MILT_DROME
ID MILT_DROME Reviewed; 1122 AA.
AC Q960V3; Q0E8S6; Q8SWX2; Q95NI8;
DT 23-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Trafficking kinesin-binding protein milt {ECO:0000303|PubMed:12495622};
DE AltName: Full=Protein milton {ECO:0000303|PubMed:12495622};
GN Name=milt; ORFNames=CG43227;
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] {ECO:0000305, ECO:0000312|EMBL:AAK74155.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=12495622; DOI=10.1016/s0896-6273(02)01094-2;
RA Stowers R.S., Megeath L.J., Gorska-Andrzejak J., Meinertzhagen I.A.,
RA Schwarz T.L.;
RT "Axonal transport of mitochondria to synapses depends on milton, a novel
RT Drosophila protein.";
RL Neuron 36:1063-1077(2002).
RN [2] {ECO:0000312|EMBL:AAN10622.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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 [3] {ECO:0000305, ECO:0000312|EMBL:AAN10622.1}
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 [4] {ECO:0000305, ECO:0000312|EMBL:AAK93249.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 583-1122.
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK93249.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
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 [5] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16887820; DOI=10.1242/dev.02514;
RA Cox R.T., Spradling A.C.;
RT "Milton controls the early acquisition of mitochondria by Drosophila
RT oocytes.";
RL Development 133:3371-3377(2006).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MIRO, SUBCELLULAR LOCATION, AND ALTERNATIVE
RP SPLICING.
RX PubMed=16717129; DOI=10.1083/jcb.200601067;
RA Glater E.E., Megeath L.J., Stowers R.S., Schwarz T.L.;
RT "Axonal transport of mitochondria requires milton to recruit kinesin heavy
RT chain and is light chain independent.";
RL J. Cell Biol. 173:545-557(2006).
RN [7] {ECO:0000305}
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-831, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=17372656; DOI=10.1039/b617545g;
RA Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA Eng J.K., Aebersold R., Tao W.A.;
RT "An integrated chemical, mass spectrometric and computational strategy for
RT (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT Kc167 cells.";
RL Mol. Biosyst. 3:275-286(2007).
RN [8] {ECO:0000305}
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-918, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo {ECO:0000269|PubMed:18327897};
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [9]
RP INTERACTION WITH OGT.
RX PubMed=24995978; DOI=10.1016/j.cell.2014.06.007;
RA Pekkurnaz G., Trinidad J.C., Wang X., Kong D., Schwarz T.L.;
RT "Glucose regulates mitochondrial motility via Milton modification by O-
RT GlcNAc transferase.";
RL Cell 158:54-68(2014).
CC -!- FUNCTION: Required for kinesin-mediated axonal transport of
CC mitochondria to nerve terminals (PubMed:12495622, PubMed:16887820,
CC PubMed:16717129). The oocyte acquires the majority of its mitochondria
CC by competitive bidirectional transport along microtubules mediated by
CC the Milton adapter. Mitochondria enter the young oocyte en mass from
CC interconnected germ cells to generate the large aggregate known as the
CC Balbiani body (PubMed:16887820). Milt and Miro form an essential
CC protein complex that links Khc to mitochondria for light chain-
CC independent, anterograde transport of mitochondria (PubMed:16717129).
CC {ECO:0000269|PubMed:12495622, ECO:0000269|PubMed:16717129,
CC ECO:0000269|PubMed:16887820}.
CC -!- SUBUNIT: Interacts with Miro (PubMed:16717129). Interacts with OGT
CC (PubMed:24995978). Note=Mitochondrial transport by milt and Khc is
CC independent of Klc. {ECO:0000269|PubMed:16717129}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:12495622,
CC ECO:0000269|PubMed:16717129, ECO:0000269|PubMed:16887820}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=B {ECO:0000269|PubMed:16717129};
CC IsoId=Q960V3-1; Sequence=Displayed;
CC Name=A {ECO:0000269|PubMed:16717129};
CC IsoId=Q960V3-2; Sequence=VSP_052933;
CC Name=C {ECO:0000269|PubMed:16717129};
CC IsoId=Q960V3-3; Sequence=Not described;
CC Name=D {ECO:0000269|PubMed:16717129};
CC IsoId=Q960V3-4; Sequence=VSP_052934;
CC -!- TISSUE SPECIFICITY: Expressed primarily in axons and synapses.
CC {ECO:0000269|PubMed:12495622}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:12495622}.
CC -!- DISRUPTION PHENOTYPE: Flies show aberrant synaptic transmission in
CC photoreceptors despite normal phototransduction. Synaptic terminals and
CC axons lack mitochondria, although mitochondria are numerous in neuronal
CC cell bodies. Synaptic vesicles continue to be transported to and
CC concentrated at synapses. In mutant oocytes mitochondria are
CC transported prematurely and excessively. {ECO:0000269|PubMed:12495622}.
CC -!- MISCELLANEOUS: Was named 'Milton' after the blind British poet.
CC -!- SIMILARITY: Belongs to the milton family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY038000; AAK74155.1; -; mRNA.
DR EMBL; AY038001; AAK74156.1; -; mRNA.
DR EMBL; AE014134; AAN10620.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10622.1; -; Genomic_DNA.
DR EMBL; AY051825; AAK93249.1; -; mRNA.
DR EMBL; AY095025; AAM11353.1; -; mRNA.
DR RefSeq; NP_542943.2; NM_080765.4. [Q960V3-2]
DR RefSeq; NP_723249.1; NM_164736.3. [Q960V3-2]
DR RefSeq; NP_723251.1; NM_164738.3. [Q960V3-1]
DR AlphaFoldDB; Q960V3; -.
DR SMR; Q960V3; -.
DR BioGRID; 69809; 8.
DR IntAct; Q960V3; 8.
DR STRING; 7227.FBpp0297341; -.
DR iPTMnet; Q960V3; -.
DR PaxDb; Q960V3; -.
DR DNASU; 45683; -.
DR EnsemblMetazoa; FBtr0306228; FBpp0297338; FBgn0262872. [Q960V3-2]
DR EnsemblMetazoa; FBtr0306229; FBpp0297339; FBgn0262872. [Q960V3-2]
DR EnsemblMetazoa; FBtr0306230; FBpp0297340; FBgn0262872. [Q960V3-1]
DR EnsemblMetazoa; FBtr0306232; FBpp0297342; FBgn0262872. [Q960V3-4]
DR GeneID; 45683; -.
DR KEGG; dme:Dmel_CG43227; -.
DR UCSC; CG13777-RA; d. melanogaster.
DR UCSC; CG13777-RB; d. melanogaster. [Q960V3-1]
DR UCSC; CG13777-RC; d. melanogaster.
DR CTD; 45683; -.
DR FlyBase; FBgn0262872; milt.
DR VEuPathDB; VectorBase:FBgn0262872; -.
DR eggNOG; KOG4360; Eukaryota.
DR GeneTree; ENSGT00940000174028; -.
DR InParanoid; Q960V3; -.
DR PhylomeDB; Q960V3; -.
DR Reactome; R-DME-9013419; RHOT2 GTPase cycle.
DR Reactome; R-DME-9013425; RHOT1 GTPase cycle.
DR SignaLink; Q960V3; -.
DR BioGRID-ORCS; 45683; 0 hits in 3 CRISPR screens.
DR ChiTaRS; milt; fly.
DR GenomeRNAi; 45683; -.
DR PRO; PR:Q960V3; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0262872; Expressed in egg cell and 65 other tissues.
DR ExpressionAtlas; Q960V3; baseline and differential.
DR Genevisible; Q960V3; DM.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0017022; F:myosin binding; IPI:FlyBase.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IMP:UniProtKB.
DR GO; GO:0019896; P:axonal transport of mitochondrion; IDA:FlyBase.
DR GO; GO:0051654; P:establishment of mitochondrion localization; IMP:UniProtKB.
DR GO; GO:0048311; P:mitochondrion distribution; IMP:FlyBase.
DR GO; GO:0007287; P:Nebenkern assembly; IMP:FlyBase.
DR GO; GO:0007310; P:oocyte dorsal/ventral axis specification; IMP:UniProtKB.
DR GO; GO:0006605; P:protein targeting; IBA:GO_Central.
DR GO; GO:0030382; P:sperm mitochondrion organization; IMP:FlyBase.
DR GO; GO:0047496; P:vesicle transport along microtubule; IBA:GO_Central.
DR InterPro; IPR006933; HAP1_N.
DR InterPro; IPR022154; TRAK1/2_C.
DR Pfam; PF04849; HAP1_N; 1.
DR Pfam; PF12448; Milton; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Mitochondrion; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1122
FT /note="Trafficking kinesin-binding protein milt"
FT /id="PRO_0000351143"
FT DOMAIN 87..382
FT /note="HAP1 N-terminal"
FT /evidence="ECO:0000255"
FT REGION 1..450
FT /note="Sufficient for interaction with Khc"
FT /evidence="ECO:0000269|PubMed:16717129"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 456..756
FT /note="Involved in interaction with OGT"
FT /evidence="ECO:0000269|PubMed:24995978"
FT REGION 536..561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 750..775
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 805..830
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 852..871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 955..1101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 142..209
FT /evidence="ECO:0000255"
FT COILED 235..382
FT /evidence="ECO:0000255"
FT COMPBIAS 1..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 536..550
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 805..826
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 957..989
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1001..1032
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 831
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MOD_RES 918
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 1..143
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:16717129"
FT /id="VSP_052934"
FT VAR_SEQ 1..135
FT /note="MTHVNNGEVMEKEMEPTGERERDRETAAGSGVHHRFLASASERDANSGNALE
FT AAATKTKTGTTITNLEDLAFEACQNWSDLHQDFFITDDELEYEDELSLGSSIGGNIATT
FT TTADAAVEGLITGEHQNEQLLMEV -> MLSATLGANGGSQPLSPSAQATLSKHLPRLQ
FT SKRLLQQTQLQSPAAARPQTCDASCLTELCSSENLPEVEIFSLLEEQIPKYKVRNDFLT
FT NFSGYANEDWFVPAPALPIPPEGLGLTKEQTRECLNYFL (in isoform A)"
FT /evidence="ECO:0000303|PubMed:12495622,
FT ECO:0000303|PubMed:16717129"
FT /id="VSP_052933"
FT CONFLICT 1098
FT /note="T -> P (in Ref. 1; AAK74155/AAK74156)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1122 AA; 120649 MW; 7BBE5E474C8112BC CRC64;
MTHVNNGEVM EKEMEPTGER ERDRETAAGS GVHHRFLASA SERDANSGNA LEAAATKTKT
GTTITNLEDL AFEACQNWSD LHQDFFITDD ELEYEDELSL GSSIGGNIAT TTTADAAVEG
LITGEHQNEQ LLMEVLCGNR VSQMTRAYDD IEAVTRLLEE KEKDLELTVQ IGKELLTQNN
ALEARVADLE TDLKASNDDR AQLVHELHKK NELISVLTND ADDGTDTDTP TMSKSITLDL
LQRKVNSLLD ENKSLKCEAT QLAHQTDEVE EHERQLMADI SAQLNDANSQ YDNLSLELER
QREENRLQHE QIVNLTARLA EAEMRLHQLT QDNDEHLSLL HVTKENQNAL ALELVEFKQR
YEEVLALLHS AQDQLKQQRK RSQPQARSSF LGGLGTSGAG MGGSLFPPDS LHCELMESSL
YSENSLDSGI SGDSQRSADR ISRMMMHMPS GGMSSSTMGG SVYAGAGNVP PYKRVFDTVR
CAGKSGNYMD SGNVSMTQLG AMSMSSSSGP RMASMAYPAG SYYRGGSNQS LGVKTLSSES
LNSQSDDGYP AQPSGVPGAP GAKELEAALK RLTPAEVLAR RAMLSYAPAG TYNYDEPMGH
GTGNVRNSDL PLGVRTPDSI MSTGSSGMSG STNHMSASMT HQWRLPEKLQ IIKPMEGSQT
LHHWSRLATP TLSGLLDERP GVTIRGGRGL DDLGMQIYTL SDVEEDVSDD LPGKQFEAPG
CTFTYTNSMV MHPDDGFVND LSFLSQSQMS SRMASTSTSR QPSCPATPRA GLSRKNSCST
FSVNLGLAGM LNERGIKAVT PSALNTPAGP NFSPTVTPCN SPEGSPPRAQ SPEPLFGLLS
CGADLIRRKI VGDQHQQQQQ KQRSSLSKQQ QQKIMLSHLE RRALRSLNLI EKVESIGLEN
IISAQRGLGS GIANRSSSPL SSGSLQSLHT SSNSIVDDIH FDRAQIKGVL HRGLKSPTPA
TASTSAAAAA SGPGISTSSS TSAYNSDDSD DQGLVMKIKP SKSATPTTTG AAQSQPSSAT
TSNGTASETR LKQMQRQKSR RQLKNGMANQ RPDLGTISGA GGGGRVRPDL GKVADSGSSS
KLSTKRSEAK PAEEEEATPQ TITQAFVGSV SSLLFGRKGG WL
