PENK_CAVPO
ID PENK_CAVPO Reviewed; 268 AA.
AC P47969;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 92.
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;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Hartley;
RX PubMed=7891703; DOI=10.1128/mcb.15.4.2080;
RA Laforge K.S., Unterwald E.M., Kreek M.J.;
RT "Structure and expression of the guinea pig preproenkephalin gene: site-
RT specific Cleavage in the 3' untranslated region yields truncated mRNA
RT transcripts in specific brain regions.";
RL Mol. Cell. Biol. 15:2080-2089(1995).
RN [2]
RP PROTEIN SEQUENCE OF 211-235, AND POSSIBLE BIOLOGICAL FUNCTION.
RX PubMed=6265943; DOI=10.1073/pnas.78.5.3265;
RA Kilpatrick D.L., Taniguchi T., Jones B.N., Stern A.S., Shively J.E.,
RA Hullihan J., Kimura S., Stein S., Udenfriend S.;
RT "A highly potent 3200-dalton adrenal opioid peptide that contains both a
RT [Met]- and [Leu]enkephalin sequence.";
RL Proc. Natl. Acad. Sci. U.S.A. 78:3265-3268(1981).
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U16138; AAA87900.1; -; Genomic_DNA.
DR PIR; A18864; A18864.
DR RefSeq; NP_001166888.1; NM_001173417.1.
DR AlphaFoldDB; P47969; -.
DR STRING; 10141.ENSCPOP00000011497; -.
DR GeneID; 100379621; -.
DR KEGG; cpoc:100379621; -.
DR CTD; 5179; -.
DR eggNOG; ENOG502QWWK; Eukaryota.
DR InParanoid; P47969; -.
DR OrthoDB; 1149395at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
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 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_0000008219"
FT PEPTIDE 100..104
FT /note="Met-enkephalin"
FT /id="PRO_0000008220"
FT PEPTIDE 107..111
FT /note="Met-enkephalin"
FT /id="PRO_0000008221"
FT PEPTIDE 114..133
FT /note="PENK(114-133)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377685"
FT PEPTIDE 136..140
FT /note="Met-enkephalin"
FT /id="PRO_0000008223"
FT PEPTIDE 143..184
FT /note="PENK(143-184)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377686"
FT PEPTIDE 187..194
FT /note="Met-enkephalin-Arg-Gly-Leu"
FT /id="PRO_0000008225"
FT PROPEP 197..208
FT /id="PRO_0000008226"
FT PEPTIDE 211..215
FT /note="Met-enkephalin"
FT /evidence="ECO:0000269|PubMed:6265943"
FT /id="PRO_0000008227"
FT PROPEP 218..228
FT /id="PRO_0000008228"
FT PEPTIDE 231..235
FT /note="Leu-enkephalin"
FT /id="PRO_0000008229"
FT PEPTIDE 238..259
FT /note="PENK(238-259)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377687"
FT PEPTIDE 262..268
FT /note="Met-enkephalin-Arg-Phe"
FT /id="PRO_0000008231"
FT REGION 163..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 163..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"
SQ SEQUENCE 268 AA; 30436 MW; 64C85EE9F480F238 CRC64;
MARLLRLCTW LVALGPGLLA TVQAECSQDC AACSYRLVRP GDLNFLACTL ECEGQLPSLK
IWETCKDLLQ VSKQELPQEG ASSLRESGKQ DESHLLSKKY GGFMKRYGGF MKKVDELYPV
EPEEEANGGE ILTKRYGGFM KKDAEDGDAL ANSSDLLKEL LGTGDDRDRE NHHQEGGDSD
EGVSKRYGGF MRGLKRSPQV EDEAKELQKR YGGFMRRVGR PEWWMDYQKR YGGFLKRFAE
FLPSDEEGES YSKEVPEMEK RYGGFMRF
