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P34998 (CRFR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
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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)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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

Receptor for corticotropin releasing factor (CRH). Shows high-affinity CRF binding. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Ref.11

Subunit structure

Interacts (via N-terminal extracellular domain) with CRF and UCN. Ref.10

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

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

Post-translational modification

C-terminal Ser or Thr residues may be phosphorylated.

Sequence similarities

Belongs to the G-protein coupled receptor 2 family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CRHP068502EBI-3870393,EBI-3870390

Alternative products

This entry describes 4 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.9
Chain24 – 444421Corticotropin-releasing factor receptor 1
PRO_0000012814

Regions

Topological domain24 – 12198Extracellular Potential
Transmembrane122 – 14221Helical; Name=1; Potential
Topological domain143 – 18038Cytoplasmic Potential
Transmembrane181 – 20020Helical; Name=2; Potential
Topological domain201 – 21818Extracellular Potential
Transmembrane219 – 24224Helical; Name=3; Potential
Topological domain243 – 25614Cytoplasmic Potential
Transmembrane257 – 27822Helical; Name=4; Potential
Topological domain279 – 29719Extracellular Potential
Transmembrane298 – 32023Helical; Name=5; Potential
Topological domain321 – 34323Cytoplasmic Potential
Transmembrane344 – 36320Helical; Name=6; Potential
Topological domain364 – 37815Extracellular Potential
Transmembrane379 – 39820Helical; Name=7; Potential
Topological domain399 – 44446Cytoplasmic Potential

Amino acid modifications

Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation781N-linked (GlcNAc...) Potential
Glycosylation901N-linked (GlcNAc...) Potential
Glycosylation981N-linked (GlcNAc...) Potential
Disulfide bond30 ↔ 54 Ref.9 Ref.11
Disulfide bond44 ↔ 87 Ref.9 Ref.11
Disulfide bond68 ↔ 102 Ref.9 Ref.11

Natural variations

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

Secondary structure

1 ..... 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

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: 7692441] [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: 8243652] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF-R2).
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: 9757017] [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: 7811272] [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: 10598591] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF-R4).
[6]"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.
[7]"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: 19054851] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF-R2).
[8]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF-R2).
[9]"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: 11425856] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-31, DISULFIDE BONDS.
[10]"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: 20966082] [Abstract]
Cited for: INTERACTION WITH CRF AND UCN.
[11]"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: 18801728] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 24-119 IN COMPLEX WITH CRH, FUNCTION, DISULFIDE BONDS.
[12]"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: 20843795] [Abstract]
Cited for: STRUCTURE BY NMR OF 25-109 IN COMPLEX WITH SYNTHETIC AGONIST.
+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.
AY457172 mRNA. Translation: AAR19768.1.
AB451466 mRNA. Translation: BAG70280.1.
BC096836 mRNA. Translation: AAH96836.1.
IPIIPI00003083.
IPI00219267.
IPI00219268.
IPI00219269.
PIRI38879.
A48260. I60975.
RefSeqNP_001138618.1. NM_001145146.1.
NP_001138619.1. NM_001145147.1.
NP_001138620.1. NM_001145148.1.
NP_004373.2. NM_004382.4.
UniGeneHs.417628.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L27NMR-A25-109[»]
3EHSX-ray2.76A24-119[»]
3EHTX-ray3.40A24-119[»]
3EHUX-ray1.96A/B24-119[»]
ProteinModelPortalP34998.
SMRP34998. Positions 24-108.
ModBaseSearch...

Protein-protein interaction databases

IntActP34998. 1 interaction.
MINTMINT-1217325.
STRINGP34998.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP34998.

Polymorphism databases

DMDM461836.

Proteomic databases

PRIDEP34998.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000398285; ENSP00000381333; ENSG00000120088.
ENST00000456940; ENSP00000407078; ENSG00000226460.
GeneID1394.
KEGGhsa:1394.
UCSCuc002ijn.1. human.
uc010dap.1. human.
uc010dar.1. human.

Organism-specific databases

CTD1394.
GeneCardsGC17P043699.
H-InvDBHIX0027131.
HGNCHGNC:2357. CRHR1.
MIM122561. gene.
neXtProtNX_P34998.
PharmGKBPA26874.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG04138.
GeneTreeENSGT00580000081433.
HOVERGENHBG106921.
OrthoDBEOG4DBTDQ.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP34998.
CleanExHS_CRHR1.
GenevestigatorP34998.
GermOnlineENSG00000120088. Homo sapiens.

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]
KOK04578.
PANTHERPTHR12011:SF73. CRF_rcpt. 1 hit.
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

NextBio5703.
SOURCESearch...

Entry information

Entry nameCRFR1_HUMAN
AccessionPrimary (citable) accession number: P34998
Secondary accession number(s): Q13008, Q4QRJ1, Q9UK64
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: January 25, 2012
This is version 117 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

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries

Human chromosome 17

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents