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P06850

- CRF_HUMAN

UniProt

P06850 - CRF_HUMAN

Protein

Corticoliberin

Gene

CRH

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 146 (01 Oct 2014)
      Sequence version 1 (01 Jan 1988)
      Previous versions | rss
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    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. protein binding Source: UniProtKB
    4. 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

    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

    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.
    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

    MRLPLLVSAG VLLVALLPCP PCRALLSRGP VPGARQAPQH PQPLDFFQPP    50
    PQSEQPQQPQ ARPVLLRMGE EYFLRLGNLN KSPAAPLSPA SSLLAGGSGS 100
    RPSPEQATAN FFRVLLQQLL LPRRSLDSPA ALAERGARNA LGGHQEAPER 150
    ERRSEEPPIS LDLTFHLLRE VLEMARAEQL AQQAHSNRKL MEIIGK 196
    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.
    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

    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 1, 2014
    This is version 146 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