ID TRAK1_HUMAN Reviewed; 953 AA. AC Q9UPV9; E9PDS2; J3KNT7; Q63HR0; Q659B5; Q96B69; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 24-JAN-2024, entry version 178. DE RecName: Full=Trafficking kinesin-binding protein 1; DE AltName: Full=106 kDa O-GlcNAc transferase-interacting protein; DE AltName: Full=Protein Milton {ECO:0000303|PubMed:24995978}; GN Name=TRAK1; Synonyms=KIAA1042, OIP106; 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 [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10470851; DOI=10.1093/dnares/6.3.197; RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIV. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:197-205(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1-508 (ISOFORM 3). RC TISSUE=Kidney, and Salivary gland; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Kidney; 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 [5] RP PROTEIN SEQUENCE OF 448-462; 535-552; 642-660; 676-685; 686-705; 717-728; RP 829-846 AND 932-945, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, RP INTERACTION WITH KIF5B; OGT; RHOT1 AND RHOT2, SUBCELLULAR LOCATION, RP GLYCOSYLATION AT SER-447; SER-680; SER-719 AND THR-935, AND MUTAGENESIS OF RP SER-447; 658-PRO--THR-672; SER-829; SER-830 AND SER-938. 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). RN [6] RP SUBCELLULAR LOCATION, INTERACTION WITH OGT, AND GLYCOSYLATION. RX PubMed=12435728; DOI=10.1074/jbc.m209384200; RA Iyer S.P.N., Akimoto Y., Hart G.W.; RT "Identification and cloning of a novel family of coiled-coil domain RT proteins that interact with O-GlcNAc transferase."; RL J. Biol. Chem. 278:5399-5409(2003). RN [7] RP INTERACTION WITH KIF5C, AND SUBCELLULAR LOCATION. RX PubMed=15644324; DOI=10.1074/jbc.m409095200; RA Brickley K., Smith M.J., Beck M., Stephenson F.A.; RT "GRIF-1 and OIP106, members of a novel gene family of coiled-coil domain RT proteins: association in vivo and in vitro with kinesin."; RL J. Biol. Chem. 280:14723-14732(2005). RN [8] RP SUBCELLULAR LOCATION, AND INTERACTION WITH RHOT1 AND RHOT2. RX PubMed=16630562; DOI=10.1016/j.bbrc.2006.03.163; RA Fransson S., Ruusala A., Aspenstroem P.; RT "The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in RT mitochondrial trafficking."; RL Biochem. Biophys. Res. Commun. 344:500-510(2006). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HGS. RX PubMed=18675823; DOI=10.1016/j.jmb.2008.07.045; RA Webber E., Li L., Chin L.S.; RT "Hypertonia-associated protein Trak1 is a novel regulator of endosome-to- RT lysosome trafficking."; RL J. Mol. Biol. 382:638-651(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND MARKER FOR GASTRIC CANCER. RX PubMed=18986759; DOI=10.1016/j.canlet.2008.09.031; RA Zhang F., Ren G., Lu Y., Jin B., Wang J., Chen X., Liu Z., Li K., Nie Y., RA Wang X., Fan D.; RT "Identification of TRAK1 (Trafficking protein, kinesin-binding 1) as MGb2- RT Ag: a novel cancer biomarker."; RL Cancer Lett. 274:250-258(2009). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=19528298; DOI=10.1083/jcb.200811033; RA Li Y., Lim S., Hoffman D., Aspenstrom P., Federoff H.J., Rempe D.A.; RT "HUMMR, a hypoxia- and HIF-1alpha-inducible protein, alters mitochondrial RT distribution and transport."; RL J. Cell Biol. 185:1065-1081(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-919, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP INVOLVEMENT IN DEE68. RX PubMed=28364549; DOI=10.1093/brain/awx002; RA Barel O., Malicdan M.C.V., Ben-Zeev B., Kandel J., Pri-Chen H., Stephen J., RA Castro I.G., Metz J., Atawa O., Moshkovitz S., Ganelin E., Barshack I., RA Polak-Charcon S., Nass D., Marek-Yagel D., Amariglio N., Shalva N., RA Vilboux T., Ferreira C., Pode-Shakked B., Heimer G., Hoffmann C., RA Yardeni T., Nissenkorn A., Avivi C., Eyal E., Kol N., Glick Saar E., RA Wallace D.C., Gahl W.A., Rechavi G., Schrader M., Eckmann D.M., RA Anikster Y.; RT "Deleterious variants in TRAK1 disrupt mitochondrial movement and cause RT fatal encephalopathy."; RL Brain 140:568-581(2017). RN [15] RP INVOLVEMENT IN DEE68. RX PubMed=28940097; DOI=10.1007/s00439-017-1843-2; RA Anazi S., Maddirevula S., Salpietro V., Asi Y.T., Alsahli S., Alhashem A., RA Shamseldin H.E., AlZahrani F., Patel N., Ibrahim N., Abdulwahab F.M., RA Hashem M., Alhashmi N., Al Murshedi F., Al Kindy A., Alshaer A., RA Rumayyan A., Al Tala S., Kurdi W., Alsaman A., Alasmari A., Banu S., RA Sultan T., Saleh M.M., Alkuraya H., Salih M.A., Aldhalaan H., Ben-Omran T., RA Al Musafri F., Ali R., Suleiman J., Tabarki B., El-Hattab A.W., Bupp C., RA Alfadhel M., Al Tassan N., Monies D., Arold S.T., Abouelhoda M., RA Lashley T., Houlden H., Faqeih E., Alkuraya F.S.; RT "Expanding the genetic heterogeneity of intellectual disability."; RL Hum. Genet. 136:1419-1429(2017). RN [16] RP ERRATUM OF PUBMED:28940097. RX PubMed=29288388; DOI=10.1007/s00439-017-1859-7; RA Anazi S., Maddirevula S., Salpietro V., Asi Y.T., Alsahli S., Alhashem A., RA Shamseldin H.E., AlZahrani F., Patel N., Ibrahim N., Abdulwahab F.M., RA Hashem M., Alhashmi N., Al Murshedi F., Al Kindy A., Alshaer A., RA Rumayyan A., Al Tala S., Kurdi W., Alsaman A., Alasmari A., Banu S., RA Sultan T., Saleh M.M., Alkuraya H., Salih M.A., Aldhalaan H., Ben-Omran T., RA Al Musafri F., Ali R., Suleiman J., Tabarki B., El-Hattab A.W., Bupp C., RA Alfadhel M., Al Tassan N., Monies D., Arold S.T., Abouelhoda M., RA Lashley T., Houlden H., Faqeih E., Alkuraya F.S.; RT "Correction to: Expanding the genetic heterogeneity of intellectual RT disability."; RL Hum. Genet. 137:105-109(2018). RN [17] RP INVOLVEMENT IN DEE68, AND VARIANT DEE68 PRO-329. RX PubMed=29846532; DOI=10.1093/brain/awy129; RA Sagie S., Lerman-Sagie T., Maljevic S., Yosovich K., Detert K., Chung S.K., RA Rees M.I., Lerche H., Lev D.; RT "Expanding the phenotype of TRAK1 mutations: hyperekplexia and refractory RT status epilepticus."; RL Brain 141:E55-E55(2018). CC -!- FUNCTION: Involved in the regulation of endosome-to-lysosome CC trafficking, including endocytic trafficking of EGF-EGFR complexes and CC GABA-A receptors (PubMed:18675823). Involved in mitochondrial motility. CC When O-glycosylated, abolishes mitochondrial motility. Crucial for CC recruiting OGT to the mitochondrial surface of neuronal processes CC (PubMed:24995978). TRAK1 and RHOT form an essential protein complex CC that links KIF5 to mitochondria for light chain-independent, CC anterograde transport of mitochondria (By similarity). CC {ECO:0000250|UniProtKB:Q960V3, ECO:0000269|PubMed:18675823, CC ECO:0000269|PubMed:24995978}. CC -!- SUBUNIT: Interacts with RHOT1 and RHOT2 (PubMed:16630562). Found in a CC complex with KIF5B, OGT, RHOT1 and RHOT2 (PubMed:24995978). Interacts CC with HGS (PubMed:18675823). Interacts with GABRA1 (By similarity). CC Interacts with KIF5C (PubMed:15644324). Interacts with OGT; stable CC interaction is not required for glycosylation of this protein by OGT. CC Isoform 1 interacts with OGT (PubMed:24995978, PubMed:12435728). CC {ECO:0000250|UniProtKB:Q6PD31, ECO:0000269|PubMed:12435728, CC ECO:0000269|PubMed:15644324, ECO:0000269|PubMed:16630562, CC ECO:0000269|PubMed:18675823, ECO:0000269|PubMed:24995978}. CC -!- INTERACTION: CC Q9UPV9; O15294: OGT; NbExp=3; IntAct=EBI-1105048, EBI-539828; CC Q9UPV9; Q8IXI2: RHOT1; NbExp=5; IntAct=EBI-1105048, EBI-1396430; CC Q9UPV9; Q8IXI1: RHOT2; NbExp=3; IntAct=EBI-1105048, EBI-1396563; CC Q9UPV9; Q2PQA9: Kif5b; Xeno; NbExp=3; IntAct=EBI-1105048, EBI-920191; CC Q9UPV9; P56558: Ogt; Xeno; NbExp=6; IntAct=EBI-1105048, EBI-7614183; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18986759}. Nucleus CC {ECO:0000269|PubMed:12435728}. Mitochondrion CC {ECO:0000269|PubMed:15644324, ECO:0000269|PubMed:16630562, CC ECO:0000269|PubMed:18675823, ECO:0000269|PubMed:19528298}. Early CC endosome {ECO:0000269|PubMed:18675823}. Endosome CC {ECO:0000269|PubMed:18675823}. Mitochondrion membrane CC {ECO:0000269|PubMed:24995978}. Cytoplasm, cell cortex CC {ECO:0000250|UniProtKB:Q6PD31}. Note=Predominantly associated with CC early endosome. The localization to early endosomes depends on its CC interaction with HGS/HRS (PubMed:18675823). Colocalizes with MGARP at CC the mitochondria (PubMed:19528298). {ECO:0000269|PubMed:18675823, CC ECO:0000269|PubMed:19528298}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Milton1 {ECO:0000303|PubMed:24995978}; CC IsoId=Q9UPV9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UPV9-2; Sequence=VSP_010839, VSP_010840, VSP_010841; CC Name=3; CC IsoId=Q9UPV9-3; Sequence=VSP_045558, VSP_045559, VSP_045560; CC -!- TISSUE SPECIFICITY: High expression in spinal cord and moderate CC expression in all other tissues and specific brain regions examined. CC Expressed in all cell lines examined. {ECO:0000269|PubMed:18986759}. CC -!- DOMAIN: The C-terminal region is required for the early endosomal and CC mitochondrial localization. CC -!- PTM: O-glycosylated (PubMed:24995978, PubMed:12435728). Glycosylated by CC OGT; glycosylation in response to increased extracellular glucose CC levels is required for and leads to regulation of mitochondrial CC motility by OGT (PubMed:24995978). {ECO:0000269|PubMed:12435728, CC ECO:0000269|PubMed:24995978}. CC -!- DISEASE: Developmental and epileptic encephalopathy 68 (DEE68) CC [MIM:618201]: A form of epileptic encephalopathy, a heterogeneous group CC of severe early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE68 is an autosomal recessive form characterized by CC onset of twitching and/or myoclonic jerks in infancy. The disorder CC progresses to refractory generalized tonic-clonic seizures, often CC resulting in status epilepticus, loss of developmental milestones, and CC early death. Other features include delayed development, axial CC hypotonia, spasticity of the limbs, and clonus. CC {ECO:0000269|PubMed:28364549, ECO:0000269|PubMed:28940097, CC ECO:0000269|PubMed:29846532}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Over-expressed in all investigated carcinomas, CC especially in gastric adenocarcinoma and signet-ring carcinoma and may CC serve as a marker of gastric cancer. CC -!- SIMILARITY: Belongs to the milton family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA82994.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AB028965; BAA82994.2; ALT_INIT; mRNA. DR EMBL; BX647199; CAH56169.1; -; mRNA. DR EMBL; AL713787; CAH56394.1; -; mRNA. DR EMBL; AC018358; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC093414; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC137935; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015922; AAH15922.1; -; mRNA. DR CCDS; CCDS2695.1; -. [Q9UPV9-2] DR CCDS; CCDS43072.1; -. [Q9UPV9-1] DR CCDS; CCDS58826.1; -. [Q9UPV9-3] DR RefSeq; NP_001036111.1; NM_001042646.2. [Q9UPV9-1] DR RefSeq; NP_001252537.1; NM_001265608.1. DR RefSeq; NP_001252539.1; NM_001265610.1. [Q9UPV9-3] DR RefSeq; NP_055780.2; NM_014965.4. [Q9UPV9-2] DR AlphaFoldDB; Q9UPV9; -. DR SMR; Q9UPV9; -. DR BioGRID; 116570; 72. DR CORUM; Q9UPV9; -. DR IntAct; Q9UPV9; 27. DR MINT; Q9UPV9; -. DR STRING; 9606.ENSP00000328998; -. DR GlyCosmos; Q9UPV9; 8 sites, 1 glycan. DR GlyGen; Q9UPV9; 8 sites, 1 O-linked glycan (8 sites). DR iPTMnet; Q9UPV9; -. DR PhosphoSitePlus; Q9UPV9; -. DR BioMuta; TRAK1; -. DR DMDM; 13124654; -. DR EPD; Q9UPV9; -. DR jPOST; Q9UPV9; -. DR MassIVE; Q9UPV9; -. DR MaxQB; Q9UPV9; -. DR PaxDb; 9606-ENSP00000328998; -. DR PeptideAtlas; Q9UPV9; -. DR ProteomicsDB; 19736; -. DR ProteomicsDB; 85456; -. [Q9UPV9-1] DR ProteomicsDB; 85457; -. [Q9UPV9-2] DR ABCD; Q9UPV9; 1 sequenced antibody. DR Antibodypedia; 1603; 226 antibodies from 34 providers. DR DNASU; 22906; -. DR Ensembl; ENST00000327628.10; ENSP00000328998.5; ENSG00000182606.17. [Q9UPV9-1] DR Ensembl; ENST00000341421.7; ENSP00000340702.3; ENSG00000182606.17. [Q9UPV9-2] DR Ensembl; ENST00000449246.5; ENSP00000410717.1; ENSG00000182606.17. [Q9UPV9-3] DR GeneID; 22906; -. DR KEGG; hsa:22906; -. DR MANE-Select; ENST00000327628.10; ENSP00000328998.5; NM_001042646.3; NP_001036111.1. DR UCSC; uc003cky.5; human. [Q9UPV9-1] DR AGR; HGNC:29947; -. DR CTD; 22906; -. DR DisGeNET; 22906; -. DR GeneCards; TRAK1; -. DR HGNC; HGNC:29947; TRAK1. DR HPA; ENSG00000182606; Tissue enhanced (heart muscle, skeletal muscle, tongue). DR MalaCards; TRAK1; -. DR MIM; 608112; gene. DR MIM; 618201; phenotype. DR neXtProt; NX_Q9UPV9; -. DR OpenTargets; ENSG00000182606; -. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR PharmGKB; PA128394593; -. DR VEuPathDB; HostDB:ENSG00000182606; -. DR eggNOG; KOG4360; Eukaryota. DR GeneTree; ENSGT00940000155697; -. DR HOGENOM; CLU_013450_0_0_1; -. DR InParanoid; Q9UPV9; -. DR OMA; RRTFSYE; -. DR OrthoDB; 2909788at2759; -. DR PhylomeDB; Q9UPV9; -. DR TreeFam; TF323495; -. DR PathwayCommons; Q9UPV9; -. DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions. DR Reactome; R-HSA-9013419; RHOT2 GTPase cycle. DR Reactome; R-HSA-9013425; RHOT1 GTPase cycle. DR SignaLink; Q9UPV9; -. DR BioGRID-ORCS; 22906; 14 hits in 1160 CRISPR screens. DR ChiTaRS; TRAK1; human. DR GeneWiki; TRAK1; -. DR GenomeRNAi; 22906; -. DR Pharos; Q9UPV9; Tbio. DR PRO; PR:Q9UPV9; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9UPV9; Protein. DR Bgee; ENSG00000182606; Expressed in secondary oocyte and 212 other cell types or tissues. DR ExpressionAtlas; Q9UPV9; baseline and differential. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0044295; C:axonal growth cone; IEA:Ensembl. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0050811; F:GABA receptor binding; IBA:GO_Central. DR GO; GO:0017022; F:myosin binding; IBA:GO_Central. DR GO; GO:0030911; F:TPR domain binding; IEA:Ensembl. DR GO; GO:0098957; P:anterograde axonal transport of mitochondrion; IBA:GO_Central. DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0008333; P:endosome to lysosome transport; IDA:UniProtKB. 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; IEA:Ensembl. DR GO; GO:0006493; P:protein O-linked glycosylation; ISS:UniProtKB. DR GO; GO:0006605; P:protein targeting; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0047496; P:vesicle transport along microtubule; IBA:GO_Central. DR InterPro; IPR006933; HAP1_N. DR InterPro; IPR022154; TRAK1/2_C. DR PANTHER; PTHR15751; TRAFFICKING KINESIN-BINDING PROTEIN; 1. DR PANTHER; PTHR15751:SF11; TRAFFICKING KINESIN-BINDING PROTEIN 1; 1. DR Pfam; PF04849; HAP1_N; 1. DR Pfam; PF12448; Milton; 1. DR SMART; SM01424; HAP1_N; 1. DR SMART; SM01423; Milton; 1. DR Genevisible; Q9UPV9; HS. PE 1: Evidence at protein level; KW Alternative splicing; Coiled coil; Cytoplasm; Direct protein sequencing; KW Disease variant; Endosome; Epilepsy; Glycoprotein; Membrane; Mitochondrion; KW Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..953 FT /note="Trafficking kinesin-binding protein 1" FT /id="PRO_0000058037" FT DOMAIN 47..354 FT /note="HAP1 N-terminal" FT REGION 359..509 FT /note="Interaction with HGS" FT /evidence="ECO:0000269|PubMed:18675823" FT REGION 472..495 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 658..672 FT /note="Interaction with OGT" FT /evidence="ECO:0000269|PubMed:24995978" FT REGION 777..796 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 104..356 FT /evidence="ECO:0000255" FT COILED 492..532 FT /evidence="ECO:0000255" FT MOD_RES 537 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PD31" FT MOD_RES 719 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PD31" FT MOD_RES 919 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 447 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000269|PubMed:24995978" FT CARBOHYD 680 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000269|PubMed:24995978" FT CARBOHYD 719 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000269|PubMed:24995978" FT CARBOHYD 935 FT /note="O-linked (GlcNAc) threonine" FT /evidence="ECO:0000269|PubMed:24995978" FT VAR_SEQ 1..97 FT /note="MALVFQFGQPVRAQPLPGLCHGKLIRTNACDVCNSTDLPEVEIISLLEEQLP FT HYKLRADTIYGYDHDDWLHTPLISPDANIDLTTEQIEETLKYFLL -> MQKFIEADYY FT ELDWYYEECSDVL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_045558" FT VAR_SEQ 1..96 FT /note="MALVFQFGQPVRAQPLPGLCHGKLIRTNACDVCNSTDLPEVEIISLLEEQLP FT HYKLRADTIYGYDHDDWLHTPLISPDANIDLTTEQIEETLKYFL -> MSLRDKGGEEE FT CFEYDCQDEERKPTHRQHDTQDLLEEV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_010839" FT VAR_SEQ 583..630 FT /note="SATLHHWQQLAQPHLGGILDPRPGVVTKGFRTLDVDLDEVYCLNDFEE -> FT DHAGPRPLSVLLGDSLWSLIHLRKAGHLCHAYSFFFRDSHPRCWFEFL (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_045559" FT VAR_SEQ 631..953 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_045560" FT VAR_SEQ 655..744 FT /note="AHHPGKCMSQTNSTFTFTTCRILHPSDELTRVTPSLNSAPTPACGSTSHLKS FT TPVATPCTPRRLSLAESFTNTRESTTTMSTSLGLVWLL -> GERSQARVTVSGSRSYP FT SRPQASPEEMQEPPAATEEEEEEEEEEGSGEGTTISPVNLAPFPEAEFWAILTSVPGTI FT RSGSLSVASARLCG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_010840" FT VAR_SEQ 745..953 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_010841" FT VARIANT 329 FT /note="L -> P (in DEE68; uncertain significance; FT dbSNP:rs770281448)" FT /evidence="ECO:0000269|PubMed:29846532" FT /id="VAR_081639" FT MUTAGEN 447 FT /note="S->A: Reduced O-glycosylation of this protein." FT /evidence="ECO:0000269|PubMed:24995978" FT MUTAGEN 658..672 FT /note="Missing: Loss of interaction with OGT, but interacts FT with KIF5B and RHOT1/2 and is able to localize to FT mitochondria. Increased O-glycosylation of this protein by FT OGT." FT /evidence="ECO:0000269|PubMed:24995978" FT MUTAGEN 829 FT /note="S->A: Reduced O-glycosylation of this protein; when FT associated with A-830." FT /evidence="ECO:0000269|PubMed:24995978" FT MUTAGEN 830 FT /note="S->A: Reduced O-glycosylation of this protein; when FT associated with A-829." FT /evidence="ECO:0000269|PubMed:24995978" FT MUTAGEN 938 FT /note="S->A: Reduced O-glycosylation of this protein." FT /evidence="ECO:0000269|PubMed:24995978" FT CONFLICT 503 FT /note="S -> P (in Ref. 2; CAH56169)" FT /evidence="ECO:0000305" FT CONFLICT 638 FT /note="S -> F (in Ref. 2; CAH56169)" FT /evidence="ECO:0000305" FT CONFLICT Q9UPV9-2:631 FT /note="E -> EE (in Ref. 2; CAH56169)" FT /evidence="ECO:0000305" FT CONFLICT Q9UPV9-2:631 FT /note="E -> EEE (in Ref. 4; AAH15922)" FT /evidence="ECO:0000305" SQ SEQUENCE 953 AA; 106040 MW; E834BE07CF41D9A4 CRC64; MALVFQFGQP VRAQPLPGLC HGKLIRTNAC DVCNSTDLPE VEIISLLEEQ LPHYKLRADT IYGYDHDDWL HTPLISPDAN IDLTTEQIEE TLKYFLLCAE RVGQMTKTYN DIDAVTRLLE EKERDLELAA RIGQSLLKKN KTLTERNELL EEQVEHIREE VSQLRHELSM KDELLQFYTS AAEESEPESV CSTPLKRNES SSSVQNYFHL DSLQKKLKDL EEENVVLRSE ASQLKTETIT YEEKEQQLVN DCVKELRDAN VQIASISEEL AKKTEDAARQ QEEITHLLSQ IVDLQKKAKA CAVENEELVQ HLGAAKDAQR QLTAELRELE DKYAECMEML HEAQEELKNL RNKTMPNTTS RRYHSLGLFP MDSLAAEIEG TMRKELQLEE AESPDITHQK RVFETVRNIN QVVKQRSLTP SPMNIPGSNQ SSAMNSLLSS CVSTPRSSFY GSDIGNVVLD NKTNSIILET EAADLGNDER SKKPGTPGTP GSHDLETALR RLSLRRENYL SERRFFEEEQ ERKLQELAEK GELRSGSLTP TESIMSLGTH SRFSEFTGFS GMSFSSRSYL PEKLQIVKPL EGSATLHHWQ QLAQPHLGGI LDPRPGVVTK GFRTLDVDLD EVYCLNDFEE DDTGDHISLP RLATSTPVQH PETSAHHPGK CMSQTNSTFT FTTCRILHPS DELTRVTPSL NSAPTPACGS TSHLKSTPVA TPCTPRRLSL AESFTNTRES TTTMSTSLGL VWLLKERGIS AAVYDPQSWD RAGRGSLLHS YTPKMAVIPS TPPNSPMQTP TSSPPSFEFK CTSPPYDNFL ASKPASSILR EVREKNVRSS ESQTDVSVSN LNLVDKVRRF GVAKVVNSGR AHVPTLTEEQ GPLLCGPPGP APALVPRGLV PEGLPLRCPT VTSAIGGLQL NSGIRRNRSF PTMVGSSMQM KAPVTLTSGI LMGAKLSKQT SLR //