UniProtKB - P01213 (PDYN_HUMAN)
Protein
Proenkephalin-B
Gene
PDYN
Organism
Homo sapiens (Human)
Status
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
- opioid peptide activity Source: UniProtKB-KW
- opioid receptor binding Source: GO_Central
GO - Biological processi
- chemical synaptic transmission Source: GO_Central
- G protein-coupled receptor signaling pathway Source: Reactome
- neuropeptide signaling pathway Source: GO_Central
- sensory perception Source: GO_Central
Keywordsi
Molecular function | Endorphin, Neuropeptide, Neurotransmitter, Opioid peptide |
Enzyme and pathway databases
PathwayCommonsi | P01213 |
Reactomei | R-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 |
SIGNORi | P01213 |
Protein family/group databases
TCDBi | 1.C.89.1.1, the dynorphin channel-forming neuropeptide (dynorphin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Proenkephalin-BAlternative name(s): Beta-neoendorphin-dynorphin Preprodynorphin Cleaved into the following 9 chains: Alternative name(s): Dynorphin B Short name: Dyn-B Dynorphin B(1-13) Alternative name(s): Dynorphin B-29 |
Gene namesi | Name:PDYN |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000101327.8 |
HGNCi | HGNC:8820, PDYN |
MIMi | 131340, gene |
neXtProti | NX_P01213 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular region Source: Reactome
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- axon terminus Source: GO_Central
- dendrite Source: GO_Central
- neuronal cell body Source: GO_Central
Keywords - Cellular componenti
SecretedPathology & 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_072266 | 22 | C → Y in SCA23. 1 PublicationCorresponds to variant dbSNP:rs773876922Ensembl. | 1 | |
Natural variantiVAR_064913 | 138 | 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. 1 PublicationCorresponds to variant dbSNP:rs267606941EnsemblClinVar. | 1 | |
Natural variantiVAR_072268 | 206 | R → C in SCA23. 1 PublicationCorresponds to variant dbSNP:rs575606358Ensembl. | 1 | |
Natural variantiVAR_072269 | 206 | R → H in SCA23. 1 PublicationCorresponds to variant dbSNP:rs1004881058Ensembl. | 1 | |
Natural variantiVAR_064914 | 211 | 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; no effect on membrane property. 2 PublicationsCorresponds to variant dbSNP:rs267606940EnsemblClinVar. | 1 | |
Natural variantiVAR_064915 | 212 | 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; disrupts membrane property. 2 PublicationsCorresponds to variant dbSNP:rs201486601EnsemblClinVar. | 1 | |
Natural variantiVAR_064916 | 215 | 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; disrupts membrane property. 2 PublicationsCorresponds to variant dbSNP:rs267606939EnsemblClinVar. | 1 | |
Natural variantiVAR_072270 | 227 | G → D in SCA23. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, Neurodegeneration, Spinocerebellar ataxiaOrganism-specific databases
DisGeNETi | 5173 |
MalaCardsi | PDYN |
MIMi | 610245, phenotype |
OpenTargetsi | ENSG00000101327 |
Orphaneti | 101108, Spinocerebellar ataxia type 23 |
PharmGKBi | PA33163 |
Miscellaneous databases
Pharosi | P01213, Tbio |
Chemistry databases
ChEMBLi | CHEMBL2227 |
Polymorphism and mutation databases
BioMutai | PDYN |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Add BLAST | 20 | |
PropeptideiPRO_0000008176 | 21 – 172 | Add BLAST | 152 | |
PeptideiPRO_0000306347 | 175 – 184 | Alpha-neoendorphin | 10 | |
PeptideiPRO_0000008177 | 175 – 183 | Beta-neoendorphin | 9 | |
PeptideiPRO_0000306348 | 175 – 179 | Leu-enkephalinBy similarity | 5 | |
PropeptideiPRO_0000008178 | 186 – 204 | Add BLAST | 19 | |
PeptideiPRO_0000306349 | 207 – 238 | Big dynorphinAdd BLAST | 32 | |
PeptideiPRO_0000008179 | 207 – 223 | Dynorphin A(1-17)Add BLAST | 17 | |
PeptideiPRO_0000306350 | 207 – 219 | Dynorphin A(1-13)By similarityAdd BLAST | 13 | |
PeptideiPRO_0000306351 | 207 – 214 | Dynorphin A(1-8)By similarity | 8 | |
PeptideiPRO_0000306352 | 207 – 211 | Leu-enkephalinBy similarity | 5 | |
PeptideiPRO_0000008180 | 226 – 254 | LeumorphinAdd BLAST | 29 | |
PeptideiPRO_0000008181 | 226 – 238 | RimorphinAdd BLAST | 13 | |
PeptideiPRO_0000008182 | 226 – 230 | Leu-enkephalin | 5 |
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 bondProteomic databases
EPDi | P01213 |
MassIVEi | P01213 |
PaxDbi | P01213 |
PeptideAtlasi | P01213 |
PRIDEi | P01213 |
ProteomicsDBi | 51345 |
PTM databases
iPTMneti | P01213 |
PhosphoSitePlusi | P01213 |
Expressioni
Gene expression databases
Bgeei | ENSG00000101327, Expressed in nucleus accumbens and 61 other tissues |
ExpressionAtlasi | P01213, baseline and differential |
Genevisiblei | P01213, HS |
Organism-specific databases
HPAi | ENSG00000101327, Tissue enriched (brain) |
Interactioni
GO - Molecular functioni
- opioid peptide activity Source: UniProtKB-KW
- opioid receptor binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 111199, 11 interactors |
IntActi | P01213, 5 interactors |
STRINGi | 9606.ENSP00000440185 |
Chemistry databases
BindingDBi | P01213 |
Miscellaneous databases
RNActi | P01213, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P01213 |
SMRi | P01213 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the opioid neuropeptide precursor family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502RXT4, Eukaryota |
GeneTreei | ENSGT00950000183149 |
HOGENOMi | CLU_070973_1_0_1 |
InParanoidi | P01213 |
OMAi | LKWDKRY |
OrthoDBi | 1410356at2759 |
PhylomeDBi | P01213 |
TreeFami | TF332620 |
Family and domain databases
InterProi | View protein in InterPro IPR006024, Opioid_neupept IPR000750, Proenkphlin_B |
PANTHERi | PTHR11438, PTHR11438, 1 hit PTHR11438:SF4, PTHR11438:SF4, 1 hit |
Pfami | View protein in Pfam PF01160, Opiods_neuropep, 1 hit |
PRINTSi | PR01028, OPIOIDPRCRSR PR01030, PENKBPRCRSR |
PROSITEi | View protein in PROSITE PS01252, OPIOIDS_PRECURSOR, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All
P01213-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A494C0B3 | A0A494C0B3_HUMAN | Alpha-neoendorphin | PDYN | 91 | Annotation score: | ||
A0A494C0B1 | A0A494C0B1_HUMAN | Alpha-neoendorphin | PDYN | 89 | Annotation score: | ||
A0A494C0X3 | A0A494C0X3_HUMAN | Alpha-neoendorphin | PDYN | 118 | Annotation score: | ||
A0A494C197 | A0A494C197_HUMAN | Alpha-neoendorphin | PDYN | 115 | Annotation score: | ||
A0A494C1E3 | A0A494C1E3_HUMAN | Alpha-neoendorphin | PDYN | 68 | Annotation score: | ||
A0A494C1J4 | A0A494C1J4_HUMAN | Alpha-neoendorphin | PDYN | 138 | Annotation score: | ||
A0A494C1U2 | A0A494C1U2_HUMAN | Alpha-neoendorphin | PDYN | 149 | Annotation score: | ||
A0A494C0Y8 | A0A494C0Y8_HUMAN | Proenkephalin-B | PDYN | 20 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_072266 | 22 | C → Y in SCA23. 1 PublicationCorresponds to variant dbSNP:rs773876922Ensembl. | 1 | |
Natural variantiVAR_072267 | 25 | R → Q Very rare neutral polymorphism. 1 PublicationCorresponds to variant dbSNP:rs369559888Ensembl. | 1 | |
Natural variantiVAR_064913 | 138 | 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. 1 PublicationCorresponds to variant dbSNP:rs267606941EnsemblClinVar. | 1 | |
Natural variantiVAR_072268 | 206 | R → C in SCA23. 1 PublicationCorresponds to variant dbSNP:rs575606358Ensembl. | 1 | |
Natural variantiVAR_072269 | 206 | R → H in SCA23. 1 PublicationCorresponds to variant dbSNP:rs1004881058Ensembl. | 1 | |
Natural variantiVAR_064914 | 211 | 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; no effect on membrane property. 2 PublicationsCorresponds to variant dbSNP:rs267606940EnsemblClinVar. | 1 | |
Natural variantiVAR_064915 | 212 | 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; disrupts membrane property. 2 PublicationsCorresponds to variant dbSNP:rs201486601EnsemblClinVar. | 1 | |
Natural variantiVAR_064916 | 215 | 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; disrupts membrane property. 2 PublicationsCorresponds to variant dbSNP:rs267606939EnsemblClinVar. | 1 | |
Natural variantiVAR_072270 | 227 | G → D in SCA23. 1 Publication | 1 |
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 |
CCDSi | CCDS13023.1 |
PIRi | A01478, DFHU |
RefSeqi | 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 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 |
Genome annotation databases
Ensembli | ENST00000217305; ENSP00000217305; ENSG00000101327 ENST00000539905; ENSP00000440185; ENSG00000101327 ENST00000540134; ENSP00000442259; ENSG00000101327 |
GeneIDi | 5173 |
KEGGi | hsa:5173 |
UCSCi | uc002wfv.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 |
CCDSi | CCDS13023.1 |
PIRi | A01478, DFHU |
RefSeqi | 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 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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2N2F | NMR | - | A | 207-219 | [»] | |
BMRBi | P01213 | |||||
SMRi | P01213 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111199, 11 interactors |
IntActi | P01213, 5 interactors |
STRINGi | 9606.ENSP00000440185 |
Chemistry databases
BindingDBi | P01213 |
ChEMBLi | CHEMBL2227 |
Protein family/group databases
TCDBi | 1.C.89.1.1, the dynorphin channel-forming neuropeptide (dynorphin) family |
PTM databases
iPTMneti | P01213 |
PhosphoSitePlusi | P01213 |
Polymorphism and mutation databases
BioMutai | PDYN |
Proteomic databases
EPDi | P01213 |
MassIVEi | P01213 |
PaxDbi | P01213 |
PeptideAtlasi | P01213 |
PRIDEi | P01213 |
ProteomicsDBi | 51345 |
Protocols and materials databases
Antibodypediai | 6667, 242 antibodies |
DNASUi | 5173 |
Genome annotation databases
Ensembli | ENST00000217305; ENSP00000217305; ENSG00000101327 ENST00000539905; ENSP00000440185; ENSG00000101327 ENST00000540134; ENSP00000442259; ENSG00000101327 |
GeneIDi | 5173 |
KEGGi | hsa:5173 |
UCSCi | uc002wfv.4, human |
Organism-specific databases
CTDi | 5173 |
DisGeNETi | 5173 |
EuPathDBi | HostDB:ENSG00000101327.8 |
GeneCardsi | PDYN |
HGNCi | HGNC:8820, PDYN |
HPAi | ENSG00000101327, Tissue enriched (brain) |
MalaCardsi | PDYN |
MIMi | 131340, gene 610245, phenotype |
neXtProti | NX_P01213 |
OpenTargetsi | ENSG00000101327 |
Orphaneti | 101108, Spinocerebellar ataxia type 23 |
PharmGKBi | PA33163 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RXT4, Eukaryota |
GeneTreei | ENSGT00950000183149 |
HOGENOMi | CLU_070973_1_0_1 |
InParanoidi | P01213 |
OMAi | LKWDKRY |
OrthoDBi | 1410356at2759 |
PhylomeDBi | P01213 |
TreeFami | TF332620 |
Enzyme and pathway databases
PathwayCommonsi | P01213 |
Reactomei | R-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 |
SIGNORi | P01213 |
Miscellaneous databases
BioGRID-ORCSi | 5173, 2 hits in 839 CRISPR screens |
GenomeRNAii | 5173 |
Pharosi | P01213, Tbio |
PROi | PR:P01213 |
RNActi | P01213, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000101327, Expressed in nucleus accumbens and 61 other tissues |
ExpressionAtlasi | P01213, baseline and differential |
Genevisiblei | P01213, HS |
Family and domain databases
InterProi | View protein in InterPro IPR006024, Opioid_neupept IPR000750, Proenkphlin_B |
PANTHERi | PTHR11438, PTHR11438, 1 hit PTHR11438:SF4, PTHR11438:SF4, 1 hit |
Pfami | View protein in Pfam PF01160, Opiods_neuropep, 1 hit |
PRINTSi | PR01028, OPIOIDPRCRSR PR01030, PENKBPRCRSR |
PROSITEi | View protein in PROSITE PS01252, OPIOIDS_PRECURSOR, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PDYN_HUMAN | |
Accessioni | P01213Primary (citable) accession number: P01213 Secondary accession number(s): A8K0Q3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | July 21, 1986 | |
Last modified: | December 2, 2020 | |
This is version 174 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations