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Proenkephalin-A [Cleaved into: Synenkephalin; Met-enkephalin (Opioid growth factor) (OGF); PENK(114-133); PENK(143-184); Met-enkephalin-Arg-Ser-Leu; Leu-enkephalin; PENK(238-259); Met-enkephalin-Arg-Phe]

 PENK_MOUSE              Reviewed;         268 AA.
P22005; Q68G73;
01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
16-JUN-2009, sequence version 2.
07-JUN-2017, entry version 123.
RecName: Full=Proenkephalin-A;
Contains:
RecName: Full=Synenkephalin;
Contains:
RecName: Full=Met-enkephalin;
AltName: Full=Opioid growth factor;
Short=OGF;
Contains:
RecName: Full=PENK(114-133);
Contains:
RecName: Full=PENK(143-184);
Contains:
RecName: Full=Met-enkephalin-Arg-Ser-Leu;
Contains:
RecName: Full=Leu-enkephalin;
Contains:
RecName: Full=PENK(238-259);
Contains:
RecName: Full=Met-enkephalin-Arg-Phe;
Flags: Precursor;
Name=Penk; Synonyms=Penk1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Testis;
PubMed=2355920; DOI=10.1128/MCB.10.7.3717;
Kilpatrick D.L., Zinn S.A., Fitzgerald M., Higuchi H., Sabol S.L.,
Meyerhardt J.;
"Transcription of the rat and mouse proenkephalin genes is initiated
at distinct sites in spermatogenic and somatic cells.";
Mol. Cell. Biol. 10:3717-3726(1990).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J; TISSUE=Testis;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
Lindblad-Toh K., Eichler E.E., Ponting C.P.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Testis;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 29-268.
TISSUE=T-cell;
PubMed=2938259; DOI=10.1126/science.2938259;
Zurawski G., Benedik M., Kamb B.J., Abrams J.S., Zurawski S.M.,
Lee F.D.;
"Activation of mouse T-helper cells induces abundant preproenkephalin
mRNA synthesis.";
Science 232:772-775(1986).
[7]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
-!- FUNCTION: 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(238-259) increase glutamate release
in the striatum. PENK(114-133) decreases GABA concentration in the
striatum.
-!- SUBCELLULAR LOCATION: Secreted.
-!- TISSUE SPECIFICITY: Spermatogenic and somatic cells.
-!- DEVELOPMENTAL STAGE: Highest expression in late pachytene
spermatocytes and postmeiotic round spermatids.
-!- PTM: The N-terminal domain contains 6 conserved cysteines thought
to be involved in disulfide bonding and/or processing.
-!- SIMILARITY: Belongs to the opioid neuropeptide precursor family.
{ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; M55181; AAA40128.1; -; mRNA.
EMBL; AK161272; BAE36283.1; -; mRNA.
EMBL; BX004841; CAM26883.1; -; Genomic_DNA.
EMBL; CH466538; EDL05699.1; -; Genomic_DNA.
EMBL; CH466538; EDL05700.1; -; Genomic_DNA.
EMBL; BC049766; AAH49766.1; -; mRNA.
EMBL; M13227; AAA37553.1; -; mRNA.
CCDS; CCDS17946.1; -.
PIR; B35678; B35678.
RefSeq; NP_001002927.1; NM_001002927.3.
RefSeq; NP_001335138.1; NM_001348209.1.
UniGene; Mm.475097; -.
ProteinModelPortal; P22005; -.
BioGrid; 202109; 1.
IntAct; P22005; 1.
MINT; MINT-4107012; -.
STRING; 10090.ENSMUSP00000066822; -.
iPTMnet; P22005; -.
PhosphoSitePlus; P22005; -.
MaxQB; P22005; -.
PaxDb; P22005; -.
PeptideAtlas; P22005; -.
PRIDE; P22005; -.
Ensembl; ENSMUST00000070375; ENSMUSP00000066822; ENSMUSG00000045573.
GeneID; 18619; -.
KEGG; mmu:18619; -.
UCSC; uc008rwz.1; mouse.
CTD; 5179; -.
MGI; MGI:104629; Penk.
eggNOG; ENOG410IJUY; Eukaryota.
eggNOG; ENOG4110ZYD; LUCA.
GeneTree; ENSGT00530000063761; -.
HOGENOM; HOG000013003; -.
HOVERGEN; HBG000063; -.
InParanoid; P22005; -.
KO; K18832; -.
OMA; GFMKKMD; -.
OrthoDB; EOG091G0HV8; -.
PhylomeDB; P22005; -.
TreeFam; TF332620; -.
Reactome; R-MMU-375276; Peptide ligand-binding receptors.
Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
Reactome; R-MMU-418594; G alpha (i) signalling events.
Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
PRO; PR:P22005; -.
Proteomes; UP000000589; Chromosome 4.
Bgee; ENSMUSG00000045573; -.
CleanEx; MM_PENK1; -.
ExpressionAtlas; P22005; baseline and differential.
Genevisible; P22005; MM.
GO; GO:0030424; C:axon; IEA:Ensembl.
GO; GO:0043679; C:axon terminus; IBA:GO_Central.
GO; GO:0070852; C:cell body fiber; IEA:Ensembl.
GO; GO:0030425; C:dendrite; IBA:GO_Central.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
GO; GO:0043204; C:perikaryon; IEA:Ensembl.
GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
GO; GO:0032280; C:symmetric synapse; IEA:Ensembl.
GO; GO:0005184; F:neuropeptide hormone activity; IBA:GO_Central.
GO; GO:0001515; F:opioid peptide activity; IEA:UniProtKB-KW.
GO; GO:0031628; F:opioid receptor binding; IBA:GO_Central.
GO; GO:0002118; P:aggressive behavior; IMP:MGI.
GO; GO:0007568; P:aging; IEA:Ensembl.
GO; GO:0001662; P:behavioral fear response; IMP:MGI.
GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl.
GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl.
GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
GO; GO:0051867; P:general adaptation syndrome, behavioral process; IEA:Ensembl.
GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl.
GO; GO:0007626; P:locomotory behavior; IMP:MGI.
GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
GO; GO:2000987; P:positive regulation of behavioral fear response; IEA:Ensembl.
GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
GO; GO:0071871; P:response to epinephrine; IEA:Ensembl.
GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
GO; GO:0043278; P:response to morphine; IEA:Ensembl.
GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
GO; GO:0009314; P:response to radiation; IEA:Ensembl.
GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
GO; GO:0019233; P:sensory perception of pain; IMP:MGI.
GO; GO:0001964; P:startle response; IMP:MGI.
InterPro; IPR006024; Opioid_neupept.
InterPro; IPR000703; Proenkphlin_A.
PANTHER; PTHR11438; PTHR11438; 1.
PANTHER; PTHR11438:SF7; PTHR11438:SF7; 1.
Pfam; PF01160; Opiods_neuropep; 1.
PRINTS; PR01028; OPIOIDPRCRSR.
PRINTS; PR01029; PENKAPRCRSR.
PROSITE; PS01252; OPIOIDS_PRECURSOR; 1.
1: Evidence at protein level;
Cleavage on pair of basic residues; Complete proteome; Disulfide bond;
Endorphin; Neuropeptide; Opioid peptide; Phosphoprotein;
Reference proteome; Secreted; Signal.
SIGNAL 1 24
PEPTIDE 25 97 Synenkephalin.
/FTId=PRO_0000008268.
PEPTIDE 100 104 Met-enkephalin.
/FTId=PRO_0000008269.
PEPTIDE 107 111 Met-enkephalin.
/FTId=PRO_0000008270.
PEPTIDE 114 133 PENK(114-133). {ECO:0000250}.
/FTId=PRO_0000377694.
PEPTIDE 136 140 Met-enkephalin.
/FTId=PRO_0000008272.
PEPTIDE 143 184 PENK(143-184). {ECO:0000250}.
/FTId=PRO_0000377695.
PEPTIDE 187 194 Met-enkephalin-Arg-Ser-Leu.
/FTId=PRO_0000008274.
PROPEP 197 208
/FTId=PRO_0000008275.
PEPTIDE 211 215 Met-enkephalin.
/FTId=PRO_0000008276.
PROPEP 218 228
/FTId=PRO_0000008277.
PEPTIDE 231 235 Leu-enkephalin.
/FTId=PRO_0000008278.
PEPTIDE 238 259 PENK(238-259). {ECO:0000250}.
/FTId=PRO_0000377696.
PEPTIDE 262 268 Met-enkephalin-Arg-Phe.
/FTId=PRO_0000008280.
MOD_RES 252 252 Phosphoserine.
{ECO:0000250|UniProtKB:P04094}.
DISULFID 26 48 {ECO:0000250|UniProtKB:P01210}.
DISULFID 30 52 {ECO:0000250|UniProtKB:P01210}.
DISULFID 33 65 {ECO:0000250|UniProtKB:P01210}.
CONFLICT 34 34 S -> T (in Ref. 1; AAA40128).
{ECO:0000305}.
CONFLICT 184 184 S -> SS (in Ref. 1; AAA40128).
{ECO:0000305}.
SEQUENCE 268 AA; 31004 MW; 637F848B49F44013 CRC64;
MARFLRLCTW LLALGSCLLA TVQAECSQDC AKCSYRLVRP GDINFLACTL ECEGQLPSFK
IWETCKDLLQ VSRPEFPWDN IDMYKDSSKQ DESHLLAKKY GGFMKRYGGF MKKMDELYPM
EPEEEANGGE ILAKRYGGFM KKDADEGDTL ANSSDLLKEL LGTGDNRAKD SHQQESTNND
EDMSKRYGGF MRSLKRSPQL EDEAKELQKR YGGFMRRVGR PEWWMDYQKR YGGFLKRFAE
SLPSDEEGEN YSKEVPEIEK RYGGFMRF


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