Analysis of the kinesin superfamily: insights into structure and function.

Kinesin superfamily proteins (KIFs) are key players or 'hub' proteins in the intracellular transport system, which is essential for cellular function and morphology. The KIF superfamily is also the first large protein family in mammals whose constituents have been completely identified and confirmed both in silico and in vivo. Numerous studies have revealed the structures and functions of individual family members; however, the relationships between members or a perspective of the whole superfamily structure until recently remained elusive. Here, we present a comprehensive summary based on a large, systematic phylogenetic analysis of the kinesin superfamily. All available sequences in public databases, including genomic information from all model organisms, were analyzed to yield the most complete phylogenetic kinesin tree thus far, comprising 14 families. This comprehensive classification builds on the recently proposed standardized nomenclature for kinesins and allows systematic analysis of the structural and functional relationships within the kinesin superfamily.

[1]  N. Hirokawa,et al.  Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A. Reddy,et al.  A Novel Plant Calmodulin-binding Protein with a Kinesin Heavy Chain Motor Domain (*) , 1996, The Journal of Biological Chemistry.

[3]  Bo Liu,et al.  Identification of a phragmoplast-associated kinesin-related protein in higher plants , 2000, Current Biology.

[4]  J. Scholey,et al.  Sequence and submolecular localization of the 115-kD accessory subunit of the heterotrimeric kinesin-II (KRP85/95) complex , 1996, The Journal of cell biology.

[5]  Michael P. Sheetz,et al.  Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility , 1985, Cell.

[6]  M. Saraste,et al.  Does Vav bind to F‐actin through a CH domain? , 1995, FEBS letters.

[7]  A. Ullrich,et al.  The Kinesin-like Motor Protein KIF1C Occurs in Intact Cells as a Dimer and Associates with Proteins of the 14-3-3 Family* , 1999, The Journal of Biological Chemistry.

[8]  Y. Nakamura,et al.  Identification, genomic organization, and alternative splicing of KNSL3, a novel human gene encoding a kinesin-like protein , 1998, Cytogenetic and Genome Research.

[9]  D. Pellman,et al.  Kinesin-related KIP3 of Saccharomyces cerevisiae Is Required for a Distinct Step in Nuclear Migration , 1997, The Journal of cell biology.

[10]  J. Scholey,et al.  A "slow" homotetrameric kinesin-related motor protein purified from Drosophila embryos. , 1994, The Journal of biological chemistry.

[11]  Russell L. Malmberg,et al.  A standardized kinesin nomenclature , 2004, The Journal of cell biology.

[12]  N. Hirokawa,et al.  Kinesin Superfamily Protein 2A (KIF2A) Functions in Suppression of Collateral Branch Extension , 2003, Cell.

[13]  L. Goldstein,et al.  The Drosophila kinesin light chain. Primary structure and interaction with kinesin heavy chain. , 1993, The Journal of biological chemistry.

[14]  I. Vernos,et al.  Kinesin subfamily UNC104 contains a FHA domain: boundaries and physicochemical characterization , 2000, FEBS letters.

[15]  R. Vallee,et al.  Retrograde transport by the microtubule-associated protein MAP 1C , 1987, Nature.

[16]  R. Stewart,et al.  Mitochondrial Association of a Plus End–Directed Microtubule Motor Expressed during Mitosis in Drosophila , 1997, The Journal of cell biology.

[17]  H. Bellen,et al.  pavarotti encodes a kinesin-like protein required to organize the central spindle and contractile ring for cytokinesis. , 1998, Genes & development.

[18]  Z. Bonday,et al.  Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome loss , 2003, The Journal of cell biology.

[19]  Matthias Platzer,et al.  Sequence and analysis of chromosome 2 of Dictyostelium discoideum , 2002, Nature.

[20]  L. Goldstein,et al.  Characterization of KIFC2, a Neuronal Kinesin Superfamily Member in Mouse , 1997, Neuron.

[21]  Susan S. Brown,et al.  Suppression of a myosin defect by a kinesin-related gene , 1992, Nature.

[22]  S. Endow,et al.  Determinants of kinesin motor polarity. , 1998, Science.

[23]  J. Potashkin,et al.  Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2 + and suc1 + , 1987, Cell.

[24]  R. Vale,et al.  Distinct conformations of the kinesin Unc104 neck regulate a monomer to dimer motor transition , 2003, The Journal of cell biology.

[25]  L. Frisén,et al.  The kinesin-related proteins, Kip2p and Kip3p, function differently in nuclear migration in yeast. , 1998, Molecular biology of the cell.

[26]  N. Hirokawa,et al.  KIFC3, a microtubule minus end–directed motor for the apical transport of annexin XIIIb–associated Triton-insoluble membranes , 2001, The Journal of cell biology.

[27]  Ronald D Vale,et al.  Microtubule Interaction Site of the Kinesin Motor , 1997, Cell.

[28]  Russell J. Stewart,et al.  The kinesin-like ncd protein of Drosophila is a minus end-directed microtubule motor , 1990, Cell.

[29]  J. McIntosh,et al.  Kinesins klp5(+) and klp6(+) are required for normal chromosome movement in mitosis. , 2002, Journal of cell science.

[30]  N. Hirokawa,et al.  Kinesin and dynein superfamily proteins and the mechanism of organelle transport. , 1998, Science.

[31]  S. H. Lillie,et al.  Smy1p, a Kinesin-related Protein That Does Not Require Microtubules , 1998, The Journal of cell biology.

[32]  B. Schaar,et al.  CENP-E is a putative kinetochore motor that accumulates just before mitosis , 1992, Nature.

[33]  R. Hawley,et al.  A kinesin-like protein required for distributive chromosome segregation in Drosophila , 1990, Cell.

[34]  N. Hirokawa,et al.  KIFC2 Is a Novel Neuron-Specific C-Terminal Type Kinesin Superfamily Motor for Dendritic Transport of Multivesicular Body-Like Organelles , 1997, Neuron.

[35]  Timothy J Mitchison,et al.  An inner centromere protein that stimulates the microtubule depolymerizing activity of a KinI kinesin. , 2003, Developmental cell.

[36]  N. Hirokawa,et al.  KIF2 is a new microtubule-based anterograde motor that transports membranous organelles distinct from those carried by kinesin heavy chain or KIF3A/B , 1995, The Journal of cell biology.

[37]  R J Fletterick,et al.  The design plan of kinesin motors. , 1997, Annual review of cell and developmental biology.

[38]  Masahide Kikkawa,et al.  15 Å Resolution Model of the Monomeric Kinesin Motor, KIF1A , 2000, Cell.

[39]  A. Murray,et al.  The Xenopus Chromokinesin Xkid Is Essential for Metaphase Chromosome Alignment and Must Be Degraded to Allow Anaphase Chromosome Movement , 2000, Cell.

[40]  Nobutaka Hirokawa,et al.  Molecular motors and mechanisms of directional transport in neurons , 2005, Nature Reviews Neuroscience.

[41]  J. Mackay,et al.  The C-terminal region of the stalk domain of ubiquitous human kinesin heavy chain contains the binding site for kinesin light chain. , 1998, Biochemistry.

[42]  F. Barr,et al.  The Rab6‐binding kinesin, Rab6‐KIFL, is required for cytokinesis , 2000, The EMBO journal.

[43]  Nobutaka Hirokawa,et al.  Kinesin Transports RNA Isolation and Characterization of an RNA-Transporting Granule , 2004, Neuron.

[44]  N. Hirokawa,et al.  Defect in Synaptic Vesicle Precursor Transport and Neuronal Cell Death in KIF1A Motor Protein–deficient Mice , 1998, The Journal of cell biology.

[45]  P. Beech,et al.  A new kinesin-like protein (Klp1) localized to a single microtubule of the Chlamydomonas flagellum , 1994, The Journal of cell biology.

[46]  S. H. Lillie,et al.  Immunofluorescence localization of the unconventional myosin, Myo2p, and the putative kinesin-related protein, Smy1p, to the same regions of polarized growth in Saccharomyces cerevisiae , 1994, The Journal of cell biology.

[47]  N. Hirokawa,et al.  A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally , 1994, The Journal of cell biology.

[48]  Edward D. Salmon,et al.  The Drosophila claret segregation protein is a minus-end directed motor molecule , 1990, Nature.

[49]  G. C. Rogers,et al.  A Kinesin-Related Protein, Krp180, Positions Prometaphase Spindle Poles during Early Sea Urchin Embryonic Cell Division , 2000, The Journal of cell biology.

[50]  R. Adler,et al.  Chromokinesin: a DNA-binding, kinesin-like nuclear protein , 1995, The Journal of cell biology.

[51]  Mitsutoshi Setou,et al.  Kinesin superfamily proteins (KIFs) in the mouse transcriptome. , 2003, Genome research.

[52]  P. Meluh,et al.  Kinesin-related proteins required for assembly of the mitotic spindle , 1992, The Journal of cell biology.

[53]  J. Inoue,et al.  Kid, a novel kinesin‐like DNA binding protein, is localized to chromosomes and the mitotic spindle. , 1996, The EMBO journal.

[54]  K. Katoh,et al.  MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. , 2002, Nucleic acids research.

[55]  J Schultz,et al.  SMART, a simple modular architecture research tool: identification of signaling domains. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[56]  J. Solowska,et al.  Expression of the mitotic kinesin Kif15 in postmitotic neurons: Implications for neuronal migration and development , 2003, Journal of neurocytology.

[57]  A. Reddy,et al.  Kinesins in the Arabidopsis genome: A comparative analysis among eukaryotes , 2001, BMC Genomics.

[58]  A. Holzinger,et al.  KINESIN‐LIKE PROTEINS ARE INVOLVED IN POSTMITOTIC NUCLEAR MIGRATION OF THE UNICELLULAR GREEN ALGA MICRASTERIAS DENTICULATA , 2002, Cell biology international.

[59]  B. Goud,et al.  Interaction of a Golgi-associated kinesin-like protein with Rab6. , 1998, Science.

[60]  G. Bloom,et al.  Monoclonal antibodies to kinesin heavy and light chains stain vesicle- like structures, but not microtubules, in cultured cells , 1989, The Journal of cell biology.

[61]  G. Bloom,et al.  IQGAP1, a Rac- and Cdc42-binding Protein, Directly Binds and Cross-links Microfilaments , 1997, The Journal of cell biology.

[62]  T. Mitchison,et al.  Identification and partial characterization of mitotic centromere- associated kinesin, a kinesin-related protein that associates with centromeres during mitosis , 1995, The Journal of cell biology.

[63]  Dyneins Motor on in Plants , 2002, Traffic.

[64]  G. C. Rogers,et al.  Microtubule motors in mitosis , 2000, Nature.

[65]  M. Hoyt,et al.  Mitotic Spindle Positioning in Saccharomyces cerevisiae Is Accomplished by Antagonistically Acting Microtubule Motor Proteins , 1997, The Journal of cell biology.

[66]  I. Vernos,et al.  Xklp2, a Novel Xenopus Centrosomal Kinesin-like Protein Required for Centrosome Separation during Mitosis , 1996, Cell.

[67]  J. Paris,et al.  Cloning by differential screening of a Xenopus cDNA that encodes a kinesin-related protein , 1991, Molecular and cellular biology.

[68]  N. Hirokawa,et al.  Role of KIFC3 motor protein in Golgi positioning and integration , 2002, The Journal of cell biology.

[69]  N. Hirokawa,et al.  Organelle transport along microtubules - the role of KIFs. , 1996, Trends in cell biology.

[70]  N. Hirokawa,et al.  A Common Mechanism for Microtubule Destabilizers—M Type Kinesins Stabilize Curling of the Protofilament Using the Class-Specific Neck and Loops , 2004, Cell.

[71]  J. Scholey,et al.  The heterotrimeric motor protein kinesin-II localizes to the midpiece and flagellum of sea urchin and sand dollar sperm. , 1997, Cell motility and the cytoskeleton.

[72]  L. Goldstein,et al.  DNA binding and meiotic chromosomal localization of the drosophila nod kinesin-like protein , 1995, Cell.

[73]  J. Doonan,et al.  P34cdc2 kinase is associated with cortical microtubules from higher plant protoplasts , 2001, FEBS letters.

[74]  A. Otsuka,et al.  The C. elegans unc-104 4 gene encodes a putative kinesin heavy chain-like protein , 1991, Neuron.

[75]  H. Lane,et al.  Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo , 1995, Cell.

[76]  J. Scholey,et al.  Novel heterotrimeric kinesin-related protein purified from sea urchin eggs , 1993, Nature.

[77]  D. Hall,et al.  Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans , 1991, Cell.

[78]  N. Hirokawa,et al.  The neuron-specific kinesin superfamily protein KIF1A is a uniqye monomeric motor for anterograde axonal transport of synaptic vesicle precursors , 1995, Cell.

[79]  S. Endow,et al.  A new kinesin tree , 2004, Journal of Cell Science.

[80]  P. Meluh,et al.  KAR3, a kinesin-related gene required for yeast nuclear fusion , 1990, Cell.

[81]  Corey Nislow,et al.  A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles , 1992, Nature.

[82]  M. Gimona,et al.  The single CH domain of calponin is neither sufficient nor necessary for F-actin binding. , 1998, Journal of cell science.

[83]  D. Drummond,et al.  Mutations in the bimC box of Cut7 indicate divergence of regulation within the bimC family of kinesin related proteins. , 1998, Journal of cell science.

[84]  R. Milligan,et al.  A mechanism for microtubule depolymerization by KinI kinesins. , 2002, Molecular cell.

[85]  D. Johnston,et al.  Kinesin light chain-independent function of the Kinesin heavy chain in cytoplasmic streaming and posterior localisation in the Drosophila oocyte , 2002, Development.

[86]  A. Khodjakov,et al.  Characterization of a minus end-directed kinesin-like motor protein from cultured mammalian cells , 1995, The Journal of cell biology.

[87]  S. Eom,et al.  An intramolecular interaction between the FHA domain and a coiled coil negatively regulates the kinesin motor KIF1A , 2004, The EMBO journal.

[88]  G. Bloom,et al.  A monoclonal antibody against kinesin inhibits both anterograde and retrograde fast axonal transport in squid axoplasm. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[89]  N. Hirokawa,et al.  KIF3A/B: a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport , 1995, The Journal of cell biology.

[90]  L. Goldstein,et al.  Isolation and characterization of the gene encoding the heavy chain of Drosophila kinesin. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[91]  N. Morris,et al.  Mutation of a gene that encodes a kinesin-like protein blocks nuclear division in A. nidulans , 1990, Cell.

[92]  Scott T. Brady,et al.  A novel brain ATPase with properties expected for the fast axonal transport motor , 1985, Nature.

[93]  J. Schmid,et al.  The Ras‐like GTPase Gem is involved in cell shape remodelling and interacts with the novel kinesin‐like protein KIF9 , 2001, The EMBO journal.

[94]  N. Hirokawa,et al.  Kinesin family in murine central nervous system , 1992, The Journal of cell biology.

[95]  M. Yanagida,et al.  Kinesin-related cut 7 protein associates with mitotic and meiotic spindles in fission yeast , 1992, Nature.

[96]  G. Steinberg,et al.  The Neurospora organelle motor: a distant relative of conventional kinesin with unconventional properties. , 1995, Molecular biology of the cell.

[97]  G. Bloom,et al.  Native structure and physical properties of bovine brain kinesin and identification of the ATP-binding subunit polypeptide. , 1988, Biochemistry.

[98]  E. Taylor,et al.  Kinetics processivity and the direction of motion of Ncd. , 1999, Biophysical journal.

[99]  T. Toda,et al.  Two Kinesin-like Kin I Family Proteins in Fission Yeast Regulate the Establishment of Metaphase and the Onset of Anaphase A , 2002, Current Biology.

[100]  N. Hirokawa,et al.  KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria , 1994, Cell.

[101]  D. Inzé,et al.  cdc2a expression in Arabidopsis is linked with competence for cell division. , 1993, The Plant cell.

[102]  Russell L. Malmberg,et al.  Maximum Likelihood Methods Reveal Conservation of Function Among Closely Related Kinesin Families , 2002, Journal of Molecular Evolution.

[103]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[104]  Timothy J. Mitchison,et al.  Kin I Kinesins Are Microtubule-Destabilizing Enzymes , 1999, Cell.

[105]  N. Hirokawa,et al.  Kinesin and dynein superfamily proteins in organelle transport and cell division. , 1998, Current opinion in cell biology.

[106]  J. Weiner,et al.  Novel Dendritic Kinesin Sorting Identified by Different Process Targeting of Two Related Kinesins: KIF21A and KIF21B , 1999, The Journal of cell biology.

[107]  Allan W. Wolkoff,et al.  Regulation of early endocytic vesicle motility and fission in a reconstituted system , 2003, Journal of Cell Science.

[108]  Masahide Kikkawa,et al.  Switch-based mechanism of kinesin motors , 2001, Nature.

[109]  Ryo Nitta,et al.  KIF1A Alternately Uses Two Loops to Bind Microtubules , 2004, Science.

[110]  Spatial pattern of cdc2 expression in relation to meristem activity and cell proliferation during plant development. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[111]  F. W. Wolf,et al.  vab-8 Is a Key Regulator of Posteriorly Directed Migrations in C. elegans and Encodes a Novel Protein with Kinesin Motor Similarity , 1998, Neuron.

[112]  S. Strome,et al.  KLP-18, a Klp2 kinesin, is required for assembly of acentrosomal meiotic spindles in Caenorhabditis elegans. , 2003, Molecular biology of the cell.

[113]  P. Zambryski.  Plasmodesmata: Plant Channels for Molecules on the Move , 1995, Science.

[114]  N. Hirokawa,et al.  All kinesin superfamily protein, KIF, genes in mouse and human , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[115]  N. Hirokawa,et al.  Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. , 2000, Science.

[116]  C. Millette,et al.  KRP3A and KRP3B: Candidate Motors in Spermatid Maturation in the Seminiferous Epithelium1 , 2002, Biology of reproduction.

[117]  G. Bloom,et al.  Submolecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration , 1989, Cell.