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Protein

Corticotropin-releasing factor receptor 2

Gene

CRHR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionG-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
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

EuPathDBiHostDB:ENSG00000106113.18
HGNCiHGNC:2358 CRHR2
MIMi602034 gene
neXtProtiNX_Q13324

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Disulfide bondi14 ↔ 501 Publication
Disulfide bondi40 ↔ 831 Publication
Glycosylationi41N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi64 ↔ 981 Publication
Glycosylationi74N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi86N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi94N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi59312
59313 [Q13324-2]
59314 [Q13324-3]

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
GeneTreeiENSGT00900000140884
HOGENOMiHOG000230719
HOVERGENiHBG106921
InParanoidiQ13324
KOiK04579
OMAiHESNEPW
OrthoDBiEOG091G0BBY
PhylomeDBiQ13324
TreeFamiTF315710

Family and domain databases

Gene3Di4.10.1240.10, 1 hit
InterProiView protein in InterPro
IPR017981 GPCR_2-like
IPR003053 GPCR_2_CRF2_rcpt
IPR003051 GPCR_2_CRF_rcpt
IPR036445 GPCR_2_extracell_dom_sf
IPR001879 GPCR_2_extracellular_dom
IPR000832 GPCR_2_secretin-like
IPR017983 GPCR_2_secretin-like_CS
PfamiView protein in Pfam
PF00002 7tm_2, 1 hit
PF02793 HRM, 1 hit
PRINTSiPR01279 CRFRECEPTOR
PR01281 CRFRECEPTOR2
PR00249 GPCRSECRETIN
SMARTiView protein in SMART
SM00008 HormR, 1 hit
SUPFAMiSSF111418 SSF111418, 1 hit
PROSITEiView protein in 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

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 dbSNP:rs34625936Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiCRFR2_HUMAN
AccessioniPrimary (citable) accession number: Q13324
Secondary accession number(s): B2R967
, B3SXS6, B3SXS7, B3SXS8, B3SXT0, F8WA81, O43461, Q4QRJ4, Q99431
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2000
Last modified: June 20, 2018
This is version 154 of the entry and version 2 of the sequence. See 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

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