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Protein

Corticotropin-releasing factor receptor 2

Gene

CRHR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for 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.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-418555. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
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 namesi
Name:CRHR2
Synonyms:CRF2R, CRH2R
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:2358. CRHR2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 108108ExtracellularBy similarityAdd
BLAST
Transmembranei109 – 13931Helical; Name=1By similarityAdd
BLAST
Topological domaini140 – 1467CytoplasmicBy similarity
Transmembranei147 – 17125Helical; Name=2By similarityAdd
BLAST
Topological domaini172 – 18514ExtracellularBy similarityAdd
BLAST
Transmembranei186 – 21429Helical; Name=3By similarityAdd
BLAST
Topological domaini215 – 2217CytoplasmicBy similarity
Transmembranei222 – 24928Helical; Name=4By similarityAdd
BLAST
Topological domaini250 – 26516ExtracellularBy similarityAdd
BLAST
Transmembranei266 – 29126Helical; Name=5By similarityAdd
BLAST
Topological domaini292 – 30211CytoplasmicBy similarityAdd
BLAST
Transmembranei303 – 32725Helical; Name=6By similarityAdd
BLAST
Topological domaini328 – 3347ExtracellularBy similarity
Transmembranei335 – 36430Helical; Name=7By similarityAdd
BLAST
Topological domaini365 – 41147CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26875.

Chemistry

ChEMBLiCHEMBL4069.
GuidetoPHARMACOLOGYi213.

Polymorphism and mutation databases

BioMutaiCRHR2.
DMDMi6226847.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 411411Corticotropin-releasing factor receptor 2PRO_0000012820Add
BLAST
Signal peptidei1 – 1919Not cleavedAdd
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi13 – 131N-linked (GlcNAc...)Sequence analysis
Disulfide bondi14 ↔ 501 Publication
Disulfide bondi40 ↔ 831 Publication
Glycosylationi41 – 411N-linked (GlcNAc...)Sequence analysis
Disulfide bondi64 ↔ 981 Publication
Glycosylationi74 – 741N-linked (GlcNAc...)Sequence analysis
Glycosylationi86 – 861N-linked (GlcNAc...)Sequence analysis
Glycosylationi94 – 941N-linked (GlcNAc...)Sequence analysis
Disulfide bondi184 ↔ 254By similarity

Post-translational modificationi

A N-glycosylation site within the signal peptide impedes its proper cleavage and function.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ13324.
PeptideAtlasiQ13324.
PRIDEiQ13324.

PTM databases

PhosphoSiteiQ13324.

Expressioni

Gene expression databases

BgeeiENSG00000106113.
CleanExiHS_CRHR2.
ExpressionAtlasiQ13324. baseline and differential.
GenevisibleiQ13324. HS.

Organism-specific databases

HPAiHPA046683.

Interactioni

Subunit structurei

Monomer. 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 UCN3.2 Publications

Protein-protein interaction databases

BioGridi107785. 2 interactions.
STRINGi9606.ENSP00000340943.

Chemistry

BindingDBiQ13324.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3N93X-ray2.50A/B3-104[»]
3N95X-ray2.72A/B/C/D3-104[»]
3N96X-ray2.75A/B/C/D3-104[»]
ProteinModelPortaliQ13324.
SMRiQ13324. Positions 3-102, 115-363.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13324.

Family & Domainsi

Domaini

The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure (By similarity).By similarity
The uncleaved pseudo signal peptide prevents receptor's oligomerization and coupling to G(i) subunits. It is also responsible for the rather low receptor localization at the plasma membrane (PubMed:22689579).1 Publication

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
GeneTreeiENSGT00760000118800.
HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiQ13324.
KOiK04579.
OMAiHESNEPW.
OrthoDBiEOG091G0BBY.
PhylomeDBiQ13324.
TreeFamiTF315710.

Family and domain databases

InterProiIPR017981. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01279. CRFRECEPTOR.
PR01281. CRFRECEPTOR2.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform CRF2-alpha (identifier: Q13324-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDAALLHSLL EANCSLALAE ELLLDGWGPP LDPEGPYSYC NTTLDQIGTC
60 70 80 90 100
WPRSAAGALV ERPCPEYFNG VKYNTTRNAY RECLENGTWA SKINYSQCEP
110 120 130 140 150
ILDDKQRKYD LHYRIALVVN YLGHCVSVAA LVAAFLLFLA LRSIRCLRNV
160 170 180 190 200
IHWNLITTFI LRNVMWFLLQ LVDHEVHESN EVWCRCITTI FNYFVVTNFF
210 220 230 240 250
WMFVEGCYLH TAIVMTYSTE RLRKCLFLFI GWCIPFPIIV AWAIGKLYYE
260 270 280 290 300
NEQCWFGKEP GDLVDYIYQG PIILVLLINF VFLFNIVRIL MTKLRASTTS
310 320 330 340 350
ETIQYRKAVK ATLVLLPLLG ITYMLFFVNP GEDDLSQIMF IYFNSFLQSF
360 370 380 390 400
QGFFVSVFYC FFNGEVRSAV RKRWHRWQDH HSLRVPMARA MSIPTSPTRI
410
SFHSIKQTAA V
Length:411
Mass (Da):47,688
Last modified:May 30, 2000 - v2
Checksum:i96B99A93594CF07F
GO
Isoform CRF2-beta (identifier: Q13324-2) [UniParc]FASTAAdd to basket

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

Note: Contains a disulfide bond in positions 51-77.
Show »
Length:438
Mass (Da):50,814
Checksum:i64E8A977B3A40DE4
GO
Isoform CRF2-gamma (identifier: Q13324-3) [UniParc]FASTAAdd to basket

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

Show »
Length:397
Mass (Da):46,491
Checksum:i6156D0F559CA678B
GO
Isoform D (identifier: Q13324-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     366-411: VRSAVRKRWHRWQDHHSLRVPMARAMSIPTSPTRISFHSIKQTAAV → SWVSKEAQAAGPHGREKPEQRW

Show »
Length:387
Mass (Da):44,831
Checksum:iF4813C5F7FF2E46D
GO
Isoform E (identifier: Q13324-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     366-411: VRSAVRKRWHRWQDHHSLRVPMARAMSIPTSPTRISFHSIKQTAAV → GLEPV

Show »
Length:370
Mass (Da):42,810
Checksum:iE33FAA767F133C69
GO
Isoform F (identifier: Q13324-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     367-411: Missing.

Show »
Length:366
Mass (Da):42,414
Checksum:i95A33C69FE9CE201
GO
Isoform desQ (identifier: Q13324-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     106-106: Missing.

Show »
Length:410
Mass (Da):47,560
Checksum:iEB3D216BD6B2D6AD
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti185 – 1851R → H in AAA91320 (PubMed:8536644).Curated
Sequence conflicti185 – 1851R → H in ABV59313 (Ref. 6) Curated
Sequence conflicti185 – 1851R → H in ABV59314 (Ref. 6) Curated
Sequence conflicti185 – 1851R → H in ABV59315 (Ref. 6) Curated
Sequence conflicti185 – 1851R → H in ABV59317 (Ref. 6) Curated
Sequence conflicti374 – 3741W → R in BAG36414 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti220 – 2201E → D.
Corresponds to variant rs34625936 [ dbSNP | Ensembl ].
VAR_049455

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3434MDAAL…PLDPE → MRGPSGPPGLLYVPHLLLCL LCLLPPPLQYAAGQSQMPKD QPLWALLEQYCHTIMTLTNL S in isoform CRF2-beta. 2 PublicationsVSP_001999Add
BLAST
Alternative sequencei1 – 3434MDAAL…PLDPE → MGREPWPEDRDLGFPQLFCQ in isoform CRF2-gamma. 1 PublicationVSP_002000Add
BLAST
Alternative sequencei106 – 1061Missing in isoform desQ. 1 PublicationVSP_053564
Alternative sequencei366 – 41146VRSAV…QTAAV → SWVSKEAQAAGPHGREKPEQ RW in isoform D. 1 PublicationVSP_053565Add
BLAST
Alternative sequencei366 – 41146VRSAV…QTAAV → GLEPV in isoform E. 1 PublicationVSP_053566Add
BLAST
Alternative sequencei367 – 41145Missing in isoform F. 1 PublicationVSP_053567Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
EU012439 mRNA. Translation: ABV59313.1.
EU012440 mRNA. Translation: ABV59314.1.
EU012441 mRNA. Translation: ABV59315.1.
EU012443 mRNA. Translation: ABV59317.1.
AK313661 mRNA. Translation: BAG36414.1.
AC004976 Genomic DNA. Translation: AAC71653.1.
AC004976 Genomic DNA. Translation: AAC71654.1.
BC096830 mRNA. Translation: AAH96830.1.
Y10151 mRNA. Translation: CAA71235.1.
CCDSiCCDS5429.1. [Q13324-1]
CCDS56477.1. [Q13324-3]
CCDS56478.1. [Q13324-2]
CCDS75576.1. [Q13324-4]
RefSeqiNP_001189404.1. NM_001202475.1. [Q13324-2]
NP_001189410.1. NM_001202481.1. [Q13324-3]
NP_001189411.1. NM_001202482.1. [Q13324-7]
NP_001189412.1. NM_001202483.1. [Q13324-4]
NP_001874.2. NM_001883.4. [Q13324-1]
XP_011513430.1. XM_011515128.2. [Q13324-5]
XP_011513431.1. XM_011515129.2. [Q13324-4]
UniGeneiHs.546246.
Hs.729970.

Genome annotation databases

EnsembliENST00000341843; ENSP00000344304; ENSG00000106113. [Q13324-3]
ENST00000348438; ENSP00000340943; ENSG00000106113. [Q13324-2]
ENST00000471646; ENSP00000418722; ENSG00000106113. [Q13324-1]
ENST00000506074; ENSP00000426498; ENSG00000106113. [Q13324-4]
GeneIDi1395.
KEGGihsa:1395.
UCSCiuc003tbn.4. human. [Q13324-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
EU012439 mRNA. Translation: ABV59313.1.
EU012440 mRNA. Translation: ABV59314.1.
EU012441 mRNA. Translation: ABV59315.1.
EU012443 mRNA. Translation: ABV59317.1.
AK313661 mRNA. Translation: BAG36414.1.
AC004976 Genomic DNA. Translation: AAC71653.1.
AC004976 Genomic DNA. Translation: AAC71654.1.
BC096830 mRNA. Translation: AAH96830.1.
Y10151 mRNA. Translation: CAA71235.1.
CCDSiCCDS5429.1. [Q13324-1]
CCDS56477.1. [Q13324-3]
CCDS56478.1. [Q13324-2]
CCDS75576.1. [Q13324-4]
RefSeqiNP_001189404.1. NM_001202475.1. [Q13324-2]
NP_001189410.1. NM_001202481.1. [Q13324-3]
NP_001189411.1. NM_001202482.1. [Q13324-7]
NP_001189412.1. NM_001202483.1. [Q13324-4]
NP_001874.2. NM_001883.4. [Q13324-1]
XP_011513430.1. XM_011515128.2. [Q13324-5]
XP_011513431.1. XM_011515129.2. [Q13324-4]
UniGeneiHs.546246.
Hs.729970.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3N93X-ray2.50A/B3-104[»]
3N95X-ray2.72A/B/C/D3-104[»]
3N96X-ray2.75A/B/C/D3-104[»]
ProteinModelPortaliQ13324.
SMRiQ13324. Positions 3-102, 115-363.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107785. 2 interactions.
STRINGi9606.ENSP00000340943.

Chemistry

BindingDBiQ13324.
ChEMBLiCHEMBL4069.
GuidetoPHARMACOLOGYi213.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ13324.

Polymorphism and mutation databases

BioMutaiCRHR2.
DMDMi6226847.

Proteomic databases

PaxDbiQ13324.
PeptideAtlasiQ13324.
PRIDEiQ13324.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000341843; ENSP00000344304; ENSG00000106113. [Q13324-3]
ENST00000348438; ENSP00000340943; ENSG00000106113. [Q13324-2]
ENST00000471646; ENSP00000418722; ENSG00000106113. [Q13324-1]
ENST00000506074; ENSP00000426498; ENSG00000106113. [Q13324-4]
GeneIDi1395.
KEGGihsa:1395.
UCSCiuc003tbn.4. human. [Q13324-1]

Organism-specific databases

CTDi1395.
GeneCardsiCRHR2.
HGNCiHGNC:2358. CRHR2.
HPAiHPA046683.
MIMi602034. gene.
neXtProtiNX_Q13324.
PharmGKBiPA26875.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4564. Eukaryota.
ENOG410XRS2. LUCA.
GeneTreeiENSGT00760000118800.
HOGENOMiHOG000230719.
HOVERGENiHBG106921.
InParanoidiQ13324.
KOiK04579.
OMAiHESNEPW.
OrthoDBiEOG091G0BBY.
PhylomeDBiQ13324.
TreeFamiTF315710.

Enzyme and pathway databases

ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-418555. G alpha (s) signalling events.

Miscellaneous databases

ChiTaRSiCRHR2. human.
EvolutionaryTraceiQ13324.
GeneWikiiCorticotropin_releasing_hormone_receptor_2.
GenomeRNAii1395.
PROiQ13324.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106113.
CleanExiHS_CRHR2.
ExpressionAtlasiQ13324. baseline and differential.
GenevisibleiQ13324. HS.

Family and domain databases

InterProiIPR017981. 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]
PfamiPF00002. 7tm_2. 1 hit.
PF02793. HRM. 1 hit.
[Graphical view]
PRINTSiPR01279. CRFRECEPTOR.
PR01281. CRFRECEPTOR2.
PR00249. GPCRSECRETIN.
SMARTiSM00008. HormR. 1 hit.
[Graphical view]
PROSITEiPS00649. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiCRFR2_HUMAN
AccessioniPrimary (citable) accession number: Q13324
Secondary accession number(s): B2R967
, B3SXS6, B3SXS7, B3SXS8, B3SXT0, F8WA81, O43461, Q4QRJ4, Q99431
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2000
Last modified: September 7, 2016
This is version 142 of the entry and version 2 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, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.