ID PENK_HUMAN Reviewed; 267 AA. AC P01210; B2RC23; Q6FHC6; Q6FHE6; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 13-FEB-2019, entry version 166. 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(143-183); DE Contains: DE RecName: Full=Met-enkephalin-Arg-Gly-Leu; DE Contains: DE RecName: Full=Leu-enkephalin; DE Contains: DE RecName: Full=PENK(237-258); DE Contains: DE RecName: Full=Met-enkephalin-Arg-Phe; DE Flags: Precursor; GN Name=PENK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7057924; DOI=10.1038/295663a0; RA Comb M., Seeburg P.H., Adelman J., Eiden L., Herbert E.; RT "Primary structure of the human Met- and Leu-enkephalin precursor and RT its mRNA."; RL Nature 295:663-666(1982). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6281660; DOI=10.1038/297431a0; RA Noda M., Teranishi Y., Takahashi H., Toyosato M., Notake M., RA Nakanishi S., Numa S.; RT "Isolation and structural organization of the human preproenkephalin RT gene."; RL Nature 297:431-434(1982). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., RA Korn B., Zuo D., Hu Y., LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP DISULFIDE BONDS. RX PubMed=9126357; DOI=10.1006/bbrc.1997.6373; RA Lecchi P., Loh Y.P., Snell C.R., Pannell L.K.; RT "The structure of synenkephalin (pro-enkephalin 1-73) is dictated by RT three disulfide bonds."; RL Biochem. Biophys. Res. Commun. 232:800-805(1997). CC -!- FUNCTION: Met- and Leu-enkephalins compete with and mimic the CC effects of opiate drugs. They play a role in a number of CC physiologic functions, including pain perception and responses to CC stress. PENK(114-133) and PENK(237-258) increase glutamate release CC in the striatum. PENK(114-133) decreases GABA concentration in the CC striatum. CC -!- INTERACTION: CC P35372:OPRM1; NbExp=3; IntAct=EBI-6656055, EBI-2624570; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- PTM: The N-terminal domain contains 6 conserved cysteines thought CC to be involved in disulfide bonding and/or processing. 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; V00509; CAA23767.1; -; Genomic_DNA. DR EMBL; J00123; AAB59409.1; -; Genomic_DNA. DR EMBL; J00122; AAB59409.1; JOINED; Genomic_DNA. DR EMBL; AK314908; BAG37420.1; -; mRNA. DR EMBL; CR541808; CAG46607.1; -; mRNA. DR EMBL; CR541828; CAG46627.1; -; mRNA. DR EMBL; CH471068; EAW86785.1; -; Genomic_DNA. DR EMBL; BC032505; AAH32505.1; -; mRNA. DR CCDS; CCDS6168.1; -. DR PIR; A93278; EQHUA. DR RefSeq; NP_001129162.1; NM_001135690.2. DR UniGene; Hs.339831; -. DR PDB; 1PLW; NMR; -; A=100-104. DR PDB; 1PLX; NMR; -; A=100-104. DR PDB; 2LWC; NMR; -; A=261-265. DR PDB; 5E33; X-ray; 1.84 A; B=261-265. DR PDB; 5E3A; X-ray; 2.05 A; B=230-234. DR PDBsum; 1PLW; -. DR PDBsum; 1PLX; -. DR PDBsum; 2LWC; -. DR PDBsum; 5E33; -. DR PDBsum; 5E3A; -. DR ProteinModelPortal; P01210; -. DR SMR; P01210; -. DR BioGrid; 111205; 8. DR IntAct; P01210; 3. DR STRING; 9606.ENSP00000324248; -. DR TCDB; 1.C.89.1.2; the dynorphin channel-forming neuropeptide (dynorphin) family. DR iPTMnet; P01210; -. DR PhosphoSitePlus; P01210; -. DR BioMuta; PENK; -. DR DMDM; 129770; -. DR PaxDb; P01210; -. DR PeptideAtlas; P01210; -. DR PRIDE; P01210; -. DR ProteomicsDB; 51344; -. DR DNASU; 5179; -. DR Ensembl; ENST00000314922; ENSP00000324248; ENSG00000181195. DR Ensembl; ENST00000451791; ENSP00000400894; ENSG00000181195. DR GeneID; 5179; -. DR KEGG; hsa:5179; -. DR UCSC; uc003xsz.3; human. DR CTD; 5179; -. DR DisGeNET; 5179; -. DR EuPathDB; HostDB:ENSG00000181195.10; -. DR GeneCards; PENK; -. DR HGNC; HGNC:8831; PENK. DR HPA; CAB016390; -. DR HPA; HPA013138; -. DR MIM; 131330; gene. DR neXtProt; NX_P01210; -. DR OpenTargets; ENSG00000181195; -. DR PharmGKB; PA33176; -. DR eggNOG; ENOG410IJUY; Eukaryota. DR eggNOG; ENOG4110ZYD; LUCA. DR GeneTree; ENSGT00530000063761; -. DR HOGENOM; HOG000013003; -. DR HOVERGEN; HBG000063; -. DR InParanoid; P01210; -. DR KO; K18832; -. DR OMA; FMKKDAE; -. DR OrthoDB; 1149395at2759; -. DR PhylomeDB; P01210; -. DR TreeFam; TF332620; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SIGNOR; P01210; -. DR EvolutionaryTrace; P01210; -. DR GenomeRNAi; 5179; -. DR PMAP-CutDB; P01210; -. DR PRO; PR:P01210; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; ENSG00000181195; Expressed in 187 organ(s), highest expression level in caudate nucleus. DR ExpressionAtlas; P01210; baseline and differential. DR Genevisible; P01210; HS. DR GO; GO:0043679; C:axon terminus; IBA:GO_Central. DR GO; GO:0070852; C:cell body fiber; IEA:Ensembl. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central. DR GO; GO:0099013; C:neuronal dense core vesicle lumen; IEA:Ensembl. DR GO; GO:0043204; C:perikaryon; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0032280; C:symmetric synapse; IEA:Ensembl. DR GO; GO:0034592; C:synaptic vesicle lumen; IEA:Ensembl. DR GO; GO:0005184; F:neuropeptide hormone activity; TAS:ProtInc. 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:0007568; P:aging; IEA:Ensembl. DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl. DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl. DR GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl. DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0051867; P:general adaptation syndrome, behavioral process; IEA:Ensembl. DR GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl. DR GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl. DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central. DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl. DR GO; GO:2000987; P:positive regulation of behavioral fear response; IEA:Ensembl. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl. DR GO; GO:0071871; P:response to epinephrine; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0043278; P:response to morphine; IEA:Ensembl. DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl. DR GO; GO:0009314; P:response to radiation; IEA:Ensembl. DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. 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 3D-structure; Cleavage on pair of basic residues; Complete proteome; KW Disulfide bond; Endorphin; Neuropeptide; Opioid peptide; KW Phosphoprotein; Polymorphism; Reference proteome; Secreted; Signal. FT SIGNAL 1 24 {ECO:0000255}. FT PEPTIDE 25 97 Synenkephalin. FT /FTId=PRO_0000008242. FT PEPTIDE 100 104 Met-enkephalin. FT /FTId=PRO_0000008243. FT PEPTIDE 107 111 Met-enkephalin. FT /FTId=PRO_0000008244. FT PEPTIDE 114 133 PENK(114-133). {ECO:0000250}. FT /FTId=PRO_0000377691. FT PEPTIDE 136 140 Met-enkephalin. FT /FTId=PRO_0000008246. FT PEPTIDE 143 183 PENK(143-183). {ECO:0000250}. FT /FTId=PRO_0000377692. FT PEPTIDE 186 193 Met-enkephalin-Arg-Gly-Leu. FT /FTId=PRO_0000008248. FT PROPEP 196 207 FT /FTId=PRO_0000008249. FT PEPTIDE 210 214 Met-enkephalin. FT /FTId=PRO_0000008250. FT PROPEP 217 227 FT /FTId=PRO_0000008251. FT PEPTIDE 230 234 Leu-enkephalin. FT /FTId=PRO_0000008252. FT PEPTIDE 237 258 PENK(237-258). {ECO:0000250}. FT /FTId=PRO_0000377693. FT PEPTIDE 261 267 Met-enkephalin-Arg-Phe. FT /FTId=PRO_0000008254. FT MOD_RES 251 251 Phosphoserine. FT {ECO:0000250|UniProtKB:P04094}. FT DISULFID 26 48 {ECO:0000269|PubMed:9126357}. FT DISULFID 30 52 {ECO:0000269|PubMed:9126357}. FT DISULFID 33 65 {ECO:0000269|PubMed:9126357}. FT VARIANT 83 83 T -> N (in dbSNP:rs11998459). FT /FTId=VAR_048935. FT VARIANT 247 247 G -> D (in dbSNP:rs1800567). FT /FTId=VAR_014584. FT CONFLICT 119 119 P -> S (in Ref. 4; CAG46627). FT {ECO:0000305}. FT CONFLICT 152 152 N -> I (in Ref. 4; CAG46607). FT {ECO:0000305}. FT TURN 262 264 {ECO:0000244|PDB:2LWC}. SQ SEQUENCE 267 AA; 30787 MW; 4189BA600C3FC8EE CRC64; MARFLTLCTW LLLLGPGLLA TVRAECSQDC ATCSYRLVRP ADINFLACVM ECEGKLPSLK IWETCKELLQ LSKPELPQDG TSTLRENSKP EESHLLAKRY GGFMKRYGGF MKKMDELYPM EPEEEANGSE ILAKRYGGFM KKDAEEDDSL ANSSDLLKEL LETGDNRERS HHQDGSDNEE EVSKRYGGFM RGLKRSPQLE DEAKELQKRY GGFMRRVGRP EWWMDYQKRY GGFLKRFAEA LPSDEEGESY SKEVPEMEKR YGGFMRF //