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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

  • corticotrophin-releasing factor receptor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000106113-MONOMER.
ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-418555. G alpha (s) signalling events.
R-HSA-422085. Synthesis, secretion, and deacylation of Ghrelin.

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)DescriptionActionsGraphical viewLength
Topological domaini1 – 108ExtracellularBy similarityAdd BLAST108
Transmembranei109 – 139Helical; Name=1By similarityAdd BLAST31
Topological domaini140 – 146CytoplasmicBy similarity7
Transmembranei147 – 171Helical; Name=2By similarityAdd BLAST25
Topological domaini172 – 185ExtracellularBy similarityAdd BLAST14
Transmembranei186 – 214Helical; Name=3By similarityAdd BLAST29
Topological domaini215 – 221CytoplasmicBy similarity7
Transmembranei222 – 249Helical; Name=4By similarityAdd BLAST28
Topological domaini250 – 265ExtracellularBy similarityAdd BLAST16
Transmembranei266 – 291Helical; Name=5By similarityAdd BLAST26
Topological domaini292 – 302CytoplasmicBy similarityAdd BLAST11
Transmembranei303 – 327Helical; Name=6By similarityAdd BLAST25
Topological domaini328 – 334ExtracellularBy similarity7
Transmembranei335 – 364Helical; Name=7By similarityAdd BLAST30
Topological domaini365 – 411CytoplasmicBy similarityAdd BLAST47

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi1395.
OpenTargetsiENSG00000106113.
PharmGKBiPA26875.

Chemistry databases

ChEMBLiCHEMBL4069.
GuidetoPHARMACOLOGYi213.

Polymorphism and mutation databases

BioMutaiCRHR2.
DMDMi6226847.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000128201 – 411Corticotropin-releasing factor receptor 2Add BLAST411
Signal peptidei1 – 19Not cleavedAdd BLAST19

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi13N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi14 ↔ 501 Publication
Disulfide bondi40 ↔ 831 Publication
Glycosylationi41N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi64 ↔ 981 Publication
Glycosylationi74N-linked (GlcNAc...)Sequence analysis1
Glycosylationi86N-linked (GlcNAc...)Sequence analysis1
Glycosylationi94N-linked (GlcNAc...)Sequence analysis1
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

PhosphoSitePlusiQ13324.

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 interactors.
STRINGi9606.ENSP00000340943.

Chemistry databases

BindingDBiQ13324.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3N93X-ray2.50A/B3-104[»]
3N95X-ray2.72A/B/C/D3-104[»]
3N96X-ray2.75A/B/C/D3-104[»]
ProteinModelPortaliQ13324.
SMRiQ13324.
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)DescriptionActionsGraphical viewLength
Sequence conflicti185R → H in AAA91320 (PubMed:8536644).Curated1
Sequence conflicti185R → H in ABV59313 (Ref. 6) Curated1
Sequence conflicti185R → H in ABV59314 (Ref. 6) Curated1
Sequence conflicti185R → H in ABV59315 (Ref. 6) Curated1
Sequence conflicti185R → H in ABV59317 (Ref. 6) Curated1
Sequence conflicti374W → R in BAG36414 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049455220E → D.Corresponds to variant rs34625936dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0019991 – 34MDAAL…PLDPE → MRGPSGPPGLLYVPHLLLCL LCLLPPPLQYAAGQSQMPKD QPLWALLEQYCHTIMTLTNL S in isoform CRF2-beta. 2 PublicationsAdd BLAST34
Alternative sequenceiVSP_0020001 – 34MDAAL…PLDPE → MGREPWPEDRDLGFPQLFCQ in isoform CRF2-gamma. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_053564106Missing in isoform desQ. 1 Publication1
Alternative sequenceiVSP_053565366 – 411VRSAV…QTAAV → SWVSKEAQAAGPHGREKPEQ RW in isoform D. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_053566366 – 411VRSAV…QTAAV → GLEPV in isoform E. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_053567367 – 411Missing in isoform F. 1 PublicationAdd BLAST45

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]
XP_016867241.1. XM_017011752.1. [Q13324-3]
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]
XP_016867241.1. XM_017011752.1. [Q13324-3]
UniGeneiHs.546246.
Hs.729970.

3D structure databases

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

Protein-protein interaction databases

BioGridi107785. 2 interactors.
STRINGi9606.ENSP00000340943.

Chemistry databases

BindingDBiQ13324.
ChEMBLiCHEMBL4069.
GuidetoPHARMACOLOGYi213.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiQ13324.

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.
DisGeNETi1395.
GeneCardsiCRHR2.
HGNCiHGNC:2358. CRHR2.
HPAiHPA046683.
MIMi602034. gene.
neXtProtiNX_Q13324.
OpenTargetsiENSG00000106113.
PharmGKBiPA26875.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000106113-MONOMER.
ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-418555. G alpha (s) signalling events.
R-HSA-422085. Synthesis, secretion, and deacylation of Ghrelin.

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: November 30, 2016
This is version 145 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.