Type |
Details |
Score |
Gene |
Type: |
gene |
Organism: |
human |
|
•
•
•
•
•
|
Gene |
Type: |
gene |
Organism: |
chimpanzee |
|
•
•
•
•
•
|
Gene |
Type: |
gene |
Organism: |
macaque, rhesus |
|
•
•
•
•
•
|
Gene |
|
•
•
•
•
•
|
Gene |
Type: |
gene |
Organism: |
cattle |
|
•
•
•
•
•
|
Gene |
Type: |
gene |
Organism: |
dog, domestic |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Publication |
First Author: |
Flaherty SE 3rd |
Year: |
2023 |
Journal: |
Nat Commun |
Title: |
Chronic UCN2 treatment desensitizes CRHR2 and improves insulin sensitivity. |
Volume: |
14 |
Issue: |
1 |
Pages: |
3953 |
|
•
•
•
•
•
|
Publication |
First Author: |
Breu J |
Year: |
2012 |
Journal: |
Behav Brain Res |
Title: |
Urocortin 2 modulates aspects of social behaviour in mice. |
Volume: |
233 |
Issue: |
2 |
Pages: |
331-6 |
|
•
•
•
•
•
|
Publication |
First Author: |
Voltolini C |
Year: |
2015 |
Journal: |
Endocrinology |
Title: |
Urocortin 2 role in placental and myometrial inflammatory mechanisms at parturition. |
Volume: |
156 |
Issue: |
2 |
Pages: |
670-9 |
|
•
•
•
•
•
|
Publication |
First Author: |
Tillinger A |
Year: |
2013 |
Journal: |
J Neurochem |
Title: |
Stress-induced changes in gene expression of urocortin 2 and other CRH peptides in rat adrenal medulla: involvement of glucocorticoids. |
Volume: |
125 |
Issue: |
2 |
Pages: |
185-92 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hao Z |
Year: |
2008 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Urocortin2 inhibits tumor growth via effects on vascularization and cell proliferation. |
Volume: |
105 |
Issue: |
10 |
Pages: |
3939-44 |
|
•
•
•
•
•
|
Publication |
First Author: |
Gao MH |
Year: |
2016 |
Journal: |
JCI Insight |
Title: |
One-time injection of AAV8 encoding urocortin 2 provides long-term resolution of insulin resistance. |
Volume: |
1 |
Issue: |
15 |
Pages: |
e88322 |
|
•
•
•
•
•
|
Publication |
First Author: |
Tsatsanis C |
Year: |
2006 |
Journal: |
J Immunol |
Title: |
Corticotropin-releasing factor and the urocortins induce the expression of TLR4 in macrophages via activation of the transcription factors PU.1 and AP-1. |
Volume: |
176 |
Issue: |
3 |
Pages: |
1869-77 |
|
•
•
•
•
•
|
Publication |
First Author: |
Zhu C |
Year: |
2024 |
Journal: |
Biochem Pharmacol |
Title: |
Urocortin2 attenuates diabetic coronary microvascular dysfunction by regulating macrophage extracellular vesicles. |
Volume: |
219 |
|
Pages: |
115976 |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
Mus caroli |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
Mus pahari |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
Mus spretus |
|
•
•
•
•
•
|
Publication |
First Author: |
Chen A |
Year: |
2006 |
Journal: |
J Neurosci |
Title: |
Urocortin 2-deficient mice exhibit gender-specific alterations in circadian hypothalamus-pituitary-adrenal axis and depressive-like behavior. |
Volume: |
26 |
Issue: |
20 |
Pages: |
5500-10 |
|
•
•
•
•
•
|
Publication |
First Author: |
Chen A |
Year: |
2006 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle. |
Volume: |
103 |
Issue: |
44 |
Pages: |
16580-5 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hsu SY |
Year: |
2001 |
Journal: |
Nat Med |
Title: |
Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. |
Volume: |
7 |
Issue: |
5 |
Pages: |
605-11 |
|
•
•
•
•
•
|
Publication |
First Author: |
Chen A |
Year: |
2005 |
Journal: |
Mol Endocrinol |
Title: |
Mouse corticotropin-releasing factor receptor type 2alpha gene: isolation, distribution, pharmacological characterization and regulation by stress and glucocorticoids. |
Volume: |
19 |
Issue: |
2 |
Pages: |
441-58 |
|
•
•
•
•
•
|
Publication |
First Author: |
Reyes TM |
Year: |
2001 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. |
Volume: |
98 |
Issue: |
5 |
Pages: |
2843-8 |
|
•
•
•
•
•
|
Publication |
First Author: |
Burns DP |
Year: |
2017 |
Journal: |
Exp Physiol |
Title: |
Restoration of pharyngeal dilator muscle force in dystrophin-deficient (mdx) mice following co-treatment with neutralizing interleukin-6 receptor antibodies and urocortin 2. |
Volume: |
102 |
Issue: |
9 |
Pages: |
1177-1193 |
|
•
•
•
•
•
|
Publication |
First Author: |
Reutenauer-Patte J |
Year: |
2012 |
Journal: |
Am J Pathol |
Title: |
Urocortins improve dystrophic skeletal muscle structure and function through both PKA- and Epac-dependent pathways. |
Volume: |
180 |
Issue: |
2 |
Pages: |
749-62 |
|
•
•
•
•
•
|
Publication |
First Author: |
Neufeld-Cohen A |
Year: |
2010 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
A triple urocortin knockout mouse model reveals an essential role for urocortins in stress recovery. |
Volume: |
107 |
Issue: |
44 |
Pages: |
19020-5 |
|
•
•
•
•
•
|
Publication |
First Author: |
Deussing JM |
Year: |
2010 |
Journal: |
J Neurosci |
Title: |
Urocortin 3 modulates social discrimination abilities via corticotropin-releasing hormone receptor type 2. |
Volume: |
30 |
Issue: |
27 |
Pages: |
9103-16 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lewis K |
Year: |
2001 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. |
Volume: |
98 |
Issue: |
13 |
Pages: |
7570-5 |
|
•
•
•
•
•
|
Publication |
First Author: |
The Gene Ontology Consortium |
Year: |
2014 |
|
Title: |
Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
DDB, FB, MGI, GOA, ZFIN curators |
Year: |
2001 |
|
Title: |
Gene Ontology annotation through association of InterPro records with GO terms |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2002 |
|
Title: |
Chromosome assignment of mouse genes using the Mouse Genome Sequencing Consortium (MGSC) assembly and the ENSEMBL Database |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Carninci P |
Year: |
2005 |
Journal: |
Science |
Title: |
The transcriptional landscape of the mammalian genome. |
Volume: |
309 |
Issue: |
5740 |
Pages: |
1559-63 |
|
•
•
•
•
•
|
Publication |
First Author: |
UniProt-GOA |
Year: |
2012 |
|
Title: |
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
GOA curators |
Year: |
2016 |
|
Title: |
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
The Gene Ontology Consortium |
Year: |
2010 |
|
Title: |
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Marc Feuermann, Huaiyu Mi, Pascale Gaudet, Dustin Ebert, Anushya Muruganujan, Paul Thomas |
Year: |
2010 |
|
Title: |
Annotation inferences using phylogenetic trees |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Database and National Center for Biotechnology Information |
Year: |
2000 |
Journal: |
Database Release |
Title: |
Entrez Gene Load |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2009 |
Journal: |
Database Download |
Title: |
Mouse Microarray Data Integration in Mouse Genome Informatics, the Affymetrix GeneChip Mouse Gene 1.0 ST Array Platform |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics (MGI) and The National Center for Biotechnology Information (NCBI) |
Year: |
2010 |
Journal: |
Database Download |
Title: |
Consensus CDS project |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Group |
Year: |
2003 |
Journal: |
Database Procedure |
Title: |
Automatic Encodes (AutoE) Reference |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Bairoch A |
Year: |
1999 |
Journal: |
Database Release |
Title: |
SWISS-PROT Annotated protein sequence database |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2005 |
|
Title: |
Obtaining and Loading Genome Assembly Coordinates from Ensembl Annotations |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics |
Year: |
2010 |
Journal: |
Database Release |
Title: |
Protein Ontology Association Load. |
|
|
|
|
•
•
•
•
•
|
Publication |
First Author: |
Mouse Genome Informatics Scientific Curators |
Year: |
2005 |
|
Title: |
Obtaining and loading genome assembly coordinates from NCBI annotations |
|
|
|
|
•
•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
123
 |
Fragment?: |
false |
|
•
•
•
•
•
|
Protein Coding Gene |
Type: |
protein_coding_gene |
Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
Publication |
First Author: |
Spyroglou A |
Year: |
2015 |
Journal: |
Endocrinology |
Title: |
Adrenal and Ovarian Phenotype of a Tissue-Specific Urocortin 2-Overexpressing Mouse Model. |
Volume: |
156 |
Issue: |
7 |
Pages: |
2646-56 |
|
•
•
•
•
•
|
Allele |
Name: |
gene trap ROSA 26, Philippe Soriano; targeted mutation 2, Jan Deussing |
Allele Type: |
Targeted |
Attribute String: |
Conditional ready, Inserted expressed sequence |
|
•
•
•
•
•
|
Publication |
First Author: |
Tsuda T |
Year: |
2017 |
Journal: |
J Exp Med |
Title: |
Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction. |
Volume: |
214 |
Issue: |
7 |
Pages: |
1877-1888 |
|
•
•
•
•
•
|
Publication |
First Author: |
Arase S |
Year: |
2016 |
Journal: |
PLoS One |
Title: |
Disturbance in the Mucosa-Associated Commensal Bacteria Is Associated with the Exacerbation of Chronic Colitis by Repeated Psychological Stress; Is That the New Target of Probiotics? |
Volume: |
11 |
Issue: |
8 |
Pages: |
e0160736 |
|
•
•
•
•
•
|
Publication |
First Author: |
Giardino WJ |
Year: |
2011 |
Journal: |
Genes Brain Behav |
Title: |
Dissection of corticotropin-releasing factor system involvement in locomotor sensitivity to methamphetamine. |
Volume: |
10 |
Issue: |
1 |
Pages: |
78-89 |
|
•
•
•
•
•
|
Publication |
First Author: |
Meister J |
Year: |
2022 |
Journal: |
Mol Metab |
Title: |
In vivo metabolic effects after acute activation of skeletal muscle Gs signaling. |
Volume: |
55 |
|
Pages: |
101415 |
|
•
•
•
•
•
|
Publication |
First Author: |
Bagosi Z |
Year: |
2018 |
Journal: |
Brain Res |
Title: |
Anxiolytic- and antidepressant-like actions of Urocortin 2 and its fragments in mice. |
Volume: |
1680 |
|
Pages: |
62-68 |
|
•
•
•
•
•
|
Publication |
First Author: |
Vita N |
Year: |
1993 |
Journal: |
FEBS Lett |
Title: |
Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptors. |
Volume: |
335 |
Issue: |
1 |
Pages: |
1-5 |
|
•
•
•
•
•
|
Publication |
First Author: |
Chen R |
Year: |
1993 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Expression cloning of a human corticotropin-releasing-factor receptor. |
Volume: |
90 |
Issue: |
19 |
Pages: |
8967-71 |
|
•
•
•
•
•
|
Publication |
First Author: |
Hollenstein K |
Year: |
2013 |
Journal: |
Nature |
Title: |
Structure of class B GPCR corticotropin-releasing factor receptor 1. |
Volume: |
499 |
Issue: |
7459 |
Pages: |
438-43 |
|
•
•
•
•
•
|
Publication |
First Author: |
Yu J |
Year: |
1996 |
Journal: |
Endocrinology |
Title: |
Molecular cloning of a type A chicken corticotropin-releasing factor receptor with high affinity for urotensin I. |
Volume: |
137 |
Issue: |
1 |
Pages: |
192-7 |
|
•
•
•
•
•
|
Publication |
First Author: |
Lovenberg TW |
Year: |
1995 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain. |
Volume: |
92 |
Issue: |
3 |
Pages: |
836-40 |
|
•
•
•
•
•
|
Publication |
First Author: |
Liaw CW |
Year: |
1996 |
Journal: |
Endocrinology |
Title: |
Cloning and characterization of the human corticotropin-releasing factor-2 receptor complementary deoxyribonucleic acid. |
Volume: |
137 |
Issue: |
1 |
Pages: |
72-7 |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Family |
Description: |
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The secretin-like GPCRs include secretin [], calcitonin [], parathyroid hormone/parathyroid hormone-related peptides []and vasoactive intestinal peptide [], all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products. Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis, playing an important role in coordinating the endocrine, autonomic and behavioral responses to stress and immune challenge []. The CRF receptor has been found in human cortex tissue, pituitary, brainstem and testis []. The protein comprises 415 amino acid residues with the characteristic 7TM architecture of the secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2 and CRF-R3) are produced as a result of alternative splicing of the same gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to CRF with a high affinity []. CRF and the related urocortin peptides (Ucn 1-3, also known as UCN, UCN2 and UCN3) mediate their actions through two CRF1 and CRF2 []. |
|
•
•
•
•
•
|
Protein Domain |
Type: |
Family |
Description: |
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The secretin-like GPCRs include secretin [], calcitonin [], parathyroid hormone/parathyroid hormone-related peptides []and vasoactive intestinal peptide [], all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products. Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis, playing an important role in coordinating the endocrine, autonomic and behavioral responses to stress and immune challenge []. The CRF receptor has been found in human cortex tissue, pituitary, brainstem and testis []. The protein comprises 415 amino acid residues with the characteristic 7TM architecture of the secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2 and CRF-R3) are produced as a result of alternative splicing of the same gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to CRF with a high affinity []. CRF and the related urocortin peptides (Ucn 1-3, also known as UCN, UCN2 and UCN3) mediate their actions through two CRF1 and CRF2 [].The sequence of the CRF-R is highly conserved from avian to mammalian species, the majority of the sequence divergence occuring in the putativesignal peptide and extracellular N-terminal domain []. Five additional amino acids are inserted in the N terminus of the avian receptor, and despite its overall similarity to the type 1 mammalian CRF-R, its ligand binding properties are similar to those of the type 2 receptor (i.e., has a higher affinity for urotensin I than for CRF) []. This entry includes CRF1 receptor (CRF1R, also known as CRHR1), which is activated by CRF and Ucn1, is expressed in brain areas including the pituitary, hypothalamus, amygdala and cortex. It is an interesting target to develop drug treatments for stress-related conditions such as anxiety, depression and irritable bowel syndrome []. |
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Protein Domain |
Type: |
Family |
Description: |
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The secretin-like GPCRs include secretin [], calcitonin [], parathyroid hormone/parathyroid hormone-related peptides []and vasoactive intestinal peptide [], all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products. Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis, playing an important role in coordinating the endocrine, autonomic and behavioral responses to stress and immune challenge []. The CRF receptor has been found in human cortex tissue, pituitary, brainstem and testis []. The protein comprises 415 amino acid residues with the characteristic 7TM architecture of the secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2 and CRF-R3) are produced as a result of alternative splicing of the same gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to CRF with a high affinity []. CRF and the related urocortin peptides (Ucn 1-3, also known as UCN, UCN2 and UCN3) mediate their actions through two CRF1 and CRF2 [].For the CRF-R2 receptor, at least 2 splice forms with different 5'-coding sequences (CRF2 alpha and CRF2 beta) have been identified in rat []. The sequence of the CRF-R is highly conserved between species, the majority of the sequence divergence occuring in the putative signal peptide and extracellular N-terminal domain. The relative abundance of CRF-R2 messenger RNA appears to be lower in humans than in rats for the heart and skeletal tissues studied to date []. CRF-R2 stimulates cAMP production in response to CRF and known CRF-like agonists []. CRF and the non-mammalian CRF-related peptides sauvagine and urotensin I stimulate adenylate cyclaseactivity in a dose-dependent manner, with a rank order of potency thatdiffers from that of the CRF1 receptor (sauvagine>urotensin>=rat/human CRF>ovine CRF). The differences in the pharmacological profiles and tissue distributions of CRF-R1 and CRF-R2 suggests important functionaldifferences between the two receptors []. |
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
82
 |
Fragment?: |
true |
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
143
 |
Fragment?: |
false |
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•
•
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
375
 |
Fragment?: |
false |
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•
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
64
 |
Fragment?: |
true |
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•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
210
 |
Fragment?: |
false |
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•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
415
 |
Fragment?: |
false |
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•
•
•
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
411
 |
Fragment?: |
false |
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•
•
•
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Protein |
Organism: |
Mus musculus/domesticus |
Length: |
410
 |
Fragment?: |
false |
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•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
420
 |
Fragment?: |
false |
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•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
431
 |
Fragment?: |
false |
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•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
420
 |
Fragment?: |
false |
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•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
415
 |
Fragment?: |
false |
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•
•
•
•
|
Protein |
Organism: |
Mus musculus/domesticus |
Length: |
430
 |
Fragment?: |
false |
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•
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Publication |
First Author: |
Ishihara T |
Year: |
1991 |
Journal: |
EMBO J |
Title: |
Molecular cloning and expression of a cDNA encoding the secretin receptor. |
Volume: |
10 |
Issue: |
7 |
Pages: |
1635-41 |
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•
•
•
•
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Publication |
First Author: |
Ishihara T |
Year: |
1992 |
Journal: |
Neuron |
Title: |
Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. |
Volume: |
8 |
Issue: |
4 |
Pages: |
811-9 |
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•
•
•
•
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Publication |
First Author: |
Lin HY |
Year: |
1991 |
Journal: |
Science |
Title: |
Expression cloning of an adenylate cyclase-coupled calcitonin receptor. |
Volume: |
254 |
Issue: |
5034 |
Pages: |
1022-4 |
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•
•
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•
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Publication |
First Author: |
Jüppner H |
Year: |
1991 |
Journal: |
Science |
Title: |
A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. |
Volume: |
254 |
Issue: |
5034 |
Pages: |
1024-6 |
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•
•
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Publication |
First Author: |
Vassilatis DK |
Year: |
2003 |
Journal: |
Proc Natl Acad Sci U S A |
Title: |
The G protein-coupled receptor repertoires of human and mouse. |
Volume: |
100 |
Issue: |
8 |
Pages: |
4903-8 |
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•
•
•
•
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Publication |
First Author: |
Attwood TK |
Year: |
1994 |
Journal: |
Protein Eng |
Title: |
Fingerprinting G-protein-coupled receptors. |
Volume: |
7 |
Issue: |
2 |
Pages: |
195-203 |
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•
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•
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Publication |
First Author: |
Kolakowski LF Jr |
Year: |
1994 |
Journal: |
Receptors Channels |
Title: |
GCRDb: a G-protein-coupled receptor database. |
Volume: |
2 |
Issue: |
1 |
Pages: |
1-7 |
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•
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Publication |
First Author: |
Foord SM |
Year: |
2005 |
Journal: |
Pharmacol Rev |
Title: |
International Union of Pharmacology. XLVI. G protein-coupled receptor list. |
Volume: |
57 |
Issue: |
2 |
Pages: |
279-88 |
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•
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•
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Publication |
First Author: |
Harmar AJ |
Year: |
2009 |
Journal: |
Nucleic Acids Res |
Title: |
IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. |
Volume: |
37 |
Issue: |
Database issue |
Pages: |
D680-5 |
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