PDYN_HUMAN
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 03-AUG-2022, entry version 181.
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 opiod activity, it is 700
CC times more potent than Leu-enkephalin (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Leumorphin has a typical opiod 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 PDBsum; 2N2F; -.
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; P01213; -.
DR PeptideAtlas; P01213; -.
DR PRIDE; P01213; -.
DR ProteomicsDB; 51345; -.
DR Antibodypedia; 6667; 251 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 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; NAYSGEV; -.
DR OrthoDB; 1410356at2759; -.
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 1066 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 tissues.
DR ExpressionAtlas; P01213; baseline and differential.
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: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; 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; 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 HELIX 211..213
FT /evidence="ECO:0007829|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
