PENK Gene (Protein Coding)

Proenkephalin

GC08M056436
GIFtS:
39
This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the pentapeptide opioids Met-enkephalin and Leu-enkephalin, which are stored in synaptic vesicles, then released into the synapse where they bind to mu- and delta-opioid receptors to modulate the perception of pain. Other non-opioid cleavage products... See more...

Aliases for PENK Gene

Aliases for PENK Gene

  • Proenkephalin 2 3 5
  • Preproenkephalin 2 3
  • Proenkephalin-A 3 4
  • Enkephalin A 3
  • Peptide F 3
  • PENK-A 3
  • PENK 5
  • PE 3

External Ids for PENK Gene

Previous GeneCards Identifiers for PENK Gene

  • GC08M056526
  • GC08M057292
  • GC08M057072
  • GC08M057403
  • GC08M057516
  • GC08M052820
  • GC08M057349

Summaries for PENK Gene

Entrez Gene Summary for PENK Gene

  • This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the pentapeptide opioids Met-enkephalin and Leu-enkephalin, which are stored in synaptic vesicles, then released into the synapse where they bind to mu- and delta-opioid receptors to modulate the perception of pain. Other non-opioid cleavage products may function in distinct biological activities. [provided by RefSeq, Jul 2015]

GeneCards Summary for PENK Gene

PENK (Proenkephalin) is a Protein Coding gene. Diseases associated with PENK include Cannabis Dependence and Radiculopathy. Among its related pathways are ERK Signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include neuropeptide hormone activity and opioid peptide activity. An important paralog of this gene is PDYN.

UniProtKB/Swiss-Prot Summary for PENK Gene

  • [Met-enkephalin]: Competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress.
  • [Leu-enkephalin]: Competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress.
  • [PENK(114-133)]: Increases glutamate release in the striatum and decreases GABA concentration in the striatum.
  • [PENK(237-258)]: Increases glutamate release in the striatum.

Additional gene information for PENK Gene

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

Genomics for PENK Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for PENK 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
GH08J056557 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE 250.1 -112.7 -112684 3.5 CTCF CEBPB REST SMC3 RAD21 SPI1 POLR2A IKZF1 ATF2 ZNF143 LINC00968 PENK ENSG00000253139 RPL37P6 piR-59769-586 LOC101929415 BPNT2
GH08J056447 Enhancer 0.9 FANTOM5 Ensembl 263.6 -1.6 -1550 0.9 CTCF SIN3A SMC3 GABPB1 RAD21 MAX ZNF48 ZNF143 ZNF580 ZBTB33 PENK lnc-SDR16C5-2 SDR16C5 LOC101929415 lnc-CHCHD7-4 BPNT2
GH08J056444 Enhancer 0.5 Ensembl 261.1 +0.7 687 1.2 SIN3A REST YY1 MIER2 EZH2 ZNF143 PENK LOC101929415 lnc-SDR16C5-2 SDR16C5
GH08J056446 Promoter 0.4 EPDnew 250.7 +0.0 10 0.1 EZH2 LOC101929415 PENK lnc-SDR16C5-2 SDR16C5
GH08J056448 Enhancer 0.3 Ensembl 256.1 -0.2 -230 0.2 EZH2 PENK LOC101929415 lnc-SDR16C5-2 lnc-CHCHD7-4 BPNT2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

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

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

Top Transcription factor binding sites by QIAGEN in the PENK gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • Nkx2-5

Genomic Locations for PENK Gene

Latest Assembly
chr8:56,436,674-56,446,671
(GRCh38/hg38)
Size:
9,998 bases
Orientation:
Minus strand

Previous Assembly
chr8:57,353,516-57,359,200
(GRCh37/hg19 by Entrez Gene)
Size:
5,685 bases
Orientation:
Minus strand

chr8:57,349,233-57,359,293
(GRCh37/hg19 by Ensembl)
Size:
10,061 bases
Orientation:
Minus strand

Genomic View for PENK Gene

Genes around PENK on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for PENK Gene

Proteins for PENK Gene

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

    Protein Symbol:
    P01210-PENK_HUMAN
    Recommended name:
    Proenkephalin-A
    Protein Accession:
    P01210
    Secondary Accessions:
    • B2RC23
    • Q6FHC6
    • Q6FHE6

    Protein attributes for PENK Gene

    Size:
    267 amino acids
    Molecular mass:
    30787 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for PENK Gene

neXtProt entry for PENK Gene

Protein Expression for PENK Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for PENK Gene

  • The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.
  • Proenkephalin-A is cleaved by CTSL to generate Met-enkephalin.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PENK Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for PENK Gene

Domains & Families for PENK Gene

Gene Families for PENK Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted secreted proteins
  • Transporters

Protein Domains for PENK Gene

InterPro:
Blocks:
  • Opioid neuropeptide precursor
  • Proenkephalin A precursor signature
ProtoNet:

Suggested Antigen Peptide Sequences for PENK Gene

GenScript: Design optimal peptide antigens:
  • Proenkephalin-A (PENK_HUMAN)
  • PENK protein (Q3B7B1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P01210

UniProtKB/Swiss-Prot:

PENK_HUMAN :
  • Belongs to the opioid neuropeptide precursor family.
Family:
  • Belongs to the opioid neuropeptide precursor family.
genes like me logo Genes that share domains with PENK: view

Function for PENK Gene

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  4. Inhibitory RNAs for research
  5. Clone products for research
  6. Cell Lines for research

Molecular function for PENK Gene

UniProtKB/Swiss-Prot Function:
[Met-enkephalin]: Competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress.
UniProtKB/Swiss-Prot Function:
[Leu-enkephalin]: Competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress.
UniProtKB/Swiss-Prot Function:
[PENK(114-133)]: Increases glutamate release in the striatum and decreases GABA concentration in the striatum.
UniProtKB/Swiss-Prot Function:
[PENK(237-258)]: Increases glutamate release in the striatum.
GENATLAS Biochemistry:
pro-enkephalin

Phenotypes From GWAS Catalog for PENK Gene

Gene Ontology (GO) - Molecular Function for PENK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001515 opioid peptide activity IEA --
GO:0005184 neuropeptide hormone activity TAS 7057924
GO:0031628 opioid receptor binding IBA 21873635
genes like me logo Genes that share ontologies with PENK: view
genes like me logo Genes that share phenotypes with PENK: view

Animal Models for PENK Gene

MGI Knock Outs for PENK:
  • Penk Penk<tm1Dwp>
  • Penk Penk<tm1Jep>
  • Penk Penk<tm1(KOMP)Mbp>

Animal Models for research

Inhibitory RNAs for research

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

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for PENK Gene

Localization for PENK Gene

Subcellular locations from UniProtKB/Swiss-Prot for PENK Gene

Cytoplasmic vesicle, secretory vesicle, chromaffin granule lumen. 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 PENK gene
Compartment Confidence
extracellular 5
plasma membrane 4
endoplasmic reticulum 4
cytoskeleton 2
mitochondrion 2
nucleus 2
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for PENK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA,TAS --
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0005886 plasma membrane IBA 21873635
GO:0030424 axon IEA --
GO:0030425 dendrite IBA 21873635
genes like me logo Genes that share ontologies with PENK: view

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

Pathways & Interactions for PENK Gene

PathCards logo

SuperPathways for PENK Gene

SuperPathway Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
Rac1 Pathway
.65
Glioma Invasiveness
.64
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
2 GPCR Pathway
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
3 Peptide ligand-binding receptors
Class A/1 (Rhodopsin-like receptors)
.71
GPCR ligand binding
.71
Peptide ligand-binding receptors
.58
Neuroactive ligand-receptor interaction
.45
G alpha (i) signalling events
.42
4 ERK Signaling
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
5 Nanog in Mammalian ESC Pluripotency
GSK3 Signaling
.61
Nanog in Mammalian ESC Pluripotency
.61
14-3-3 Induced Intracellular Signaling
.59
eNOS Signaling
.48
genes like me logo Genes that share pathways with PENK: view

Pathways by source for PENK Gene

1 KEGG pathway for PENK Gene
54 Qiagen pathways for PENK Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR

SIGNOR curated interactions for PENK Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for PENK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001649 osteoblast differentiation IEA --
GO:0001662 behavioral fear response IEA --
GO:0001666 response to hypoxia IEA --
GO:0001964 startle response IEA --
GO:0002118 aggressive behavior IEA --
genes like me logo Genes that share ontologies with PENK: view

Drugs & Compounds for PENK Gene

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  1. Drug products for research

(24) Drugs for PENK Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(11) Additional Compounds for PENK Gene - From: Novoseek

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

Transcripts for PENK Gene

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mRNA/cDNA for PENK Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
9 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 PENK

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

No ASD Table

Relevant External Links for PENK Gene

GeneLoc Exon Structure for
PENK

Expression for PENK Gene

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  1. Primer products for research
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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PENK Gene

mRNA expression in normal human tissues for PENK Gene
mRNA expression by GTEx for PENK GenemRNA expression by BioGPS for PENK Gene

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

This gene is overexpressed in Brain - Putamen (basal ganglia) (x14.6), Brain - Nucleus accumbens (basal ganglia) (x14.0), and Brain - Caudate (basal ganglia) (x11.1).

Protein differential expression in normal tissues from HIPED for PENK Gene

This gene is overexpressed in Cerebrospinal fluid (48.3) and Urine (16.2).

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



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

SOURCE GeneReport for Unigene cluster for PENK Gene:

Hs.339831

Evidence on tissue expression from TISSUES for PENK Gene

  • Nervous system(4.8)
  • Adrenal gland(3.7)
  • Bone(2.4)
  • Muscle(2.4)
  • Heart(2.3)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with PENK: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for PENK Gene

Orthologs for PENK Gene

This gene was present in the common ancestor of chordates.

Orthologs for PENK Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia PENK 30 31
  • 99.63 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia PENK 30 31
  • 86.47 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia PENK 30 31
  • 86.06 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Penk 30
  • 83.33 (n)
Mouse
(Mus musculus)
 Mammalia Penk 30 17 31
  • 82.9 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia PENK 31
  • 76 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia PENK 31
  • 73 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves PENK 30 31
  • 75.65 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia PENK 31
  • 69 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia penk 30
  • 66.67 (n)
Zebrafish
(Danio rerio)
 Actinopterygii penka 30 31
  • 63.16 (n)
 OneToMany
penkb 31
  • 37 (a)
 OneToMany
penk 30
Species where no ortholog for PENK 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)
  • 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 PENK Gene

ENSEMBL:
Gene Tree for PENK (if available)
TreeFam:
Gene Tree for PENK (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PENK: view image

Paralogs for PENK Gene

Paralogs for PENK Gene

(1) SIMAP similar genes for PENK Gene using alignment to 6 proteins:

  • PENK_HUMAN
  • E5RFR1_HUMAN
  • E5RIP6_HUMAN
  • E5RJ72_HUMAN
  • H0YBT5_HUMAN
  • Q3B7B1_HUMAN
genes like me logo Genes that share paralogs with PENK: view

Variants for PENK Gene

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

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
rs1004308282 Likely Benign: not provided 56,441,815(-) A/G
NM_001135690.3(PENK):c.261T>C (p.Asn87=) 		SYNONYMOUS
rs11998459 Benign: not provided. - 56,441,828(-) G/Tp.Thr83Asn
NM_001135690.3(PENK):c.248C>A (p.Thr83Asn) 		MISSENSE
rs142176507 Likely Benign: not provided 56,441,429(-) C/T
NM_001135690.3(PENK):c.647G>A (p.Arg216Lys) 		MISSENSE
rs149051933 Benign: not provided 56,445,888(-) C/T
NM_001135690.3(PENK):c.66G>A (p.Val22=) 		NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS
rs187034999 Likely Benign: not provided 56,441,946(-) A/G
NM_001135690.3(PENK):c.139-9T>C 		INTRON

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

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

Variation tolerance for PENK Gene

Residual Variation Intolerance Score: 68.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.50; 43.75% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PENK Gene

Human Gene Mutation Database (HGMD)
PENK
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PENK

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for PENK Gene

Disorders for PENK Gene

MalaCards: The human disease database

(16) MalaCards diseases for PENK Gene - From: COP and GCD

Disorder Aliases PubMed IDs
cannabis dependence
  • marijuana abuse
radiculopathy
  • pinched nerve
drug dependence
bone cancer
  • bone neoplasm
pheochromocytoma
  • pheochromocytoma, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search PENK in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PENK

Genetic Association Database
(GAD)
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 PENK: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PENK Gene

Publications for PENK Gene

  1. Opioid neuropeptide genotypes in relation to heroin abuse: dopamine tone contributes to reversed mesolimbic proenkephalin expression. (PMID: 18184800) Nikoshkov A … Hurd YL (Proceedings of the National Academy of Sciences of the United States of America 2008) 3 23 41
  2. The opioid system in alcohol and drug dependence: family-based association study. (PMID: 17503481) Xuei X … Edenberg HJ (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2007) 3 23 41
  3. Isolation and structural organization of the human preproenkephalin gene. (PMID: 6281660) Noda M … Numa S (Nature 1982) 2 3 4
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  5. A large-scale candidate gene association study of age at menarche and age at natural menopause. (PMID: 20734064) He C … Hunter DJ (Human genetics 2010) 3 41

ExternalLinks

View latest publications for PENK gene in Mastermind

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