TRAK1_MOUSE
ID TRAK1_MOUSE Reviewed; 939 AA.
AC Q6PD31; Q8BYA3;
DT 15-JUN-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Trafficking kinesin-binding protein 1;
DE AltName: Full=Protein Milton {ECO:0000303|PubMed:24995978};
GN Name=Trak1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; 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 [4]
RP INTERACTION WITH GABRA1, TISSUE SPECIFICITY, AND DISEASE.
RX PubMed=16380713; DOI=10.1038/ng1715;
RA Gilbert S.L., Zhang L., Forster M.L., Anderson J.R., Iwase T., Soliven B.,
RA Donahue L.R., Sweet H.O., Bronson R.T., Davisson M.T., Wollmann R.L.,
RA Lahn B.T.;
RT "Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice.";
RL Nat. Genet. 38:245-250(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-534; SER-716 AND SER-905, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, and Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
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: Involved in the regulation of endosome-to-lysosome
CC trafficking, including endocytic trafficking of EGF-EGFR complexes and
CC GABA-A receptors (By similarity). Involved in mitochondrial motility
CC (PubMed:24995978). When O-glycosylated, abolishes mitochondrial
CC motility. Crucial for recruiting OGT to the mitochondrial surface of
CC neuronal processes (By similarity). TRAK1 and RHOT form an essential
CC protein complex that links KIF5 to mitochondria for light chain-
CC independent, anterograde transport of mitochondria (By similarity).
CC {ECO:0000250|UniProtKB:Q960V3, ECO:0000250|UniProtKB:Q9UPV9,
CC ECO:0000269|PubMed:24995978}.
CC -!- SUBUNIT: Interacts with RHOT1 and RHOT2. Found in a complex with KIF5B,
CC OGT, RHOT1 and RHOT2. Interacts with HGS (By similarity). Interacts
CC with GABRA1 (PubMed:16380713). Interacts with KIF5C. Interacts with
CC OGT; stable interaction is not required for glycosylation of this
CC protein by OGT. Isoform 1 interacts with OGT (By similarity).
CC {ECO:0000250|UniProtKB:Q9UPV9, ECO:0000269|PubMed:16380713}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24995978}. Nucleus
CC {ECO:0000250|UniProtKB:Q9UPV9}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9UPV9}. Early endosome
CC {ECO:0000250|UniProtKB:Q9UPV9}. Endosome
CC {ECO:0000250|UniProtKB:Q9UPV9}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:Q9UPV9}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:24995978}. Note=Predominantly associated with early
CC endosome. The localization to early endosomes depends on its
CC interaction with HGS/HRS. Colocalizes with MGARP at the mitochondria.
CC {ECO:0000250|UniProtKB:Q9UPV9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6PD31-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6PD31-2; Sequence=VSP_039277, VSP_039278, VSP_039279;
CC -!- TISSUE SPECIFICITY: Widely expressed with the greatest expression in
CC brain, liver and kidney. Detected throughout the CNS, including the
CC cortex, hippocamps, thalamus and various subcortical nuclei of the
CC forebrain and midbrain, the granule of Purkinje layers of the
CC cerebellum and the gray matter of the spinal cord. High level detected
CC in lower moter neurons (at protein level).
CC {ECO:0000269|PubMed:16380713}.
CC -!- PTM: O-glycosylated (PubMed:24995978). Glycosylated by OGT;
CC glycosylation in response to increased extracellular glucose levels is
CC required for and leads to regulation of mitochondrial motility by OGT
CC (By similarity). {ECO:0000250|UniProtKB:Q9UPV9,
CC ECO:0000269|PubMed:24995978}.
CC -!- DISEASE: Note=A spontaneous mutation (hyrt mice) causes a recessively
CC transmitted form of hypertonia neurological dysfunction characterized
CC by postural abnormalities, jerky movements and tremormutant. Hyrt mice
CC have much lower levels of GABA(A) receptors in the CNS, particularly
CC the lower motor neurons, than do wild-type mice, indicating that the
CC hypertonicity of the mutants is likely to be caused by deficits in
CC GABA-mediated motor neuron inhibition. {ECO:0000269|PubMed:16380713}.
CC -!- SIMILARITY: Belongs to the milton family. {ECO:0000305}.
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DR EMBL; AK041436; BAC30946.1; -; mRNA.
DR EMBL; BC058971; AAH58971.1; -; mRNA.
DR EMBL; CH466587; EDL09157.1; -; Genomic_DNA.
DR CCDS; CCDS40810.1; -. [Q6PD31-1]
DR RefSeq; NP_780323.2; NM_175114.3. [Q6PD31-1]
DR AlphaFoldDB; Q6PD31; -.
DR SMR; Q6PD31; -.
DR STRING; 10090.ENSMUSP00000044482; -.
DR GlyGen; Q6PD31; 3 sites.
DR iPTMnet; Q6PD31; -.
DR PhosphoSitePlus; Q6PD31; -.
DR jPOST; Q6PD31; -.
DR MaxQB; Q6PD31; -.
DR PaxDb; Q6PD31; -.
DR PRIDE; Q6PD31; -.
DR ProteomicsDB; 298285; -. [Q6PD31-1]
DR ProteomicsDB; 298286; -. [Q6PD31-2]
DR Antibodypedia; 1603; 203 antibodies from 34 providers.
DR DNASU; 67095; -.
DR Ensembl; ENSMUST00000045903; ENSMUSP00000044482; ENSMUSG00000032536. [Q6PD31-1]
DR GeneID; 67095; -.
DR KEGG; mmu:67095; -.
DR UCSC; uc009sdd.1; mouse. [Q6PD31-1]
DR CTD; 22906; -.
DR MGI; MGI:1914345; Trak1.
DR VEuPathDB; HostDB:ENSMUSG00000032536; -.
DR eggNOG; KOG4360; Eukaryota.
DR GeneTree; ENSGT00940000155697; -.
DR HOGENOM; CLU_013450_0_0_1; -.
DR InParanoid; Q6PD31; -.
DR OMA; RRTFSYE; -.
DR OrthoDB; 1003820at2759; -.
DR PhylomeDB; Q6PD31; -.
DR TreeFam; TF323495; -.
DR Reactome; R-MMU-9013419; RHOT2 GTPase cycle.
DR Reactome; R-MMU-9013425; RHOT1 GTPase cycle.
DR BioGRID-ORCS; 67095; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Trak1; mouse.
DR PRO; PR:Q6PD31; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q6PD31; protein.
DR Bgee; ENSMUSG00000032536; Expressed in aortic valve and 266 other tissues.
DR ExpressionAtlas; Q6PD31; baseline and differential.
DR Genevisible; Q6PD31; MM.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0044295; C:axonal growth cone; ISO:MGI.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0050811; F:GABA receptor binding; IDA:MGI.
DR GO; GO:0017022; F:myosin binding; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030911; F:TPR domain binding; ISO:MGI.
DR GO; GO:0098957; P:anterograde axonal transport of mitochondrion; IMP:SynGO.
DR GO; GO:0019896; P:axonal transport of mitochondrion; ISO:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; ISO:MGI.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0048311; P:mitochondrion distribution; IBA:GO_Central.
DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central.
DR GO; GO:0050772; P:positive regulation of axonogenesis; ISO:MGI.
DR GO; GO:0006605; P:protein targeting; IBA:GO_Central.
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; Cytoplasm; Endosome; Glycoprotein;
KW Membrane; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..939
FT /note="Trafficking kinesin-binding protein 1"
FT /id="PRO_0000394506"
FT DOMAIN 46..353
FT /note="HAP1 N-terminal"
FT REGION 359..509
FT /note="Interaction with HGS"
FT /evidence="ECO:0000250"
FT REGION 472..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 655..669
FT /note="Interaction with OGT"
FT /evidence="ECO:0000250|UniProtKB:Q9UPV9"
FT COILED 106..354
FT /evidence="ECO:0000255"
FT COILED 490..524
FT /evidence="ECO:0000255"
FT MOD_RES 534
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 716
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 905
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 444
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPV9"
FT CARBOHYD 677
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPV9"
FT CARBOHYD 716
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPV9"
FT VAR_SEQ 1..35
FT /note="MALAIQLRQPSRAQPLPGLSHTLAGTDSCDVCNST -> MLPATESTGMPAP
FT SPTCATAP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_039277"
FT VAR_SEQ 580..627
FT /note="SATLHHWQQLAQPHLGGILDPRPGVVTKGFRTLDVDLDEVYCLNDFEE ->
FT DHQGLSVLLCDSLWALIHHRKASHQCHTYSFFFRDSHPRCWFEFL (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_039278"
FT VAR_SEQ 628..939
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_039279"
SQ SEQUENCE 939 AA; 104467 MW; 64B1D5D34DF36FCB CRC64;
MALAIQLRQP SRAQPLPGLS HTLAGTDSCD VCNSTNLPEV EIISLLEEQL PHYKLRADTI
YGYDHDDWLH TPLISPDANI DLTTEQIEET LKYFLLCAER VGQMTKTYND IDAVTRLLEE
KERDLELAAR IGQSLLKKNK TLTERNELLE EQVEHIREEV SQLRHELSMK DELLQFYTSA
AEESEPESVC STPLKRNESS SSVQNYFHLD SLQKKLKDLE EENVVLRSEA CQLKTETITY
EEKEQQLVND CVKELRDANV QIASISEELA KKTEDAARQQ EEITHLLSQI VDLQKKAKSC
AVENEELVQH LGAAKDAQRQ LTAELRELED KYAECMEMLH EAQEELKNLR NKTMPTSRRY
HSLGLFPMDS LAAEIEGTMR KELQLEELES PDITHQKRVF ETVRNVNQVV KQRSLTPSPM
NIPGSNQSSA MNSLLSSCVS TPRSSFYGSD VSNVVLDNKT NSILLETEAA DLGNEDHNKK
PGTPGTPGSH DLETALRRLS LRRENYLSER RFFEEEQERK LRELAEKGEL HSGSLTPTES
IMSLGTHSRF SEFTGFSGMS FSSRSYLPEK LQIVKPLEGS ATLHHWQQLA QPHLGGILDP
RPGVVTKGFR TLDVDLDEVY CLNDFEEDDT GDHISLAGLA TSTPIQHPET SAHHPGKCMS
QTNSTFTFTT CRILHPSDEL TRVTPSLNSA PAPACSSTSH LKSTPVATPC TPRRLSLAES
FTNVRESTTT MSTSLGLVWL LKERGISAAV YDPQSWDRAG RGSLLHSYTP RMAVIPSTPP
NSPMQTPSAS PPSFEFKCTS PPYNNFLASK PASSILREVR EKRPVRSSES QTDVSVSNLN
LVDKVRRFGV ARVVNSGRAR IPTLTEEQGP LLCGPTGPAQ ALVPGGLVPE GLPLGCPSGI
RRNRSFPTMV GSSVQMRAPV ILTSGILMGA KLPKQTSLR
