ID   PDYN_HUMAN              Reviewed;         254 AA.
AC   P01213; A8K0Q3;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 190.
DE   RecName: Full=Proenkephalin-B;
DE   AltName: Full=Beta-neoendorphin-dynorphin;
DE   AltName: Full=Preprodynorphin;
DE   Contains:
DE     RecName: Full=Alpha-neoendorphin;
DE   Contains:
DE     RecName: Full=Beta-neoendorphin;
DE   Contains:
DE     RecName: Full=Big dynorphin;
DE              Short=Big Dyn;
DE   Contains:
DE     RecName: Full=Dynorphin A(1-17);
DE              Short=Dyn-A17;
DE              Short=Dynorphin A;
DE   Contains:
DE     RecName: Full=Dynorphin A(1-13);
DE   Contains:
DE     RecName: Full=Dynorphin A(1-8);
DE   Contains:
DE     RecName: Full=Leu-enkephalin;
DE   Contains:
DE     RecName: Full=Rimorphin;
DE     AltName: Full=Dynorphin B;
DE              Short=Dyn-B;
DE     AltName: Full=Dynorphin B(1-13);
DE   Contains:
DE     RecName: Full=Leumorphin;
DE     AltName: Full=Dynorphin B-29;
DE   Flags: Precursor;
GN   Name=PDYN;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6316163; DOI=10.1038/306611a0;
RA   Horikawa S., Takai T., Toyosato M., Takahashi H., Noda M., Kakidani H.,
RA   Kubo T., Hirose T., Inayama S., Hayashida H., Miyata T., Numa S.;
RT   "Isolation and structural organization of the human preproenkephalin B
RT   gene.";
RL   Nature 306:611-614(1983).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Amygdala;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   STRUCTURE BY NMR OF DYNORPHIN A(1-17).
RX   PubMed=9047294; DOI=10.1021/bi961457h;
RA   Tessmer M.R., Kallick D.A.;
RT   "NMR and structural model of dynorphin A (1-17) bound to
RT   dodecylphosphocholine micelles.";
RL   Biochemistry 36:1971-1981(1997).
RN   [7]
RP   FUNCTION.
RX   PubMed=17316701; DOI=10.1016/j.lfs.2007.01.018;
RA   Chen Y., Chen C., Liu-Chen L.-Y.;
RT   "Dynorphin peptides differentially regulate the human kappa opioid
RT   receptor.";
RL   Life Sci. 80:1439-1448(2007).
RN   [8]
RP   FUNCTION.
RX   PubMed=16515546; DOI=10.1111/j.1471-4159.2006.03732.x;
RA   Merg F., Filliol D., Usynin I., Bazov I., Bark N., Hurd Y.L., Yakovleva T.,
RA   Kieffer B.L., Bakalkin G.;
RT   "Big dynorphin as a putative endogenous ligand for the kappa-opioid
RT   receptor.";
RL   J. Neurochem. 97:292-301(2006).
RN   [9]
RP   VARIANTS SCA23 SER-138; SER-211; TRP-212 AND CYS-215, AND CHARACTERIZATION
RP   OF VARIANTS SCA23 SER-138; SER-211; TRP-212 AND CYS-215.
RX   PubMed=21035104; DOI=10.1016/j.ajhg.2010.10.001;
RA   Bakalkin G., Watanabe H., Jezierska J., Depoorter C.,
RA   Verschuuren-Bemelmans C., Bazov I., Artemenko K.A., Yakovleva T.,
RA   Dooijes D., Van de Warrenburg B.P., Zubarev R.A., Kremer B., Knapp P.E.,
RA   Hauser K.F., Wijmenga C., Nyberg F., Sinke R.J., Verbeek D.S.;
RT   "Prodynorphin mutations cause the neurodegenerative disorder
RT   spinocerebellar ataxia type 23.";
RL   Am. J. Hum. Genet. 87:593-603(2010).
RN   [10]
RP   ERRATUM OF PUBMED:21035104.
RA   Bakalkin G., Watanabe H., Jezierska J., Depoorter C.,
RA   Verschuuren-Bemelmans C., Bazov I., Artemenko K.A., Yakovleva T.,
RA   Dooijes D., Van de Warrenburg B.P., Zubarev R.A., Kremer B., Knapp P.E.,
RA   Hauser K.F., Wijmenga C., Nyberg F., Sinke R.J., Verbeek D.S.;
RL   Am. J. Hum. Genet. 87:736-736(2010).
RN   [11]
RP   VARIANTS SCA23 SER-211; TRP-212 AND CYS-215, AND CHARACTERIZATION OF
RP   VARIANTS SCA23 SER-211; TRP-212 AND CYS-215.
RX   PubMed=21712028; DOI=10.1016/j.bbrc.2011.06.105;
RA   Madani F., Taqi M.M., Warmlander S.K., Verbeek D.S., Bakalkin G.,
RA   Graslund A.;
RT   "Perturbations of model membranes induced by pathogenic dynorphin A mutants
RT   causing neurodegeneration in human brain.";
RL   Biochem. Biophys. Res. Commun. 411:111-114(2011).
RN   [12]
RP   VARIANT SCA23 TYR-22, AND VARIANT GLN-25.
RX   PubMed=23108490; DOI=10.1007/s00415-012-6721-1;
RA   Fawcett K., Mehrabian M., Liu Y.T., Hamed S., Elahi E., Revesz T.,
RA   Koutsis G., Herscheson J., Schottlaender L., Wardle M., Morrison P.J.,
RA   Morris H.R., Giunti P., Wood N., Houlden H.;
RT   "The frequency of spinocerebellar ataxia type 23 in a UK population.";
RL   J. Neurol. 260:856-859(2013).
RN   [13]
RP   VARIANTS SCA23 CYS-206; HIS-206 AND ASP-227.
RX   PubMed=23471613; DOI=10.1007/s00415-013-6882-6;
RA   Jezierska J., Stevanin G., Watanabe H., Fokkens M.R., Zagnoli F., Kok J.,
RA   Goas J.Y., Bertrand P., Robin C., Brice A., Bakalkin G., Durr A.,
RA   Verbeek D.S.;
RT   "Identification and characterization of novel PDYN mutations in dominant
RT   cerebellar ataxia cases.";
RL   J. Neurol. 260:1807-1812(2013).
CC   -!- FUNCTION: Leu-enkephalins compete with and mimic the effects of opiate
CC       drugs. They play a role in a number of physiologic functions, including
CC       pain perception and responses to stress (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: Dynorphin peptides differentially regulate the kappa opioid
CC       receptor. Dynorphin A(1-13) has a typical opioid activity, it is 700
CC       times more potent than Leu-enkephalin (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: Leumorphin has a typical opioid activity and may have anti-
CC       apoptotic effect. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- PTM: The N-terminal domain contains 6 conserved cysteines thought to be
CC       involved in disulfide bonding and/or processing.
CC   -!- DISEASE: Spinocerebellar ataxia 23 (SCA23) [MIM:610245]:
CC       Spinocerebellar ataxia is a clinically and genetically heterogeneous
CC       group of cerebellar disorders. Patients show progressive incoordination
CC       of gait and often poor coordination of hands, speech and eye movements,
CC       due to degeneration of the cerebellum with variable involvement of the
CC       brainstem and spinal cord. SCA23 is an adult-onset autosomal dominant
CC       form characterized by slowly progressive gait and limb ataxia, with
CC       variable additional features, including peripheral neuropathy and
CC       dysarthria. {ECO:0000269|PubMed:21035104, ECO:0000269|PubMed:21712028,
CC       ECO:0000269|PubMed:23108490, ECO:0000269|PubMed:23471613}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the opioid neuropeptide precursor family.
CC       {ECO:0000305}.
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DR   EMBL; X02536; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; K02267; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AH002816; AAA58456.2; -; Genomic_DNA.
DR   EMBL; X00176; CAA24999.1; -; Genomic_DNA.
DR   EMBL; AK289618; BAF82307.1; -; mRNA.
DR   EMBL; AL034562; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471133; EAX10604.1; -; Genomic_DNA.
DR   EMBL; BC026334; AAH26334.1; -; mRNA.
DR   CCDS; CCDS13023.1; -.
DR   PIR; A01478; DFHU.
DR   RefSeq; NP_001177821.1; NM_001190892.1.
DR   RefSeq; NP_001177827.1; NM_001190898.2.
DR   RefSeq; NP_001177828.1; NM_001190899.2.
DR   RefSeq; NP_001177829.1; NM_001190900.1.
DR   RefSeq; NP_077722.1; NM_024411.4.
DR   RefSeq; XP_011527546.1; XM_011529244.1.
DR   RefSeq; XP_011527547.1; XM_011529245.1.
DR   RefSeq; XP_011527548.1; XM_011529246.2.
DR   RefSeq; XP_011527549.1; XM_011529247.1.
DR   RefSeq; XP_011527550.1; XM_011529248.1.
DR   RefSeq; XP_011527551.1; XM_011529249.2.
DR   RefSeq; XP_011527552.1; XM_011529250.2.
DR   RefSeq; XP_016883367.1; XM_017027878.1.
DR   PDB; 2N2F; NMR; -; A=207-219.
DR   PDB; 7Y1F; EM; 3.30 A; F=207-219.
DR   PDB; 8F7W; EM; 3.19 A; P=207-214.
DR   PDBsum; 2N2F; -.
DR   PDBsum; 7Y1F; -.
DR   PDBsum; 8F7W; -.
DR   AlphaFoldDB; P01213; -.
DR   BMRB; P01213; -.
DR   SMR; P01213; -.
DR   BioGRID; 111199; 13.
DR   IntAct; P01213; 5.
DR   STRING; 9606.ENSP00000440185; -.
DR   BindingDB; P01213; -.
DR   ChEMBL; CHEMBL2227; -.
DR   TCDB; 1.C.89.1.1; the dynorphin channel-forming neuropeptide (dynorphin) family.
DR   iPTMnet; P01213; -.
DR   PhosphoSitePlus; P01213; -.
DR   BioMuta; PDYN; -.
DR   EPD; P01213; -.
DR   MassIVE; P01213; -.
DR   PaxDb; 9606-ENSP00000440185; -.
DR   PeptideAtlas; P01213; -.
DR   ProteomicsDB; 51345; -.
DR   Antibodypedia; 6667; 265 antibodies from 27 providers.
DR   DNASU; 5173; -.
DR   Ensembl; ENST00000217305.3; ENSP00000217305.2; ENSG00000101327.9.
DR   Ensembl; ENST00000539905.5; ENSP00000440185.1; ENSG00000101327.9.
DR   Ensembl; ENST00000540134.5; ENSP00000442259.1; ENSG00000101327.9.
DR   GeneID; 5173; -.
DR   KEGG; hsa:5173; -.
DR   MANE-Select; ENST00000217305.3; ENSP00000217305.2; NM_024411.5; NP_077722.1.
DR   UCSC; uc002wfv.4; human.
DR   AGR; HGNC:8820; -.
DR   CTD; 5173; -.
DR   DisGeNET; 5173; -.
DR   GeneCards; PDYN; -.
DR   HGNC; HGNC:8820; PDYN.
DR   HPA; ENSG00000101327; Tissue enriched (brain).
DR   MalaCards; PDYN; -.
DR   MIM; 131340; gene.
DR   MIM; 610245; phenotype.
DR   neXtProt; NX_P01213; -.
DR   OpenTargets; ENSG00000101327; -.
DR   Orphanet; 101108; Spinocerebellar ataxia type 23.
DR   PharmGKB; PA33163; -.
DR   VEuPathDB; HostDB:ENSG00000101327; -.
DR   eggNOG; ENOG502RXT4; Eukaryota.
DR   GeneTree; ENSGT00950000183149; -.
DR   HOGENOM; CLU_070973_1_0_1; -.
DR   InParanoid; P01213; -.
DR   OMA; CSMCAVQ; -.
DR   OrthoDB; 5318835at2759; -.
DR   PhylomeDB; P01213; -.
DR   TreeFam; TF332620; -.
DR   PathwayCommons; P01213; -.
DR   Reactome; R-HSA-111885; Opioid Signalling.
DR   Reactome; R-HSA-202040; G-protein activation.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; P01213; -.
DR   SIGNOR; P01213; -.
DR   BioGRID-ORCS; 5173; 8 hits in 1144 CRISPR screens.
DR   GenomeRNAi; 5173; -.
DR   Pharos; P01213; Tbio.
DR   PRO; PR:P01213; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; P01213; Protein.
DR   Bgee; ENSG00000101327; Expressed in nucleus accumbens and 72 other cell types or tissues.
DR   ExpressionAtlas; P01213; baseline and differential.
DR   GO; GO:0043679; C:axon terminus; IBA:GO_Central.
DR   GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR   GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR   GO; GO:0098992; C:neuronal dense core vesicle; IDA:SynGO.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0001515; F:opioid peptide activity; IEA:UniProtKB-KW.
DR   GO; GO:0031628; F:opioid receptor binding; IBA:GO_Central.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR   GO; GO:0007600; P:sensory perception; IBA:GO_Central.
DR   InterPro; IPR006024; Opioid_neupept.
DR   InterPro; IPR000750; Proenkphlin_B.
DR   PANTHER; PTHR11438; PROENKEPHALIN; 1.
DR   PANTHER; PTHR11438:SF4; PROENKEPHALIN-B; 1.
DR   Pfam; PF01160; Opiods_neuropep; 1.
DR   PRINTS; PR01028; OPIOIDPRCRSR.
DR   PRINTS; PR01030; PENKBPRCRSR.
DR   PROSITE; PS01252; OPIOIDS_PRECURSOR; 1.
DR   Genevisible; P01213; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues; Disease variant;
KW   Disulfide bond; Endorphin; Neurodegeneration; Neuropeptide;
KW   Neurotransmitter; Opioid peptide; Reference proteome; Secreted; Signal;
KW   Spinocerebellar ataxia.
FT   SIGNAL          1..20
FT   PROPEP          21..172
FT                   /id="PRO_0000008176"
FT   PEPTIDE         175..184
FT                   /note="Alpha-neoendorphin"
FT                   /id="PRO_0000306347"
FT   PEPTIDE         175..183
FT                   /note="Beta-neoendorphin"
FT                   /id="PRO_0000008177"
FT   PEPTIDE         175..179
FT                   /note="Leu-enkephalin"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306348"
FT   PROPEP          186..204
FT                   /id="PRO_0000008178"
FT   PEPTIDE         207..238
FT                   /note="Big dynorphin"
FT                   /id="PRO_0000306349"
FT   PEPTIDE         207..223
FT                   /note="Dynorphin A(1-17)"
FT                   /id="PRO_0000008179"
FT   PEPTIDE         207..219
FT                   /note="Dynorphin A(1-13)"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306350"
FT   PEPTIDE         207..214
FT                   /note="Dynorphin A(1-8)"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306351"
FT   PEPTIDE         207..211
FT                   /note="Leu-enkephalin"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000306352"
FT   PEPTIDE         226..254
FT                   /note="Leumorphin"
FT                   /id="PRO_0000008180"
FT   PEPTIDE         226..238
FT                   /note="Rimorphin"
FT                   /id="PRO_0000008181"
FT   PEPTIDE         226..230
FT                   /note="Leu-enkephalin"
FT                   /id="PRO_0000008182"
FT   VARIANT         22
FT                   /note="C -> Y (in SCA23; dbSNP:rs773876922)"
FT                   /evidence="ECO:0000269|PubMed:23108490"
FT                   /id="VAR_072266"
FT   VARIANT         25
FT                   /note="R -> Q (in dbSNP:rs369559888)"
FT                   /evidence="ECO:0000269|PubMed:23108490"
FT                   /id="VAR_072267"
FT   VARIANT         138
FT                   /note="R -> S (in SCA23; PDYN, dynorphin A and dynorphin B
FT                   are located in Purkinje cells as observed in control
FT                   cerebellum, but cerebellar tissue with the mutation has
FT                   decreased levels of SLC1A6 and CALB1, both of which are
FT                   markers of Purkinje cells; SLC1A6 accumulates and
FT                   aggregates in patient cerebellar tissue;
FT                   dbSNP:rs267606941)"
FT                   /evidence="ECO:0000269|PubMed:21035104"
FT                   /id="VAR_064913"
FT   VARIANT         206
FT                   /note="R -> C (in SCA23; dbSNP:rs575606358)"
FT                   /evidence="ECO:0000269|PubMed:23471613"
FT                   /id="VAR_072268"
FT   VARIANT         206
FT                   /note="R -> H (in SCA23; dbSNP:rs1004881058)"
FT                   /evidence="ECO:0000269|PubMed:23471613"
FT                   /id="VAR_072269"
FT   VARIANT         211
FT                   /note="L -> S (in SCA23; the mutant PDYN protein is
FT                   produced, but processing to opioid peptides is dramatically
FT                   affected, with increased levels of dynorphin A compared to
FT                   dynorphin B; these results suggest slow conversion of
FT                   dynorphin A to short enkephalins; mutant S-211 dynorphin A
FT                   is not neurotoxic to cultured striatal neurons; no effect
FT                   on membrane property; dbSNP:rs267606940)"
FT                   /evidence="ECO:0000269|PubMed:21035104,
FT                   ECO:0000269|PubMed:21712028"
FT                   /id="VAR_064914"
FT   VARIANT         212
FT                   /note="R -> W (in SCA23; the mutant PDYN protein is
FT                   produced, but processing to opioid peptides is dramatically
FT                   affected, with increased levels of dynorphin A compared to
FT                   dynorphin B; mutant dynorphin A is neurotoxic to cultured
FT                   striatal neurons, suggesting a dominant-negative effect;
FT                   disrupts membrane property; dbSNP:rs201486601)"
FT                   /evidence="ECO:0000269|PubMed:21035104,
FT                   ECO:0000269|PubMed:21712028"
FT                   /id="VAR_064915"
FT   VARIANT         215
FT                   /note="R -> C (in SCA23; the mutant PDYN protein is
FT                   produced, but processing to opioid peptides is dramatically
FT                   affected, resulting in an approximately 2-fold decreased
FT                   level of dynorphin B compared to dynorphin A; mutant
FT                   dynorphin A is neurotoxic to cultured striatal neurons,
FT                   suggesting a dominant-negative effect; disrupts membrane
FT                   property; dbSNP:rs267606939)"
FT                   /evidence="ECO:0000269|PubMed:21035104,
FT                   ECO:0000269|PubMed:21712028"
FT                   /id="VAR_064916"
FT   VARIANT         227
FT                   /note="G -> D (in SCA23)"
FT                   /evidence="ECO:0000269|PubMed:23471613"
FT                   /id="VAR_072270"
FT   STRAND          209..211
FT                   /evidence="ECO:0007829|PDB:8F7W"
SQ   SEQUENCE   254 AA;  28385 MW;  783E7D6AC068CE68 CRC64;
     MAWQGLVLAA CLLMFPSTTA DCLSRCSLCA VKTQDGPKPI NPLICSLQCQ AALLPSEEWE
     RCQSFLSFFT PSTLGLNDKE DLGSKSVGEG PYSELAKLSG SFLKELEKSK FLPSISTKEN
     TLSKSLEEKL RGLSDGFREG AESELMRDAQ LNDGAMETGT LYLAEEDPKE QVKRYGGFLR
     KYPKRSSEVA GEGDGDSMGH EDLYKRYGGF LRRIRPKLKW DNQKRYGGFL RRQFKVVTRS
     QEDPNAYSGE LFDA
//