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UniProtKB - P01213 (PDYN_HUMAN)

Protein

Proenkephalin-B

Gene

PDYN

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

Functioni

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).By similarity
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).By similarity
Leumorphin has a typical opiod activity and may have anti-apoptotic effect.By similarity

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionEndorphin, Neuropeptide, Neurotransmitter, Opioid peptide

Enzyme and pathway databases

ReactomeiR-HSA-111885 Opioid Signalling
R-HSA-202040 G-protein activation
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-418594 G alpha (i) signalling events
SIGNORiP01213

Protein family/group databases

TCDBi1.C.89.1.1 the dynorphin channel-forming neuropeptide (dynorphin) family

Names & Taxonomyi

Protein namesi
Recommended name:
Proenkephalin-B
Alternative name(s):
Beta-neoendorphin-dynorphin
Preprodynorphin
Cleaved into the following 9 chains:
Alpha-neoendorphin
Beta-neoendorphin
Big dynorphin
Short name:
Big Dyn
Dynorphin A(1-17)
Short name:
Dyn-A17
Short name:
Dynorphin A
Dynorphin A(1-13)
Dynorphin A(1-8)
Leu-enkephalin
Rimorphin
Alternative name(s):
Dynorphin B
Short name:
Dyn-B
Dynorphin B(1-13)
Leumorphin
Alternative name(s):
Dynorphin B-29
Gene namesi
Name:PDYN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000101327.8
HGNCiHGNC:8820 PDYN
MIMi131340 gene
neXtProtiNX_P01213

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia 23 (SCA23)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSpinocerebellar 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.
See also OMIM:610245
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07226622C → Y in SCA23. 1 PublicationCorresponds to variant dbSNP:rs773876922Ensembl.1
Natural variantiVAR_064913138R → 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. 1 PublicationCorresponds to variant dbSNP:rs267606941EnsemblClinVar.1
Natural variantiVAR_072268206R → C in SCA23. 1 PublicationCorresponds to variant dbSNP:rs575606358Ensembl.1
Natural variantiVAR_072269206R → H in SCA23. 1 PublicationCorresponds to variant dbSNP:rs1004881058Ensembl.1
Natural variantiVAR_064914211L → 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; no effect on membrane property. 2 PublicationsCorresponds to variant dbSNP:rs267606940EnsemblClinVar.1
Natural variantiVAR_064915212R → 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; disrupts membrane property. 2 PublicationsCorresponds to variant dbSNP:rs201486601EnsemblClinVar.1
Natural variantiVAR_064916215R → 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; disrupts membrane property. 2 PublicationsCorresponds to variant dbSNP:rs267606939EnsemblClinVar.1
Natural variantiVAR_072270227G → D in SCA23. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Spinocerebellar ataxia

Organism-specific databases

DisGeNETi5173
MalaCardsiPDYN
MIMi610245 phenotype
OpenTargetsiENSG00000101327
Orphaneti101108 Spinocerebellar ataxia type 23
PharmGKBiPA33163

Chemistry databases

ChEMBLiCHEMBL2227

Polymorphism and mutation databases

BioMutaiPDYN

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Add BLAST20
PropeptideiPRO_000000817621 – 172Add BLAST152
PeptideiPRO_0000306347175 – 184Alpha-neoendorphin10
PeptideiPRO_0000008177175 – 183Beta-neoendorphin9
PeptideiPRO_0000306348175 – 179Leu-enkephalinBy similarity5
PropeptideiPRO_0000008178186 – 204Add BLAST19
PeptideiPRO_0000306349207 – 238Big dynorphinAdd BLAST32
PeptideiPRO_0000008179207 – 223Dynorphin A(1-17)Add BLAST17
PeptideiPRO_0000306350207 – 219Dynorphin A(1-13)By similarityAdd BLAST13
PeptideiPRO_0000306351207 – 214Dynorphin A(1-8)By similarity8
PeptideiPRO_0000306352207 – 211Leu-enkephalinBy similarity5
PeptideiPRO_0000008180226 – 254LeumorphinAdd BLAST29
PeptideiPRO_0000008181226 – 238RimorphinAdd BLAST13
PeptideiPRO_0000008182226 – 230Leu-enkephalin5

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

EPDiP01213
PaxDbiP01213
PeptideAtlasiP01213
PRIDEiP01213
ProteomicsDBi51345

PTM databases

iPTMnetiP01213
PhosphoSitePlusiP01213

Miscellaneous databases

PMAP-CutDBiP01213

Expressioni

Gene expression databases

BgeeiENSG00000101327 Expressed in 46 organ(s), highest expression level in nucleus accumbens
CleanExiHS_PDYN
GenevisibleiP01213 HS

Organism-specific databases

HPAiHPA049841
HPA053342

Interactioni

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi111199, 11 interactors
STRINGi9606.ENSP00000217305

Chemistry databases

BindingDBiP01213

Structurei

Secondary structure

1254
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP01213
SMRiP01213
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the opioid neuropeptide precursor family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IIMD Eukaryota
ENOG4111RTT LUCA
GeneTreeiENSGT00530000063761
HOGENOMiHOG000013003
HOVERGENiHBG000063
InParanoidiP01213
KOiK15840
OMAiVGHEDLY
OrthoDBiEOG091G0HV8
PhylomeDBiP01213
TreeFamiTF332620

Family and domain databases

InterProiView protein in InterPro
IPR006024 Opioid_neupept
IPR000750 Proenkphlin_B
PANTHERiPTHR11438 PTHR11438, 1 hit
PTHR11438:SF4 PTHR11438:SF4, 1 hit
PfamiView protein in Pfam
PF01160 Opiods_neuropep, 1 hit
PRINTSiPR01028 OPIOIDPRCRSR
PR01030 PENKBPRCRSR
PROSITEiView protein in PROSITE
PS01252 OPIOIDS_PRECURSOR, 1 hit

Sequencei

Sequence statusi: Complete.

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

P01213-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAWQGLVLAA CLLMFPSTTA DCLSRCSLCA VKTQDGPKPI NPLICSLQCQ 
        60         70         80         90        100
AALLPSEEWE RCQSFLSFFT PSTLGLNDKE DLGSKSVGEG PYSELAKLSG 
       110        120        130        140        150
SFLKELEKSK FLPSISTKEN TLSKSLEEKL RGLSDGFREG AESELMRDAQ 
       160        170        180        190        200
LNDGAMETGT LYLAEEDPKE QVKRYGGFLR KYPKRSSEVA GEGDGDSMGH 
       210        220        230        240        250
EDLYKRYGGF LRRIRPKLKW DNQKRYGGFL RRQFKVVTRS QEDPNAYSGE 

LFDA
Length:254
Mass (Da):28,385
Last modified:July 21, 1986 - v1
Checksum:i783E7D6AC068CE68
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07226622C → Y in SCA23. 1 PublicationCorresponds to variant dbSNP:rs773876922Ensembl.1
Natural variantiVAR_07226725R → Q Very rare neutral polymorphism. 1 PublicationCorresponds to variant dbSNP:rs369559888Ensembl.1
Natural variantiVAR_064913138R → 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. 1 PublicationCorresponds to variant dbSNP:rs267606941EnsemblClinVar.1
Natural variantiVAR_072268206R → C in SCA23. 1 PublicationCorresponds to variant dbSNP:rs575606358Ensembl.1
Natural variantiVAR_072269206R → H in SCA23. 1 PublicationCorresponds to variant dbSNP:rs1004881058Ensembl.1
Natural variantiVAR_064914211L → 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; no effect on membrane property. 2 PublicationsCorresponds to variant dbSNP:rs267606940EnsemblClinVar.1
Natural variantiVAR_064915212R → 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; disrupts membrane property. 2 PublicationsCorresponds to variant dbSNP:rs201486601EnsemblClinVar.1
Natural variantiVAR_064916215R → 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; disrupts membrane property. 2 PublicationsCorresponds to variant dbSNP:rs267606939EnsemblClinVar.1
Natural variantiVAR_072270227G → D in SCA23. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
CH471133 Genomic DNA Translation: EAX10604.1
BC026334 mRNA Translation: AAH26334.1
CCDSiCCDS13023.1
PIRiA01478 DFHU
RefSeqiNP_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
XP_011527546.1, XM_011529244.1
XP_011527547.1, XM_011529245.1
XP_011527548.1, XM_011529246.2
XP_011527549.1, XM_011529247.1
XP_011527550.1, XM_011529248.1
XP_011527551.1, XM_011529249.2
XP_011527552.1, XM_011529250.2
XP_016883367.1, XM_017027878.1
UniGeneiHs.22584

Genome annotation databases

EnsembliENST00000217305; ENSP00000217305; ENSG00000101327
ENST00000539905; ENSP00000440185; ENSG00000101327
ENST00000540134; ENSP00000442259; ENSG00000101327
GeneIDi5173
KEGGihsa:5173
UCSCiuc002wfv.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
CH471133 Genomic DNA Translation: EAX10604.1
BC026334 mRNA Translation: AAH26334.1
CCDSiCCDS13023.1
PIRiA01478 DFHU
RefSeqiNP_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
XP_011527546.1, XM_011529244.1
XP_011527547.1, XM_011529245.1
XP_011527548.1, XM_011529246.2
XP_011527549.1, XM_011529247.1
XP_011527550.1, XM_011529248.1
XP_011527551.1, XM_011529249.2
XP_011527552.1, XM_011529250.2
XP_016883367.1, XM_017027878.1
UniGeneiHs.22584

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N2FNMR-A207-219[»]
ProteinModelPortaliP01213
SMRiP01213
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111199, 11 interactors
STRINGi9606.ENSP00000217305

Chemistry databases

BindingDBiP01213
ChEMBLiCHEMBL2227

Protein family/group databases

TCDBi1.C.89.1.1 the dynorphin channel-forming neuropeptide (dynorphin) family

PTM databases

iPTMnetiP01213
PhosphoSitePlusiP01213

Polymorphism and mutation databases

BioMutaiPDYN

Proteomic databases

EPDiP01213
PaxDbiP01213
PeptideAtlasiP01213
PRIDEiP01213
ProteomicsDBi51345

Protocols and materials databases

DNASUi5173
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000217305; ENSP00000217305; ENSG00000101327
ENST00000539905; ENSP00000440185; ENSG00000101327
ENST00000540134; ENSP00000442259; ENSG00000101327
GeneIDi5173
KEGGihsa:5173
UCSCiuc002wfv.4 human

Organism-specific databases

CTDi5173
DisGeNETi5173
EuPathDBiHostDB:ENSG00000101327.8
GeneCardsiPDYN
HGNCiHGNC:8820 PDYN
HPAiHPA049841
HPA053342
MalaCardsiPDYN
MIMi131340 gene
610245 phenotype
neXtProtiNX_P01213
OpenTargetsiENSG00000101327
Orphaneti101108 Spinocerebellar ataxia type 23
PharmGKBiPA33163
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIMD Eukaryota
ENOG4111RTT LUCA
GeneTreeiENSGT00530000063761
HOGENOMiHOG000013003
HOVERGENiHBG000063
InParanoidiP01213
KOiK15840
OMAiVGHEDLY
OrthoDBiEOG091G0HV8
PhylomeDBiP01213
TreeFamiTF332620

Enzyme and pathway databases

ReactomeiR-HSA-111885 Opioid Signalling
R-HSA-202040 G-protein activation
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-418594 G alpha (i) signalling events
SIGNORiP01213

Miscellaneous databases

GenomeRNAii5173
PMAP-CutDBiP01213
PROiPR:P01213
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101327 Expressed in 46 organ(s), highest expression level in nucleus accumbens
CleanExiHS_PDYN
GenevisibleiP01213 HS

Family and domain databases

InterProiView protein in InterPro
IPR006024 Opioid_neupept
IPR000750 Proenkphlin_B
PANTHERiPTHR11438 PTHR11438, 1 hit
PTHR11438:SF4 PTHR11438:SF4, 1 hit
PfamiView protein in Pfam
PF01160 Opiods_neuropep, 1 hit
PRINTSiPR01028 OPIOIDPRCRSR
PR01030 PENKBPRCRSR
PROSITEiView protein in PROSITE
PS01252 OPIOIDS_PRECURSOR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPDYN_HUMAN
AccessioniPrimary (citable) accession number: P01213
Secondary accession number(s): A8K0Q3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 7, 2018
This is version 162 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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