P01210 (PENK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proenkephalin-A

Cleaved into the following 8 chains:

1. Synenkephalin
2. Met-enkephalin
   Alternative name(s):
   Opioid growth factor
   Short name=OGF
3. PENK(114-133)
4. PENK(143-183)
5. Met-enkephalin-Arg-Gly-Leu
6. Leu-enkephalin
7. PENK(237-258)
8. Met-enkephalin-Arg-Phe

Gene names

Name:

PENK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	267 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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(237-258) increase glutamate release in the striatum. PENK(114-133) decreases GABA concentration in the striatum.
Subcellular location	Secreted.
Post-translational modification	The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.
Sequence similarities	Belongs to the opioid neuropeptide precursor family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Endorphin Neuropeptide Opioid peptide
PTM	Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavioral fear response Inferred from electronic annotation. Source: Compara neuropeptide signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of pain Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	extracellular region Traceable author statement. Source: Reactome
Molecular_function	neuropeptide hormone activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Peptide	25 – 97	73	Synenkephalin		PRO_0000008242
	Peptide	100 – 104	5	Met-enkephalin		PRO_0000008243
	Peptide	107 – 111	5	Met-enkephalin		PRO_0000008244
	Peptide	114 – 133	20	PENK(114-133) By similarity		PRO_0000377691
	Peptide	136 – 140	5	Met-enkephalin		PRO_0000008246
	Peptide	143 – 183	41	PENK(143-183) By similarity		PRO_0000377692
	Peptide	186 – 193	8	Met-enkephalin-Arg-Gly-Leu		PRO_0000008248
	Propeptide	196 – 207	12			PRO_0000008249
	Peptide	210 – 214	5	Met-enkephalin		PRO_0000008250
	Propeptide	217 – 227	11			PRO_0000008251
	Peptide	230 – 234	5	Leu-enkephalin		PRO_0000008252
	Peptide	237 – 258	22	PENK(237-258) By similarity		PRO_0000377693
	Peptide	261 – 267	7	Met-enkephalin-Arg-Phe		PRO_0000008254
Amino acid modifications
	Disulfide bond	26 ↔ 48		Ref.7
	Disulfide bond	30 ↔ 52		Ref.7
	Disulfide bond	33 ↔ 65		Ref.7
Natural variations
	Natural variant	83	1	T → N. Corresponds to variant rs11998459 [ dbSNP | Ensembl ].		VAR_048935
	Natural variant	247	1	G → D. Corresponds to variant rs1800567 [ dbSNP | Ensembl ].		VAR_014584
Experimental info
	Sequence conflict	119	1	P → S in CAG46627. Ref.4
	Sequence conflict	152	1	N → I in CAG46607. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P01210 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 4189BA600C3FC8EE	FASTA	267	30,787
	10 20 30 40 50 60 MARFLTLCTW LLLLGPGLLA TVRAECSQDC ATCSYRLVRP ADINFLACVM ECEGKLPSLK 70 80 90 100 110 120 IWETCKELLQ LSKPELPQDG TSTLRENSKP EESHLLAKRY GGFMKRYGGF MKKMDELYPM 130 140 150 160 170 180 EPEEEANGSE ILAKRYGGFM KKDAEEDDSL ANSSDLLKEL LETGDNRERS HHQDGSDNEE 190 200 210 220 230 240 EVSKRYGGFM RGLKRSPQLE DEAKELQKRY GGFMRRVGRP EWWMDYQKRY GGFLKRFAEA 250 260 LPSDEEGESY SKEVPEMEKR YGGFMRF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00000828.

PIR

EQHUA. A93278.

RefSeq

NP_001129162.1. NM_001135690.1.
NP_006202.1. NM_006211.3.

UniGene

Hs.339831.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PLW	NMR	-	A	100-104	[»]
1PLX	NMR	-	A	100-104	[»]

ProteinModelPortal

P01210.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000324248.

Protein family/group databases

TCDB

1.C.89.1.2. dynorphin channel-forming neuropeptide (Dynorphin) family.

PTM databases

PhosphoSite

P01210.

Polymorphism databases

DMDM

129770.

Proteomic databases

PaxDb

P01210.

PRIDE

P01210.

Protocols and materials databases

DNASU

5179.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000314922; ENSP00000324248; ENSG00000181195.
ENST00000451791; ENSP00000400894; ENSG00000181195.

GeneID

5179.

KEGG

hsa:5179.

UCSC

uc003xsz.2. human.

Organism-specific databases

CTD

5179.

GeneCards

GC08M057349.

HGNC

HGNC:8831. PENK.

HPA

CAB016390.
HPA013138.

MIM

131330. gene.

neXtProt

NX_P01210.

PharmGKB

PA33176.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40630.

HOGENOM

HOG000013003.

HOVERGEN

HBG000063.

InParanoid

P01210.

OMA

GGFMKKD.

OrthoDB

EOG4HMJBF.

PhylomeDB

P01210.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P01210.

Bgee

P01210.

CleanEx

HS_PENK.

Genevestigator

P01210.

GermOnline

ENSG00000181195. Homo sapiens.

Family and domain databases

InterPro

IPR006024. Opioid_neupept.
IPR000703. Proenkphlin_A.
[Graphical view]

PANTHER

PTHR11438. PTHR11438. 1 hit.
PTHR11438:SF3. PTHR11438:SF3. 1 hit.

Pfam

PF01160. Opiods_neuropep. 1 hit.
[Graphical view]

PRINTS

PR01028. OPIOIDPRCRSR.
PR01029. PENKAPRCRSR.

PROSITE

PS01252. OPIOIDS_PRECURSOR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P01210.

GenomeRNAi

5179.

NextBio

20046.

PMAP-CutDB

P01210.

SOURCE

Search...

Entry information

Entry name

PENK_HUMAN

Accession

Primary (citable) accession number: P01210
Secondary accession number(s): B2RC23, Q6FHC6, Q6FHE6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	April 3, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.