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P34998 (CRFR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Corticotropin-releasing factor receptor 1

Short name=CRF-R-1
Short name=CRF-R1
Short name=CRFR-1
Alternative name(s):
Corticotropin-releasing hormone receptor 1
Short name=CRH-R-1
Short name=CRH-R1
Gene names
Name:CRHR1
Synonyms:CRFR, CRFR1, CRHR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length444 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli. Ref.15 Ref.17 Ref.18 Ref.20

Subunit structure

Heterodimer; heterodimerizes with GPER1 By similarity. Interacts (via N-terminal extracellular domain) with CRH and UCN. Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist binding. Ref.16 Ref.17

Subcellular location

Cell membrane; Multi-pass membrane protein. Endosome. Note: Agonist-binding promotes endocytosis. Ref.15 Ref.17 Ref.20

Tissue specificity

Predominantly expressed in the cerebellum, pituitary, cerebral cortex and olfactory lobe. Ref.2

Domain

The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure. The antagonist CP-376395 binds at an allosteric site, far from the presumed binding site for the physiological peptide ligand.

Post-translational modification

C-terminal Ser or Thr residues may be phosphorylated. Ref.14

Phosphorylation at Ser-330 by PKA prevents maximal coupling to Gq-protein, and thereby negatively regulates downstream signaling.

Sequence similarities

Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
   Cellular componentCell membrane
Endosome
Membrane
   Coding sequence diversityAlternative splicing
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of adenylate cyclase activity

Traceable author statement Ref.5. Source: ProtInc

adrenal gland development

Inferred from electronic annotation. Source: Ensembl

behavioral response to cocaine

Inferred from electronic annotation. Source: Ensembl

behavioral response to ethanol

Inferred from electronic annotation. Source: Ensembl

behavioral response to pain

Inferred from electronic annotation. Source: Ensembl

cellular response to corticotropin-releasing hormone stimulus

Inferred from direct assay Ref.15. Source: UniProtKB

corticotropin secretion

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

fear response

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Non-traceable author statement PubMed 7585095. Source: ProtInc

general adaptation syndrome, behavioral process

Inferred from electronic annotation. Source: Ensembl

hypothalamus development

Inferred from electronic annotation. Source: Ensembl

immune response

Traceable author statement Ref.1. Source: ProtInc

locomotory exploration behavior

Inferred from electronic annotation. Source: Ensembl

long-term synaptic potentiation

Inferred from electronic annotation. Source: Ensembl

memory

Inferred from electronic annotation. Source: Ensembl

negative regulation of epinephrine secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of feeding behavior

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron death

Inferred from electronic annotation. Source: Ensembl

negative regulation of voltage-gated calcium channel activity

Inferred from direct assay Ref.15. Source: UniProtKB

neuropeptide signaling pathway

Inferred from electronic annotation. Source: Ensembl

parturition

Traceable author statement Ref.5. Source: ProtInc

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of mast cell degranulation

Inferred from electronic annotation. Source: Ensembl

regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway

Inferred from mutant phenotype Ref.20. Source: UniProtKB

regulation of corticosterone secretion

Inferred from sequence or structural similarity. Source: UniProtKB

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to immobilization stress

Inferred from electronic annotation. Source: Ensembl

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical part of cell

Inferred from electronic annotation. Source: Ensembl

dendrite

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from direct assay Ref.20. Source: UniProtKB

integral component of plasma membrane

Traceable author statement Ref.5. Source: ProtInc

intrinsic component of plasma membrane

Inferred from direct assay Ref.15. Source: UniProtKB

multivesicular body

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

trans-Golgi network

Inferred from electronic annotation. Source: Ensembl

vesicle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncorticotrophin-releasing factor receptor activity

Inferred from direct assay Ref.15. Source: UniProtKB

corticotropin-releasing hormone binding

Inferred from electronic annotation. Source: Ensembl

corticotropin-releasing hormone receptor activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.18. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CRHP068502EBI-3870393,EBI-3870390

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform CRF-R1 (identifier: P34998-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform CRF-R2 (identifier: P34998-2)

The sequence of this isoform differs from the canonical sequence as follows:
     146-174: Missing.
Note: Major isoform.
Isoform CRF-R3 (identifier: P34998-3)

The sequence of this isoform differs from the canonical sequence as follows:
     41-81: GLQCNASVDLIGTCWPRSPAGQLVVRPCPAFFYGVRYNTTN → D
     146-174: Missing.
Note: Does not bind to CRF with high affinity.
Isoform CRF-R4 (identifier: P34998-4)

Also known as: 1D;

The sequence of this isoform differs from the canonical sequence as follows:
     146-174: Missing.
     385-398: Missing.
Isoform 5 (identifier: P34998-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-204: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.13
Chain24 – 444421Corticotropin-releasing factor receptor 1
PRO_0000012814

Regions

Topological domain24 – 11188Extracellular Ref.20
Transmembrane112 – 14231Helical; Name=1
Topological domain143 – 17836Cytoplasmic Ref.20
Transmembrane179 – 20325Helical; Name=2
Topological domain204 – 21815Extracellular Ref.20
Transmembrane219 – 24729Helical; Name=3
Topological domain248 – 2547Cytoplasmic Ref.20
Transmembrane255 – 28228Helical; Name=4
Topological domain283 – 29816Extracellular Ref.20
Transmembrane299 – 32426Helical; Name=5
Topological domain325 – 33511Cytoplasmic Ref.20
Transmembrane336 – 36025Helical; Name=6
Topological domain361 – 3677Extracellular Ref.20
Transmembrane368 – 39730Helical; Name=7
Topological domain398 – 44447Cytoplasmic Ref.20
Region99 – 10810Important for peptide agonist binding
Region309 – 31911Important for antagonist binding

Amino acid modifications

Modified residue3301Phosphoserine; by PKA Ref.14
Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation781N-linked (GlcNAc...) Potential
Glycosylation901N-linked (GlcNAc...) Potential
Glycosylation981N-linked (GlcNAc...) Potential
Disulfide bond30 ↔ 54 Ref.13 Ref.18 Ref.20
Disulfide bond44 ↔ 87 Ref.13 Ref.18 Ref.20
Disulfide bond68 ↔ 102 Ref.13 Ref.18 Ref.20
Disulfide bond217 ↔ 287 Ref.13 Ref.18 Ref.20

Natural variations

Alternative sequence1 – 204204Missing in isoform 5.
VSP_045434
Alternative sequence41 – 8141GLQCN…YNTTN → D in isoform CRF-R3.
VSP_001996
Alternative sequence146 – 17429Missing in isoform CRF-R2, isoform CRF-R3 and isoform CRF-R4.
VSP_001997
Alternative sequence385 – 39814Missing in isoform CRF-R4.
VSP_001998

Experimental info

Mutagenesis2321F → A: Nearly abolishes antagonist binding. Ref.20
Mutagenesis2351M → A: Strongly reduces antagonist binding. Ref.20
Mutagenesis3091L → A: Nearly abolishes antagonist binding. Ref.20
Mutagenesis3121N → A: Nearly abolishes antagonist binding. Ref.20
Mutagenesis3131F → A: Slightly reduces antagonist binding. Ref.20
Mutagenesis3161L → A: Strongly reduces antagonist binding. Ref.20
Mutagenesis3191I → A: Strongly reduces antagonist binding. Ref.20
Mutagenesis3561Y → A: Strongly reduces antagonist binding. Ref.20
Mutagenesis3841Q → A: Increases antagonist binding. Ref.20

Secondary structure

........................................ 444
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform CRF-R1 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 7221AEFB0E7AA8ED

FASTA44450,719
        10         20         30         40         50         60 
MGGHPQLRLV KALLLLGLNP VSASLQDQHC ESLSLASNIS GLQCNASVDL IGTCWPRSPA 

        70         80         90        100        110        120 
GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS ECQEILNEEK KSKVHYHVAV 

       130        140        150        160        170        180 
IINYLGHCIS LVALLVAFVL FLRLRPGCTH WGDQADGALE VGAPWSGAPF QVRRSIRCLR 

       190        200        210        220        230        240 
NIIHWNLISA FILRNATWFV VQLTMSPEVH QSNVGWCRLV TAAYNYFHVT NFFWMFGEGC 

       250        260        270        280        290        300 
YLHTAIVLTY STDRLRKWMF ICIGWGVPFP IIVAWAIGKL YYDNEKCWFG KRPGVYTDYI 

       310        320        330        340        350        360 
YQGPMILVLL INFIFLFNIV RILMTKLRAS TTSETIQYRK AVKATLVLLP LLGITYMLFF 

       370        380        390        400        410        420 
VNPGEDEVSR VVFIYFNSFL ESFQGFFVSV FYCFLNSEVR SAIRKRWHRW QDKHSIRARV 

       430        440 
ARAMSIPTSP TRVSFHSIKQ STAV 

« Hide

Isoform CRF-R2 [UniParc].

Checksum: 81445283CCE34C6E
Show »

FASTA41547,671
Isoform CRF-R3 [UniParc].

Checksum: 6A2068BE9386F8B0
Show »

FASTA37543,331
Isoform CRF-R4 (1D) [UniParc].

Checksum: 3D8FF9B128810372
Show »

FASTA40146,030
Isoform 5 [UniParc].

Checksum: F4465F15BF7C52E4
Show »

FASTA24028,122

References

« Hide 'large scale' references
[1]"Expression cloning of a human corticotropin-releasing-factor receptor."
Chen R., Lewis K.A., Perrin M.H., Vale W.W.
Proc. Natl. Acad. Sci. U.S.A. 90:8967-8971(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS CRF-R1 AND CRF-R2).
Tissue: Pituitary.
[2]"Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptors."
Vita N., Laurent P., Lefort S., Chalon P., Lelias J.-M., Kaghad M., le Fur G., Caput D., Ferrara P.
FEBS Lett. 335:1-5(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF-R2), TISSUE SPECIFICITY.
Tissue: Brain.
[3]"The genomic organization of the human corticotropin-releasing factor type-1 receptor."
Sakai K., Yamada M., Horiba N., Wakui M., Demura H., Suda T.
Gene 219:125-130(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"A variant of the human corticotropin-releasing factor (CRF) receptor: cloning, expression and pharmacology."
Ross P.C., Kostas C.M., Ramabhadran T.V.
Biochem. Biophys. Res. Commun. 205:1836-1842(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF-R3).
Tissue: Hippocampus.
[5]"A novel spliced variant of the type 1 corticotropin-releasing hormone receptor with a deletion in the seventh transmembrane domain present in the human pregnant term myometrium and fetal membranes."
Grammatopoulos D.K., Dai Y., Randeva H.S., Levine M.A., Karteris E., Easton A.J., Hillhouse E.W.
Mol. Endocrinol. 13:2189-2202(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF-R4).
[6]"A novel CRF1 splice isoform involved in neurodegenerative and stress disorders."
Sherrin T., Murthy S.R., Spiess J.
Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[7]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
King M.M., Aronstam R.S., Sharma S.V.
Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF-R2).
Tissue: Brain.
[8]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF-R2).
[9]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
Tissue: Hippocampus.
[10]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]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].
[12]"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] (ISOFORM CRF-R2).
[13]"Expression, purification, and characterization of a soluble form of the first extracellular domain of the human type 1 corticotropin releasing factor receptor."
Perrin M.H., Fischer W.H., Kunitake K.S., Craig A.G., Koerber S.C., Cervini L.A., Rivier J.E., Groppe J.C., Greenwald J., Moller Nielsen S., Vale W.W.
J. Biol. Chem. 276:31528-31534(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-31, DISULFIDE BONDS.
[14]"Protein kinase A-induced negative regulation of the corticotropin-releasing hormone R1alpha receptor-extracellularly regulated kinase signal transduction pathway: the critical role of Ser301 for signaling switch and selectivity."
Papadopoulou N., Chen J., Randeva H.S., Levine M.A., Hillhouse E.W., Grammatopoulos D.K.
Mol. Endocrinol. 18:624-639(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-330.
[15]"Activation of corticotropin-releasing factor receptor 1 selectively inhibits CaV3.2 T-type calcium channels."
Tao J., Hildebrand M.E., Liao P., Liang M.C., Tan G., Li S., Snutch T.P., Soong T.W.
Mol. Pharmacol. 73:1596-1609(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[16]"Structural basis for hormone recognition by the Human CRFR2{alpha} G protein-coupled receptor."
Pal K., Swaminathan K., Xu H.E., Pioszak A.A.
J. Biol. Chem. 285:40351-40361(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRF AND UCN.
[17]"Role of SAP97 protein in the regulation of corticotropin-releasing factor receptor 1 endocytosis and extracellular signal-regulated kinase 1/2 signaling."
Dunn H.A., Walther C., Godin C.M., Hall R.A., Ferguson S.S.
J. Biol. Chem. 288:15023-15034(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DLG1.
[18]"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 24-119 IN COMPLEX WITH CRH, FUNCTION, DISULFIDE BONDS.
[19]"NMR structure of the first extracellular domain of corticotropin-releasing factor receptor 1 (ECD1-CRF-R1) complexed with a high affinity agonist."
Grace C.R., Perrin M.H., Gulyas J., Rivier J.E., Vale W.W., Riek R.
J. Biol. Chem. 285:38580-38589(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 25-109 IN COMPLEX WITH SYNTHETIC CRH ANALOG.
[20]"Structure of class B GPCR corticotropin-releasing factor receptor 1."
Hollenstein K., Kean J., Bortolato A., Cheng R.K., Dore A.S., Jazayeri A., Cooke R.M., Weir M., Marshall F.H.
Nature 499:438-443(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.98 ANGSTROMS) OF 104-373 IN COMPLEX WITH THE SYNTHETIC ANTAGONIST CP-376395, FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, DISULFIDE BOND, ANTAGONIST BINDING SITES, MUTAGENESIS OF PHE-232; MET-235; LEU-309; ASN-312; PHE-313; LEU-316; ILE-319; TYR-356 AND GLN-384.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L23333 mRNA. Translation: AAA35719.1.
L23332 mRNA. Translation: AAA35718.1.
X72304 mRNA. Translation: CAA51052.1.
AF039523 expand/collapse EMBL AC list , AF039510, AF039511, AF039512, AF039513, AF039514, AF039515, AF039516, AF039517, AF039518, AF039519, AF039520, AF039521, AF039522 Genomic DNA. Translation: AAC69993.1.
U16273 mRNA. Translation: AAC50073.1.
AF180301 mRNA. Translation: AAD52688.1.
FJ543100 mRNA. Translation: ACU68591.1.
AY457172 mRNA. Translation: AAR19768.1.
AB451466 mRNA. Translation: BAG70280.1.
AK295559 mRNA. Translation: BAG58461.1.
AC126544 Genomic DNA. No translation available.
AC217770 Genomic DNA. No translation available.
AC217771 Genomic DNA. No translation available.
AC217774 Genomic DNA. No translation available.
AC225613 Genomic DNA. No translation available.
CH471233 Genomic DNA. Translation: EAW93557.1.
BC096836 mRNA. Translation: AAH96836.1.
CCDSCCDS42350.1. [P34998-2]
CCDS45712.1. [P34998-1]
CCDS45713.1. [P34998-4]
CCDS45714.1. [P34998-3]
CCDS58556.1. [P34998-5]
PIRI38879.
A48260. I60975.
RefSeqNP_001138618.1. NM_001145146.1. [P34998-1]
NP_001138619.1. NM_001145147.1. [P34998-3]
NP_001138620.1. NM_001145148.1. [P34998-4]
NP_001243228.1. NM_001256299.1. [P34998-5]
NP_004373.2. NM_004382.4. [P34998-2]
UniGeneHs.417628.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L27NMR-A25-108[»]
3EHSX-ray2.76A24-119[»]
3EHTX-ray3.40A24-119[»]
3EHUX-ray1.96A/B24-119[»]
4K5YX-ray2.98A/B/C104-373[»]
ProteinModelPortalP34998.
SMRP34998. Positions 24-108, 117-397.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107784. 8 interactions.
IntActP34998. 2 interactions.
MINTMINT-1217325.
STRING9606.ENSP00000381333.

Chemistry

BindingDBP34998.
ChEMBLCHEMBL1800.
GuidetoPHARMACOLOGY212.

Protein family/group databases

TCDB9.A.14.4.3. the g-protein-coupled receptor (gpcr) family.
GPCRDBSearch...

PTM databases

PhosphoSiteP34998.

Polymorphism databases

DMDM461836.

Proteomic databases

PaxDbP34998.
PRIDEP34998.

Protocols and materials databases

DNASU1394.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293493; ENSP00000293493; ENSG00000120088. [P34998-5]
ENST00000314537; ENSP00000326060; ENSG00000120088. [P34998-2]
ENST00000352855; ENSP00000344068; ENSG00000120088. [P34998-3]
ENST00000398285; ENSP00000381333; ENSG00000120088. [P34998-1]
ENST00000577353; ENSP00000462016; ENSG00000120088. [P34998-4]
GeneID1394.
KEGGhsa:1394.
UCSCuc002ijm.3. human. [P34998-2]
uc002ijn.3. human. [P34998-3]
uc002ijo.2. human. [P34998-1]
uc010dar.3. human. [P34998-4]

Organism-specific databases

CTD1394.
GeneCardsGC17P043704.
HGNCHGNC:2357. CRHR1.
MIM122561. gene.
neXtProtNX_P34998.
PharmGKBPA26874.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295825.
HOGENOMHOG000230719.
HOVERGENHBG106921.
KOK04578.
OMAVGWCRLV.
PhylomeDBP34998.
TreeFamTF315710.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP34998.
BgeeP34998.
CleanExHS_CRHR1.
GenevestigatorP34998.

Family and domain databases

InterProIPR017981. GPCR_2-like.
IPR003052. GPCR_2_CRF1_rcpt.
IPR003051. GPCR_2_CRF_rcpt.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]
PfamPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSPR01279. CRFRECEPTOR.
PR01280. CRFRECEPTOR1.
PR00249. GPCRSECRETIN.
SMARTSM00008. HormR. 1 hit.
[Graphical view]
PROSITEPS00649. G_PROTEIN_RECEP_F2_1. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP34998.
GeneWikiCorticotropin_releasing_hormone_receptor_1.
GenomeRNAi1394.
NextBio5703.
PROP34998.
SOURCESearch...

Entry information

Entry nameCRFR1_HUMAN
AccessionPrimary (citable) accession number: P34998
Secondary accession number(s): B4DIE9 expand/collapse secondary AC list , Q13008, Q4QRJ1, Q9UK64
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: July 9, 2014
This is version 144 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 17

Human chromosome 17: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries