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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PROK1
prokineticin 1
Chromosome 1 · 1p13.3
NCBI Gene: 84432Ensembl: ENSG00000143125.6HGNC: HGNC:18454UniProt: P58294
79PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
endothelial cell proliferationextracellular regionHirschsprung diseaseHypercholesterolemianeoplasmmetabolic syndrome
✦AI Summary

PROK1 (prokineticin 1), also known as EG-VEGF, is a secreted 86-amino acid protein that regulates multiple physiological processes through binding to G-protein coupled receptors PROKR1 and PROKR2 1. PROK1 acts as a potent gastrointestinal smooth muscle contractile agent and promotes angiogenesis specifically in steroidogenic glands and reproductive organs 2. The protein activates complex signaling cascades including Gq-phospholipase C-β-cSrc-EGFR-MAPK/ERK pathways, leading to inositol phosphate mobilization and regulation of implantation-related genes such as COX-2, IL-6, IL-8, and leukemia inhibitory factor 3. PROK1 plays critical roles in human placentation by controlling trophoblast proliferation, survival, and invasion while promoting placental endothelial cell angiogenesis and permeability 1. The protein exhibits peak placental expression during early pregnancy before feto-maternal circulation establishment and is upregulated by hypoxia 1. Dysregulated PROK1 signaling contributes to pregnancy pathologies including preeclampsia and intrauterine growth restriction, with elevated serum levels observed in affected patients 4. A common genetic variant (V67I) acts as a disease modifier through downregulated gene expression while maintaining similar biological activities 5. PROKR2 antagonism shows therapeutic potential for preeclampsia treatment 6.

Sources cited
1
PROK1 is an 86-amino acid peptide that acts via PROKR1 and PROKR2 receptors, highly expressed in placenta with roles in trophoblast function and angiogenesis
PMID: 27172869
2
PROK1 mediates gut motility and promotes angiogenesis in steroidogenic glands and reproductive organs
PMID: 18440852
3
PROK1-PROKR1 interaction activates specific signaling pathways and regulates implantation-related genes including COX-2
PMID: 18339712
4
PROK1 controls placental angiogenesis and its deregulation contributes to pregnancy pathologies like preeclampsia
PMID: 24955357
5
V67I variant acts as genetic modifier through downregulated PROK1 expression while maintaining biological activities
PMID: 26828479
6
PROKR2 antagonism shows therapeutic potential for preeclampsia treatment
PMID: 39817714
Disease Associationsⓘ20
Hirschsprung diseaseOpen Targets
0.37Weak
HypercholesterolemiaOpen Targets
0.31Weak
neoplasmOpen Targets
0.09Suggestive
metabolic syndromeOpen Targets
0.08Suggestive
intestinal impactionOpen Targets
0.07Suggestive
posterior cortical atrophyOpen Targets
0.07Suggestive
colorectal cancerOpen Targets
0.07Suggestive
cancerOpen Targets
0.07Suggestive
polycystic ovary syndromeOpen Targets
0.07Suggestive
infectionOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.04Suggestive
pachyonychia congenitaOpen Targets
0.04Suggestive
prostate cancerOpen Targets
0.04Suggestive
gliomaOpen Targets
0.04Suggestive
papillary thyroid carcinomaOpen Targets
0.04Suggestive
endometriosisOpen Targets
0.03Suggestive
neuroblastomaOpen Targets
0.03Suggestive
colorectal carcinomaOpen Targets
0.03Suggestive
Chédiak-Higashi syndromeOpen Targets
0.03Suggestive
Posterior Leukoencephalopathy SyndromeOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PROKR1Protein interaction80%PROKR2Protein interaction80%CLPSProtein interaction77%ADCY3Protein interaction76%ALDH18A1Protein interaction71%GPR83Protein interaction70%
Tissue Expression6 tissues
Ovary
100%
Heart
0%
Brain
0%
Liver
0%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PROK1PROKR1PROKR2CLPSADCY3ALDH18A1GPR83
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P58294
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.65LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.04 [0.66–1.65]
RankingsWhere PROK1 stands among ~20K protein-coding genes
  • #6,021of 20,598
    Most Researched79
  • #15,898of 17,882
    Most Constrained (LOEUF)1.65
Genes detectedPROK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Prokineticin1 and pregnancy.
PMID: 27172869
Ann Endocrinol (Paris) · 2016
1.00
2
Prokineticin-signaling pathway.
PMID: 18440852
Int J Biochem Cell Biol · 2008
0.90
3
Prokineticin 2/PROK2 and Male Infertility.
PMID: 36289651
Biomedicines · 2022
0.80
4
Prokineticin 1 signaling and gene regulation in early human pregnancy.
PMID: 18339712
Endocrinology · 2008
0.70
5
The multiple roles of EG-VEGF/PROK1 in normal and pathological placental angiogenesis.
PMID: 24955357
Biomed Res Int · 2014
0.60