMAN
AccessioniPrimary (citable) accession number: P06850
Secondary accession number(s): B3KQS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: October 29, 2014
This is version 147 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