ID   TRAK2_HUMAN             Reviewed;         914 AA.
AC   O60296; E7EV21; Q8WVH7; Q96NS2; Q9C0K5; Q9C0K6;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2002, sequence version 2.
DT   24-JAN-2024, entry version 178.
DE   RecName: Full=Trafficking kinesin-binding protein 2;
DE   AltName: Full=Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 3 protein;
GN   Name=TRAK2; Synonyms=ALS2CR3, KIAA0549;
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 [MRNA] (ISOFORM 1), AND VARIANTS ILE-142 AND ILE-528.
RX   PubMed=11161814; DOI=10.1006/geno.2000.6392;
RA   Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., Martindale D.,
RA   Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E.,
RA   Hayden M.R.;
RT   "Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and
RT   ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical
RT   region at chromosome 2q33-q34: candidate genes for ALS2.";
RL   Genomics 71:200-213(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ILE-142.
RC   TISSUE=Cerebellum;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 446-914 (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA   Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA   Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. IX. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 5:31-39(1998).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 798-914 (ISOFORM 1), AND VARIANT
RP   ASN-863.
RC   TISSUE=Skin;
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   [6]
RP   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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-420, 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   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: May regulate endosome-to-lysosome trafficking of membrane
CC       cargo, including EGFR. {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with GABA-A receptor and O-GlcNAc transferase.
CC       Interacts with HGS (By similarity). Interacts with RHOT1/Miro-1 and
CC       RHOT2/Miro-2. {ECO:0000250, ECO:0000269|PubMed:16630562}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Early endosome
CC       {ECO:0000250}. Mitochondrion {ECO:0000250}. Note=Colocalizes with MGARP
CC       at the mitochondria. Translocates from the cytoplasm to the
CC       mitochondria in a MGARP-dependent manner (By similarity).
CC       {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O60296-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O60296-2; Sequence=VSP_053418, VSP_053419;
CC   -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in heart.
CC   -!- PTM: O-glycosylated. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the milton family. {ECO:0000305}.
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DR   EMBL; AB038964; BAB32550.1; -; Genomic_DNA.
DR   EMBL; AB038951; BAB32501.1; -; mRNA.
DR   EMBL; AK054763; BAB70803.1; -; mRNA.
DR   EMBL; AC007256; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC007282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC080069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AB011121; BAA25475.1; -; mRNA.
DR   EMBL; BC017999; AAH17999.1; -; mRNA.
DR   CCDS; CCDS2347.1; -. [O60296-1]
DR   RefSeq; NP_055864.2; NM_015049.2. [O60296-1]
DR   RefSeq; XP_011509992.1; XM_011511690.1.
DR   AlphaFoldDB; O60296; -.
DR   SMR; O60296; -.
DR   BioGRID; 122452; 66.
DR   CORUM; O60296; -.
DR   IntAct; O60296; 31.
DR   MINT; O60296; -.
DR   STRING; 9606.ENSP00000328875; -.
DR   GlyGen; O60296; 5 sites, 1 O-linked glycan (5 sites).
DR   iPTMnet; O60296; -.
DR   PhosphoSitePlus; O60296; -.
DR   BioMuta; TRAK2; -.
DR   EPD; O60296; -.
DR   jPOST; O60296; -.
DR   MassIVE; O60296; -.
DR   MaxQB; O60296; -.
DR   PaxDb; 9606-ENSP00000328875; -.
DR   PeptideAtlas; O60296; -.
DR   ProteomicsDB; 18553; -.
DR   ProteomicsDB; 49328; -. [O60296-1]
DR   ABCD; O60296; 1 sequenced antibody.
DR   Antibodypedia; 19936; 291 antibodies from 32 providers.
DR   DNASU; 66008; -.
DR   Ensembl; ENST00000332624.8; ENSP00000328875.3; ENSG00000115993.13. [O60296-1]
DR   Ensembl; ENST00000430254.1; ENSP00000409333.1; ENSG00000115993.13. [O60296-2]
DR   GeneID; 66008; -.
DR   KEGG; hsa:66008; -.
DR   MANE-Select; ENST00000332624.8; ENSP00000328875.3; NM_015049.3; NP_055864.2.
DR   UCSC; uc002uyb.5; human. [O60296-1]
DR   AGR; HGNC:13206; -.
DR   CTD; 66008; -.
DR   DisGeNET; 66008; -.
DR   GeneCards; TRAK2; -.
DR   HGNC; HGNC:13206; TRAK2.
DR   HPA; ENSG00000115993; Tissue enhanced (brain).
DR   MIM; 607334; gene.
DR   neXtProt; NX_O60296; -.
DR   OpenTargets; ENSG00000115993; -.
DR   PharmGKB; PA24744; -.
DR   VEuPathDB; HostDB:ENSG00000115993; -.
DR   eggNOG; KOG4360; Eukaryota.
DR   GeneTree; ENSGT00940000158202; -.
DR   HOGENOM; CLU_013450_0_1_1; -.
DR   InParanoid; O60296; -.
DR   OMA; LDGSHKF; -.
DR   OrthoDB; 2909788at2759; -.
DR   PhylomeDB; O60296; -.
DR   TreeFam; TF323495; -.
DR   PathwayCommons; O60296; -.
DR   Reactome; R-HSA-9013419; RHOT2 GTPase cycle.
DR   Reactome; R-HSA-9013425; RHOT1 GTPase cycle.
DR   SignaLink; O60296; -.
DR   SIGNOR; O60296; -.
DR   BioGRID-ORCS; 66008; 4 hits in 1156 CRISPR screens.
DR   ChiTaRS; TRAK2; human.
DR   GeneWiki; TRAK2; -.
DR   GenomeRNAi; 66008; -.
DR   Pharos; O60296; Tbio.
DR   PRO; PR:O60296; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; O60296; Protein.
DR   Bgee; ENSG00000115993; Expressed in dorsal motor nucleus of vagus nerve and 214 other cell types or tissues.
DR   ExpressionAtlas; O60296; baseline and differential.
DR   GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR   GO; GO:0005737; C:cytoplasm; ISS: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:0032839; C:dendrite cytoplasm; IEA:GOC.
DR   GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; 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; ISS:UniProtKB.
DR   GO; GO:0098957; P:anterograde axonal transport of mitochondrion; IBA:GO_Central.
DR   GO; GO:0098972; P:anterograde dendritic transport of mitochondrion; IEA:Ensembl.
DR   GO; GO:0048311; P:mitochondrion distribution; IBA:GO_Central.
DR   GO; GO:0022008; P:neurogenesis; IBA:GO_Central.
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   PANTHER; PTHR15751; TRAFFICKING KINESIN-BINDING PROTEIN; 1.
DR   PANTHER; PTHR15751:SF13; TRAFFICKING KINESIN-BINDING PROTEIN 2; 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; O60296; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Coiled coil; Cytoplasm; Endosome; Glycoprotein;
KW   Mitochondrion; Phosphoprotein; Reference proteome; Transport.
FT   CHAIN           1..914
FT                   /note="Trafficking kinesin-binding protein 2"
FT                   /id="PRO_0000064538"
FT   DOMAIN          48..353
FT                   /note="HAP1 N-terminal"
FT   REGION          1..30
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          359..509
FT                   /note="Interaction with HGS"
FT                   /evidence="ECO:0000250"
FT   REGION          447..482
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          765..787
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          134..354
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        1..28
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        447..475
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        770..787
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         420
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         301..311
FT                   /note="HVIEKEELKLH -> VGLFIHSTDIC (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_053418"
FT   VAR_SEQ         312..914
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_053419"
FT   VARIANT         142
FT                   /note="V -> I (in dbSNP:rs13022344)"
FT                   /evidence="ECO:0000269|PubMed:11161814,
FT                   ECO:0000269|PubMed:14702039"
FT                   /id="VAR_014201"
FT   VARIANT         528
FT                   /note="T -> I (in dbSNP:rs2244438)"
FT                   /evidence="ECO:0000269|PubMed:11161814"
FT                   /id="VAR_014434"
FT   VARIANT         863
FT                   /note="I -> N (in dbSNP:rs34594680)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_051458"
SQ   SEQUENCE   914 AA;  101419 MW;  C26525C223A70D6D CRC64;
     MSQSQNAIFT SPTGEENLMN SNHRDSESIT DVCSNEDLPE VELVSLLEEQ LPQYRLKVDT
     LFLYENQDWT QSPHQRQHAS DALSPVLAEE TFRYMILGTD RVEQMTKTYN DIDMVTHLLA
     ERDRDLELAA RIGQALLKRN HVLSEQNESL EEQLGQAFDQ VNQLQHELCK KDELLRIVSI
     ASEESETDSS CSTPLRFNES FSLSQGLLQL EMLQEKLKEL EEENMALRSK ACHIKTETVT
     YEEKEQQLVS DCVKELRETN AQMSRMTEEL SGKSDELIRY QEELSSLLSQ IVDLQHKLKE
     HVIEKEELKL HLQASKDAQR QLTMELHELQ DRNMECLGML HESQEEIKEL RSRSGPTAHL
     YFSQSYGAFT GESLAAEIEG TMRKKLSLDE ESSLFKQKAQ QKRVFDTVRI ANDTRGRSIS
     FPALLPIPGS NRSSVIMTAK PFESGLQQTE DKSLLNQGSS SEEVAGSSQK MGQPGPSGDS
     DLATALHRLS LRRQNYLSEK QFFAEEWQRK IQVLADQKEG VSGCVTPTES LASLCTTQSE
     ITDLSSASCL RGFMPEKLQI VKPLEGSQTL YHWQQLAQPN LGTILDPRPG VITKGFTQLP
     GDAIYHISDL EEDEEEGITF QVQQPLEVEE KLSTSKPVTG IFLPPITSAG GPVTVATANP
     GKCLSCTNST FTFTTCRILH PSDITQVTPS SGFPSLSCGS SGSSSSNTAV NSPALSYRLS
     IGESITNRRD STTTFSSTMS LAKLLQERGI SAKVYHSPIS ENPLQPLPKS LAIPSTPPNS
     PSHSPCPSPL PFEPRVHLSE NFLASRPAET FLQEMYGLRP SRNPPDVGQL KMNLVDRLKR
     LGIARVVKNP GAQENGRCQE AEIGPQKPDS AVYLNSGSSL LGGLRRNQSL PVIMGSFAAP
     VCTSSPKMGV LKED
//