This gene encodes a protein expressed in the suprachiasmatic nucleus (SCN) circadian clock that may function as the output component of the circadian clock. The secreted form of the encoded protein may also serve as a chemoattractant for neuronal precursor cells in the olfactory bulb. Proteins from other vertebrates which are similar to this gene product were isolated based on ... See more...

Aliases for PROK2 Gene

Aliases for PROK2 Gene

  • Prokineticin 2 2 3 5
  • Protein Bv8 Homolog 2 3 4
  • BV8 2 3 4
  • PK2 2 3 4
  • Prokineticin-2 3 4
  • KAL4 2 3
  • MIT1 2 3
  • PROK2 5
  • HH4 3

External Ids for PROK2 Gene

Previous GeneCards Identifiers for PROK2 Gene

  • GC03P070509
  • GC03M071434
  • GC03M071625
  • GC03M071741
  • GC03M071903
  • GC03M071820

Summaries for PROK2 Gene

Entrez Gene Summary for PROK2 Gene

  • This gene encodes a protein expressed in the suprachiasmatic nucleus (SCN) circadian clock that may function as the output component of the circadian clock. The secreted form of the encoded protein may also serve as a chemoattractant for neuronal precursor cells in the olfactory bulb. Proteins from other vertebrates which are similar to this gene product were isolated based on homology to snake venom and secretions from frog skin, and have been shown to have diverse functions. Mutations in this gene are associated with Kallmann syndrome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for PROK2 Gene

PROK2 (Prokineticin 2) is a Protein Coding gene. Diseases associated with PROK2 include Hypogonadotropic Hypogonadism 4 With Or Without Anosmia and Kallmann Syndrome 4. Among its related pathways are Signaling by GPCR and Peptide ligand-binding receptors. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor binding. An important paralog of this gene is PROK1.

UniProtKB/Swiss-Prot Summary for PROK2 Gene

  • May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm. May also function locally within the SCN to synchronize output. Potently contracts gastrointestinal (GI) smooth muscle.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PROK2 Gene

Genomics for PROK2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PROK2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J071781 Promoter/Enhancer 1.5 EPDnew FANTOM5 Ensembl 313.9 +1.5 1505 3.8 ZNF341 PRDM6 GLI4 ZBTB48 MYC MAX POLR2A FOXM1 ZNF664 ZNF561 PROK2 ENSG00000287131 HSALNG0026781 LOC105377156 GPR27 EIF4E3 FOXP1 lnc-PROK2-1
GH03J071786 Promoter 0.6 Ensembl 250.7 -0.9 -895 0.2 ATF2 CREB1 EZH2 ENSG00000287131 HSALNG0026781 LOC105377156 PROK2 lnc-PROK2-1 RYBP
GH03J071779 Enhancer 0.8 FANTOM5 ENCODE 67.9 +5.1 5147 0.9 CTCF GABPA ZNF316 NFE2 PRDM6 MYC ETV1 FOXM1 MAX POLR2A PROK2 GPR27 EIF4E3 FOXP1 HSALNG0026781
GH03J071850 Enhancer 1.1 FANTOM5 Ensembl ENCODE 41.6 -68.1 -68095 13 ZNF654 NFIC CTCF REST FEZF1 RAD21 SPI1 MYC ETV1 MAX HSALNG0026786 PROK2 GPR27 EIF4E3 FOXP1 lnc-GPR27-8 RYBP
GH03J072076 Promoter/Enhancer 1.7 FANTOM5 Ensembl ENCODE dbSUPER 16.6 -295.0 -294993 6.9 BCLAF1 ZNF207 NCOR1 POLR2A NFIC SMAD5 HES1 BHLHE40 FEZF1 ZNF341 RYBP PROK2 GPR27 EIF4E3 LINC00877 FOXP1 ENSG00000276471 ENSG00000273461
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PROK2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PROK2

Top Transcription factor binding sites by QIAGEN in the PROK2 gene promoter:
  • E47
  • HOXA5
  • ITF-2
  • LCR-F1
  • MyoD
  • Nkx2-5
  • POU3F2
  • Tal-1
  • Tal-1beta
  • USF-1

Genomic Locations for PROK2 Gene

Latest Assembly
chr3:71,771,655-71,785,206
(GRCh38/hg38)
Size:
13,552 bases
Orientation:
Minus strand

Previous Assembly
chr3:71,820,806-71,834,299
(GRCh37/hg19 by Entrez Gene)
Size:
13,494 bases
Orientation:
Minus strand

chr3:71,820,807-71,834,357
(GRCh37/hg19 by Ensembl)
Size:
13,551 bases
Orientation:
Minus strand

Genomic View for PROK2 Gene

Genes around PROK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PROK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PROK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PROK2 Gene

Proteins for PROK2 Gene

  • Protein details for PROK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HC23-PROK2_HUMAN
    Recommended name:
    Prokineticin-2
    Protein Accession:
    Q9HC23
    Secondary Accessions:
    • Q53Z79
    • Q6ISR0

    Protein attributes for PROK2 Gene

    Size:
    129 amino acids
    Molecular mass:
    14314 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for PROK2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PROK2 Gene

Post-translational modifications for PROK2 Gene

No Post-translational modifications

Other Protein References for PROK2 Gene

No data available for DME Specific Peptides for PROK2 Gene

Domains & Families for PROK2 Gene

Gene Families for PROK2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for PROK2 Gene

InterPro:
Blocks:
  • Prokineticin

Suggested Antigen Peptide Sequences for PROK2 Gene

GenScript: Design optimal peptide antigens:
  • Protein Bv8 homolog (PROK2_HUMAN)
  • Prokineticin 2, isoform CRA_a (Q6ISR0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9HC23

UniProtKB/Swiss-Prot:

PROK2_HUMAN :
  • Belongs to the AVIT (prokineticin) family.
Family:
  • Belongs to the AVIT (prokineticin) family.
genes like me logo Genes that share domains with PROK2: view

Function for PROK2 Gene

Molecular function for PROK2 Gene

UniProtKB/Swiss-Prot Function:
May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm. May also function locally within the SCN to synchronize output. Potently contracts gastrointestinal (GI) smooth muscle.
UniProtKB/Swiss-Prot Induction:
Activated by CLOCK and BMAL1 heterodimers and light; inhibited by period genes (PER1, PER2 and PER3) and cryptochrome genes (CRY1 and CRY2).

Phenotypes From GWAS Catalog for PROK2 Gene

Gene Ontology (GO) - Molecular Function for PROK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001664 G protein-coupled receptor binding TAS 12728244
GO:0005515 protein binding IPI 32296183
genes like me logo Genes that share ontologies with PROK2: view
genes like me logo Genes that share phenotypes with PROK2: view

Human Phenotype Ontology for PROK2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PROK2 Gene

MGI Knock Outs for PROK2:

Animal Models for research

  • Taconic Biosciences Mouse Models for PROK2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PROK2

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for PROK2 Gene

Localization for PROK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PROK2 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PROK2 gene
Compartment Confidence
extracellular 5
plasma membrane 2
nucleus 2
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1

Gene Ontology (GO) - Cellular Components for PROK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IBA,TAS 12466223
genes like me logo Genes that share ontologies with PROK2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for PROK2 Gene

Pathways & Interactions for PROK2 Gene

genes like me logo Genes that share pathways with PROK2: view

SIGNOR curated interactions for PROK2 Gene

Activates:

Gene Ontology (GO) - Biological Process for PROK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity TAS 12728244
GO:0001525 angiogenesis IDA 12604792
GO:0001935 endothelial cell proliferation IDA 12604792
GO:0006935 chemotaxis IDA 12604792
GO:0006954 inflammatory response NAS 11259612
genes like me logo Genes that share ontologies with PROK2: view

Drugs & Compounds for PROK2 Gene

(1) Additional Compounds for PROK2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PROK2: view

Transcripts for PROK2 Gene

mRNA/cDNA for PROK2 Gene

2 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PROK2

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for PROK2 Gene

No ASD Table

Relevant External Links for PROK2 Gene

GeneLoc Exon Structure for
PROK2

Expression for PROK2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PROK2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PROK2 Gene

This gene is overexpressed in Whole Blood (x47.7).

Protein differential expression in normal tissues from HIPED for PROK2 Gene

This gene is overexpressed in Monocytes (58.5) and Platelet (10.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PROK2 Gene



Protein tissue co-expression partners for PROK2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PROK2

SOURCE GeneReport for Unigene cluster for PROK2 Gene:

Hs.528665

mRNA Expression by UniProt/SwissProt for PROK2 Gene:

Q9HC23-PROK2_HUMAN
Tissue specificity: Expressed in the testis and, at low levels, in the small intestine.

Evidence on tissue expression from TISSUES for PROK2 Gene

  • Blood(3.1)
  • Nervous system(2.7)
  • Bone marrow(2.6)
  • Heart(2.3)
  • Intestine(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PROK2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • eye
  • face
  • head
  • hypothalamus
  • jaw
  • larynx
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • olfactory bulb
  • pharynx
  • pituitary gland
  • skull
  • vocal cord
Thorax:
  • breast
  • chest wall
  • clavicle
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • kidney
Pelvis:
  • fallopian tube
  • ovary
  • pelvis
  • penis
  • prostate
  • testicle
  • uterus
  • vagina
  • vas deferens
  • vulva
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • hair
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with PROK2: view

Primer products for research

Orthologs for PROK2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for PROK2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PROK2 29 30
  • 99.22 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia LOC610873 29
  • 92.78 (n)
Rat
(Rattus norvegicus)
Mammalia Prok2 29
  • 85.93 (n)
Mouse
(Mus musculus)
Mammalia Prok2 29 16 30
  • 85.63 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PROK2 29 30
  • 85.16 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia PROK2 30
  • 59 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PROK2 29 30
  • 68.49 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PROK2 30
  • 49 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100485995 29
  • 68.25 (n)
Zebrafish
(Danio rerio)
Actinopterygii prok2 29 30
  • 63.79 (n)
OneToOne
Species where no ortholog for PROK2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for PROK2 Gene

ENSEMBL:
Gene Tree for PROK2 (if available)
TreeFam:
Gene Tree for PROK2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PROK2: view image
Alliance of Genome Resources:
Additional Orthologs for PROK2

Paralogs for PROK2 Gene

Paralogs for PROK2 Gene

(1) SIMAP similar genes for PROK2 Gene using alignment to 1 proteins:

  • PROK2_HUMAN
genes like me logo Genes that share paralogs with PROK2: view

Variants for PROK2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PROK2 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
997621 Pathogenic: Hypogonadotropic hypogonadism 4 with or without anosmia 71,774,509(-) T/C
NM_001126128.2(PROK2):c.223-2A>G
SPLICE_ACCEPTOR_VARIANT,INTRON
rs104893767 Pathogenic: Hypogonadotropic hypogonadism 4 with or without anosmia. Hypogonadotropic hypogonadism 4 with or without anosmia (HH4) [MIM:610628] 71,784,959(-) C/Gp.Gly32Arg
NM_001126128.2(PROK2):c.94G>C (p.Gly32Arg)
MISSENSE
rs121434272 Pathogenic: Hypogonadotropic hypogonadism 4 with or without anosmia. Hypogonadotropic hypogonadism 4 with or without anosmia (HH4) [MIM:610628] 71,781,472(-) G/Ap.Arg73Cys
NM_001126128.2(PROK2):c.217C>T (p.Arg73Cys)
MISSENSE
rs138829087 Hypogonadotropic hypogonadism 4 with or without anosmia (HH4) [MIM:610628] p.Ile50Met
rs142701726 Hypogonadotropic hypogonadism 4 with or without anosmia (HH4) [MIM:610628] p.Cys46Tyr

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for PROK2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for PROK2 Gene

Variant ID Type Subtype PubMed ID
nsv524847 CNV loss 19592680
nsv590600 CNV loss 21841781

Variation tolerance for PROK2 Gene

Residual Variation Intolerance Score: 57% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.70; 32.44% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PROK2 Gene

Human Gene Mutation Database (HGMD)
PROK2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PROK2
Leiden Open Variation Database (LOVD)
PROK2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PROK2 Gene

Disorders for PROK2 Gene

MalaCards: The human disease database

(18) MalaCards diseases for PROK2 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
hypogonadotropic hypogonadism 4 with or without anosmia
  • hh4
kallmann syndrome 4
  • kal4
kallmann syndrome
  • familial hypogonadism with anosmia
normosmic congenital hypogonadotropic hypogonadism
  • normosmic idiopathic hypogonadotropic hypogonadism
hypogonadotropic hypogonadism
  • congenital idiopathic hypogonadotropic hypogonadism
- elite association - COSMIC cancer census association via MalaCards
Search PROK2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PROK2_HUMAN
  • Hypogonadotropic hypogonadism 4 with or without anosmia (HH4) [MIM:610628]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269 PubMed:17054399, ECO:0000269 PubMed:18559922, ECO:0000269 PubMed:23643382, ECO:0000269 PubMed:25077900}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in PROK2 as well as in other HH-associated genes including PROKR2 (PubMed:23643382). {ECO:0000269 PubMed:23643382}.

Additional Disease Information for PROK2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with PROK2: view

No data available for Genatlas for PROK2 Gene

Publications for PROK2 Gene

  1. Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome. (PMID: 18682503) Abreu AP … Latronico AC (The Journal of clinical endocrinology and metabolism 2008) 3 22 40 72
  2. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. (PMID: 17054399) Dodé C … Hardelin JP (PLoS genetics 2006) 3 4 22 72
  3. Identification of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle. (PMID: 11259612) Li M … Zhou QY (Molecular pharmacology 2001) 2 3 4 22
  4. A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes. (PMID: 20022991) Sarfati J … Young J (The Journal of clinical endocrinology and metabolism 2010) 3 22 40
  5. Genetic analysis in patients with Kallmann syndrome: coexistence of mutations in prokineticin receptor 2 and KAL1. (PMID: 18723471) Canto P … Méndez JP (Journal of andrology 2009) 3 22 40

Products for PROK2 Gene

Sources for PROK2 Gene