PENK_MESAU
ID PENK_MESAU Reviewed; 268 AA.
AC P50175; Q64030;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 70.
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) {ECO:0000250|UniProtKB:P04094};
DE Contains:
DE RecName: Full=PENK(143-184) {ECO:0000250|UniProtKB:P04094};
DE Contains:
DE RecName: Full=Met-enkephalin-Arg-Gly-Leu;
DE Contains:
DE RecName: Full=Leu-enkephalin;
DE Contains:
DE RecName: Full=PENK(238-259) {ECO:0000250|UniProtKB:P04094};
DE Contains:
DE RecName: Full=Met-enkephalin-Arg-Phe;
DE Flags: Precursor;
GN Name=PENK; Synonyms=ENK;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Syrian; TISSUE=Liver;
RX PubMed=8286036; DOI=10.1089/dna.1994.13.25;
RA Zhu Y.S., Branch A.D., Robertson H.D., Inturrisi C.E.;
RT "Cloning and characterization of hamster proenkephalin gene.";
RL DNA Cell Biol. 13:25-35(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Syrian; TISSUE=Adrenal gland;
RX PubMed=7917015; DOI=10.1089/dna.1994.13.933;
RA Beaulieu M., Ouellette M., Desgroseillers L., Brakier-Gingras L.;
RT "Molecular cloning and characterization of the hamster preproenkephalin A
RT cDNA.";
RL DNA Cell Biol. 13:933-940(1994).
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. Met-
CC enkephalin-Arg-Phe-binding to OPRM1 in the nucleus accumbens of the
CC brain increases activation of OPRM1, leading to long-term synaptic
CC depression of glutamate release. {ECO:0000250|UniProtKB:P22005}.
CC -!- FUNCTION: [PENK(114-133)]: Increases glutamate release in the striatum
CC and decreases GABA concentration in the striatum.
CC {ECO:0000250|UniProtKB:P04094}.
CC -!- FUNCTION: [PENK(238-259)]: Increases glutamate release in the striatum.
CC {ECO:0000250|UniProtKB:P04094}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule lumen {ECO:0000250|UniProtKB:P01211}. Secreted
CC {ECO:0000250|UniProtKB:P01211}.
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:0000250|UniProtKB:P04094}.
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 -!- SIMILARITY: Belongs to the opioid neuropeptide precursor family.
CC {ECO:0000305}.
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DR EMBL; U09941; AAA63650.1; -; Genomic_DNA.
DR EMBL; S74095; AAB32115.1; -; mRNA.
DR PIR; I53029; I53029.
DR AlphaFoldDB; P50175; -.
DR STRING; 10036.XP_005087638.1; -.
DR eggNOG; ENOG502QWWK; Eukaryota.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0034466; C:chromaffin granule lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0001515; F:opioid peptide activity; IEA:UniProtKB-KW.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Cytoplasmic vesicle; Disulfide bond;
KW Endorphin; Neuropeptide; Opioid peptide; Phosphoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PEPTIDE 25..97
FT /note="Synenkephalin"
FT /id="PRO_0000008255"
FT PEPTIDE 100..104
FT /note="Met-enkephalin"
FT /id="PRO_0000008256"
FT PEPTIDE 107..111
FT /note="Met-enkephalin"
FT /id="PRO_0000008257"
FT PEPTIDE 114..133
FT /note="PENK(114-133)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377688"
FT PEPTIDE 136..140
FT /note="Met-enkephalin"
FT /id="PRO_0000008259"
FT PEPTIDE 143..184
FT /note="PENK(143-184)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377689"
FT PEPTIDE 187..194
FT /note="Met-enkephalin-Arg-Gly-Leu"
FT /id="PRO_0000008261"
FT PROPEP 197..208
FT /id="PRO_0000008262"
FT PEPTIDE 211..215
FT /note="Met-enkephalin"
FT /id="PRO_0000008263"
FT PROPEP 218..228
FT /id="PRO_0000008264"
FT PEPTIDE 231..235
FT /note="Leu-enkephalin"
FT /id="PRO_0000008265"
FT PEPTIDE 238..259
FT /note="PENK(238-259)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377690"
FT PEPTIDE 262..268
FT /note="Met-enkephalin-Arg-Phe"
FT /id="PRO_0000008267"
FT REGION 162..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 162..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 215..216
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 219..220
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000250|UniProtKB:P01211"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04094"
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 78
FT /note="C -> W (in Ref. 2; AAB32115)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 268 AA; 30733 MW; 9670D1DEEA936725 CRC64;
MARFLRLCTW LLVLGSCLLA TVQAECSQDC AKCSYHLVSP GDINFLACTL ECEGQMPSHK
IWETCKDLLQ VSKPEFPCDS INMFKDSNKQ DESHLLAKKY GGFMKRYGGF MKKMDELYPV
EPEEEANGGE ILAKKYGGFM KKDADEGDTL ANSSDLLKEL LGTGDNRARE GRHQESTDND
DNMSKRYGGF MRGLKRSPQV EDEAKELQKR YGGFMRRVGR PEWWMDYQKR YGGFLKRFAE
SLPSDEEAES YSKEVPEIEK RYGGFMRF
