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Protein

Proenkephalin-A

Gene

PENK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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(237-258) increase glutamate release in the striatum. PENK(114-133) decreases GABA concentration in the striatum.

GO - Molecular functioni

  • neuropeptide hormone activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Endorphin, Neuropeptide, Opioid peptide

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_19231. G alpha (i) signalling events.

Protein family/group databases

TCDBi1.C.89.1.2. the dynorphin channel-forming neuropeptide (dynorphin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Proenkephalin-A
Cleaved into the following 8 chains:
Gene namesi
Name:PENK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:8831. PENK.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33176.

Polymorphism and mutation databases

BioMutaiPENK.
DMDMi129770.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Peptidei25 – 9773SynenkephalinPRO_0000008242Add
BLAST
Peptidei100 – 1045Met-enkephalinPRO_0000008243
Peptidei107 – 1115Met-enkephalinPRO_0000008244
Peptidei114 – 13320PENK(114-133)By similarityPRO_0000377691Add
BLAST
Peptidei136 – 1405Met-enkephalinPRO_0000008246
Peptidei143 – 18341PENK(143-183)By similarityPRO_0000377692Add
BLAST
Peptidei186 – 1938Met-enkephalin-Arg-Gly-LeuPRO_0000008248
Propeptidei196 – 20712PRO_0000008249Add
BLAST
Peptidei210 – 2145Met-enkephalinPRO_0000008250
Propeptidei217 – 22711PRO_0000008251Add
BLAST
Peptidei230 – 2345Leu-enkephalinPRO_0000008252
Peptidei237 – 25822PENK(237-258)By similarityPRO_0000377693Add
BLAST
Peptidei261 – 2677Met-enkephalin-Arg-PhePRO_0000008254

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi26 ↔ 481 Publication
Disulfide bondi30 ↔ 521 Publication
Disulfide bondi33 ↔ 651 Publication

Post-translational modificationi

The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

PaxDbiP01210.
PRIDEiP01210.

PTM databases

PhosphoSiteiP01210.

Miscellaneous databases

PMAP-CutDBP01210.

Expressioni

Gene expression databases

BgeeiP01210.
CleanExiHS_PENK.
ExpressionAtlasiP01210. baseline and differential.
GenevisibleiP01210. HS.

Organism-specific databases

HPAiCAB016390.
HPA013138.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
OPRM1P353723EBI-6656055,EBI-2624570

Protein-protein interaction databases

BioGridi111205. 7 interactions.
IntActiP01210. 2 interactions.
STRINGi9606.ENSP00000324248.

Structurei

Secondary structure

1
267
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni262 – 2643Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1PLWNMR-A100-104[»]
1PLXNMR-A100-104[»]
2LWCNMR-A261-265[»]
ProteinModelPortaliP01210.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01210.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG40630.
GeneTreeiENSGT00530000063761.
HOGENOMiHOG000013003.
HOVERGENiHBG000063.
InParanoidiP01210.
KOiK18832.
OMAiFMKKMDE.
PhylomeDBiP01210.
TreeFamiTF332620.

Family and domain databases

InterProiIPR006024. Opioid_neupept.
IPR000703. Proenkphlin_A.
[Graphical view]
PANTHERiPTHR11438. PTHR11438. 1 hit.
PTHR11438:SF3. PTHR11438:SF3. 1 hit.
PfamiPF01160. Opiods_neuropep. 1 hit.
[Graphical view]
PRINTSiPR01028. OPIOIDPRCRSR.
PR01029. PENKAPRCRSR.
PROSITEiPS01252. OPIOIDS_PRECURSOR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01210-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARFLTLCTW LLLLGPGLLA TVRAECSQDC ATCSYRLVRP ADINFLACVM
60 70 80 90 100
ECEGKLPSLK IWETCKELLQ LSKPELPQDG TSTLRENSKP EESHLLAKRY
110 120 130 140 150
GGFMKRYGGF MKKMDELYPM EPEEEANGSE ILAKRYGGFM KKDAEEDDSL
160 170 180 190 200
ANSSDLLKEL LETGDNRERS HHQDGSDNEE EVSKRYGGFM RGLKRSPQLE
210 220 230 240 250
DEAKELQKRY GGFMRRVGRP EWWMDYQKRY GGFLKRFAEA LPSDEEGESY
260
SKEVPEMEKR YGGFMRF
Length:267
Mass (Da):30,787
Last modified:July 21, 1986 - v1
Checksum:i4189BA600C3FC8EE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti119 – 1191P → S in CAG46627 (Ref. 4) Curated
Sequence conflicti152 – 1521N → I in CAG46607 (Ref. 4) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti83 – 831T → N.
Corresponds to variant rs11998459 [ dbSNP | Ensembl ].
VAR_048935
Natural varianti247 – 2471G → D.
Corresponds to variant rs1800567 [ dbSNP | Ensembl ].
VAR_014584

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00509 Genomic DNA. Translation: CAA23767.1.
J00123, J00122 Genomic DNA. Translation: AAB59409.1.
AK314908 mRNA. Translation: BAG37420.1.
CR541808 mRNA. Translation: CAG46607.1.
CR541828 mRNA. Translation: CAG46627.1.
CH471068 Genomic DNA. Translation: EAW86785.1.
BC032505 mRNA. Translation: AAH32505.1.
CCDSiCCDS6168.1.
PIRiA93278. EQHUA.
RefSeqiNP_001129162.1. NM_001135690.1.
NP_006202.1. NM_006211.3.
UniGeneiHs.339831.

Genome annotation databases

EnsembliENST00000314922; ENSP00000324248; ENSG00000181195.
ENST00000451791; ENSP00000400894; ENSG00000181195.
GeneIDi5179.
KEGGihsa:5179.
UCSCiuc003xsz.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00509 Genomic DNA. Translation: CAA23767.1.
J00123, J00122 Genomic DNA. Translation: AAB59409.1.
AK314908 mRNA. Translation: BAG37420.1.
CR541808 mRNA. Translation: CAG46607.1.
CR541828 mRNA. Translation: CAG46627.1.
CH471068 Genomic DNA. Translation: EAW86785.1.
BC032505 mRNA. Translation: AAH32505.1.
CCDSiCCDS6168.1.
PIRiA93278. EQHUA.
RefSeqiNP_001129162.1. NM_001135690.1.
NP_006202.1. NM_006211.3.
UniGeneiHs.339831.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1PLWNMR-A100-104[»]
1PLXNMR-A100-104[»]
2LWCNMR-A261-265[»]
ProteinModelPortaliP01210.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111205. 7 interactions.
IntActiP01210. 2 interactions.
STRINGi9606.ENSP00000324248.

Protein family/group databases

TCDBi1.C.89.1.2. the dynorphin channel-forming neuropeptide (dynorphin) family.

PTM databases

PhosphoSiteiP01210.

Polymorphism and mutation databases

BioMutaiPENK.
DMDMi129770.

Proteomic databases

PaxDbiP01210.
PRIDEiP01210.

Protocols and materials databases

DNASUi5179.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000314922; ENSP00000324248; ENSG00000181195.
ENST00000451791; ENSP00000400894; ENSG00000181195.
GeneIDi5179.
KEGGihsa:5179.
UCSCiuc003xsz.2. human.

Organism-specific databases

CTDi5179.
GeneCardsiGC08M057349.
HGNCiHGNC:8831. PENK.
HPAiCAB016390.
HPA013138.
MIMi131330. gene.
neXtProtiNX_P01210.
PharmGKBiPA33176.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG40630.
GeneTreeiENSGT00530000063761.
HOGENOMiHOG000013003.
HOVERGENiHBG000063.
InParanoidiP01210.
KOiK18832.
OMAiFMKKMDE.
PhylomeDBiP01210.
TreeFamiTF332620.

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_19231. G alpha (i) signalling events.

Miscellaneous databases

EvolutionaryTraceiP01210.
GenomeRNAii5179.
NextBioi20046.
PMAP-CutDBP01210.
PROiP01210.
SOURCEiSearch...

Gene expression databases

BgeeiP01210.
CleanExiHS_PENK.
ExpressionAtlasiP01210. baseline and differential.
GenevisibleiP01210. HS.

Family and domain databases

InterProiIPR006024. Opioid_neupept.
IPR000703. Proenkphlin_A.
[Graphical view]
PANTHERiPTHR11438. PTHR11438. 1 hit.
PTHR11438:SF3. PTHR11438:SF3. 1 hit.
PfamiPF01160. Opiods_neuropep. 1 hit.
[Graphical view]
PRINTSiPR01028. OPIOIDPRCRSR.
PR01029. PENKAPRCRSR.
PROSITEiPS01252. OPIOIDS_PRECURSOR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Primary structure of the human Met- and Leu-enkephalin precursor and its mRNA."
    Comb M., Seeburg P.H., Adelman J., Eiden L., Herbert E.
    Nature 295:663-666(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Isolation and structural organization of the human preproenkephalin gene."
    Noda M., Teranishi Y., Takahashi H., Toyosato M., Notake M., Nakanishi S., Numa S.
    Nature 297:431-434(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Cerebellum.
  4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  7. "The structure of synenkephalin (pro-enkephalin 1-73) is dictated by three disulfide bonds."
    Lecchi P., Loh Y.P., Snell C.R., Pannell L.K.
    Biochem. Biophys. Res. Commun. 232:800-805(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.

Entry informationi

Entry nameiPENK_HUMAN
AccessioniPrimary (citable) accession number: P01210
Secondary accession number(s): B2RC23, Q6FHC6, Q6FHE6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: June 24, 2015
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.