PENK_RAT
ID PENK_RAT Reviewed; 269 AA.
AC P04094; Q53X05;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Proenkephalin-A;
DE Contains:
DE RecName: Full=Synenkephalin;
DE Contains:
DE RecName: Full=Met-enkephalin;
DE AltName: Full=Opioid growth factor;
DE Short=OGF;
DE Contains:
DE RecName: Full=PENK(114-133);
DE Contains:
DE RecName: Full=PENK(143-185);
DE Contains:
DE RecName: Full=Met-enkephalin-Arg-Gly-Leu;
DE Contains:
DE RecName: Full=Leu-enkephalin;
DE Contains:
DE RecName: Full=PENK(239-260);
DE Contains:
DE RecName: Full=Met-enkephalin-Arg-Phe {ECO:0000303|PubMed:20487892};
DE Flags: Precursor;
GN Name=Penk; Synonyms=Penk-rs, Penk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Fischer 344; TISSUE=Brain;
RX PubMed=6548748; DOI=10.1016/s0021-9258(18)89893-3;
RA Yoshikawa K., Williams C., Sabol S.L.;
RT "Rat brain preproenkephalin mRNA. cDNA cloning, primary structure, and
RT distribution in the central nervous system.";
RL J. Biol. Chem. 259:14301-14308(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Fischer 344;
RX PubMed=6094550; DOI=10.1016/s0021-9258(18)89894-5;
RA Rosen H., Douglass J., Herbert E.;
RT "Isolation and characterization of the rat proenkephalin gene.";
RL J. Biol. Chem. 259:14309-14313(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Fischer 344; TISSUE=Brain;
RX PubMed=6594709; DOI=10.1073/pnas.81.23.7651;
RA Howells R.D., Kilpatrick D.L., Bhatt R., Monahan J.J., Poonian M.,
RA Udenfriend S.;
RT "Molecular cloning and sequence determination of rat preproenkephalin cDNA:
RT sensitive probe for studying transcriptional changes in rat tissues.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:7651-7655(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=3093884;
RA Howells R.D.;
RT "Proenkephalin biosynthesis in the rat.";
RL NIDA Res. Monogr. 70:43-65(1986).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Testis;
RX PubMed=2707437; DOI=10.1016/0014-5793(89)80281-9;
RA Yoshikawa K., Maruyama K., Aizawa T., Yamamoto A.;
RT "A new species of enkephalin precursor mRNA with a distinct 5'-untranslated
RT region in haploid germ cells.";
RL FEBS Lett. 246:193-196(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=1438982; DOI=10.1016/0167-0115(92)90526-z;
RA Rao S.M., Howells R.D.;
RT "Molecular cloning, sequence analysis and translation of proenkephalin mRNA
RT from rat heart.";
RL Regul. Pept. 40:397-408(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 114-133; 143-185 AND 239-260, FUNCTION, MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC STRAIN=Wistar; TISSUE=Corpus striatum;
RX PubMed=19164277; DOI=10.1074/mcp.m800501-mcp200;
RA Bernay B., Gaillard M.-C., Guryca V., Emadali A., Kuhn L., Bertrand A.,
RA Detraz I., Carcenac C., Savasta M., Brouillet E., Garin J., Elalouf J.-M.;
RT "Discovering new bioactive neuropeptides in the striatum secretome using in
RT vivo microdialysis and versatile proteomics.";
RL Mol. Cell. Proteomics 8:946-958(2009).
RN [9]
RP PROTEOLYTIC CLEAVAGE (MET-ENKEPHALIN-ARG-PHE).
RX PubMed=20487892; DOI=10.1016/0197-0186(82)90081-x;
RA Benuck M., Berg M.J., Marks N.;
RT "Separate metabolic pathways for Leu-enkephalin and Met-enkephalin-Arg(6)-
RT Phe(7) degradation by rat striatal synaptosomal membranes.";
RL Neurochem. Int. 4:389-396(1982).
RN [10]
RP FUNCTION (MET-ENKEPHALIN-ARG-PHE).
RX PubMed=8624732; DOI=10.1016/0006-8993(95)00928-j;
RA Mansour A., Hoversten M.T., Taylor L.P., Watson S.J., Akil H.;
RT "The cloned mu, delta and kappa receptors and their endogenous ligands:
RT evidence for two opioid peptide recognition cores.";
RL Brain Res. 700:89-98(1995).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-253, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: [Met-enkephalin]: Neuropeptide that competes with and mimic
CC the effects of opiate drugs. They play a role in a number of
CC physiologic functions, including pain perception and responses to
CC stress. {ECO:0000250|UniProtKB:P01210}.
CC -!- FUNCTION: [Leu-enkephalin]: Neuropeptide that competes with and mimic
CC the effects of opiate drugs. They play a role in a number of
CC physiologic functions, including pain perception and responses to
CC stress. {ECO:0000250|UniProtKB:P01210}.
CC -!- FUNCTION: [Met-enkephalin-Arg-Phe]: Met-enkephalin-Arg-Phe neuropeptide
CC acts as a strong ligand of Mu-type opioid receptor OPRM1
CC (PubMed:8624732). Met-enkephalin-Arg-Phe-binding to OPRM1 in the
CC nucleus accumbens of the brain increases activation of OPRM1, leading
CC to long-term synaptic depression of glutamate release (By similarity).
CC {ECO:0000250|UniProtKB:P22005, ECO:0000269|PubMed:8624732}.
CC -!- FUNCTION: [PENK(114-133)]: Increases glutamate release in the striatum
CC and decreases GABA concentration in the striatum.
CC {ECO:0000269|PubMed:19164277}.
CC -!- FUNCTION: [PENK(239-260)]: Increases glutamate release in the striatum.
CC {ECO:0000269|PubMed:19164277}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19164277}.
CC Cytoplasmic vesicle, secretory vesicle, chromaffin granule lumen
CC {ECO:0000250|UniProtKB:P01211}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart and testis.
CC {ECO:0000269|PubMed:2707437, ECO:0000269|PubMed:6548748,
CC ECO:0000269|PubMed:6594709}.
CC -!- PTM: Proenkephalin-A is cleaved by CTSL to generate Met-enkephalin.
CC {ECO:0000250|UniProtKB:P01211}.
CC -!- PTM: [Met-enkephalin]: Processed and degraded by ACE.
CC {ECO:0000250|UniProtKB:P01210}.
CC -!- PTM: [Leu-enkephalin]: Processed and degraded by ACE.
CC {ECO:0000250|UniProtKB:P01210}.
CC -!- PTM: [Met-enkephalin-Arg-Gly-Leu]: Probably cleaved by ACE.
CC {ECO:0000250|UniProtKB:P01210}.
CC -!- PTM: [Met-enkephalin-Arg-Phe]: Processed by ACE to generate Met-
CC enkephalin in the nucleus accumbens of the brain.
CC {ECO:0000269|PubMed:20487892}.
CC -!- PTM: The N-terminal domain contains 6 conserved cysteines thought to be
CC involved in disulfide bonding and/or processing.
CC {ECO:0000250|UniProtKB:P01210}.
CC -!- MASS SPECTROMETRY: [PENK(114-133)]: Mass=2203.971; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:19164277};
CC -!- MASS SPECTROMETRY: [PENK(143-185)]: Mass=4592.8; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:19164277};
CC -!- MASS SPECTROMETRY: [PENK(239-260)]: Mass=2504.027; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:19164277};
CC -!- SIMILARITY: Belongs to the opioid neuropeptide precursor family.
CC {ECO:0000305}.
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DR EMBL; K02807; AAA60734.1; -; Genomic_DNA.
DR EMBL; M28263; AAA41115.1; -; mRNA.
DR EMBL; Y07503; CAA68804.1; -; mRNA.
DR EMBL; S49491; AAB24022.1; -; mRNA.
DR EMBL; BC083563; AAH83563.1; -; mRNA.
DR PIR; A92464; EQRTA.
DR RefSeq; NP_058835.1; NM_017139.1.
DR RefSeq; XP_006237897.1; XM_006237835.1.
DR AlphaFoldDB; P04094; -.
DR STRING; 10116.ENSRNOP00000011892; -.
DR iPTMnet; P04094; -.
DR PhosphoSitePlus; P04094; -.
DR PaxDb; P04094; -.
DR PRIDE; P04094; -.
DR Ensembl; ENSRNOT00000011892; ENSRNOP00000011892; ENSRNOG00000008943.
DR GeneID; 29237; -.
DR KEGG; rno:29237; -.
DR UCSC; RGD:68946; rat.
DR CTD; 5179; -.
DR RGD; 68946; Penk.
DR eggNOG; ENOG502QWWK; Eukaryota.
DR GeneTree; ENSGT00950000183149; -.
DR InParanoid; P04094; -.
DR OMA; CAACAYR; -.
DR OrthoDB; 1149395at2759; -.
DR PhylomeDB; P04094; -.
DR TreeFam; TF332620; -.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:P04094; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000008943; Expressed in cerebellum and 18 other tissues.
DR Genevisible; P04094; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0070852; C:cell body fiber; IDA:RGD.
DR GO; GO:0034466; C:chromaffin granule lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0099013; C:neuronal dense core vesicle lumen; IDA:SynGO.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032280; C:symmetric synapse; IDA:RGD.
DR GO; GO:0034592; C:synaptic vesicle lumen; IDA:SynGO.
DR GO; GO:0001515; F:opioid peptide activity; IEA:UniProtKB-KW.
DR GO; GO:0031628; F:opioid receptor binding; IBA:GO_Central.
DR GO; GO:0002118; P:aggressive behavior; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0001662; P:behavioral fear response; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0098586; P:cellular response to virus; IEP:RGD.
DR GO; GO:0071305; P:cellular response to vitamin D; IEP:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0051867; P:general adaptation syndrome, behavioral process; IEP:RGD.
DR GO; GO:0014009; P:glial cell proliferation; IEP:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0035641; P:locomotory exploration behavior; IMP:RGD.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:RGD.
DR GO; GO:2000987; P:positive regulation of behavioral fear response; IMP:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0071871; P:response to epinephrine; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0043278; P:response to morphine; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0009314; P:response to radiation; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0007600; P:sensory perception; IBA:GO_Central.
DR GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
DR GO; GO:0001964; P:startle response; ISO:RGD.
DR GO; GO:0099538; P:synaptic signaling via neuropeptide; IMP:SynGO.
DR InterPro; IPR006024; Opioid_neupept.
DR InterPro; IPR000703; Proenkphlin_A.
DR PANTHER; PTHR11438; PTHR11438; 1.
DR PANTHER; PTHR11438:SF3; PTHR11438:SF3; 1.
DR Pfam; PF01160; Opiods_neuropep; 1.
DR PRINTS; PR01028; OPIOIDPRCRSR.
DR PRINTS; PR01029; PENKAPRCRSR.
DR PROSITE; PS01252; OPIOIDS_PRECURSOR; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Endorphin; Neuropeptide;
KW Opioid peptide; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PEPTIDE 25..97
FT /note="Synenkephalin"
FT /id="PRO_0000008281"
FT PEPTIDE 100..104
FT /note="Met-enkephalin"
FT /id="PRO_0000008282"
FT PEPTIDE 107..111
FT /note="Met-enkephalin"
FT /id="PRO_0000008283"
FT PEPTIDE 114..133
FT /note="PENK(114-133)"
FT /evidence="ECO:0000269|PubMed:19164277"
FT /id="PRO_0000008284"
FT PEPTIDE 136..140
FT /note="Met-enkephalin"
FT /id="PRO_0000008285"
FT PEPTIDE 143..185
FT /note="PENK(143-185)"
FT /evidence="ECO:0000269|PubMed:19164277"
FT /id="PRO_0000008286"
FT PEPTIDE 188..195
FT /note="Met-enkephalin-Arg-Gly-Leu"
FT /id="PRO_0000008287"
FT PROPEP 198..209
FT /id="PRO_0000008288"
FT PEPTIDE 212..216
FT /note="Met-enkephalin"
FT /id="PRO_0000008289"
FT PROPEP 219..229
FT /id="PRO_0000008290"
FT PEPTIDE 232..236
FT /note="Leu-enkephalin"
FT /id="PRO_0000008291"
FT PEPTIDE 239..260
FT /note="PENK(239-260)"
FT /evidence="ECO:0000269|PubMed:19164277"
FT /id="PRO_0000008292"
FT PEPTIDE 263..269
FT /note="Met-enkephalin-Arg-Phe"
FT /evidence="ECO:0000269|PubMed:20487892"
FT /id="PRO_0000008293"
FT REGION 165..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 165..182
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 111..112
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000250|UniProtKB:P01211"
FT SITE 112..113
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000250|UniProtKB:P01211"
FT SITE 133..134
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000250|UniProtKB:P01211"
FT SITE 216..217
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000250|UniProtKB:P01211"
FT SITE 217..218
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000250|UniProtKB:P01211"
FT SITE 220..221
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000250|UniProtKB:P01211"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT DISULFID 26..48
FT /evidence="ECO:0000250|UniProtKB:P01210"
FT DISULFID 30..52
FT /evidence="ECO:0000250|UniProtKB:P01210"
FT DISULFID 33..65
FT /evidence="ECO:0000250|UniProtKB:P01210"
FT CONFLICT 12
FT /note="L -> V (in Ref. 2; AAA60734 and 5; CAA68804)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 269 AA; 30932 MW; 2BF0EA81A1D59692 CRC64;
MAQFLRLCIW LLALGSCLLA TVQADCSQDC AKCSYRLVRP GDINFLACTL ECEGQLPSFK
IWETCKDLLQ VSKPEFPWDN IDMYKDSSKQ DESHLLAKKY GGFMKRYGGF MKKMDELYPV
EPEEEANGGE ILAKRYGGFM KKDADEGDTL ANSSDLLKEL LGTGDNRAKD SHQQESTNND
EDSTSKRYGG FMRGLKRSPQ LEDEAKELQK RYGGFMRRVG RPEWWMDYQK RYGGFLKRFA
ESLPSDEEGE SYSKEVPEME KRYGGFMRF
