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P01213 (PDYN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length254 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020
Propeptide21 – 172152
PRO_0000008176
Peptide175 – 18410Alpha-neoendorphin
PRO_0000306347
Peptide175 – 1839Beta-neoendorphin
PRO_0000008177
Peptide175 – 1795Leu-enkephalin By similarity
PRO_0000306348
Propeptide186 – 20419
PRO_0000008178
Peptide207 – 23832Big dynorphin
PRO_0000306349
Peptide207 – 22317Dynorphin A(1-17)
PRO_0000008179
Peptide207 – 21913Dynorphin A(1-13) By similarity
PRO_0000306350
Peptide207 – 2148Dynorphin A(1-8) By similarity
PRO_0000306351
Peptide207 – 2115Leu-enkephalin By similarity
PRO_0000306352
Peptide226 – 25429Leumorphin
PRO_0000008180
Peptide226 – 23813Rimorphin
PRO_0000008181
Peptide226 – 2305Leu-enkephalin
PRO_0000008182

Natural variations

Natural variant1381R → 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 variant2111L → 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 variant2121R → 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
Corresponds to variant rs201486601 [ dbSNP | Ensembl ].
VAR_064915
Natural variant2151R → 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 LengthMass (Da)Tools
P01213 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 783E7D6AC068CE68

FASTA25428,385
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS13023.1.
PIRDFHU. A01478.
RefSeqNP_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.
UniGeneHs.22584.

3D structure databases

ProteinModelPortalP01213.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111199. 1 interaction.
STRING9606.ENSP00000217305.

Chemistry

BindingDBP01213.
ChEMBLCHEMBL2227.

Protein family/group databases

TCDB1.C.89.1.1. the dynorphin channel-forming neuropeptide (dynorphin) family.

PTM databases

PhosphoSiteP01213.

Proteomic databases

PaxDbP01213.
PeptideAtlasP01213.
PRIDEP01213.

Protocols and materials databases

DNASU5173.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000217305; ENSP00000217305; ENSG00000101327.
ENST00000539905; ENSP00000440185; ENSG00000101327.
ENST00000540134; ENSP00000442259; ENSG00000101327.
GeneID5173.
KEGGhsa:5173.
UCSCuc002wfv.3. human.

Organism-specific databases

CTD5173.
GeneCardsGC20M001907.
HGNCHGNC:8820. PDYN.
HPAHPA049841.
HPA053342.
MIM131340. gene.
610245. phenotype.
neXtProtNX_P01213.
Orphanet101108. Spinocerebellar ataxia type 23.
PharmGKBPA33163.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46156.
HOGENOMHOG000013003.
HOVERGENHBG000063.
InParanoidP01213.
KOK15840.
OMAWERCQGL.
OrthoDBEOG7BW0K5.
PhylomeDBP01213.
TreeFamTF332620.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP01213.
BgeeP01213.
CleanExHS_PDYN.
GenevestigatorP01213.

Family and domain databases

InterProIPR006024. Opioid_neupept.
IPR000750. Proenkphlin_B.
[Graphical view]
PANTHERPTHR11438. PTHR11438. 1 hit.
PTHR11438:SF4. PTHR11438:SF4. 1 hit.
PfamPF01160. Opiods_neuropep. 1 hit.
[Graphical view]
PRINTSPR01028. OPIOIDPRCRSR.
PR01030. PENKBPRCRSR.
PROSITEPS01252. OPIOIDS_PRECURSOR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi5173.
NextBio20018.
PMAP-CutDBP01213.
PROP01213.
SOURCESearch...

Entry information

Entry namePDYN_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM