TRAK2_HUMAN
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 03-AUG-2022, entry version 170.
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. [O60296-1]
DR AlphaFoldDB; O60296; -.
DR SMR; O60296; -.
DR BioGRID; 122452; 65.
DR CORUM; O60296; -.
DR IntAct; O60296; 33.
DR MINT; O60296; -.
DR STRING; 9606.ENSP00000328875; -.
DR iPTMnet; O60296; -.
DR PhosphoSitePlus; O60296; -.
DR BioMuta; TRAK2; -.
DR EPD; O60296; -.
DR jPOST; O60296; -.
DR MassIVE; O60296; -.
DR MaxQB; O60296; -.
DR PaxDb; O60296; -.
DR PeptideAtlas; O60296; -.
DR PRIDE; O60296; -.
DR ProteomicsDB; 18553; -.
DR ProteomicsDB; 49328; -. [O60296-1]
DR ABCD; O60296; 1 sequenced antibody.
DR Antibodypedia; 19936; 280 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 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; RSKKACH; -.
DR OrthoDB; 1003820at2759; -.
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 1079 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 212 other tissues.
DR ExpressionAtlas; O60296; baseline and differential.
DR Genevisible; O60296; HS.
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 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 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
