P01213 (PDYN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proenkephalin-B

Alternative name(s):
Beta-neoendorphin-dynorphin
Preprodynorphin

Cleaved into the following 9 chains:

1. Alpha-neoendorphin
2. Beta-neoendorphin
3. Big dynorphin
   Short name=Big Dyn
4. Dynorphin A(1-17)
   Short name=Dyn-A17
   Short name=Dynorphin A
5. Dynorphin A(1-13)
6. Dynorphin A(1-8)
7. Leu-enkephalin
8. Rimorphin
   Alternative name(s):
   Dynorphin B
   Short name=Dyn-B
   Dynorphin B(1-13)
9. Leumorphin
   Alternative name(s):
   Dynorphin B-29

Gene names

Name:

PDYN

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	254 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	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 By similarity. Ref.7 Ref.8 Dynorphin peptides differentially regulate the kappa opioid receptor. Dynorphin A(1-13) has a typical opiod activity, it is 700 times more potent than Leu-enkephalin By similarity. Ref.7 Ref.8 Leumorphin has a typical opiod activity and may have anti-apoptotic effect By similarity. Ref.7 Ref.8
Subcellular location	Secreted.
Post-translational modification	The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.
Involvement in disease	Spinocerebellar ataxia 23 (SCA23) [MIM:610245]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA23 is an adult-onset autosomal dominant form characterized by slowly progressive gait and limb ataxia, with variable additional features, including peripheral neuropathy and dysarthria. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the opioid neuropeptide precursor family.

Ontologies

Keywords
Cellular component	Secreted
Disease	Disease mutation Neurodegeneration Spinocerebellar ataxia
Domain	Signal
Molecular function	Endorphin Neuropeptide Neurotransmitter Opioid peptide
PTM	Cleavage on pair of basic residues Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW neuropeptide signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW synaptic transmission Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20
	Propeptide	21 – 172	152			PRO_0000008176
	Peptide	175 – 184	10	Alpha-neoendorphin		PRO_0000306347
	Peptide	175 – 183	9	Beta-neoendorphin		PRO_0000008177
	Peptide	175 – 179	5	Leu-enkephalin By similarity		PRO_0000306348
	Propeptide	186 – 204	19			PRO_0000008178
	Peptide	207 – 238	32	Big dynorphin		PRO_0000306349
	Peptide	207 – 223	17	Dynorphin A(1-17)		PRO_0000008179
	Peptide	207 – 219	13	Dynorphin A(1-13) By similarity		PRO_0000306350
	Peptide	207 – 214	8	Dynorphin A(1-8) By similarity		PRO_0000306351
	Peptide	207 – 211	5	Leu-enkephalin By similarity		PRO_0000306352
	Peptide	226 – 254	29	Leumorphin		PRO_0000008180
	Peptide	226 – 238	13	Rimorphin		PRO_0000008181
	Peptide	226 – 230	5	Leu-enkephalin		PRO_0000008182
Natural variations
	Natural variant	138	1	R → S in SCA23; PDYN, dynorphin A and dynorphin B are located in Purkinje cells as observed in control cerebellum, but cerebellar tissue with the mutation has decreased levels of SLC1A6 and CALB1, both of which are markers of Purkinje cells; SLC1A6 accumulates and aggregates in patient cerebellar tissue. Ref.9		VAR_064913
	Natural variant	211	1	L → S in SCA23; the mutant PDYN protein is produced, but processing to opioid peptides is dramatically affected, with increased levels of dynorphin A compared to dynorphin B; these results suggest slow conversion of dynorphin A to short enkephalins; mutant S-211 dynorphin A is not neurotoxic to cultured striatal neurons. Ref.9		VAR_064914
	Natural variant	212	1	R → W in SCA23; the mutant PDYN protein is produced, but processing to opioid peptides is dramatically affected, with increased levels of dynorphin A compared to dynorphin B; mutant dynorphin A is neurotoxic to cultured striatal neurons, suggesting a dominant-negative effect. Ref.9		VAR_064915
	Natural variant	215	1	R → C in SCA23; the mutant PDYN protein is produced, but processing to opioid peptides is dramatically affected, resulting in an approximately 2-fold decreased level of dynorphin B compared to dynorphin A; mutant dynorphin A is neurotoxic to cultured striatal neurons, suggesting a dominant-negative effect. Ref.9		VAR_064916

Sequences

	Sequence		Length	Mass (Da)
	P01213 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 783E7D6AC068CE68	FASTA	254	28,385
	10 20 30 40 50 60 MAWQGLVLAA CLLMFPSTTA DCLSRCSLCA VKTQDGPKPI NPLICSLQCQ AALLPSEEWE 70 80 90 100 110 120 RCQSFLSFFT PSTLGLNDKE DLGSKSVGEG PYSELAKLSG SFLKELEKSK FLPSISTKEN 130 140 150 160 170 180 TLSKSLEEKL RGLSDGFREG AESELMRDAQ LNDGAMETGT LYLAEEDPKE QVKRYGGFLR 190 200 210 220 230 240 KYPKRSSEVA GEGDGDSMGH EDLYKRYGGF LRRIRPKLKW DNQKRYGGFL RRQFKVVTRS 250 QEDPNAYSGE LFDA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and structural organization of the human preproenkephalin B gene." Horikawa S., Takai T., Toyosato M., Takahashi H., Noda M., Kakidani H., Kubo T., Hirose T., Inayama S., Hayashida H., Miyata T., Numa S. Nature 306:611-614(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"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: Amygdala.
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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.
[6]	"NMR and structural model of dynorphin A (1-17) bound to dodecylphosphocholine micelles." Tessmer M.R., Kallick D.A. Biochemistry 36:1971-1981(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF DYNORPHIN A(1-17).
[7]	"Dynorphin peptides differentially regulate the human kappa opioid receptor." Chen Y., Chen C., Liu-Chen L.-Y. Life Sci. 80:1439-1448(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Big dynorphin as a putative endogenous ligand for the kappa-opioid receptor." Merg F., Filliol D., Usynin I., Bazov I., Bark N., Hurd Y.L., Yakovleva T., Kieffer B.L., Bakalkin G. J. Neurochem. 97:292-301(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23." Bakalkin G., Watanabe H., Jezierska J., Depoorter C., Verschuuren-Bemelmans C., Bazov I., Artemenko K.A., Yakovleva T., Dooijes D., Van de Warrenburg B.P., Zubarev R.A., Kremer B., Knapp P.E., Hauser K.F., Wijmenga C., Nyberg F., Sinke R.J., Verbeek D.S. Am. J. Hum. Genet. 87:593-603(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SCA23 SER-138; SER-211; TRP-212 AND CYS-215, CHARACTERIZATION OF VARIANTS SCA23 SER-138; SER-211; TRP-212 AND CYS-215.
[10]	Erratum Bakalkin G., Watanabe H., Jezierska J., Depoorter C., Verschuuren-Bemelmans C., Bazov I., Artemenko K.A., Yakovleva T., Dooijes D., Van de Warrenburg B.P., Zubarev R.A., Kremer B., Knapp P.E., Hauser K.F., Wijmenga C., Nyberg F., Sinke R.J., Verbeek D.S. Am. J. Hum. Genet. 87:736-736(2010)
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X02536 Genomic DNA. No translation available. K02267 Genomic DNA. No translation available. AH002816 Genomic DNA. Translation: AAA58456.2. X00176 Genomic DNA. Translation: CAA24999.1. AK289618 mRNA. Translation: BAF82307.1. AL034562 Genomic DNA. Translation: CAB38875.1. CH471133 Genomic DNA. Translation: EAX10604.1. BC026334 mRNA. Translation: AAH26334.1.
IPI	IPI00000832.
PIR	DFHU. A01478.
RefSeq	NP_001177821.1. NM_001190892.1. NP_001177827.1. NM_001190898.2. NP_001177828.1. NM_001190899.2. NP_001177829.1. NM_001190900.1. NP_077722.1. NM_024411.4.
UniGene	Hs.22584.
3D structure databases
ProteinModelPortal	P01213.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000217305.
Protein family/group databases
TCDB	1.C.89.1.1. dynorphin channel-forming neuropeptide (Dynorphin) family.
PTM databases
PhosphoSite	P01213.
Polymorphism databases
DMDM	127976.
Proteomic databases
PaxDb	P01213.
PeptideAtlas	P01213.
PRIDE	P01213.
Protocols and materials databases
DNASU	5173.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000217305; ENSP00000217305; ENSG00000101327. ENST00000539905; ENSP00000440185; ENSG00000101327. ENST00000540134; ENSP00000442259; ENSG00000101327.
GeneID	5173.
KEGG	hsa:5173.
UCSC	uc002wfv.3. human.
Organism-specific databases
CTD	5173.
GeneCards	GC20M001907.
HGNC	HGNC:8820. PDYN.
HPA	HPA049841. HPA053342.
MIM	131340. gene. 610245. phenotype.
neXtProt	NX_P01213.
Orphanet	101108. Spinocerebellar ataxia type 23.
PharmGKB	PA33163.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46156.
HOGENOM	HOG000013003.
HOVERGEN	HBG000063.
InParanoid	P01213.
KO	K15840.
OMA	RRQFKVV.
OrthoDB	EOG4QFWFK.
PhylomeDB	P01213.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P01213.
Bgee	P01213.
CleanEx	HS_PDYN.
Genevestigator	P01213.
GermOnline	ENSG00000101327. Homo sapiens.
Family and domain databases
InterPro	IPR006024. Opioid_neupept. IPR000750. Proenkphlin_B. [Graphical view]
PANTHER	PTHR11438. PTHR11438. 1 hit. PTHR11438:SF4. PTHR11438:SF4. 1 hit.
Pfam	PF01160. Opiods_neuropep. 1 hit. [Graphical view]
PRINTS	PR01028. OPIOIDPRCRSR. PR01030. PENKBPRCRSR.
PROSITE	PS01252. OPIOIDS_PRECURSOR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P01213.
ChEMBL	CHEMBL2227.
GenomeRNAi	5173.
NextBio	20018.
PMAP-CutDB	P01213.
SOURCE	Search...

Entry information

Entry name

PDYN_HUMAN

Accession

Primary (citable) accession number: P01213
Secondary accession number(s): A8K0Q3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 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.