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Protein

Corticotropin-releasing factor receptor 1

Gene

CRHR1

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

Functioni

G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin). Has high affinity for CRH and 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. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli.4 Publications

GO - Molecular functioni

  • corticotrophin-releasing factor receptor activity Source: UniProtKB

GO - Biological processi

  • activation of adenylate cyclase activity Source: ProtInc
  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • cell surface receptor signaling pathway Source: InterPro
  • cellular response to corticotropin-releasing hormone stimulus Source: UniProtKB
  • corticotropin secretion Source: UniProtKB
  • female pregnancy Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: Reactome
  • immune response Source: ProtInc
  • negative regulation of voltage-gated calcium channel activity Source: UniProtKB
  • parturition Source: ProtInc
  • regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway Source: UniProtKB
  • regulation of corticosterone secretion Source: UniProtKB

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
SIGNORiP34998

Protein family/group databases

TCDBi9.A.14.4.3 the g-protein-coupled receptor (gpcr) family

Names & Taxonomyi

Protein namesi
Recommended name:
Corticotropin-releasing factor receptor 1
Short name:
CRF-R-1
Short name:
CRF-R1
Short name:
CRFR-1
Alternative name(s):
Corticotropin-releasing hormone receptor 1
Short name:
CRH-R-1
Short name:
CRH-R1
Gene namesi
Name:CRHR1
Synonyms:CRFR, CRFR1, CRHR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000120088.14
HGNCiHGNC:2357 CRHR1
MIMi122561 gene
neXtProtiNX_P34998

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 domaini24 – 111ExtracellularAdd BLAST88
Transmembranei112 – 142Helical; Name=1Add BLAST31
Topological domaini143 – 178CytoplasmicAdd BLAST36
Transmembranei179 – 203Helical; Name=2Add BLAST25
Topological domaini204 – 218ExtracellularAdd BLAST15
Transmembranei219 – 247Helical; Name=3Add BLAST29
Topological domaini248 – 254Cytoplasmic7
Transmembranei255 – 282Helical; Name=4Add BLAST28
Topological domaini283 – 298ExtracellularAdd BLAST16
Transmembranei299 – 324Helical; Name=5Add BLAST26
Topological domaini325 – 335CytoplasmicAdd BLAST11
Transmembranei336 – 360Helical; Name=6Add BLAST25
Topological domaini361 – 367Extracellular7
Transmembranei368 – 397Helical; Name=7Add BLAST30
Topological domaini398 – 444CytoplasmicAdd BLAST47

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi232F → A: Nearly abolishes antagonist binding. 1 Publication1
Mutagenesisi235M → A: Strongly reduces antagonist binding. 1 Publication1
Mutagenesisi309L → A: Nearly abolishes antagonist binding. 1 Publication1
Mutagenesisi312N → A: Nearly abolishes antagonist binding. 1 Publication1
Mutagenesisi313F → A: Slightly reduces antagonist binding. 1 Publication1
Mutagenesisi316L → A: Strongly reduces antagonist binding. 1 Publication1
Mutagenesisi319I → A: Strongly reduces antagonist binding. 1 Publication1
Mutagenesisi356Y → A: Strongly reduces antagonist binding. 1 Publication1
Mutagenesisi384Q → A: Increases antagonist binding. 1 Publication1

Organism-specific databases

DisGeNETi104909134
1394
OpenTargetsiENSG00000120088
ENSG00000263715
PharmGKBiPA26874

Chemistry databases

ChEMBLiCHEMBL1800
DrugBankiDB09067 Corticorelin ovine triflutate
GuidetoPHARMACOLOGYi212

Polymorphism and mutation databases

BioMutaiCRHR1
DMDMi461836

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000001281424 – 444Corticotropin-releasing factor receptor 1Add BLAST421

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 54
Glycosylationi38N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi44 ↔ 87
Glycosylationi45N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi68 ↔ 102
Glycosylationi78N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi90N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi98N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi217 ↔ 287
Modified residuei330Phosphoserine; by PKA1 Publication1

Post-translational modificationi

C-terminal Ser or Thr residues may be phosphorylated.1 Publication
Phosphorylation at Ser-330 by PKA prevents maximal coupling to Gq-protein, and thereby negatively regulates downstream signaling.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP34998
PeptideAtlasiP34998
PRIDEiP34998
ProteomicsDBi54968
54969 [P34998-2]
54970 [P34998-3]
54971 [P34998-4]

PTM databases

iPTMnetiP34998
PhosphoSitePlusiP34998

Expressioni

Tissue specificityi

Predominantly expressed in the cerebellum, pituitary, cerebral cortex and olfactory lobe.1 Publication

Gene expression databases

BgeeiENSG00000120088
CleanExiHS_CRHR1
ExpressionAtlasiP34998 baseline and differential
GenevisibleiP34998 HS

Organism-specific databases

HPAiCAB025251

Interactioni

Subunit structurei

Heterodimer; heterodimerizes with GPER1 (By similarity). Interacts (via N-terminal extracellular domain) with CRH and UCN. Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist binding.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CRHP068502EBI-3870393,EBI-3870390

Protein-protein interaction databases

BioGridi107784, 8 interactors
IntActiP34998, 3 interactors
MINTiP34998
STRINGi9606.ENSP00000381333

Chemistry databases

BindingDBiP34998

Structurei

Secondary structure

1444
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni25 – 27Combined sources3
Helixi28 – 32Combined sources5
Beta strandi49 – 52Combined sources4
Beta strandi62 – 67Combined sources6
Beta strandi70 – 74Combined sources5
Beta strandi81 – 87Combined sources7
Turni89 – 91Combined sources3
Beta strandi93 – 98Combined sources6
Helixi99 – 101Combined sources3
Helixi103 – 107Combined sources5
Helixi116 – 143Combined sources28
Helixi175 – 177Combined sources3
Helixi179 – 205Combined sources27
Helixi207 – 212Combined sources6
Helixi215 – 247Combined sources33
Helixi253 – 264Combined sources12
Turni265 – 267Combined sources3
Helixi268 – 282Combined sources15
Helixi286 – 288Combined sources3
Helixi299 – 325Combined sources27
Helixi333 – 360Combined sources28
Helixi368 – 396Combined sources29

3D structure databases

ProteinModelPortaliP34998
SMRiP34998
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP34998

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni99 – 108Important for peptide agonist binding10
Regioni309 – 319Important for antagonist bindingAdd BLAST11

Domaini

The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure. The antagonist CP-376395 binds at an allosteric site, far from the presumed binding site for the physiological peptide ligand.

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4564 Eukaryota
ENOG410XRS2 LUCA
GeneTreeiENSGT00900000140884
HOGENOMiHOG000230719
HOVERGENiHBG106921
InParanoidiP34998
KOiK04578
OMAiFICIGWC
OrthoDBiEOG091G0BBY
PhylomeDBiP34998
TreeFamiTF315710

Family and domain databases

CDDicd15445 7tmB1_CRF-R1, 1 hit
Gene3Di4.10.1240.10, 1 hit
InterProiView protein in InterPro
IPR017981 GPCR_2-like
IPR003052 GPCR_2_CRF1_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
PR01280 CRFRECEPTOR1
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 (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform CRF-R1 (identifier: P34998-1) [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
MGGHPQLRLV KALLLLGLNP VSASLQDQHC ESLSLASNIS GLQCNASVDL
60 70 80 90 100
IGTCWPRSPA GQLVVRPCPA FFYGVRYNTT NNGYRECLAN GSWAARVNYS
110 120 130 140 150
ECQEILNEEK KSKVHYHVAV IINYLGHCIS LVALLVAFVL FLRLRPGCTH
160 170 180 190 200
WGDQADGALE VGAPWSGAPF QVRRSIRCLR NIIHWNLISA FILRNATWFV
210 220 230 240 250
VQLTMSPEVH QSNVGWCRLV TAAYNYFHVT NFFWMFGEGC YLHTAIVLTY
260 270 280 290 300
STDRLRKWMF ICIGWGVPFP IIVAWAIGKL YYDNEKCWFG KRPGVYTDYI
310 320 330 340 350
YQGPMILVLL INFIFLFNIV RILMTKLRAS TTSETIQYRK AVKATLVLLP
360 370 380 390 400
LLGITYMLFF VNPGEDEVSR VVFIYFNSFL ESFQGFFVSV FYCFLNSEVR
410 420 430 440
SAIRKRWHRW QDKHSIRARV ARAMSIPTSP TRVSFHSIKQ STAV
Length:444
Mass (Da):50,719
Last modified:February 1, 1994 - v1
Checksum:i7221AEFB0E7AA8ED
GO
Isoform CRF-R2 (identifier: P34998-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-174: Missing.

Note: Major isoform.
Show »
Length:415
Mass (Da):47,671
Checksum:i81445283CCE34C6E
GO
Isoform CRF-R3 (identifier: P34998-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:375
Mass (Da):43,331
Checksum:i6A2068BE9386F8B0
GO
Isoform CRF-R4 (identifier: P34998-4) [UniParc]FASTAAdd to basket
Also known as: 1D

The sequence of this isoform differs from the canonical sequence as follows:
     146-174: Missing.
     385-398: Missing.

Show »
Length:401
Mass (Da):46,030
Checksum:i3D8FF9B128810372
GO
Isoform 5 (identifier: P34998-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-204: Missing.

Show »
Length:240
Mass (Da):28,122
Checksum:iF4465F15BF7C52E4
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0454341 – 204Missing in isoform 5. 2 PublicationsAdd BLAST204
Alternative sequenceiVSP_00199641 – 81GLQCN…YNTTN → D in isoform CRF-R3. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_001997146 – 174Missing in isoform CRF-R2, isoform CRF-R3 and isoform CRF-R4. 7 PublicationsAdd BLAST29
Alternative sequenceiVSP_001998385 – 398Missing in isoform CRF-R4. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
FJ543100 mRNA Translation: ACU68591.1
AY457172 mRNA Translation: AAR19768.1
AB451466 mRNA Translation: BAG70280.1
AK295559 mRNA Translation: BAG58461.1
AC126544 Genomic DNA No translation available.
AC217770 Genomic DNA No translation available.
AC217771 Genomic DNA No translation available.
AC217774 Genomic DNA No translation available.
AC225613 Genomic DNA No translation available.
CH471233 Genomic DNA Translation: EAW93557.1
BC096836 mRNA Translation: AAH96836.1
CCDSiCCDS42350.1 [P34998-2]
CCDS45712.1 [P34998-1]
CCDS45713.1 [P34998-4]
CCDS45714.1 [P34998-3]
CCDS58556.1 [P34998-5]
PIRiI38879
I60975 A48260
RefSeqiNP_001138618.1, NM_001145146.1 [P34998-1]
NP_001138619.1, NM_001145147.1 [P34998-3]
NP_001138620.1, NM_001145148.1 [P34998-4]
NP_001243228.1, NM_001256299.2 [P34998-5]
NP_001289945.1, NM_001303016.1
NP_001289947.1, NM_001303018.1 [P34998-5]
NP_004373.2, NM_004382.4 [P34998-2]
UniGeneiHs.417628

Genome annotation databases

EnsembliENST00000314537; ENSP00000326060; ENSG00000120088 [P34998-2]
ENST00000352855; ENSP00000344068; ENSG00000120088 [P34998-3]
ENST00000398285; ENSP00000381333; ENSG00000120088 [P34998-1]
ENST00000577353; ENSP00000462016; ENSG00000120088 [P34998-4]
ENST00000613260; ENSP00000484387; ENSG00000278232 [P34998-1]
ENST00000615345; ENSP00000480752; ENSG00000278232 [P34998-3]
ENST00000616274; ENSP00000480396; ENSG00000276191 [P34998-1]
ENST00000616748; ENSP00000478177; ENSG00000276191 [P34998-3]
ENST00000617905; ENSP00000483802; ENSG00000276191 [P34998-2]
ENST00000618382; ENSP00000477786; ENSG00000278232 [P34998-2]
ENST00000633723; ENSP00000488342; ENSG00000276191 [P34998-4]
GeneIDi104909134
1394
KEGGihsa:104909134
hsa:1394
UCSCiuc002ijm.4 human [P34998-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCRFR1_HUMAN
AccessioniPrimary (citable) accession number: P34998
Secondary accession number(s): B4DIE9
, Q13008, Q4QRJ1, Q9UK64
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: July 18, 2018
This is version 188 of the entry and version 1 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, Direct protein sequencing, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

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