TIM_DROME
ID TIM_DROME Reviewed; 1398 AA.
AC P49021; A4V040; B7Z007; B7Z008; C9QPB7; M9MRE9; O44380; Q1WWF5; Q59E16;
AC Q8I037; Q95U67; Q9VQR6; Q9VQR7;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Protein timeless;
GN Name=tim; ORFNames=CG3234;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM R).
RX PubMed=7481771; DOI=10.1126/science.270.5237.805;
RA Myers M.P., Wager-Smith K., Wesley C.S., Young M.W., Sehgal A.;
RT "Positional cloning and sequence analysis of the Drosophila clock gene,
RT timeless.";
RL Science 270:805-808(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9365248; DOI=10.1093/nar/25.23.4710;
RA Myers M.P., Rothenfluh A., Chang M., Young M.W.;
RT "Comparison of chromosomal DNA composing timeless in Drosophila
RT melanogaster and D. virilis suggests a new conserved structure for the
RT TIMELESS protein.";
RL Nucleic Acids Res. 25:4710-4714(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30, AND ALTERNATIVE INITIATION.
RC STRAIN=Canton-S, CO-TG14, CO-TG20, PER+, PER01, and PERS;
RX PubMed=9016581; DOI=10.1093/nar/25.3.455;
RA Rosato E., Trevisan A., Sandrelli F., Zordan M., Kyriacou C.P., Costa R.;
RT "Conceptual translation of timeless reveals alternative initiating
RT methionines in Drosophila.";
RL Nucleic Acids Res. 25:455-458(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-1398 (ISOFORM O), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1115-1398 (ISOFORMS B/L/R).
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM N), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 907-1398 (ISOFORMS B/L/R).
RC STRAIN=Berkeley;
RA Stapleton M., Booth B., Carlson J., Chavez C., Frise E., George R.,
RA Pacleb J., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 220-284, FUNCTION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=9504927; DOI=10.1093/genetics/148.2.815;
RA Ousley A., Zafarullah K., Chen Y., Emerson M., Hickman L., Sehgal A.;
RT "Conserved regions of the timeless (tim) clock gene in Drosophila analyzed
RT through phylogenetic and functional studies.";
RL Genetics 148:815-825(1998).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8128247; DOI=10.1126/science.8128247;
RA Vosshall L.B., Price J.L., Sehgal A., Saez L., Young M.W.;
RT "Block in nuclear localization of period protein by a second clock
RT mutation, timeless.";
RL Science 263:1606-1609(1994).
RN [10]
RP FUNCTION.
RX PubMed=7481772; DOI=10.1126/science.270.5237.808;
RA Sehgal A., Rothenfluh-Hilfiker A., Hunter-Ensor M., Chen Y., Myers M.P.,
RA Young M.W.;
RT "Rhythmic expression of timeless: a basis for promoting circadian cycles in
RT period gene autoregulation.";
RL Science 270:808-810(1995).
RN [11]
RP FUNCTION, AND INTERACTION WITH PER.
RX PubMed=7481773; DOI=10.1126/science.270.5237.811;
RA Gekakis N., Saez L., Delahaye-Brown A.M., Myers M.P., Sehgal A.,
RA Young M.W., Weitz C.J.;
RT "Isolation of timeless by PER protein interaction: defective interaction
RT between timeless protein and long-period mutant PERL.";
RL Science 270:811-815(1995).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=8625406; DOI=10.1016/s0092-8674(00)81046-6;
RA Hunter-Ensor M., Ousley A., Sehgal A.;
RT "Regulation of the Drosophila protein timeless suggests a mechanism for
RT resetting the circadian clock by light.";
RL Cell 84:677-685(1996).
CC -!- FUNCTION: Required for the production of circadian rhythms. The
CC biological cycle depends on the rhythmic formation and nuclear
CC localization of the TIM-PER complex. Light induces the degradation of
CC TIM, which promotes elimination of PER. Nuclear activity of the
CC heterodimer coordinatively regulates PER and TIM transcription through
CC a negative feedback loop. Behaves as a negative element in circadian
CC transcriptional loop. Does not appear to bind DNA, suggesting indirect
CC transcriptional inhibition. {ECO:0000269|PubMed:7481772,
CC ECO:0000269|PubMed:7481773, ECO:0000269|PubMed:8128247,
CC ECO:0000269|PubMed:8625406, ECO:0000269|PubMed:9504927}.
CC -!- SUBUNIT: Forms a heterodimer with period (PER); the complex then
CC translocates into the nucleus.
CC -!- INTERACTION:
CC P49021; P07663-1: per; NbExp=2; IntAct=EBI-266295, EBI-15718452;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8625406}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:8625406}. Note=Nuclear at
CC specific periods of the day. First accumulates in the perinuclear
CC region about one hour before translocation into the nucleus.
CC Interaction with per is required for nuclear localization.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=7;
CC Name=B {ECO:0000312|FlyBase:FBgn0014396}; Synonyms=P
CC {ECO:0000312|FlyBase:FBgn0014396};
CC IsoId=P49021-4; Sequence=Displayed;
CC Name=R {ECO:0000312|FlyBase:FBgn0014396};
CC IsoId=P49021-2; Sequence=VSP_004457;
CC Name=O {ECO:0000312|FlyBase:FBgn0014396};
CC IsoId=P49021-3; Sequence=VSP_007693, VSP_007694;
CC Name=N {ECO:0000312|FlyBase:FBgn0014396};
CC IsoId=P49021-5; Sequence=VSP_054859, VSP_007693, VSP_007694;
CC Name=S {ECO:0000312|FlyBase:FBgn0014396};
CC IsoId=P49021-6; Sequence=VSP_004457, VSP_054860, VSP_054861;
CC Name=M {ECO:0000312|FlyBase:FBgn0014396};
CC IsoId=P49021-7; Sequence=VSP_054860, VSP_054861;
CC Name=L {ECO:0000312|FlyBase:FBgn0014396};
CC IsoId=P49021-8; Sequence=VSP_054859;
CC -!- TISSUE SPECIFICITY: Expressed in head, photoreceptors, lateral neurons
CC and glial cells in the lamina and medulla of the optic lobes.
CC Expression follows a light-dark cycle, levels show a significant
CC decrease at the end of the night and then remain low throughout the
CC light period (at protein level). {ECO:0000269|PubMed:8625406,
CC ECO:0000269|PubMed:9504927}.
CC -!- PTM: Phosphorylated with a circadian rhythmicity.
CC -!- DISRUPTION PHENOTYPE: Mutant flies show loss of both behavioral
CC circadian rhythms and molecular oscillations of per RNA and protein.
CC {ECO:0000269|PubMed:8128247, ECO:0000269|PubMed:9504927}.
CC -!- SIMILARITY: Belongs to the timeless family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC46920.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAL13507.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAN71179.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAN71179.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=ACX54883.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U37018; AAC46920.1; ALT_INIT; mRNA.
DR EMBL; AF032401; AAB94890.1; -; Genomic_DNA.
DR EMBL; AF032400; AAB94890.1; JOINED; Genomic_DNA.
DR EMBL; AE014134; AAF51098.4; -; Genomic_DNA.
DR EMBL; AE014134; AAN10371.3; -; Genomic_DNA.
DR EMBL; AE014134; AAN10372.3; -; Genomic_DNA.
DR EMBL; AE014134; AAX52649.2; -; Genomic_DNA.
DR EMBL; AE014134; ABC65862.2; -; Genomic_DNA.
DR EMBL; AE014134; ACL82987.2; -; Genomic_DNA.
DR EMBL; AE014134; ACL82988.2; -; Genomic_DNA.
DR EMBL; AE014134; ADV36936.2; -; Genomic_DNA.
DR EMBL; Y09930; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y09931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y09932; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y09933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y09934; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y09935; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY058278; AAL13507.1; ALT_INIT; mRNA.
DR EMBL; BT001424; AAN71179.1; ALT_SEQ; mRNA.
DR EMBL; BT024951; ABE01181.1; -; mRNA.
DR EMBL; BT099999; ACX54883.1; ALT_INIT; mRNA.
DR EMBL; AF038501; AAB94929.1; -; Genomic_DNA.
DR PIR; A57655; A57655.
DR RefSeq; NP_001014463.2; NM_001014463.4. [P49021-6]
DR RefSeq; NP_001033872.2; NM_001038783.3. [P49021-7]
DR RefSeq; NP_001137780.2; NM_001144308.3. [P49021-2]
DR RefSeq; NP_001137781.2; NM_001144309.4. [P49021-3]
DR RefSeq; NP_001188686.2; NM_001201757.2. [P49021-5]
DR RefSeq; NP_722912.3; NM_164540.4. [P49021-4]
DR RefSeq; NP_722913.3; NM_164541.6. [P49021-8]
DR RefSeq; NP_722914.3; NM_164542.5. [P49021-4]
DR AlphaFoldDB; P49021; -.
DR SMR; P49021; -.
DR BioGRID; 59781; 30.
DR DIP; DIP-29425N; -.
DR IntAct; P49021; 8.
DR STRING; 7227.FBpp0305454; -.
DR PaxDb; P49021; -.
DR DNASU; 33571; -.
DR EnsemblMetazoa; FBtr0077567; FBpp0077256; FBgn0014396. [P49021-4]
DR EnsemblMetazoa; FBtr0333252; FBpp0305450; FBgn0014396. [P49021-8]
DR EnsemblMetazoa; FBtr0333253; FBpp0305451; FBgn0014396. [P49021-7]
DR EnsemblMetazoa; FBtr0333254; FBpp0305452; FBgn0014396. [P49021-5]
DR EnsemblMetazoa; FBtr0333255; FBpp0305453; FBgn0014396. [P49021-3]
DR EnsemblMetazoa; FBtr0333256; FBpp0305454; FBgn0014396. [P49021-4]
DR EnsemblMetazoa; FBtr0333258; FBpp0305456; FBgn0014396. [P49021-2]
DR EnsemblMetazoa; FBtr0333259; FBpp0305457; FBgn0014396. [P49021-6]
DR GeneID; 33571; -.
DR KEGG; dme:Dmel_CG3234; -.
DR UCSC; CG3234-RA; d. melanogaster. [P49021-4]
DR UCSC; CG3234-RE; d. melanogaster.
DR CTD; 107698; -.
DR FlyBase; FBgn0014396; tim.
DR VEuPathDB; VectorBase:FBgn0014396; -.
DR eggNOG; KOG1974; Eukaryota.
DR GeneTree; ENSGT00390000015124; -.
DR InParanoid; P49021; -.
DR OMA; SKCNQRS; -.
DR PhylomeDB; P49021; -.
DR Reactome; R-DME-432395; Degradation of TIM.
DR Reactome; R-DME-432490; Nuclear import of PER and TIM.
DR Reactome; R-DME-432501; Transcription repression by PER and activation by PDP1.
DR Reactome; R-DME-432553; Phosphorylation of PER and TIM.
DR Reactome; R-DME-432620; Dephosphorylation of PER.
DR Reactome; R-DME-538898; Dephosphorylation of TIM.
DR SignaLink; P49021; -.
DR BioGRID-ORCS; 33571; 0 hits in 1 CRISPR screen.
DR ChiTaRS; tim; fly.
DR GenomeRNAi; 33571; -.
DR PRO; PR:P49021; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0014396; Expressed in capitellum (Drosophila) and 31 other tissues.
DR ExpressionAtlas; P49021; baseline and differential.
DR Genevisible; P49021; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0031298; C:replication fork protection complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:FlyBase.
DR GO; GO:0008134; F:transcription factor binding; IPI:FlyBase.
DR GO; GO:0071482; P:cellular response to light stimulus; IMP:FlyBase.
DR GO; GO:0048512; P:circadian behavior; IMP:FlyBase.
DR GO; GO:0003053; P:circadian regulation of heart rate; IMP:FlyBase.
DR GO; GO:0060086; P:circadian temperature homeostasis; IMP:FlyBase.
DR GO; GO:0007620; P:copulation; IMP:FlyBase.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IBA:GO_Central.
DR GO; GO:0008062; P:eclosion rhythm; TAS:FlyBase.
DR GO; GO:0009649; P:entrainment of circadian clock; IMP:FlyBase.
DR GO; GO:0045475; P:locomotor rhythm; IMP:FlyBase.
DR GO; GO:0007617; P:mating behavior; IMP:FlyBase.
DR GO; GO:0046957; P:negative phototaxis; IMP:FlyBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; IDA:FlyBase.
DR GO; GO:0009648; P:photoperiodism; IMP:FlyBase.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IMP:CACAO.
DR GO; GO:0042749; P:regulation of circadian sleep/wake cycle; IMP:FlyBase.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; IMP:FlyBase.
DR GO; GO:0050764; P:regulation of phagocytosis; IMP:CACAO.
DR GO; GO:0042306; P:regulation of protein import into nucleus; TAS:FlyBase.
DR GO; GO:0043111; P:replication fork arrest; IBA:GO_Central.
DR GO; GO:0048478; P:replication fork protection; IBA:GO_Central.
DR GO; GO:0007622; P:rhythmic behavior; TAS:FlyBase.
DR InterPro; IPR044998; Timeless.
DR InterPro; IPR007725; TIMELESS_C.
DR InterPro; IPR006906; Timeless_N.
DR PANTHER; PTHR22940; PTHR22940; 1.
DR Pfam; PF04821; TIMELESS; 1.
DR Pfam; PF05029; TIMELESS_C; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Alternative splicing; Biological rhythms;
KW Cytoplasm; Nucleus; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..1398
FT /note="Protein timeless"
FT /id="PRO_0000022532"
FT REGION 237..268
FT /note="Necessary for normal circadian rhythm"
FT REGION 254..300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..452
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 478..555
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1127..1147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1220..1239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 550..560
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 254..292
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 361..376
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 377..391
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..424
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 487..540
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 237..268
FT /note="Missing (in isoform R and isoform S)"
FT /evidence="ECO:0000303|PubMed:7481771"
FT /id="VSP_004457"
FT VAR_SEQ 613
FT /note="Missing (in isoform L and isoform N)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_054859"
FT VAR_SEQ 891
FT /note="C -> W (in isoform N and isoform O)"
FT /evidence="ECO:0000303|PubMed:12537569, ECO:0000303|Ref.7"
FT /id="VSP_007693"
FT VAR_SEQ 892..1398
FT /note="Missing (in isoform N and isoform O)"
FT /evidence="ECO:0000303|PubMed:12537569, ECO:0000303|Ref.7"
FT /id="VSP_007694"
FT VAR_SEQ 1114..1131
FT /note="LNLKFDASELEDATASSP -> RELKSTTEKNNPFVIPQR (in isoform
FT S and isoform M)"
FT /evidence="ECO:0000305"
FT /id="VSP_054860"
FT VAR_SEQ 1132..1398
FT /note="Missing (in isoform S and isoform M)"
FT /evidence="ECO:0000305"
FT /id="VSP_054861"
FT CONFLICT 1233
FT /note="I -> V (in Ref. 2; AAB94890)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1398 AA; 156382 MW; E7974EDCF6F94A88 CRC64;
MDWLLATPQL YSAFSSLGCL EGDTYVVNPN ALAILEEINY KLTYEDQTLR TFRRAIGFGQ
NVRSDLIPLL ENAKDDAVLE SVIRILVNLT VPVECLFSVD VMYRTDVGRH TIFELNKLLY
TSKEAFTEAR STKSVVEYMK HILESDPKLS PHKCDQINNC LLLLRNILHI PETHAHCVMP
MMQSMPHGIS MQNTILWNLF IQSIDKLLLY LMTCPQRAFW GVTMVQLIAL IYKDQHVSTL
QKLLSLWFEA SLSESSEDNE SNTSPPKQGS GDSSPMLTSD PTSDSSDNGS NGRGMGGGMR
EGTAATLQEV SRKGQEYQNA MARVPADKPD GSEEASDMTG NDSEQPGSPE QSQPAGESMD
DGDYEDQRHR QLNEHGEEDE DEDEVEEEEY LQLGPASEPL NLTQQPADKV NNTTNPTSSA
PQGCLGNEPF KPPPPLPVRA STSAHAQMQK FNESSYASHV SAVKLGQKSP HAGQLQLTKG
KCCPQKRECP SSQSELSDCG YGTQVENQES ISTSSNDDDG PQGKPQHQKP PCNTKPRNKP
RTIMSPMDKK ELRRKKLVKR SKSSLINMKG LVQHTPTDDD ISNLLKEFTV DFLLKGYSYL
VEELHMQLLS NAKVPIDTSH FFWLVTYFLK FAAQLELDME HIDTILTYDV LSYLTYEGVS
LCEQLELNAR QEGSDLKPYL RRMHLVVTAI REFLQAIDTY NKVTHLNEDD KAHLRQLQLQ
ISEMSDLRCL FVLLLRRFNP SIHSKQYLQD LVVTNHILLL ILDSSAKLGG CQTIRLSEHI
TQFATLEVMH YYGILLEDFN NNGEFVNDCI FTMMHHIGGD LGQIGVLFQP IILKTYSRIW
EADYELCDDW SDLIEYVIHK FMNTPPKSPL TIPTTSLTEM TKEHNQEHTV CSWSQEEMDT
LYWYYVQSKK NNDIVGKIVK LFSNNGNKLK TRISIIQQLL QQDIITLLEY DDLMKFEDAE
YQRTLLTTPT SATTESGIEI KECAYGKPSD DVQILLDLII KENKAQHLLW LQRILIECCF
VKLTLRSGLK VPEGDHIMEP VAYHCICKQK SIPVVQWNNE QSTTMLYQPF VLLLHKLGIQ
LPADAGSIFA RIPDYWTPET MYGLAKKLGP LDKLNLKFDA SELEDATASS PSRYHHTGPR
NSLSSVSSLD VDLGDTEELA LIPEVDAAVE KAHAMASTPS PSEIFAVPKT KHCNSIIRYT
PDPTPPVPNW LQLVMRSKCN HRTGPSGDPS DCIGSSSTTV DDEGFGKSIS AATSQAASTS
MSTVNPTTTL SLNMLNTFMG SHNENSSSSG CGGTVSSLSM VALMSTGAAG GGGNTSGLEM
DVDASMKSSF ERLEVNGSHF SRANNLDQEY SAMVASVYEK EKELNSDNVS LASDLTRMYV
SDEDDRLERT EIRVPHYH
