Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Associated Proteins
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 384 | 20p12.3 | PROKR2 | prokineticin receptor 2 | 24,46 |
| Mouse | 7 | 381 | 2 F2 | Prokr2 | prokineticin receptor 2 | 11 |
| Rat | 7 | 383 | 3q36 | Prokr2 | prokineticin receptor 2 | 27,33 |
| Previous and Unofficial Names |
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| GPR73b [24] | VEGFR-2 [23] | GPRg2 [46] | GPR73a [24] | I5E [27] | |
| Database Links |
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| Specialist databases | |
| GPCRdb | pkr2_human (Hs), pkr2_mouse (Mm), pkr2_rat (Rn) |
| Other databases | |
| Alphafold | Q8NFJ6 (Hs), Q8K458 (Mm), Q8R415 (Rn) |
| ChEMBL Target | CHEMBL5548 (Hs) |
| Ensembl Gene | ENSG00000101292 (Hs), ENSMUSG00000050558 (Mm), ENSRNOG00000021266 (Rn) |
| Entrez Gene | 128674 (Hs), 246313 (Mm), 192649 (Rn) |
| Human Protein Atlas | ENSG00000101292 (Hs) |
| KEGG Gene | hsa:128674 (Hs), mmu:246313 (Mm), rno:192649 (Rn) |
| OMIM | 607123 (Hs) |
| Orphanet | ORPHA118044 (Hs) |
| Pharos | Q8NFJ6 (Hs) |
| RefSeq Nucleotide | NM_144773 (Hs), NM_144944 (Mm), NM_138978 (Rn) |
| RefSeq Protein | NP_658986 (Hs), NP_659193 (Mm), NP_620434 (Rn) |
| UniProtKB | Q8NFJ6 (Hs), Q8K458 (Mm), Q8R415 (Rn) |
| Wikipedia | PROKR2 (Hs) |
| Associated Proteins |
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| Natural/Endogenous Ligands |
| prokineticin-2β {Sp: Human} |
| prokineticin-1 {Sp: Human} |
| prokineticin-2 {Sp: Human} |
| prokineticin-1 {Sp: Mouse} |
| prokineticin-2 {Sp: Mouse, Rat} |
| prokineticin-1 {Sp: Rat} |
| Comments: Prokineticin-2 is the higher potency endogenous agonist |
| Potency order of endogenous ligands (Human) |
| prokineticin-2 (PROK2, Q9HC23) > prokineticin-1 (PROK1, Q9HC23) > prokineticin-2β (PROK2, Q9HC23) [10,24,27,46] |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| Comments: Coexpression of Gqi5 with the PKR2 receptor increases the PK stimulated Ca2+ response in HEK 293 cells transfected with the human PKR2 receptor [10]. | |
| References: 10,30 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
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Gs family Gi/Go family |
Adenylyl cyclase stimulation Other - See Comments |
| Comments: Pertussis toxin (PTX) inhibits PK1-induced mitogen-activated protein kinase signaling suggesting that PKR2 couples to Gi/Go proteins [25]. | |
| References: 10,25 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| In zebrafish knock-down of the PKR2 orthologue provided a model that has been used to uncover the complex regulatory role that this receptor plays in the hypothalamus-pituitary-gonadal axis [4]. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Clinically-Relevant Mutations and Pathophysiology Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutations found in the homozygous state: Kallmann syndrome (R85C, R85H, Y140X, R164Q, L173R, V274D, P290S, G234D, R268C). For other possible variants of PKR2 due to single nucleotide polymorphism (SNP) see reference [48] and the Exome Variant Server Data Browser. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biologically Significant Variants
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| Biologically Significant Variant Comments | ||||||||||||
| In most cases, only one allele is affected by the mutation. In heterozygotes the two main clinical features of Kallmann syndrome may be incomplete. Several phenotypes are possible for individuals harboring only one mutant allele: (1) no symptoms, with normal olfaction and complete pubertal development (2) congenital isolated (idiopathic) hypogonadotropic hypogonadism (IHH) but normal olfaction (3) anosmia/hyposmia but normal pubertal development and gonadal function (4) the two cardinal clinical Kallmann syndrome signs, anosmia and IHH. These phenotypic dissociations can be seen in family members with the same PROKR2 mutations. By contrast, patients with two mutant alleles almost always have the cardinal signs of Kallmann syndrome. Other mutations in PROKR2 associated with cancer [35] (*, stop codon; fs, frameshift) carcinoma: lung: D38N, R47W, K53N, K83N, D99N, W121*, I174N, A175S, P213H, E231D ovary: R85C, L95P, R298C, R353H breast: S23F, G293S, M341I liver L95P, I184fs*56 rectum C242*, R368I larynx D112Y, C279S pharynx R268G prostate Y220* kidney: G124C endometrium: V115M colon: A322T melanoma: E110K, R298C neuroblastoma: F109L glioma: M165I others: pancreas: A77T, V331M |
References
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