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   13-FEB-2019, entry version 164.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Kakidani H., Kubo T., Hirose T., Inayama S., Hayashida H., Miyata T.,
RA   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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   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.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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.,
RA   Yakovleva T., 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
RP   CHARACTERIZATION OF VARIANTS SCA23 SER-138; SER-211; TRP-212 AND
RP   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.,
RA   Knapp P.E., Hauser K.F., Wijmenga C., Nyberg F., Sinke R.J.,
RA   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.
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.,
RA   Knapp P.E., Hauser K.F., Wijmenga C., Nyberg F., Sinke R.J.,
RA   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
RT   mutants 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.,
RA   Kok J., Goas J.Y., Bertrand P., Robin C., Brice A., Bakalkin G.,
RA   Durr A., Verbeek D.S.;
RT   "Identification and characterization of novel PDYN mutations in
RT   dominant cerebellar ataxia cases.";
RL   J. Neurol. 260:1807-1812(2013).
CC   -!- FUNCTION: Leu-enkephalins compete with and mimic the effects of
CC       opiate drugs. They play a role in a number of physiologic
CC       functions, including pain perception and responses to stress (By
CC       similarity). {ECO:0000250}.
CC   -!- FUNCTION: Dynorphin peptides differentially regulate the kappa
CC       opioid receptor. Dynorphin A(1-13) has a typical opiod activity,
CC       it is 700 times more potent than Leu-enkephalin (By similarity).
CC       {ECO:0000250}.
CC   -!- FUNCTION: Leumorphin has a typical opiod activity and may have
CC       anti-apoptotic effect. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- PTM: The N-terminal domain contains 6 conserved cysteines thought
CC       to be involved in disulfide bonding and/or processing.
CC   -!- DISEASE: Spinocerebellar ataxia 23 (SCA23) [MIM:610245]:
CC       Spinocerebellar ataxia is a clinically and genetically
CC       heterogeneous group of cerebellar disorders. Patients show
CC       progressive incoordination of gait and often poor coordination of
CC       hands, speech and eye movements, due to degeneration of the
CC       cerebellum with variable involvement of the brainstem and spinal
CC       cord. SCA23 is an adult-onset autosomal dominant form
CC       characterized by slowly progressive gait and limb ataxia, with
CC       variable additional features, including peripheral neuropathy and
CC       dysarthria. {ECO:0000269|PubMed:21035104,
CC       ECO:0000269|PubMed:21712028, ECO:0000269|PubMed:23108490,
CC       ECO:0000269|PubMed:23471613}. Note=The disease is caused by
CC       mutations affecting the gene represented in this 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   UniGene; Hs.22584; -.
DR   PDB; 2N2F; NMR; -; A=207-219.
DR   PDBsum; 2N2F; -.
DR   ProteinModelPortal; P01213; -.
DR   SMR; P01213; -.
DR   BioGrid; 111199; 11.
DR   STRING; 9606.ENSP00000217305; -.
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   jPOST; P01213; -.
DR   PaxDb; P01213; -.
DR   PeptideAtlas; P01213; -.
DR   PRIDE; P01213; -.
DR   ProteomicsDB; 51345; -.
DR   DNASU; 5173; -.
DR   Ensembl; ENST00000217305; ENSP00000217305; ENSG00000101327.
DR   Ensembl; ENST00000539905; ENSP00000440185; ENSG00000101327.
DR   Ensembl; ENST00000540134; ENSP00000442259; ENSG00000101327.
DR   GeneID; 5173; -.
DR   KEGG; hsa:5173; -.
DR   UCSC; uc002wfv.4; human.
DR   CTD; 5173; -.
DR   DisGeNET; 5173; -.
DR   EuPathDB; HostDB:ENSG00000101327.8; -.
DR   GeneCards; PDYN; -.
DR   HGNC; HGNC:8820; PDYN.
DR   HPA; HPA049841; -.
DR   HPA; HPA053342; -.
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   eggNOG; ENOG410IIMD; Eukaryota.
DR   eggNOG; ENOG4111RTT; LUCA.
DR   GeneTree; ENSGT00530000063761; -.
DR   HOGENOM; HOG000013003; -.
DR   HOVERGEN; HBG000063; -.
DR   InParanoid; P01213; -.
DR   KO; K15840; -.
DR   OMA; VGHEDLY; -.
DR   OrthoDB; 1410356at2759; -.
DR   PhylomeDB; P01213; -.
DR   TreeFam; TF332620; -.
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   SIGNOR; P01213; -.
DR   GenomeRNAi; 5173; -.
DR   PMAP-CutDB; P01213; -.
DR   PRO; PR:P01213; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   Bgee; ENSG00000101327; Expressed in 46 organ(s), highest expression level in nucleus accumbens.
DR   Genevisible; P01213; HS.
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:0043025; C:neuronal cell body; IBA:GO_Central.
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:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR   InterPro; IPR006024; Opioid_neupept.
DR   InterPro; IPR000750; Proenkphlin_B.
DR   PANTHER; PTHR11438; PTHR11438; 1.
DR   PANTHER; PTHR11438:SF4; PTHR11438:SF4; 1.
DR   Pfam; PF01160; Opiods_neuropep; 1.
DR   PRINTS; PR01028; OPIOIDPRCRSR.
DR   PRINTS; PR01030; PENKBPRCRSR.
DR   PROSITE; PS01252; OPIOIDS_PRECURSOR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues; Complete proteome;
KW   Disease mutation; Disulfide bond; Endorphin; Neurodegeneration;
KW   Neuropeptide; Neurotransmitter; Opioid peptide; Reference proteome;
KW   Secreted; Signal; Spinocerebellar ataxia.
FT   SIGNAL        1     20
FT   PROPEP       21    172
FT                                /FTId=PRO_0000008176.
FT   PEPTIDE     175    184       Alpha-neoendorphin.
FT                                /FTId=PRO_0000306347.
FT   PEPTIDE     175    183       Beta-neoendorphin.
FT                                /FTId=PRO_0000008177.
FT   PEPTIDE     175    179       Leu-enkephalin. {ECO:0000250}.
FT                                /FTId=PRO_0000306348.
FT   PROPEP      186    204
FT                                /FTId=PRO_0000008178.
FT   PEPTIDE     207    238       Big dynorphin.
FT                                /FTId=PRO_0000306349.
FT   PEPTIDE     207    223       Dynorphin A(1-17).
FT                                /FTId=PRO_0000008179.
FT   PEPTIDE     207    219       Dynorphin A(1-13). {ECO:0000250}.
FT                                /FTId=PRO_0000306350.
FT   PEPTIDE     207    214       Dynorphin A(1-8). {ECO:0000250}.
FT                                /FTId=PRO_0000306351.
FT   PEPTIDE     207    211       Leu-enkephalin. {ECO:0000250}.
FT                                /FTId=PRO_0000306352.
FT   PEPTIDE     226    254       Leumorphin.
FT                                /FTId=PRO_0000008180.
FT   PEPTIDE     226    238       Rimorphin.
FT                                /FTId=PRO_0000008181.
FT   PEPTIDE     226    230       Leu-enkephalin.
FT                                /FTId=PRO_0000008182.
FT   VARIANT      22     22       C -> Y (in SCA23; dbSNP:rs773876922).
FT                                {ECO:0000269|PubMed:23108490}.
FT                                /FTId=VAR_072266.
FT   VARIANT      25     25       R -> Q (very rare neutral polymorphism;
FT                                dbSNP:rs369559888).
FT                                {ECO:0000269|PubMed:23108490}.
FT                                /FTId=VAR_072267.
FT   VARIANT     138    138       R -> S (in SCA23; PDYN, dynorphin A and
FT                                dynorphin B are located in Purkinje cells
FT                                as observed in control cerebellum, but
FT                                cerebellar tissue with the mutation has
FT                                decreased levels of SLC1A6 and CALB1,
FT                                both of which are markers of Purkinje
FT                                cells; SLC1A6 accumulates and aggregates
FT                                in patient cerebellar tissue;
FT                                dbSNP:rs267606941).
FT                                {ECO:0000269|PubMed:21035104}.
FT                                /FTId=VAR_064913.
FT   VARIANT     206    206       R -> C (in SCA23; dbSNP:rs575606358).
FT                                {ECO:0000269|PubMed:23471613}.
FT                                /FTId=VAR_072268.
FT   VARIANT     206    206       R -> H (in SCA23; dbSNP:rs1004881058).
FT                                {ECO:0000269|PubMed:23471613}.
FT                                /FTId=VAR_072269.
FT   VARIANT     211    211       L -> S (in SCA23; the mutant PDYN protein
FT                                is produced, but processing to opioid
FT                                peptides is dramatically affected, with
FT                                increased levels of dynorphin A compared
FT                                to dynorphin B; these results suggest
FT                                slow conversion of dynorphin A to short
FT                                enkephalins; mutant S-211 dynorphin A is
FT                                not neurotoxic to cultured striatal
FT                                neurons; no effect on membrane property;
FT                                dbSNP:rs267606940).
FT                                {ECO:0000269|PubMed:21035104,
FT                                ECO:0000269|PubMed:21712028}.
FT                                /FTId=VAR_064914.
FT   VARIANT     212    212       R -> W (in SCA23; the mutant PDYN protein
FT                                is produced, but processing to opioid
FT                                peptides is dramatically affected, with
FT                                increased levels of dynorphin A compared
FT                                to dynorphin B; mutant dynorphin A is
FT                                neurotoxic to cultured striatal neurons,
FT                                suggesting a dominant-negative effect;
FT                                disrupts membrane property;
FT                                dbSNP:rs201486601).
FT                                {ECO:0000269|PubMed:21035104,
FT                                ECO:0000269|PubMed:21712028}.
FT                                /FTId=VAR_064915.
FT   VARIANT     215    215       R -> C (in SCA23; the mutant PDYN protein
FT                                is produced, but processing to opioid
FT                                peptides is dramatically affected,
FT                                resulting in an approximately 2-fold
FT                                decreased level of dynorphin B compared
FT                                to dynorphin A; mutant dynorphin A is
FT                                neurotoxic to cultured striatal neurons,
FT                                suggesting a dominant-negative effect;
FT                                disrupts membrane property;
FT                                dbSNP:rs267606939).
FT                                {ECO:0000269|PubMed:21035104,
FT                                ECO:0000269|PubMed:21712028}.
FT                                /FTId=VAR_064916.
FT   VARIANT     227    227       G -> D (in SCA23).
FT                                {ECO:0000269|PubMed:23471613}.
FT                                /FTId=VAR_072270.
FT   HELIX       211    213       {ECO:0000244|PDB:2N2F}.
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
//