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Protein

Proenkephalin-A

Gene

PENK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Met- and Leu-enkephalins compete 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) and PENK(237-258) increase glutamate release in the striatum. PENK(114-133) decreases GABA concentration in the striatum.

GO - Molecular functioni

  • neuropeptide hormone activity Source: ProtInc
  • opioid peptide activity Source: UniProtKB-KW
  • opioid receptor binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionEndorphin, Neuropeptide, Opioid peptide

Enzyme and pathway databases

ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-HSA-418594. G alpha (i) signalling events.
R-HSA-8957275. Post-translational protein phosphorylation.

Protein family/group databases

TCDBi1.C.89.1.2. the dynorphin channel-forming neuropeptide (dynorphin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Proenkephalin-A
Cleaved into the following 8 chains:
Gene namesi
Name:PENK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000181195.10.
HGNCiHGNC:8831. PENK.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi5179.
OpenTargetsiENSG00000181195.
PharmGKBiPA33176.

Polymorphism and mutation databases

BioMutaiPENK.
DMDMi129770.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
PeptideiPRO_000000824225 – 97SynenkephalinAdd BLAST73
PeptideiPRO_0000008243100 – 104Met-enkephalin5
PeptideiPRO_0000008244107 – 111Met-enkephalin5
PeptideiPRO_0000377691114 – 133PENK(114-133)By similarityAdd BLAST20
PeptideiPRO_0000008246136 – 140Met-enkephalin5
PeptideiPRO_0000377692143 – 183PENK(143-183)By similarityAdd BLAST41
PeptideiPRO_0000008248186 – 193Met-enkephalin-Arg-Gly-Leu8
PropeptideiPRO_0000008249196 – 207Add BLAST12
PeptideiPRO_0000008250210 – 214Met-enkephalin5
PropeptideiPRO_0000008251217 – 227Add BLAST11
PeptideiPRO_0000008252230 – 234Leu-enkephalin5
PeptideiPRO_0000377693237 – 258PENK(237-258)By similarityAdd BLAST22
PeptideiPRO_0000008254261 – 267Met-enkephalin-Arg-Phe7

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi26 ↔ 481 Publication
Disulfide bondi30 ↔ 521 Publication
Disulfide bondi33 ↔ 651 Publication
Modified residuei251PhosphoserineBy similarity1

Post-translational modificationi

The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Phosphoprotein

Proteomic databases

PaxDbiP01210.
PeptideAtlasiP01210.
PRIDEiP01210.

PTM databases

iPTMnetiP01210.
PhosphoSitePlusiP01210.

Miscellaneous databases

PMAP-CutDBiP01210.

Expressioni

Gene expression databases

BgeeiENSG00000181195.
CleanExiHS_PENK.
ExpressionAtlasiP01210. baseline and differential.
GenevisibleiP01210. HS.

Organism-specific databases

HPAiCAB016390.
HPA013138.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
OPRM1P353723EBI-6656055,EBI-2624570

GO - Molecular functioni

  • neuropeptide hormone activity Source: ProtInc
  • opioid peptide activity Source: UniProtKB-KW
  • opioid receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi111205. 8 interactors.
IntActiP01210. 3 interactors.
STRINGi9606.ENSP00000324248.

Structurei

Secondary structure

1267
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni262 – 264Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PLWNMR-A100-104[»]
1PLXNMR-A100-104[»]
2LWCNMR-A261-265[»]
5E33X-ray1.84B261-265[»]
5E3AX-ray2.05B230-234[»]
ProteinModelPortaliP01210.
SMRiP01210.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01210.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IJUY. Eukaryota.
ENOG4110ZYD. LUCA.
GeneTreeiENSGT00530000063761.
HOGENOMiHOG000013003.
HOVERGENiHBG000063.
InParanoidiP01210.
KOiK18832.
OMAiGFMKKMD.
OrthoDBiEOG091G0HV8.
PhylomeDBiP01210.
TreeFamiTF332620.

Family and domain databases

InterProiView protein in InterPro
IPR006024. Opioid_neupept.
IPR000703. Proenkphlin_A.
PANTHERiPTHR11438. PTHR11438. 1 hit.
PTHR11438:SF7. PTHR11438:SF7. 1 hit.
PfamiView protein in Pfam
PF01160. Opiods_neuropep. 1 hit.
PRINTSiPR01028. OPIOIDPRCRSR.
PR01029. PENKAPRCRSR.
PROSITEiView protein in PROSITE
PS01252. OPIOIDS_PRECURSOR. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01210-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARFLTLCTW LLLLGPGLLA TVRAECSQDC ATCSYRLVRP ADINFLACVM
60 70 80 90 100
ECEGKLPSLK IWETCKELLQ LSKPELPQDG TSTLRENSKP EESHLLAKRY
110 120 130 140 150
GGFMKRYGGF MKKMDELYPM EPEEEANGSE ILAKRYGGFM KKDAEEDDSL
160 170 180 190 200
ANSSDLLKEL LETGDNRERS HHQDGSDNEE EVSKRYGGFM RGLKRSPQLE
210 220 230 240 250
DEAKELQKRY GGFMRRVGRP EWWMDYQKRY GGFLKRFAEA LPSDEEGESY
260
SKEVPEMEKR YGGFMRF
Length:267
Mass (Da):30,787
Last modified:July 21, 1986 - v1
Checksum:i4189BA600C3FC8EE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti119P → S in CAG46627 (Ref. 4) Curated1
Sequence conflicti152N → I in CAG46607 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04893583T → N. Corresponds to variant dbSNP:rs11998459Ensembl.1
Natural variantiVAR_014584247G → D. Corresponds to variant dbSNP:rs1800567Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00509 Genomic DNA. Translation: CAA23767.1.
J00123, J00122 Genomic DNA. Translation: AAB59409.1.
AK314908 mRNA. Translation: BAG37420.1.
CR541808 mRNA. Translation: CAG46607.1.
CR541828 mRNA. Translation: CAG46627.1.
CH471068 Genomic DNA. Translation: EAW86785.1.
BC032505 mRNA. Translation: AAH32505.1.
CCDSiCCDS6168.1.
PIRiA93278. EQHUA.
RefSeqiNP_001129162.1. NM_001135690.2.
UniGeneiHs.339831.

Genome annotation databases

EnsembliENST00000314922; ENSP00000324248; ENSG00000181195.
ENST00000451791; ENSP00000400894; ENSG00000181195.
GeneIDi5179.
KEGGihsa:5179.
UCSCiuc003xsz.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPENK_HUMAN
AccessioniPrimary (citable) accession number: P01210
Secondary accession number(s): B2RC23, Q6FHC6, Q6FHE6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: September 27, 2017
This is version 155 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families