PENK_BOVIN
ID PENK_BOVIN Reviewed; 263 AA.
AC P01211; Q2T9T4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Proenkephalin-A;
DE Contains:
DE RecName: Full=Synenkephalin;
DE Contains:
DE RecName: Full=Met-enkephalin {ECO:0000303|PubMed:12869695};
DE AltName: Full=Opioid growth factor;
DE Short=OGF;
DE Contains:
DE RecName: Full=PENK(111-130) {ECO:0000250|UniProtKB:P04094};
DE Contains:
DE RecName: Full=PENK(140-179) {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=Enkelytin {ECO:0000303|PubMed:8654396};
DE Contains:
DE RecName: Full=PENK(233-254) {ECO:0000250|UniProtKB:P04094};
DE Contains:
DE RecName: Full=Met-enkephalin-Arg-Phe;
DE Flags: Precursor;
GN Name=PENK;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6276759; DOI=10.1038/295202a0;
RA Noda M., Furutani Y., Takahashi H., Toyosato M., Hirose T., Inayama S.,
RA Nakanishi S., Numa S.;
RT "Cloning and sequence analysis of cDNA for bovine adrenal
RT preproenkephalin.";
RL Nature 295:202-206(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 47-263.
RX PubMed=6173760; DOI=10.1038/295206a0;
RA Gubler U., Seeburg P., Hoffman B.J., Gage L.P., Udenfriend S.;
RT "Molecular cloning establishes proenkephalin as precursor of enkephalin-
RT containing peptides.";
RL Nature 295:206-208(1982).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 211-229.
RX PubMed=6952189; DOI=10.1073/pnas.79.2.360;
RA Comb M., Herbert E., Crea R.;
RT "Partial characterization of the mRNA that codes for enkephalins in bovine
RT adrenal medulla and human pheochromocytoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:360-364(1982).
RN [5]
RP PROTEIN SEQUENCE OF 233-261, AND FUNCTION.
RC TISSUE=Chromaffin cell;
RX PubMed=8654396; DOI=10.1111/j.1432-1033.1996.t01-1-00516.x;
RA Goumon Y., Strub J.-M., Moniatte M., Nulans G., Poteur L., Hubert P.,
RA van Dorsselaer A., Aunis D., Metz-Boutigue M.-H.;
RT "The C-terminal bisphosphorylated proenkephalin-A-(209-237)-peptide from
RT adrenal medullary chromaffin granules possesses antibacterial activity.";
RL Eur. J. Biochem. 235:516-525(1996).
RN [6]
RP PROTEOLYTIC CLEAVAGE, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=12869695; DOI=10.1073/pnas.1531542100;
RA Yasothornsrikul S., Greenbaum D., Medzihradszky K.F., Toneff T., Bundey R.,
RA Miller R., Schilling B., Petermann I., Dehnert J., Logvinova A.,
RA Goldsmith P., Neveu J.M., Lane W.S., Gibson B., Reinheckel T., Peters C.,
RA Bogyo M., Hook V.;
RT "Cathepsin L in secretory vesicles functions as a prohormone-processing
RT enzyme for production of the enkephalin peptide neurotransmitter.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:9590-9595(2003).
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(111-130)]: Increases glutamate release in the striatum
CC and decreases GABA concentration in the striatum.
CC {ECO:0000250|UniProtKB:P04094}.
CC -!- FUNCTION: [PENK(233-254)]: Increases glutamate release in the striatum.
CC {ECO:0000250|UniProtKB:P04094}.
CC -!- FUNCTION: [Enkelytin]: Enkelytin possesses antibacterial activity
CC against Gram-positive bacteria such as Micrococcus luteus and Bacillus
CC megaterium. {ECO:0000269|PubMed:8654396}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule lumen {ECO:0000269|PubMed:12869695}. Secreted
CC {ECO:0000305|PubMed:12869695}.
CC -!- TISSUE SPECIFICITY: Secreted by neuroendocrine chromaffin cells through
CC cromaffin granules. {ECO:0000269|PubMed:12869695}.
CC -!- PTM: Proenkephalin-A is cleaved by CTSL to generate Met-enkephalin.
CC {ECO:0000269|PubMed:12869695}.
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; V00109; CAA23443.1; -; mRNA.
DR EMBL; BC111279; AAI11280.1; -; mRNA.
DR EMBL; V00108; CAA23442.1; -; mRNA.
DR EMBL; J00012; AAA30673.1; -; mRNA.
DR PIR; A93272; EQBOA.
DR RefSeq; NP_776566.1; NM_174141.2.
DR AlphaFoldDB; P01211; -.
DR STRING; 9913.ENSBTAP00000006478; -.
DR iPTMnet; P01211; -.
DR PaxDb; P01211; -.
DR PRIDE; P01211; -.
DR Ensembl; ENSBTAT00000006478; ENSBTAP00000006478; ENSBTAG00000004924.
DR Ensembl; ENSBTAT00000087134; ENSBTAP00000066399; ENSBTAG00000004924.
DR GeneID; 281387; -.
DR KEGG; bta:281387; -.
DR CTD; 5179; -.
DR VEuPathDB; HostDB:ENSBTAG00000004924; -.
DR VGNC; VGNC:32746; PENK.
DR eggNOG; ENOG502QWWK; Eukaryota.
DR GeneTree; ENSGT00950000183149; -.
DR HOGENOM; CLU_070973_0_0_1; -.
DR InParanoid; P01211; -.
DR OMA; CAACAYR; -.
DR OrthoDB; 1149395at2759; -.
DR TreeFam; TF332620; -.
DR Reactome; R-BTA-375276; Peptide ligand-binding receptors.
DR Reactome; R-BTA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-BTA-418594; G alpha (i) signalling events.
DR Reactome; R-BTA-8957275; Post-translational protein phosphorylation.
DR Proteomes; UP000009136; Chromosome 14.
DR Bgee; ENSBTAG00000004924; Expressed in urethra and 88 other tissues.
DR GO; GO:0043679; C:axon terminus; IBA:GO_Central.
DR GO; GO:0034466; C:chromaffin granule lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:0007600; P:sensory perception; IBA:GO_Central.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0001964; P:startle response; IEA:Ensembl.
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 Antibiotic; Antimicrobial; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond; Endorphin;
KW Neuropeptide; Opioid peptide; Phosphoprotein; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PEPTIDE 25..94
FT /note="Synenkephalin"
FT /id="PRO_0000008206"
FT PEPTIDE 97..101
FT /note="Met-enkephalin"
FT /id="PRO_0000008207"
FT PEPTIDE 104..108
FT /note="Met-enkephalin"
FT /id="PRO_0000008208"
FT PEPTIDE 111..130
FT /note="PENK(111-130)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377682"
FT PEPTIDE 133..137
FT /note="Met-enkephalin"
FT /id="PRO_0000008210"
FT PEPTIDE 140..179
FT /note="PENK(140-179)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377683"
FT PEPTIDE 182..189
FT /note="Met-enkephalin-Arg-Gly-Leu"
FT /id="PRO_0000008212"
FT PROPEP 192..203
FT /id="PRO_0000008213"
FT PEPTIDE 206..210
FT /note="Met-enkephalin"
FT /id="PRO_0000008214"
FT PROPEP 213..223
FT /id="PRO_0000008215"
FT PEPTIDE 226..230
FT /note="Leu-enkephalin"
FT /id="PRO_0000008216"
FT PEPTIDE 233..261
FT /note="Enkelytin"
FT /evidence="ECO:0000269|PubMed:8654396"
FT /id="PRO_0000008217"
FT PEPTIDE 233..254
FT /note="PENK(233-254)"
FT /evidence="ECO:0000250|UniProtKB:P04094"
FT /id="PRO_0000377684"
FT PEPTIDE 257..263
FT /note="Met-enkephalin-Arg-Phe"
FT /id="PRO_0000008218"
FT SITE 108..109
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000269|PubMed:12869695"
FT SITE 109..110
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000269|PubMed:12869695"
FT SITE 130..131
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000269|PubMed:12869695"
FT SITE 210..211
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000269|PubMed:12869695"
FT SITE 211..212
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000269|PubMed:12869695"
FT SITE 214..215
FT /note="Cleavage; by CTSL"
FT /evidence="ECO:0000269|PubMed:12869695"
FT MOD_RES 247
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 263 AA; 29788 MW; 0E400338A228B0D8 CRC64;
MARFLGLCTW LLALGPGLLA TVRAECSQDC ATCSYRLARP TDLNPLACTL ECEGKLPSLK
TWETCKELLQ LTKLELPPDA TSALSKQEES HLLAKKYGGF MKRYGGFMKK MDELYPLEVE
EEANGGEVLG KRYGGFMKKD AEEDDGLGNS SNLLKELLGA GDQREGSLHQ EGSDAEDVSK
RYGGFMRGLK RSPHLEDETK ELQKRYGGFM RRVGRPEWWM DYQKRYGGFL KRFAEPLPSE
EEGESYSKEV PEMEKRYGGF MRF
