Q13324 (CRFR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Corticotropin-releasing factor receptor 2
Short name=CRF-R-2
Short name=CRF-R2
Short name=CRFR-2

Alternative name(s):
Corticotropin-releasing hormone receptor 2
Short name=CRH-R-2
Short name=CRH-R2

Gene names

Name:	CRHR2
Synonyms:	CRF2R, CRH2R

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	411 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. Also binds to urocortin I, II and III. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Subunit structure	Interacts (via N-terminal extracellular domain) with CRF, UCN, UCN2 and UCN3. Has highest affinity for UCN, and considerably lower affinity for CRF, UNC2 and UCN3. Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 2 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-modulating G-protein coupled receptor signaling pathway Traceable author statement Ref.1. Source: ProtInc negative regulation of angiogenesis Inferred from electronic annotation. Source: Compara negative regulation of cAMP-mediated signaling Inferred from electronic annotation. Source: Compara positive regulation of cAMP-mediated signaling Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	corticotrophin-releasing factor receptor activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform CRF2-alpha (identifier: Q13324-1)

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 CRF2-beta (identifier: Q13324-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MDAALLHSLLEANCSLALAEELLLDGWGPPLDPE → MRGPSGPPGL...HTIMTLTNLS

Isoform CRF2-gamma (identifier: Q13324-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MDAALLHSLLEANCSLALAEELLLDGWGPPLDPE → MGREPWPEDRDLGFPQLFCQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Chain	18 – 411	394	Corticotropin-releasing factor receptor 2		PRO_0000012820
Regions
	Topological domain	18 – 118	101	Extracellular Potential
	Transmembrane	119 – 139	21	Helical; Name=1; Potential
	Topological domain	140 – 148	9	Cytoplasmic Potential
	Transmembrane	149 – 168	20	Helical; Name=2; Potential
	Topological domain	169 – 185	17	Extracellular Potential
	Transmembrane	186 – 209	24	Helical; Name=3; Potential
	Topological domain	210 – 223	14	Cytoplasmic Potential
	Transmembrane	224 – 245	22	Helical; Name=4; Potential
	Topological domain	246 – 264	19	Extracellular Potential
	Transmembrane	265 – 287	23	Helical; Name=5; Potential
	Topological domain	288 – 310	23	Cytoplasmic Potential
	Transmembrane	311 – 330	20	Helical; Name=6; Potential
	Topological domain	331 – 345	15	Extracellular Potential
	Transmembrane	346 – 365	20	Helical; Name=7; Potential
	Topological domain	366 – 411	46	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	41	1	N-linked (GlcNAc...) Potential
	Glycosylation	74	1	N-linked (GlcNAc...) Potential
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	94	1	N-linked (GlcNAc...) Potential
	Disulfide bond	14 ↔ 50		Ref.9
	Disulfide bond	40 ↔ 83		Ref.9
	Disulfide bond	64 ↔ 98		Ref.9
Natural variations
	Alternative sequence	1 – 34	34	MDAAL…PLDPE → MRGPSGPPGLLYVPHLLLCL LCLLPPPLQYAAGQSQMPKD QPLWALLEQYCHTIMTLTNL S in isoform CRF2-beta.		VSP_001999
	Alternative sequence	1 – 34	34	MDAAL…PLDPE → MGREPWPEDRDLGFPQLFCQ in isoform CRF2-gamma.		VSP_002000
	Natural variant	220	1	E → D. Corresponds to variant rs34625936 [ dbSNP | Ensembl ].		VAR_049455
Experimental info
	Sequence conflict	185	1	R → H in AAA91320. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform CRF2-alpha [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 96B99A93594CF07F	FASTA	411	47,688
	10 20 30 40 50 60 MDAALLHSLL EANCSLALAE ELLLDGWGPP LDPEGPYSYC NTTLDQIGTC WPRSAAGALV 70 80 90 100 110 120 ERPCPEYFNG VKYNTTRNAY RECLENGTWA SKINYSQCEP ILDDKQRKYD LHYRIALVVN 130 140 150 160 170 180 YLGHCVSVAA LVAAFLLFLA LRSIRCLRNV IHWNLITTFI LRNVMWFLLQ LVDHEVHESN 190 200 210 220 230 240 EVWCRCITTI FNYFVVTNFF WMFVEGCYLH TAIVMTYSTE RLRKCLFLFI GWCIPFPIIV 250 260 270 280 290 300 AWAIGKLYYE NEQCWFGKEP GDLVDYIYQG PIILVLLINF VFLFNIVRIL MTKLRASTTS 310 320 330 340 350 360 ETIQYRKAVK ATLVLLPLLG ITYMLFFVNP GEDDLSQIMF IYFNSFLQSF QGFFVSVFYC 370 380 390 400 410 FFNGEVRSAV RKRWHRWQDH HSLRVPMARA MSIPTSPTRI SFHSIKQTAA V
	Isoform CRF2-beta [UniParc]. Checksum: 64E8A977B3A40DE4	FASTA	438	50,814
	10 20 30 40 50 60 MRGPSGPPGL LYVPHLLLCL LCLLPPPLQY AAGQSQMPKD QPLWALLEQY CHTIMTLTNL 70 80 90 100 110 120 SGPYSYCNTT LDQIGTCWPR SAAGALVERP CPEYFNGVKY NTTRNAYREC LENGTWASKI 130 140 150 160 170 180 NYSQCEPILD DKQRKYDLHY RIALVVNYLG HCVSVAALVA AFLLFLALRS IRCLRNVIHW 190 200 210 220 230 240 NLITTFILRN VMWFLLQLVD HEVHESNEVW CRCITTIFNY FVVTNFFWMF VEGCYLHTAI 250 260 270 280 290 300 VMTYSTERLR KCLFLFIGWC IPFPIIVAWA IGKLYYENEQ CWFGKEPGDL VDYIYQGPII 310 320 330 340 350 360 LVLLINFVFL FNIVRILMTK LRASTTSETI QYRKAVKATL VLLPLLGITY MLFFVNPGED 370 380 390 400 410 420 DLSQIMFIYF NSFLQSFQGF FVSVFYCFFN GEVRSAVRKR WHRWQDHHSL RVPMARAMSI 430 PTSPTRISFH SIKQTAAV
	Isoform CRF2-gamma [UniParc]. Checksum: 6156D0F559CA678B	FASTA	397	46,491
	10 20 30 40 50 60 MGREPWPEDR DLGFPQLFCQ GPYSYCNTTL DQIGTCWPRS AAGALVERPC PEYFNGVKYN 70 80 90 100 110 120 TTRNAYRECL ENGTWASKIN YSQCEPILDD KQRKYDLHYR IALVVNYLGH CVSVAALVAA 130 140 150 160 170 180 FLLFLALRSI RCLRNVIHWN LITTFILRNV MWFLLQLVDH EVHESNEVWC RCITTIFNYF 190 200 210 220 230 240 VVTNFFWMFV EGCYLHTAIV MTYSTERLRK CLFLFIGWCI PFPIIVAWAI GKLYYENEQC 250 260 270 280 290 300 WFGKEPGDLV DYIYQGPIIL VLLINFVFLF NIVRILMTKL RASTTSETIQ YRKAVKATLV 310 320 330 340 350 360 LLPLLGITYM LFFVNPGEDD LSQIMFIYFN SFLQSFQGFF VSVFYCFFNG EVRSAVRKRW 370 380 390 HRWQDHHSLR VPMARAMSIP TSPTRISFHS IKQTAAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the human corticotropin-releasing factor-2 receptor complementary deoxyribonucleic acid." Liaw C.W., Lovenberg T.W., Barry G., Oltersdorf T., Grigoriadis D.E., de Souza E.B. Endocrinology 137:72-77(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-ALPHA).
[2]	"Molecular cloning of the human CRH2B receptor isoform: divergence from the rodent isoform in sequence and expression pattern." Kostich W.A., Chen A., Sperle K., Horlick R.A., Patterson J., Hyde T.M., Largent B.L. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-BETA). Tissue: Amygdala.
[3]	"Molecular identification and analysis of a novel human corticotropin-releasing factor (CRF) receptor: the CRF2gamma receptor." Kostich W.A., Chen A., Sperle K., Largent B.L. Mol. Endocrinol. 12:1077-1085(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CRF2-GAMMA). Tissue: Amygdala.
[4]	"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes." Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM CRF2-ALPHA).
[5]	"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 (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CRF2-ALPHA). Tissue: Brain.
[6]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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 CRF2-ALPHA).
[8]	"A new functional isoform of the human CRF2 receptor for corticotropin-releasing factor." Valdenaire O., Giller T., Breu V., Gottowik J., Kilpatrick G. Biochim. Biophys. Acta 1352:129-132(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-88 (ISOFORM CRF2-BETA). Tissue: Skeletal muscle.
[9]	"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: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 3-104 IN COMPLEXES WITH UCN; UCN2 AND UCN3, INTERACTION WITH CRF; UCN; UCN2 AND UCN3, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U34587 mRNA. Translation: AAA91320.1.
AF011406 mRNA. Translation: AAB94503.1.
AF019381 mRNA. Translation: AAB94562.1.
AB065699 Genomic DNA. Translation: BAC05922.1.
AY449734 mRNA. Translation: AAR18078.1.
AC004976 Genomic DNA. Translation: AAC71653.1.
AC004976 Genomic DNA. Translation: AAC71654.1.
BC096830 mRNA. Translation: AAH96830.1.
Y10151 mRNA. Translation: CAA71235.1.

IPI

IPI00181589.
IPI00219074.
IPI00297620.

RefSeq

NP_001189404.1. NM_001202475.1.
NP_001189410.1. NM_001202481.1.
NP_001189411.1. NM_001202482.1.
NP_001189412.1. NM_001202483.1.
NP_001874.2. NM_001883.4.

UniGene

Hs.546246.
Hs.729970.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3N93	X-ray	2.50	A/B	3-104	[»]
3N95	X-ray	2.72	A/B/C/D	3-104	[»]
3N96	X-ray	2.75	A/B/C/D	3-104	[»]

ProteinModelPortal

Q13324.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000222836.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

Q13324.

Polymorphism databases

DMDM

6226847.

Proteomic databases

PaxDb

Q13324.

PRIDE

Q13324.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000341843; ENSP00000344304; ENSG00000106113.
ENST00000348438; ENSP00000340943; ENSG00000106113.
ENST00000471646; ENSP00000418722; ENSG00000106113.

GeneID

1395.

KEGG

hsa:1395.

UCSC

uc003tbn.3. human.
uc003tbo.3. human.
uc003tbp.3. human.

Organism-specific databases

CTD

1395.

GeneCards

GC07M030658.

HGNC

HGNC:2358. CRHR2.

HPA

HPA046683.

MIM

602034. gene.

neXtProt

NX_Q13324.

PharmGKB

PA26875.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG295825.

HOGENOM

HOG000230719.

HOVERGEN

HBG106921.

KO

K04579.

OrthoDB

EOG4DBTDQ.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q13324.

Bgee

Q13324.

CleanEx

HS_CRHR2.

Genevestigator

Q13324.

GermOnline

ENSG00000106113. Homo sapiens.

Family and domain databases

InterPro

IPR017981. GPCR_2-like.
IPR003053. GPCR_2_CRF2_rcpt.
IPR003051. GPCR_2_CRF_rcpt.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
[Graphical view]

PANTHER

PTHR12011:SF73. PTHR12011:SF73. 1 hit.

Pfam

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

PRINTS

PR01279. CRFRECEPTOR.
PR01281. CRFRECEPTOR2.
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

BindingDB

Q13324.

ChEMBL

CHEMBL4069.

ChiTaRS

CRHR2. human.

EvolutionaryTrace

Q13324.

GenomeRNAi

1395.

NextBio

5709.

SOURCE

Search...

Entry information

Entry name

CRFR2_HUMAN

Accession

Primary (citable) accession number: Q13324
Secondary accession number(s): O43461, Q4QRJ4, Q99431

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 30, 2000
Last modified:	May 1, 2013
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.