UniProtKB - P34998 (CRFR1_HUMAN)
Corticotropin-releasing factor receptor 1
CRHR1
Functioni
GO - Molecular functioni
- corticotrophin-releasing factor receptor activity Source: UniProtKB
- corticotropin-releasing hormone binding Source: GO_Central
- corticotropin-releasing hormone receptor activity Source: GO_Central
- G-protein alpha-subunit binding Source: Ensembl
- G protein-coupled peptide receptor activity Source: GO_Central
- peptide hormone binding Source: GO_Central
- protein-containing complex binding Source: Ensembl
GO - Biological processi
- activation of adenylate cyclase activity Source: ProtInc
- adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: UniProtKB
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway Source: GO_Central
- adrenal gland development Source: Ensembl
- behavioral response to cocaine Source: Ensembl
- behavioral response to ethanol Source: Ensembl
- behavioral response to pain Source: Ensembl
- cell surface receptor signaling pathway Source: InterPro
- cellular response to corticotropin-releasing hormone stimulus Source: UniProtKB
- corticotropin secretion Source: UniProtKB
- epithelial cell differentiation Source: Ensembl
- fear response Source: Ensembl
- feeding behavior Source: Ensembl
- female pregnancy Source: ProtInc
- general adaptation syndrome, behavioral process Source: Ensembl
- G protein-coupled receptor signaling pathway Source: Reactome
- hypothalamus development Source: Ensembl
- immune response Source: ProtInc
- locomotory exploration behavior Source: Ensembl
- long-term synaptic potentiation Source: Ensembl
- memory Source: Ensembl
- negative regulation of epinephrine secretion Source: Ensembl
- negative regulation of feeding behavior Source: Ensembl
- negative regulation of neuron death Source: Ensembl
- negative regulation of voltage-gated calcium channel activity Source: UniProtKB
- neuropeptide signaling pathway Source: Ensembl
- parturition Source: ProtInc
- phospholipase C-activating G protein-coupled receptor signaling pathway Source: Ensembl
- positive regulation of cAMP-mediated signaling Source: Ensembl
- positive regulation of cytosolic calcium ion concentration Source: Ensembl
- positive regulation of mast cell degranulation Source: Ensembl
- regulation of adenylate cyclase activity involved in G protein-coupled receptor signaling pathway Source: UniProtKB
- regulation of corticosterone secretion Source: UniProtKB
- response to electrical stimulus Source: Ensembl
- response to hypoxia Source: Ensembl
- response to immobilization stress Source: Ensembl
- visual learning Source: Ensembl
Keywordsi
Molecular function | G-protein coupled receptor, Receptor, Transducer |
Enzyme and pathway databases
PathwayCommonsi | P34998 |
Reactomei | R-HSA-373080, Class B/2 (Secretin family receptors) R-HSA-418555, G alpha (s) signalling events R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SIGNORi | P34998 |
Protein family/group databases
TCDBi | 9.A.14.4.3, the g-protein-coupled receptor (gpcr) family |
Names & Taxonomyi
Protein namesi | Recommended name: Corticotropin-releasing factor receptor 1Short 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2357, CRHR1 |
MIMi | 122561, gene |
neXtProti | NX_P34998 |
VEuPathDBi | HostDB:ENSG00000120088.14 |
Subcellular locationi
Plasma membrane
Endosome
Note: Agonist-binding promotes endocytosis.
Endosome
- multivesicular body Source: Ensembl
Golgi apparatus
- trans-Golgi network Source: Ensembl
Plasma Membrane
- integral component of plasma membrane Source: ProtInc
- intrinsic component of plasma membrane Source: UniProtKB
- plasma membrane Source: GO_Central
Other locations
- apical part of cell Source: Ensembl
- dendrite Source: Ensembl
- integral component of membrane Source: UniProtKB
- neuron projection Source: GO_Central
- neuronal cell body Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 24 – 111 | ExtracellularAdd BLAST | 88 | |
Transmembranei | 112 – 142 | Helical; Name=1Add BLAST | 31 | |
Topological domaini | 143 – 178 | CytoplasmicAdd BLAST | 36 | |
Transmembranei | 179 – 203 | Helical; Name=2Add BLAST | 25 | |
Topological domaini | 204 – 218 | ExtracellularAdd BLAST | 15 | |
Transmembranei | 219 – 247 | Helical; Name=3Add BLAST | 29 | |
Topological domaini | 248 – 254 | Cytoplasmic | 7 | |
Transmembranei | 255 – 282 | Helical; Name=4Add BLAST | 28 | |
Topological domaini | 283 – 298 | ExtracellularAdd BLAST | 16 | |
Transmembranei | 299 – 324 | Helical; Name=5Add BLAST | 26 | |
Topological domaini | 325 – 335 | CytoplasmicAdd BLAST | 11 | |
Transmembranei | 336 – 360 | Helical; Name=6Add BLAST | 25 | |
Topological domaini | 361 – 367 | Extracellular | 7 | |
Transmembranei | 368 – 397 | Helical; Name=7Add BLAST | 30 | |
Topological domaini | 398 – 444 | CytoplasmicAdd BLAST | 47 |
Keywords - Cellular componenti
Cell membrane, Endosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 232 | F → A: Nearly abolishes antagonist binding. 1 Publication | 1 | |
Mutagenesisi | 235 | M → A: Strongly reduces antagonist binding. 1 Publication | 1 | |
Mutagenesisi | 309 | L → A: Nearly abolishes antagonist binding. 1 Publication | 1 | |
Mutagenesisi | 312 | N → A: Nearly abolishes antagonist binding. 1 Publication | 1 | |
Mutagenesisi | 313 | F → A: Slightly reduces antagonist binding. 1 Publication | 1 | |
Mutagenesisi | 316 | L → A: Strongly reduces antagonist binding. 1 Publication | 1 | |
Mutagenesisi | 319 | I → A: Strongly reduces antagonist binding. 1 Publication | 1 | |
Mutagenesisi | 356 | Y → A: Strongly reduces antagonist binding. 1 Publication | 1 | |
Mutagenesisi | 384 | Q → A: Increases antagonist binding. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 104909134 1394 |
OpenTargetsi | ENSG00000120088 ENSG00000263715 |
PharmGKBi | PA26874 |
Miscellaneous databases
Pharosi | P34998, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1800 |
DrugBanki | DB09067, Corticorelin ovine triflutate |
DrugCentrali | P34998 |
GuidetoPHARMACOLOGYi | 212 |
Genetic variation databases
BioMutai | CRHR1 |
DMDMi | 461836 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 23 | 1 PublicationAdd BLAST | 23 | |
ChainiPRO_0000012814 | 24 – 444 | Corticotropin-releasing factor receptor 1Add BLAST | 421 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 30 ↔ 54 | |||
Glycosylationi | 38 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 44 ↔ 87 | |||
Glycosylationi | 45 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 68 ↔ 102 | |||
Glycosylationi | 78 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 90 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 98 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 217 ↔ 287 | |||
Modified residuei | 330 | Phosphoserine; by PKA1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | P34998 |
PeptideAtlasi | P34998 |
PRIDEi | P34998 |
ProteomicsDBi | 4300 54968 [P34998-1] 54969 [P34998-2] 54970 [P34998-3] 54971 [P34998-4] |
PTM databases
GlyGeni | P34998, 5 sites |
iPTMneti | P34998 |
PhosphoSitePlusi | P34998 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000120088, Expressed in pituitary gland and 86 other tissues |
ExpressionAtlasi | P34998, baseline and differential |
Genevisiblei | P34998, HS |
Organism-specific databases
HPAi | ENSG00000120088, Group enriched (brain, pituitary gland) |
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 PublicationsBinary interactionsi
Hide detailsP34998
GO - Molecular functioni
- G-protein alpha-subunit binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 107784, 18 interactors |
IntActi | P34998, 7 interactors |
MINTi | P34998 |
STRINGi | 9606.ENSP00000381333 |
Chemistry databases
BindingDBi | P34998 |
Miscellaneous databases
RNActi | P34998, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P34998 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P34998 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 99 – 108 | Important for peptide agonist binding | 10 | |
Regioni | 309 – 319 | Important for antagonist bindingAdd BLAST | 11 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4564, Eukaryota |
GeneTreei | ENSGT00940000158410 |
InParanoidi | P34998 |
OMAi | VHYHIAV |
OrthoDBi | 1163977at2759 |
PhylomeDBi | P34998 |
TreeFami | TF315710 |
Family and domain databases
Gene3Di | 4.10.1240.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00002, 7tm_2, 1 hit PF02793, HRM, 1 hit |
PRINTSi | PR01279, CRFRECEPTOR PR01280, CRFRECEPTOR1 PR00249, GPCRSECRETIN |
SMARTi | View protein in SMART SM00008, HormR, 1 hit |
SUPFAMi | SSF111418, SSF111418, 1 hit |
PROSITEi | View 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 |
s (5+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
The sequence of this isoform differs from the canonical sequence as follows:
146-174: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
41-81: GLQCNASVDLIGTCWPRSPAGQLVVRPCPAFFYGVRYNTTN → D
146-174: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
146-174: Missing.
385-398: Missing.
Computationally mapped potential isoform sequencesi
There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0A0MQZ1 | A0A0A0MQZ1_HUMAN | Corticotropin-releasing factor rece... | CRHR1 | 430 | Annotation score: | ||
B3TIK8 | B3TIK8_HUMAN | CRF1 receptor isoform I variant B | CRHR1 | 314 | Annotation score: | ||
J9JIC6 | J9JIC6_HUMAN | Corticotropin-releasing factor rece... | CRHR1 | 145 | Annotation score: | ||
J3KSM0 | J3KSM0_HUMAN | Corticotropin-releasing factor rece... | CRHR1 | 152 | Annotation score: | ||
K9J956 | K9J956_HUMAN | CRH receptor 1 variant B | CRHR1 | 154 | Annotation score: | ||
J3QQR1 | J3QQR1_HUMAN | Corticotropin-releasing factor rece... | CRHR1 | 93 | Annotation score: | ||
J3QKP8 | J3QKP8_HUMAN | Corticotropin-releasing factor rece... | CRHR1 | 75 | Annotation score: | ||
A0A0G2JM19 | A0A0G2JM19_HUMAN | Corticotropin-releasing factor rece... | CRHR1 | 186 | Annotation score: | ||
H0YFR5 | H0YFR5_HUMAN | Corticotropin-releasing factor rece... | CRHR1 | 52 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045434 | 1 – 204 | Missing in isoform 5. 2 PublicationsAdd BLAST | 204 | |
Alternative sequenceiVSP_001996 | 41 – 81 | GLQCN…YNTTN → D in isoform CRF-R3. 1 PublicationAdd BLAST | 41 | |
Alternative sequenceiVSP_001997 | 146 – 174 | Missing in isoform CRF-R2, isoform CRF-R3 and isoform CRF-R4. 7 PublicationsAdd BLAST | 29 | |
Alternative sequenceiVSP_001998 | 385 – 398 | Missing in isoform CRF-R4. 1 PublicationAdd BLAST | 14 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2L27 | NMR | - | A | 25-108 | [»] | |
3EHS | X-ray | 2.76 | A | 24-119 | [»] | |
3EHT | X-ray | 3.40 | A | 24-119 | [»] | |
3EHU | X-ray | 1.96 | A/B | 24-119 | [»] | |
4K5Y | X-ray | 2.98 | A/B/C | 104-373 | [»] | |
4Z9G | X-ray | 3.18 | A/B/C | 104-249 | [»] | |
A/B/C | 252-401 | [»] | ||||
6P9X | electron microscopy | 2.91 | R | 23-444 | [»] | |
6PB0 | electron microscopy | 3.00 | R | 24-427 | [»] | |
SMRi | P34998 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107784, 18 interactors |
IntActi | P34998, 7 interactors |
MINTi | P34998 |
STRINGi | 9606.ENSP00000381333 |
Chemistry databases
BindingDBi | P34998 |
ChEMBLi | CHEMBL1800 |
DrugBanki | DB09067, Corticorelin ovine triflutate |
DrugCentrali | P34998 |
GuidetoPHARMACOLOGYi | 212 |
Protein family/group databases
TCDBi | 9.A.14.4.3, the g-protein-coupled receptor (gpcr) family |
GPCRDBi | Search... |
PTM databases
GlyGeni | P34998, 5 sites |
iPTMneti | P34998 |
PhosphoSitePlusi | P34998 |
Genetic variation databases
BioMutai | CRHR1 |
DMDMi | 461836 |
Proteomic databases
PaxDbi | P34998 |
PeptideAtlasi | P34998 |
PRIDEi | P34998 |
ProteomicsDBi | 4300 54968 [P34998-1] 54969 [P34998-2] 54970 [P34998-3] 54971 [P34998-4] |
Protocols and materials databases
Antibodypediai | 8417, 369 antibodies |
DNASUi | 1394 |
Genome annotation databases
Organism-specific databases
CTDi | 104909134 1394 |
DisGeNETi | 104909134 1394 |
GeneCardsi | CRHR1 |
HGNCi | HGNC:2357, CRHR1 |
HPAi | ENSG00000120088, Group enriched (brain, pituitary gland) |
MIMi | 122561, gene |
neXtProti | NX_P34998 |
OpenTargetsi | ENSG00000120088 ENSG00000263715 |
PharmGKBi | PA26874 |
VEuPathDBi | HostDB:ENSG00000120088.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4564, Eukaryota |
GeneTreei | ENSGT00940000158410 |
InParanoidi | P34998 |
OMAi | VHYHIAV |
OrthoDBi | 1163977at2759 |
PhylomeDBi | P34998 |
TreeFami | TF315710 |
Enzyme and pathway databases
PathwayCommonsi | P34998 |
Reactomei | R-HSA-373080, Class B/2 (Secretin family receptors) R-HSA-418555, G alpha (s) signalling events R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SIGNORi | P34998 |
Miscellaneous databases
BioGRID-ORCSi | 104909134, 1 hit in 24 CRISPR screens 1394, 6 hits in 869 CRISPR screens |
EvolutionaryTracei | P34998 |
GeneWikii | Corticotropin_releasing_hormone_receptor_1 |
Pharosi | P34998, Tclin |
PROi | PR:P34998 |
RNActi | P34998, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000120088, Expressed in pituitary gland and 86 other tissues |
ExpressionAtlasi | P34998, baseline and differential |
Genevisiblei | P34998, HS |
Family and domain databases
Gene3Di | 4.10.1240.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00002, 7tm_2, 1 hit PF02793, HRM, 1 hit |
PRINTSi | PR01279, CRFRECEPTOR PR01280, CRFRECEPTOR1 PR00249, GPCRSECRETIN |
SMARTi | View protein in SMART SM00008, HormR, 1 hit |
SUPFAMi | SSF111418, SSF111418, 1 hit |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CRFR1_HUMAN | |
Accessioni | P34998Primary (citable) accession number: P34998 Secondary accession number(s): B4DIE9 Q9UK64 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1994 |
Last sequence update: | February 1, 1994 | |
Last modified: | February 10, 2021 | |
This is version 205 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- 7-transmembrane G-linked receptors
List of 7-transmembrane G-linked receptor entries - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM