Gene Symbol: TRAK2
Description: trafficking kinesin protein 2
Alias: ALS2CR3, CALS-C, GRIF-1, GRIF1, MILT2, OIP98, trafficking kinesin-binding protein 2, O-linked N-acetylglucosamine transferase interacting protein 98, amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 3, amyotrophic lateral sclerosis 2 chromosomal region candidate gene 3 protein, gamma-aminobutyric acid(A) receptor-interacting factor, milton homolog 2, trafficking protein, kinesin binding 2
Species: human
Products:     TRAK2

Top Publications

  1. Kinney N, Larsen T, Kim D, Varghese R, Poelzing S, Garner H, et al. Whole-exome sequencing reveals microsatellite DNA markers for response to dofetilide initiation in patients with persistent atrial fibrillation: A pilot study. Clin Cardiol. 2018;41:849-854 pubmed publisher
    ..Two genes, MYH6 and TRAK2, are known to have expression in the atria...
  2. Oeding S, Majstrowicz K, Hu X, Schwarz V, Freitag A, Honnert U, et al. Identification of Miro1 and Miro2 as mitochondrial receptors for myosin XIX. J Cell Sci. 2018;131: pubmed publisher
    ..are transported predominantly along microtubules by kinesin and dynein motors that bind indirectly via TRAK1 and TRAK2 to outer mitochondrial membrane proteins Miro1 and Miro2 (Miro1/2)...
  3. Onodera Y, Nam J, Horikawa M, Shirato H, Sabe H. Arf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe. Nat Commun. 2018;9:2682 pubmed publisher
    ..The Arf6-based pathway promotes the localization of ILK to focal adhesions to block RhoT1-TRAK2 association, which controls mitochondrial retrograde trafficking...
  4. Li M, Wang J, Niu T, Ma J, Seneviratne C, Ait Daoud N, et al. Transcriptome profiling and pathway analysis of genes expressed differentially in participants with or without a positive response to topiramate treatment for methamphetamine addiction. BMC Med Genomics. 2014;7:65 pubmed publisher
    ..Many of these genes, such as GRINA, PRKACA, PRKCI, SNAP23, and TRAK2, which are involved in glutamate receptor and GABA receptor signaling, are direct targets for TPM...
  5. Rydzanicz M, Jagła M, Kosinska J, Tomasik T, Sobczak A, Pollak A, et al. KIF5A de novo mutation associated with myoclonic seizures and neonatal onset progressive leukoencephalopathy. Clin Genet. 2017;91:769-773 pubmed publisher
    ..The binding between KIF5A and its cargoes is mediated by kinesin adaptor proteins such as TRAK1 and TRAK2. Numerous missense KIF5A mutations in the motor and stalk domains cause spastic paraplegia type 10 (SPG10, OMIM ..
  6. Norkett R, Modi S, Birsa N, Atkin T, Ivankovic D, Pathania M, et al. DISC1-dependent Regulation of Mitochondrial Dynamics Controls the Morphogenesis of Complex Neuronal Dendrites. J Biol Chem. 2016;291:613-29 pubmed publisher
    ..machinery via interaction with the outer mitochondrial membrane GTPase proteins Miro1 and Miro2, the TRAK1 and TRAK2 mitochondrial trafficking adaptors, and the mitochondrial fusion proteins (mitofusins)...
  7. López Doménech G, Covill Cooke C, Ivankovic D, Halff E, Sheehan D, Norkett R, et al. Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution. EMBO J. 2018;37:321-336 pubmed publisher
    ..Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial ..
  8. Lumsden A, Young R, Pezos N, Keating D. Huntingtin-associated protein 1: Eutherian adaptation from a TRAK-like protein, conserved gene promoter elements, and localization in the human intestine. BMC Evol Biol. 2016;16:214 pubmed
    ..HAP1 shares a conserved "HAP1_N" domain with TRAfficking Kinesin proteins TRAK1 and TRAK2 (vertebrate), Milton (Drosophila) and T27A3.1 (C. elegans)...
  9. Das Banerjee T, Dagda R, Dagda M, Chu C, Rice M, Vazquez Mayorga E, et al. PINK1 regulates mitochondrial trafficking in dendrites of cortical neurons through mitochondrial PKA. J Neurochem. 2017;142:545-559 pubmed publisher
    ..D-AKAP1/PKA governs mitochondrial trafficking in dendrites via the Miro-2/TRAK2 complex and by increasing the phosphorylation of Miro-2...

More Information


  1. Beck M, Brickley K, Wilkinson H, Sharma S, Smith M, Chazot P, et al. Identification, molecular cloning, and characterization of a novel GABAA receptor-associated protein, GRIF-1. J Biol Chem. 2002;277:30079-90 pubmed
    ..GRIF-1 has no homology with proteins of known function, but it is the rat orthologue of the human ALS2CR3/KIAA0549 gene...
  2. Iyer S, Akimoto Y, Hart G. Identification and cloning of a novel family of coiled-coil domain proteins that interact with O-GlcNAc transferase. J Biol Chem. 2003;278:5399-409 pubmed
    ..Similarly, GRIF-1 may serve to target OGT to GABA(A) receptor complexes for mediating GABA signaling cascades. ..
  3. Grishin A, Li H, Levitan E, Zaks Makhina E. Identification of gamma-aminobutyric acid receptor-interacting factor 1 (TRAK2) as a trafficking factor for the K+ channel Kir2.1. J Biol Chem. 2006;281:30104-11 pubmed
    ..Yeast two-hybrid assays showed that an N-terminal region of GRIF-1 interacts with a C-terminal region of Kir2.1. These results indicate that GRIF-1 binds to Kir2.1 and facilitates trafficking of this channel to the cell surface. ..
  4. Loss O, Stephenson F. Developmental changes in trak-mediated mitochondrial transport in neurons. Mol Cell Neurosci. 2017;80:134-147 pubmed publisher
    Previous studies established that the kinesin adaptor proteins, TRAK1 and TRAK2, play an important role in mitochondrial transport in neurons...
  5. Hadano S, Yanagisawa Y, Skaug J, Fichter K, Nasir J, Martindale D, et al. Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2. Genomics. 2001;71:200-13 pubmed
    ..three novel full-length transcripts encoded by three distinct genes (HGMW-approved symbols ALS2CR1, ALS2CR2, and ALS2CR3) within the ALS2 critical region...
  6. Brickley K, Smith M, Beck M, Stephenson F. GRIF-1 and OIP106, members of a novel gene family of coiled-coil domain proteins: association in vivo and in vitro with kinesin. J Biol Chem. 2005;280:14723-32 pubmed
  7. Mills K, Brocardo M, Henderson B. APC binds the Miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane. Mol Biol Cell. 2016;27:466-82 pubmed publisher
    ..We propose that APC helps drive mitochondria to the membrane to supply energy for cellular processes such as directed cell migration, a process disrupted by cancer mutations. ..
  8. Koutsopoulos O, Laine D, Osellame L, Chudakov D, Parton R, Frazier A, et al. Human Miltons associate with mitochondria and induce microtubule-dependent remodeling of mitochondrial networks. Biochim Biophys Acta. 2010;1803:564-74 pubmed publisher
    ..We conclude that the human Miltons are important mediators of the mitochondrial trafficking machinery. ..
  9. Gilbert S, Zhang L, Forster M, Anderson J, Iwase T, Soliven B, et al. Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice. Nat Genet. 2006;38:245-50 pubmed
    ..Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases...
  10. van Spronsen M, Mikhaylova M, Lipka J, Schlager M, van den Heuvel D, Kuijpers M, et al. TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites. Neuron. 2013;77:485-502 pubmed publisher
    ..Here, we show that TRAK family adaptor proteins, TRAK1 and TRAK2, which link mitochondria to microtubule-based motors, are required for axonal and dendritic mitochondrial motility ..
  11. Fransson S, Ruusala A, Aspenstrom P. The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking. Biochem Biophys Res Commun. 2006;344:500-10 pubmed
    ..Moreover, we show that Miro interacts with the Kinesin-binding proteins, GRIF-1 and OIP106, suggesting that the Miro GTPases form a link between the mitochondria and the trafficking apparatus of the microtubules. ..
  12. Loss O, Stephenson F. Localization of the kinesin adaptor proteins trafficking kinesin proteins 1 and 2 in primary cultures of hippocampal pyramidal and cortical neurons. J Neurosci Res. 2015;93:1056-66 pubmed publisher
    ..Previous work has established that trafficking kinesin proteins (TRAKs),TRAK1 and TRAK2, are kinesin adaptor proteins that link mitochondria to kinesin motor proteins via an acceptor protein in the ..
  13. Machado R, Pauciulo M, Fretwell N, Veal C, Thomson J, Vilariño Güell C, et al. A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension. The International PPH Consortium. Genomics. 2000;68:220-8 pubmed
    ..8 Mb at 2q33. Numerous expressed sequence tags and known genes were placed on the YAC/BAC contig spanning the PPH1 gene critical region. ..
  14. Okumoto K, Ono T, Toyama R, Shimomura A, Nagata A, Fujiki Y. New splicing variants of mitochondrial Rho GTPase-1 (Miro1) transport peroxisomes. J Cell Biol. 2018;217:619-633 pubmed publisher
    ..for the first time peroxisome-localized Miro1 variants as adapter proteins that link peroxisomes to the microtubule-dependent transport complexes including TRAK2 in the intracellular translocation of peroxisomes in mammalian cells.
  15. Macaskill A, Brickley K, Stephenson F, Kittler J. GTPase dependent recruitment of Grif-1 by Miro1 regulates mitochondrial trafficking in hippocampal neurons. Mol Cell Neurosci. 2009;40:301-12 pubmed publisher
    ..These data suggest that Miro1 and the kinesin adaptor Grif-1 play an important role in regulating mitochondrial transport in neurons. ..
  16. Smith M, Pozo K, Brickley K, Stephenson F. Mapping the GRIF-1 binding domain of the kinesin, KIF5C, substantiates a role for GRIF-1 as an adaptor protein in the anterograde trafficking of cargoes. J Biol Chem. 2006;281:27216-28 pubmed
    ..These findings support a role for GRIF-1 as a kinesin adaptor molecule requisite for the anterograde delivery of defined cargoes such as mitochondria and/or vesicles incorporating beta2 subunit-containing GABAA receptors, in the brain. ..