Reviewed, UniProtKB/Swiss-Prot P34998 (CRFR1_HUMAN)

Names and origin

Protein names

Recommended name:
    Corticotropin-releasing factor receptor 1
      Short name=CRF-R
      Short name=CRF1
Alternative name(s):
    Corticotropin-releasing hormone receptor 1
      Short name=CRH-R 1

Gene names

Name:	CRHR1
Synonyms:	CRFR, CRFR1, CRHR

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	444 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is a receptor for corticotropin releasing factor. Shows high-affinity CRF binding. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cAMP nucleotide second messenger Ref.1 Traceable author statement. Source: ProtInc activation of adenylate cyclase activity Ref.5 Traceable author statement. Source: ProtInc female pregnancy Non-traceable author statement. Source: ProtInc immune response Ref.1 Traceable author statement. Source: ProtInc parturition Ref.5 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.5 Traceable author statement. Source: ProtInc
Molecular function	corticotrophin-releasing factor receptor activity Ref.5 Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Ref.7

Chain

24 – 444

421

Corticotropin-releasing factor receptor 1

PRO_0000012814

Regions

Topological domain

24 – 121

98

Extracellular Potential

Transmembrane

122 – 142

21

1 Potential

Topological domain

143 – 180

38

Cytoplasmic Potential

Transmembrane

181 – 200

20

2 Potential

Topological domain

201 – 218

18

Extracellular Potential

Transmembrane

219 – 242

24

3 Potential

Topological domain

243 – 256

14

Cytoplasmic Potential

Transmembrane

257 – 278

22

4 Potential

Topological domain

279 – 297

19

Extracellular Potential

Transmembrane

298 – 320

23

5 Potential

Topological domain

321 – 343

23

Cytoplasmic Potential

Transmembrane

344 – 363

20

6 Potential

Topological domain

364 – 378

15

Extracellular Potential

Transmembrane

379 – 398

20

7 Potential

Topological domain

399 – 444

46

Cytoplasmic Potential

Amino acid modifications

Glycosylation

38

1

N-linked (GlcNAc...) Potential

Glycosylation

45

1

N-linked (GlcNAc...) Potential

Glycosylation

78

1

N-linked (GlcNAc...) Potential

Glycosylation

90

1

N-linked (GlcNAc...) Potential

Glycosylation

98

1

N-linked (GlcNAc...) Potential

Disulfide bond

30 ↔ 54

Ref.7

Disulfide bond

44 ↔ 87

Ref.7

Disulfide bond

68 ↔ 102

Ref.7

Natural variations

Alternative sequence

41 – 81

41

GLQCN…YNTTN → D in isoform CRF-R3.

VSP_001996

Alternative sequence

146 – 174

29

Missing in isoform CRF-R2, isoform CRF-R3 and isoform CRF-R4.

VSP_001997

Alternative sequence

385 – 398

14

Missing in isoform CRF-R4.

VSP_001998

Secondary structure

1

.

.

.

.

.

444

Helix Strand Turn

Details...

Helix

28 – 32

5

Beta strand

85 – 87

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform CRF-R1 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 7221AEFB0E7AA8ED	FASTA	444	50,719
	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
	Isoform CRF-R2. Checksum: 81445283CCE34C6E	FASTA	415	47,671
	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 FLRLRSIRCL RNIIHWNLIS AFILRNATWF VVQLTMSPEV 190 200 210 220 230 240 HQSNVGWCRL VTAAYNYFHV TNFFWMFGEG CYLHTAIVLT YSTDRLRKWM FICIGWGVPF 250 260 270 280 290 300 PIIVAWAIGK LYYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA 310 320 330 340 350 360 STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF LESFQGFFVS 370 380 390 400 410 VFYCFLNSEV RSAIRKRWHR WQDKHSIRAR VARAMSIPTS PTRVSFHSIK QSTAV
	Isoform CRF-R3. Checksum: 6A2068BE9386F8B0	FASTA	375	43,331
	10 20 30 40 50 60 MGGHPQLRLV KALLLLGLNP VSASLQDQHC ESLSLASNIS DNGYRECLAN GSWAARVNYS 70 80 90 100 110 120 ECQEILNEEK KSKVHYHVAV IINYLGHCIS LVALLVAFVL FLRLRSIRCL RNIIHWNLIS 130 140 150 160 170 180 AFILRNATWF VVQLTMSPEV HQSNVGWCRL VTAAYNYFHV TNFFWMFGEG CYLHTAIVLT 190 200 210 220 230 240 YSTDRLRKWM FICIGWGVPF PIIVAWAIGK LYYDNEKCWF GKRPGVYTDY IYQGPMILVL 250 260 270 280 290 300 LINFIFLFNI VRILMTKLRA STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS 310 320 330 340 350 360 RVVFIYFNSF LESFQGFFVS VFYCFLNSEV RSAIRKRWHR WQDKHSIRAR VARAMSIPTS 370 PTRVSFHSIK QSTAV
	Isoform CRF-R4 (1D). Checksum: 3D8FF9B128810372	FASTA	401	46,030
	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 FLRLRSIRCL RNIIHWNLIS AFILRNATWF VVQLTMSPEV 190 200 210 220 230 240 HQSNVGWCRL VTAAYNYFHV TNFFWMFGEG CYLHTAIVLT YSTDRLRKWM FICIGWGVPF 250 260 270 280 290 300 PIIVAWAIGK LYYDNEKCWF GKRPGVYTDY IYQGPMILVL LINFIFLFNI VRILMTKLRA 310 320 330 340 350 360 STTSETIQYR KAVKATLVLL PLLGITYMLF FVNPGEDEVS RVVFIYFNSF LESFQVRSAI 370 380 390 400 RKRWHRWQDK HSIRARVARA MSIPTSPTRV SFHSIKQSTA V

References

	« Hide 'large scale' referencesShow '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]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L23333 mRNA. Translation: AAA35719.1.
L23332 mRNA. Translation: AAA35718.1.
X72304 mRNA. Translation: CAA51052.1.
AF039523 , 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.

IPI

IPI00219267.
IPI00219268.
IPI00219269.
IPI00873090.

PIR

I38879.
A48260. I60975.

RefSeq

NP_001138618.1.
NP_001138619.1.
NP_001138620.1.
NP_004373.2.

UniGene

Hs.417628

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EHS	X-ray	2.76	A	24-119	[»]
3EHT	X-ray	3.40	A	24-119	[»]
3EHU	X-ray	1.96	A/B	24-119	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P34998.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

P34998.

Proteomic databases

PRIDE

P34998.

Genome annotation databases

Ensembl

ENST00000293493; ENSP00000293493; ENSG00000120088; Homo sapiens. [Genome view]
ENST00000314537; ENSP00000326060; ENSG00000120088; Homo sapiens. [Genome view]
ENST00000339069; ENSP00000340522; ENSG00000120088; Homo sapiens. [Genome view]
ENST00000347197; ENSP00000239167; ENSG00000120088; Homo sapiens. [Genome view]
ENST00000352855; ENSP00000344068; ENSG00000120088; Homo sapiens. [Genome view]
ENST00000398285; ENSP00000381333; ENSG00000120088; Homo sapiens. [Genome view]
ENST00000423694; ENSP00000416995; ENSG00000226460; Homo sapiens. [Genome view]
ENST00000429123; ENSP00000405747; ENSG00000226460; Homo sapiens. [Genome view]
ENST00000430106; ENSP00000388294; ENSG00000120088; Homo sapiens. [Genome view]
ENST00000441899; ENSP00000391273; ENSG00000226460; Homo sapiens. [Genome view]
ENST00000451487; ENSP00000415867; ENSG00000226460; Homo sapiens. [Genome view]
ENST00000455759; ENSP00000391795; ENSG00000226460; Homo sapiens. [Genome view]
ENST00000456940; ENSP00000407078; ENSG00000226460; Homo sapiens. [Genome view]
ENST00000457569; ENSP00000389407; ENSG00000226460; Homo sapiens. [Genome view]

GeneID

1394.

KEGG

hsa:1394.

UCSC

uc002ijn.1. human.
uc010dap.1. human.
uc010dar.1. human.

Organism-specific databases

CTD

1394.

GeneCards

GC17P041217.

H-InvDB

HIX0027131.

HGNC

HGNC:2357. CRHR1.

MIM

122561. gene.

PharmGKB

PA26874.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P34998.

Enzyme and pathway databases

Reactome

REACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpress

P34998.

Bgee

P34998.

CleanEx

HS_CRHR1.

Genevestigator

P34998.

GermOnline

ENSG00000120088. Homo sapiens.

Family and domain databases

InterPro

IPR017981. GPCR_2-like.
IPR003052. GPCR_2_CRF1_rcpt.
IPR003051. GPCR_2_CRF_rcpt.
IPR001879. GPCR_2_extracellular.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]

PANTHER

PTHR12011:SF73. CRF_rcpt. 1 hit.

Pfam

PF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]

PRINTS

PR01279. CRFRECEPTOR.
PR01280. CRFRECEPTOR1.
PR00249. GPCRSECRETIN.

SMART

SM00008. HormR. 1 hit.
[Graphical view]

PROSITE

PS00649. 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]

ProtoNet

Search...

Other Resources

NextBio

5703.

SOURCE

Search...

Entry information

Entry name

CRFR1_HUMAN

Accession

Primary (citable) accession number: P34998
Secondary accession number(s): Q13008, Q9UK64

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	October 13, 2009
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.