TRAK1_HUMAN
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 03-AUG-2022, entry version 170.
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};
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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; 62.
DR CORUM; Q9UPV9; -.
DR IntAct; Q9UPV9; 18.
DR MINT; Q9UPV9; -.
DR STRING; 9606.ENSP00000328998; -.
DR GlyGen; Q9UPV9; 8 sites, 1 O-linked glycan (7 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; Q9UPV9; -.
DR PeptideAtlas; Q9UPV9; -.
DR PRIDE; Q9UPV9; -.
DR ProteomicsDB; 19736; -.
DR ProteomicsDB; 85456; -. [Q9UPV9-1]
DR ProteomicsDB; 85457; -. [Q9UPV9-2]
DR ABCD; Q9UPV9; 1 sequenced antibody.
DR Antibodypedia; 1603; 203 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 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; 1003820at2759; -.
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; 13 hits in 1082 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 210 other tissues.
DR ExpressionAtlas; Q9UPV9; baseline and differential.
DR Genevisible; Q9UPV9; HS.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
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:0050811; F:GABA receptor binding; IBA:GO_Central.
DR GO; GO:0017022; F:myosin binding; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0098957; P:anterograde axonal transport of mitochondrion; IBA:GO_Central.
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: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 Pfam; PF04849; HAP1_N; 1.
DR Pfam; PF12448; Milton; 1.
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; unknown pathological 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
