Full text data of KIF5B
KIF5B
(KNS, KNS1)
[Confidence: low (only semi-automatic identification from reviews)]
Kinesin-1 heavy chain (Conventional kinesin heavy chain; Ubiquitous kinesin heavy chain; UKHC)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Kinesin-1 heavy chain (Conventional kinesin heavy chain; Ubiquitous kinesin heavy chain; UKHC)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P33176
ID KINH_HUMAN Reviewed; 963 AA.
AC P33176; A0AVB2; Q5VZ85;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1993, sequence version 1.
DT 22-JAN-2014, entry version 138.
DE RecName: Full=Kinesin-1 heavy chain;
DE AltName: Full=Conventional kinesin heavy chain;
DE AltName: Full=Ubiquitous kinesin heavy chain;
DE Short=UKHC;
GN Name=KIF5B; Synonyms=KNS, KNS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=1607388; DOI=10.1083/jcb.117.6.1263;
RA Navone F., Niclas J., Hom-Booher N., Sparks L., Bernstein H.D.,
RA McCaffrey G., Vale R.D.;
RT "Cloning and expression of a human kinesin heavy chain gene:
RT interaction of the COOH-terminal domain with cytoplasmic microtubules
RT in transfected CV-1 cells.";
RL J. Cell Biol. 117:1263-1275(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH SYBU.
RX PubMed=15459722; DOI=10.1038/ncb1169;
RA Su Q., Cai Q., Gerwin C., Smith C.L., Sheng Z.-H.;
RT "Syntabulin is a microtubule-associated protein implicated in syntaxin
RT transport in neurons.";
RL Nat. Cell Biol. 6:941-953(2004).
RN [5]
RP INTERACTION WITH PLEKHM2.
RX PubMed=15905402; DOI=10.1126/science.1110225;
RA Boucrot E., Henry T., Borg J.-P., Gorvel J.-P., Meresse S.;
RT "The intracellular fate of Salmonella depends on the recruitment of
RT kinesin.";
RL Science 308:1174-1178(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [7]
RP INTERACTION WITH JAKMIP1.
RX PubMed=17532644; DOI=10.1016/j.mcn.2007.04.008;
RA Vidal R.L., Ramirez O.A., Sandoval L., Koenig-Robert R., Haertel S.,
RA Couve A.;
RT "Marlin-1 and conventional kinesin link GABAB receptors to the
RT cytoskeleton and regulate receptor transport.";
RL Mol. Cell. Neurosci. 35:501-512(2007).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP INTERACTION WITH ECM29.
RX PubMed=20682791; DOI=10.1074/jbc.M110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S.,
RA Hughes R.E., Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-933, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-349 IN COMPLEX WITH ADP.
RX PubMed=8606779; DOI=10.1038/380550a0;
RA Kull F.J., Sablin E.P., Lau R., Fletterick R.J., Vale R.D.;
RT "Crystal structure of the kinesin motor domain reveals a structural
RT similarity to myosin.";
RL Nature 380:550-555(1996).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-349 IN COMPLEX WITH ADP.
RX PubMed=12368902; DOI=10.1038/nsb852;
RA Sindelar C.V., Budny M.J., Rice S., Naber N., Fletterick R., Cooke R.;
RT "Two conformations in the human kinesin power stroke defined by X-ray
RT crystallography and EPR spectroscopy.";
RL Nat. Struct. Biol. 9:844-848(2002).
RN [15]
RP STRUCTURE BY ELECTRON MICROSCOPY (9.0 ANGSTROMS) OF 1-325.
RX PubMed=17470637; DOI=10.1083/jcb.200612090;
RA Sindelar C.V., Downing K.H.;
RT "The beginning of kinesin's force-generating cycle visualized at 9-A
RT resolution.";
RL J. Cell Biol. 177:377-385(2007).
CC -!- FUNCTION: Microtubule-dependent motor required for normal
CC distribution of mitochondria and lysosomes (By similarity).
CC -!- SUBUNIT: Oligomer composed of two heavy chains and two light
CC chains. Interacts with GRIP1 and PPP1R42 (By similarity).
CC Interacts with SYBU. Interacts with JAKMIP1. Interacts with
CC PLEKHM2. Interacts with ECM29.
CC -!- INTERACTION:
CC P68619:VACWR159 (xeno); NbExp=3; IntAct=EBI-355878, EBI-7133540;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity).
CC Note=Uniformly distributed between soma and neurites in
CC hippocampal neurons (By similarity).
CC -!- DOMAIN: Composed of three structural domains: a large globular N-
CC terminal domain which is responsible for the motor activity of
CC kinesin (it hydrolyzes ATP and binds microtubule), a central
CC alpha-helical coiled coil domain that mediates the heavy chain
CC dimerization; and a small globular C-terminal domain which
CC interacts with other proteins (such as the kinesin light chains),
CC vesicles and membranous organelles.
CC -!- SIMILARITY: Belongs to the kinesin-like protein family. Kinesin
CC subfamily.
CC -!- SIMILARITY: Contains 1 kinesin-motor domain.
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DR EMBL; X65873; CAA46703.1; -; mRNA.
DR EMBL; AL161932; CAH71618.1; -; Genomic_DNA.
DR EMBL; BC126279; AAI26280.1; -; mRNA.
DR EMBL; BC126281; AAI26282.1; -; mRNA.
DR PIR; A41919; A41919.
DR RefSeq; NP_004512.1; NM_004521.2.
DR UniGene; Hs.327736; -.
DR PDB; 1BG2; X-ray; 1.80 A; A=1-325.
DR PDB; 1MKJ; X-ray; 2.70 A; A=1-349.
DR PDB; 2P4N; EM; 9.00 A; K=1-325.
DR PDB; 4HNA; X-ray; 3.19 A; K=1-349.
DR PDBsum; 1BG2; -.
DR PDBsum; 1MKJ; -.
DR PDBsum; 2P4N; -.
DR PDBsum; 4HNA; -.
DR ProteinModelPortal; P33176; -.
DR SMR; P33176; 3-325.
DR DIP; DIP-29244N; -.
DR IntAct; P33176; 22.
DR MINT; MINT-4999704; -.
DR STRING; 9606.ENSP00000307078; -.
DR BindingDB; P33176; -.
DR ChEMBL; CHEMBL5864; -.
DR PhosphoSite; P33176; -.
DR DMDM; 417216; -.
DR PaxDb; P33176; -.
DR PRIDE; P33176; -.
DR Ensembl; ENST00000302418; ENSP00000307078; ENSG00000170759.
DR GeneID; 3799; -.
DR KEGG; hsa:3799; -.
DR UCSC; uc001iwe.4; human.
DR CTD; 3799; -.
DR GeneCards; GC10M032340; -.
DR HGNC; HGNC:6324; KIF5B.
DR HPA; CAB009846; -.
DR MIM; 602809; gene.
DR neXtProt; NX_P33176; -.
DR PharmGKB; PA30108; -.
DR eggNOG; COG5059; -.
DR HOVERGEN; HBG006210; -.
DR InParanoid; P33176; -.
DR KO; K10396; -.
DR OMA; LAECNIK; -.
DR OrthoDB; EOG7T4MJD; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; KIF5B; human.
DR EvolutionaryTrace; P33176; -.
DR GeneWiki; KIF5B; -.
DR GenomeRNAi; 3799; -.
DR NextBio; 14917; -.
DR PRO; PR:P33176; -.
DR ArrayExpress; P33176; -.
DR Bgee; P33176; -.
DR CleanEx; HS_KIF5B; -.
DR Genevestigator; P33176; -.
DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl.
DR GO; GO:0005871; C:kinesin complex; TAS:ProtInc.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:HGNC.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; ISS:HGNC.
DR GO; GO:0003777; F:microtubule motor activity; ISS:HGNC.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0007028; P:cytoplasm organization; IEA:Ensembl.
DR GO; GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IDA:BHF-UCL.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IDA:BHF-UCL.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:BHF-UCL.
DR GO; GO:0035617; P:stress granule disassembly; ISS:BHF-UCL.
DR GO; GO:0047496; P:vesicle transport along microtubule; ISS:HGNC.
DR Gene3D; 3.40.850.10; -; 1.
DR InterPro; IPR027640; Kinesin-like_fam.
DR InterPro; IPR019821; Kinesin_motor_CS.
DR InterPro; IPR001752; Kinesin_motor_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24115; PTHR24115; 1.
DR Pfam; PF00225; Kinesin; 1.
DR PRINTS; PR00380; KINESINHEAVY.
DR SMART; SM00129; KISc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00411; KINESIN_MOTOR_DOMAIN1; 1.
DR PROSITE; PS50067; KINESIN_MOTOR_DOMAIN2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Coiled coil;
KW Complete proteome; Cytoplasm; Cytoskeleton; Microtubule;
KW Motor protein; Nucleotide-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 963 Kinesin-1 heavy chain.
FT /FTId=PRO_0000125351.
FT DOMAIN 2 328 Kinesin-motor.
FT NP_BIND 85 92 ATP.
FT REGION 915 963 Globular.
FT COILED 329 914
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 933 933 Phosphoserine.
FT STRAND 8 15
FT HELIX 20 25
FT STRAND 32 34
FT TURN 35 37
FT STRAND 38 41
FT STRAND 44 47
FT STRAND 49 52
FT HELIX 58 65
FT HELIX 67 74
FT STRAND 79 84
FT HELIX 91 95
FT TURN 102 104
FT HELIX 107 122
FT STRAND 124 138
FT STRAND 141 146
FT STRAND 155 157
FT STRAND 163 165
FT STRAND 171 173
FT HELIX 176 189
FT TURN 190 193
FT HELIX 197 203
FT STRAND 204 216
FT TURN 217 219
FT STRAND 222 231
FT HELIX 238 241
FT STRAND 242 244
FT HELIX 256 269
FT HELIX 277 279
FT HELIX 281 285
FT HELIX 286 288
FT STRAND 290 293
FT STRAND 295 302
FT HELIX 306 308
FT HELIX 309 320
FT STRAND 326 329
FT HELIX 337 348
SQ SEQUENCE 963 AA; 109685 MW; A1FE5760C3250C8B CRC64;
MADLAECNIK VMCRFRPLNE SEVNRGDKYI AKFQGEDTVV IASKPYAFDR VFQSSTSQEQ
VYNDCAKKIV KDVLEGYNGT IFAYGQTSSG KTHTMEGKLH DPEGMGIIPR IVQDIFNYIY
SMDENLEFHI KVSYFEIYLD KIRDLLDVSK TNLSVHEDKN RVPYVKGCTE RFVCSPDEVM
DTIDEGKSNR HVAVTNMNEH SSRSHSIFLI NVKQENTQTE QKLSGKLYLV DLAGSEKVSK
TGAEGAVLDE AKNINKSLSA LGNVISALAE GSTYVPYRDS KMTRILQDSL GGNCRTTIVI
CCSPSSYNES ETKSTLLFGQ RAKTIKNTVC VNVELTAEQW KKKYEKEKEK NKILRNTIQW
LENELNRWRN GETVPIDEQF DKEKANLEAF TVDKDITLTN DKPATAIGVI GNFTDAERRK
CEEEIAKLYK QLDDKDEEIN QQSQLVEKLK TQMLDQEELL ASTRRDQDNM QAELNRLQAE
NDASKEEVKE VLQALEELAV NYDQKSQEVE DKTKEYELLS DELNQKSATL ASIDAELQKL
KEMTNHQKKR AAEMMASLLK DLAEIGIAVG NNDVKQPEGT GMIDEEFTVA RLYISKMKSE
VKTMVKRCKQ LESTQTESNK KMEENEKELA ACQLRISQHE AKIKSLTEYL QNVEQKKRQL
EESVDALSEE LVQLRAQEKV HEMEKEHLNK VQTANEVKQA VEQQIQSHRE THQKQISSLR
DEVEAKAKLI TDLQDQNQKM MLEQERLRVE HEKLKATDQE KSRKLHELTV MQDRREQARQ
DLKGLEETVA KELQTLHNLR KLFVQDLATR VKKSAEIDSD DTGGSAAQKQ KISFLENNLE
QLTKVHKQLV RDNADLRCEL PKLEKRLRAT AERVKALESA LKEAKENASR DRKRYQQEVD
RIKEAVRSKN MARRGHSAQI AKPIRPGQHP AASPTHPSAI RGGGAFVQNS QPVAVRGGGG
KQV
//
ID KINH_HUMAN Reviewed; 963 AA.
AC P33176; A0AVB2; Q5VZ85;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1993, sequence version 1.
DT 22-JAN-2014, entry version 138.
DE RecName: Full=Kinesin-1 heavy chain;
DE AltName: Full=Conventional kinesin heavy chain;
DE AltName: Full=Ubiquitous kinesin heavy chain;
DE Short=UKHC;
GN Name=KIF5B; Synonyms=KNS, KNS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=1607388; DOI=10.1083/jcb.117.6.1263;
RA Navone F., Niclas J., Hom-Booher N., Sparks L., Bernstein H.D.,
RA McCaffrey G., Vale R.D.;
RT "Cloning and expression of a human kinesin heavy chain gene:
RT interaction of the COOH-terminal domain with cytoplasmic microtubules
RT in transfected CV-1 cells.";
RL J. Cell Biol. 117:1263-1275(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH SYBU.
RX PubMed=15459722; DOI=10.1038/ncb1169;
RA Su Q., Cai Q., Gerwin C., Smith C.L., Sheng Z.-H.;
RT "Syntabulin is a microtubule-associated protein implicated in syntaxin
RT transport in neurons.";
RL Nat. Cell Biol. 6:941-953(2004).
RN [5]
RP INTERACTION WITH PLEKHM2.
RX PubMed=15905402; DOI=10.1126/science.1110225;
RA Boucrot E., Henry T., Borg J.-P., Gorvel J.-P., Meresse S.;
RT "The intracellular fate of Salmonella depends on the recruitment of
RT kinesin.";
RL Science 308:1174-1178(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [7]
RP INTERACTION WITH JAKMIP1.
RX PubMed=17532644; DOI=10.1016/j.mcn.2007.04.008;
RA Vidal R.L., Ramirez O.A., Sandoval L., Koenig-Robert R., Haertel S.,
RA Couve A.;
RT "Marlin-1 and conventional kinesin link GABAB receptors to the
RT cytoskeleton and regulate receptor transport.";
RL Mol. Cell. Neurosci. 35:501-512(2007).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP INTERACTION WITH ECM29.
RX PubMed=20682791; DOI=10.1074/jbc.M110.154120;
RA Gorbea C., Pratt G., Ustrell V., Bell R., Sahasrabudhe S.,
RA Hughes R.E., Rechsteiner M.;
RT "A protein interaction network for Ecm29 links the 26 S proteasome to
RT molecular motors and endosomal components.";
RL J. Biol. Chem. 285:31616-31633(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-933, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-349 IN COMPLEX WITH ADP.
RX PubMed=8606779; DOI=10.1038/380550a0;
RA Kull F.J., Sablin E.P., Lau R., Fletterick R.J., Vale R.D.;
RT "Crystal structure of the kinesin motor domain reveals a structural
RT similarity to myosin.";
RL Nature 380:550-555(1996).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-349 IN COMPLEX WITH ADP.
RX PubMed=12368902; DOI=10.1038/nsb852;
RA Sindelar C.V., Budny M.J., Rice S., Naber N., Fletterick R., Cooke R.;
RT "Two conformations in the human kinesin power stroke defined by X-ray
RT crystallography and EPR spectroscopy.";
RL Nat. Struct. Biol. 9:844-848(2002).
RN [15]
RP STRUCTURE BY ELECTRON MICROSCOPY (9.0 ANGSTROMS) OF 1-325.
RX PubMed=17470637; DOI=10.1083/jcb.200612090;
RA Sindelar C.V., Downing K.H.;
RT "The beginning of kinesin's force-generating cycle visualized at 9-A
RT resolution.";
RL J. Cell Biol. 177:377-385(2007).
CC -!- FUNCTION: Microtubule-dependent motor required for normal
CC distribution of mitochondria and lysosomes (By similarity).
CC -!- SUBUNIT: Oligomer composed of two heavy chains and two light
CC chains. Interacts with GRIP1 and PPP1R42 (By similarity).
CC Interacts with SYBU. Interacts with JAKMIP1. Interacts with
CC PLEKHM2. Interacts with ECM29.
CC -!- INTERACTION:
CC P68619:VACWR159 (xeno); NbExp=3; IntAct=EBI-355878, EBI-7133540;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton (By similarity).
CC Note=Uniformly distributed between soma and neurites in
CC hippocampal neurons (By similarity).
CC -!- DOMAIN: Composed of three structural domains: a large globular N-
CC terminal domain which is responsible for the motor activity of
CC kinesin (it hydrolyzes ATP and binds microtubule), a central
CC alpha-helical coiled coil domain that mediates the heavy chain
CC dimerization; and a small globular C-terminal domain which
CC interacts with other proteins (such as the kinesin light chains),
CC vesicles and membranous organelles.
CC -!- SIMILARITY: Belongs to the kinesin-like protein family. Kinesin
CC subfamily.
CC -!- SIMILARITY: Contains 1 kinesin-motor domain.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; X65873; CAA46703.1; -; mRNA.
DR EMBL; AL161932; CAH71618.1; -; Genomic_DNA.
DR EMBL; BC126279; AAI26280.1; -; mRNA.
DR EMBL; BC126281; AAI26282.1; -; mRNA.
DR PIR; A41919; A41919.
DR RefSeq; NP_004512.1; NM_004521.2.
DR UniGene; Hs.327736; -.
DR PDB; 1BG2; X-ray; 1.80 A; A=1-325.
DR PDB; 1MKJ; X-ray; 2.70 A; A=1-349.
DR PDB; 2P4N; EM; 9.00 A; K=1-325.
DR PDB; 4HNA; X-ray; 3.19 A; K=1-349.
DR PDBsum; 1BG2; -.
DR PDBsum; 1MKJ; -.
DR PDBsum; 2P4N; -.
DR PDBsum; 4HNA; -.
DR ProteinModelPortal; P33176; -.
DR SMR; P33176; 3-325.
DR DIP; DIP-29244N; -.
DR IntAct; P33176; 22.
DR MINT; MINT-4999704; -.
DR STRING; 9606.ENSP00000307078; -.
DR BindingDB; P33176; -.
DR ChEMBL; CHEMBL5864; -.
DR PhosphoSite; P33176; -.
DR DMDM; 417216; -.
DR PaxDb; P33176; -.
DR PRIDE; P33176; -.
DR Ensembl; ENST00000302418; ENSP00000307078; ENSG00000170759.
DR GeneID; 3799; -.
DR KEGG; hsa:3799; -.
DR UCSC; uc001iwe.4; human.
DR CTD; 3799; -.
DR GeneCards; GC10M032340; -.
DR HGNC; HGNC:6324; KIF5B.
DR HPA; CAB009846; -.
DR MIM; 602809; gene.
DR neXtProt; NX_P33176; -.
DR PharmGKB; PA30108; -.
DR eggNOG; COG5059; -.
DR HOVERGEN; HBG006210; -.
DR InParanoid; P33176; -.
DR KO; K10396; -.
DR OMA; LAECNIK; -.
DR OrthoDB; EOG7T4MJD; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; KIF5B; human.
DR EvolutionaryTrace; P33176; -.
DR GeneWiki; KIF5B; -.
DR GenomeRNAi; 3799; -.
DR NextBio; 14917; -.
DR PRO; PR:P33176; -.
DR ArrayExpress; P33176; -.
DR Bgee; P33176; -.
DR CleanEx; HS_KIF5B; -.
DR Genevestigator; P33176; -.
DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl.
DR GO; GO:0005871; C:kinesin complex; TAS:ProtInc.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:HGNC.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; ISS:HGNC.
DR GO; GO:0003777; F:microtubule motor activity; ISS:HGNC.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0007028; P:cytoplasm organization; IEA:Ensembl.
DR GO; GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IDA:BHF-UCL.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IDA:BHF-UCL.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:BHF-UCL.
DR GO; GO:0035617; P:stress granule disassembly; ISS:BHF-UCL.
DR GO; GO:0047496; P:vesicle transport along microtubule; ISS:HGNC.
DR Gene3D; 3.40.850.10; -; 1.
DR InterPro; IPR027640; Kinesin-like_fam.
DR InterPro; IPR019821; Kinesin_motor_CS.
DR InterPro; IPR001752; Kinesin_motor_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24115; PTHR24115; 1.
DR Pfam; PF00225; Kinesin; 1.
DR PRINTS; PR00380; KINESINHEAVY.
DR SMART; SM00129; KISc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00411; KINESIN_MOTOR_DOMAIN1; 1.
DR PROSITE; PS50067; KINESIN_MOTOR_DOMAIN2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Coiled coil;
KW Complete proteome; Cytoplasm; Cytoskeleton; Microtubule;
KW Motor protein; Nucleotide-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 963 Kinesin-1 heavy chain.
FT /FTId=PRO_0000125351.
FT DOMAIN 2 328 Kinesin-motor.
FT NP_BIND 85 92 ATP.
FT REGION 915 963 Globular.
FT COILED 329 914
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 933 933 Phosphoserine.
FT STRAND 8 15
FT HELIX 20 25
FT STRAND 32 34
FT TURN 35 37
FT STRAND 38 41
FT STRAND 44 47
FT STRAND 49 52
FT HELIX 58 65
FT HELIX 67 74
FT STRAND 79 84
FT HELIX 91 95
FT TURN 102 104
FT HELIX 107 122
FT STRAND 124 138
FT STRAND 141 146
FT STRAND 155 157
FT STRAND 163 165
FT STRAND 171 173
FT HELIX 176 189
FT TURN 190 193
FT HELIX 197 203
FT STRAND 204 216
FT TURN 217 219
FT STRAND 222 231
FT HELIX 238 241
FT STRAND 242 244
FT HELIX 256 269
FT HELIX 277 279
FT HELIX 281 285
FT HELIX 286 288
FT STRAND 290 293
FT STRAND 295 302
FT HELIX 306 308
FT HELIX 309 320
FT STRAND 326 329
FT HELIX 337 348
SQ SEQUENCE 963 AA; 109685 MW; A1FE5760C3250C8B CRC64;
MADLAECNIK VMCRFRPLNE SEVNRGDKYI AKFQGEDTVV IASKPYAFDR VFQSSTSQEQ
VYNDCAKKIV KDVLEGYNGT IFAYGQTSSG KTHTMEGKLH DPEGMGIIPR IVQDIFNYIY
SMDENLEFHI KVSYFEIYLD KIRDLLDVSK TNLSVHEDKN RVPYVKGCTE RFVCSPDEVM
DTIDEGKSNR HVAVTNMNEH SSRSHSIFLI NVKQENTQTE QKLSGKLYLV DLAGSEKVSK
TGAEGAVLDE AKNINKSLSA LGNVISALAE GSTYVPYRDS KMTRILQDSL GGNCRTTIVI
CCSPSSYNES ETKSTLLFGQ RAKTIKNTVC VNVELTAEQW KKKYEKEKEK NKILRNTIQW
LENELNRWRN GETVPIDEQF DKEKANLEAF TVDKDITLTN DKPATAIGVI GNFTDAERRK
CEEEIAKLYK QLDDKDEEIN QQSQLVEKLK TQMLDQEELL ASTRRDQDNM QAELNRLQAE
NDASKEEVKE VLQALEELAV NYDQKSQEVE DKTKEYELLS DELNQKSATL ASIDAELQKL
KEMTNHQKKR AAEMMASLLK DLAEIGIAVG NNDVKQPEGT GMIDEEFTVA RLYISKMKSE
VKTMVKRCKQ LESTQTESNK KMEENEKELA ACQLRISQHE AKIKSLTEYL QNVEQKKRQL
EESVDALSEE LVQLRAQEKV HEMEKEHLNK VQTANEVKQA VEQQIQSHRE THQKQISSLR
DEVEAKAKLI TDLQDQNQKM MLEQERLRVE HEKLKATDQE KSRKLHELTV MQDRREQARQ
DLKGLEETVA KELQTLHNLR KLFVQDLATR VKKSAEIDSD DTGGSAAQKQ KISFLENNLE
QLTKVHKQLV RDNADLRCEL PKLEKRLRAT AERVKALESA LKEAKENASR DRKRYQQEVD
RIKEAVRSKN MARRGHSAQI AKPIRPGQHP AASPTHPSAI RGGGAFVQNS QPVAVRGGGG
KQV
//
MIM
602809
*RECORD*
*FIELD* NO
602809
*FIELD* TI
*602809 KINESIN FAMILY MEMBER 5B; KIF5B
;;KINESIN 1 HEAVY CHAIN; KNS1;;
KINESIN, HEAVY CHAIN, UBIQUITOUS; UKHC;;
read moreKINH
*FIELD* TX
DESCRIPTION
Kinesins are microtubule-based motor proteins involved in the transport
of organelles in eukaryotic cells. They typically consist of 2
identical, approximately 110- to 120-kD heavy chains, such as KIF5B, and
2 identical, approximately 60- to 70-kD light chains. The heavy chain
contains 3 domains: a globular N-terminal motor domain, which converts
the chemical energy of ATP into a motile force along microtubules in 1
fixed direction; a central alpha-helical rod domain, which enables the 2
heavy chains to dimerize; and a globular C-terminal domain, which
interacts with light chains and possibly an organelle receptor (summary
by Navone et al. (1992) and Niclas et al. (1994)).
CLONING
By screening a human placenta cDNA library with a probe based on a
conserved region of the Drosophila and squid kinesin heavy chains
(KHCs), Navone et al. (1992) isolated cDNAs encoding KNS1. The predicted
963-amino acid protein has 63% sequence identity to the Drosophila KHC.
Immunoblot analysis using antibodies against squid KHC detected a 120-kD
protein in CV-1 monkey kidney epithelial cells. Immunofluorescence
studies showed that KNS1 expressed in CV-1 cells had both a diffuse
distribution and a filamentous staining pattern that coaligned with
microtubules but not vimentin (VIM; 193060) intermediate filaments; the
KNS1 N- and C-terminal domains, but not the alpha-helical rod domain,
also colocalized with microtubules.
By Northern blot analysis, Niclas et al. (1994) demonstrated that Ukhc
was expressed as multiple transcripts in all rat tissues examined.
Immunoblot analysis of rat tissue extracts using antibodies specific for
UKHC detected a 120-kD protein in all examined tissues. Niclas et al.
(1994) found that UKHC is distributed uniformly between the cell body
and processes of cultured hippocampal neurons.
MAPPING
Niclas et al. (1994) stated that the placenta UKHC cDNA isolated by
Navone et al. (1992) hybridizes to a region on mouse chromosome 18 that
shows homology of synteny with human 18q. However, Gross (2013) mapped
the human KIF5B gene to chromosome 10p11.22 based on an alignment of the
KIF5B sequence (GenBank GENBANK BC126279) with the genomic sequence
(GRCh37).
NOMENCLATURE
Lawrence et al. (2004) presented a standardized kinesin nomenclature
based on 14 family designations. Under this system, KIF5B belongs to the
kinesin-1 family.
GENE FUNCTION
Kamal et al. (2000) demonstrated that the axonal transport of APP in
neurons is mediated by the direct binding of APP to the kinesin light
chain (600025) subunit of kinesin-I. Kamal et al. (2001) identified an
axonal membrane compartment that contains APP, beta-secretase (604252),
and presenilin-1 (104311). The fast anterograde axonal transport of this
compartment is mediated by APP and kinesin-I. Proteolytic processing of
APP can occur in the compartment in vitro and in vivo in axons. This
proteolysis generates amyloid-beta and a carboxy-terminal fragment of
APP, and liberates kinesin-I from the membrane. Kamal et al. (2001)
concluded that APP functions as a kinesin-I membrane receptor, mediating
the axonal transport of beta-secretase and presenilin-1, and that
processing of APP to amyloid-beta by secretases can occur in an axonal
membrane compartment transported by kinesin-I.
Kanai et al. (2004) found that the hinge and C-terminal tail regions of
Kif5a (602821), Kif5b, and Kif5c (604593) bound a large
detergent-resistant RNase-sensitive granule from mouse brain. Mass
spectrometric analysis showed that the granule contained mRNAs for
Camk2-alpha (CAMK2A; 114078) and Arc (NOL3; 605235) and 42 proteins,
including those for RNA transport, protein synthesis, and translational
silencing. The granule localized to dendrites and underwent
bidirectional movement. Distally directed movement of the granule was
enhanced by Kif5 overexpression and reduced by Kif5 functional blockage.
Kanai et al. (2004) concluded that kinesins transport RNA in dendrites
via this large granule.
Kural et al. (2005) used fluorescence imaging with 1-nanometer accuracy
(FIONA) to analyze organelle movement by conventional kinesin and
cytoplasmic dynein (see 600112) in a cell. They located a green
fluorescent protein (GFP)-tagged peroxisome in cultured Drosophila S2
cells to within 1.5 nanometers in 1.1 milliseconds, a 400-fold
improvement in temporal resolution, sufficient to determine the average
step size to be approximately 8 nanometers for both dynein and kinesin.
Furthermore, Kural et al. (2005) found that dynein and kinesin do not
work against each other in vivo during peroxisome transport. Rather,
multiple kinesins or multiple dyneins work together, producing up to 10
times the in vitro speed.
To determine the effects of tau (157140) on dynein and kinesin motility,
Dixit et al. (2008) conducted single-molecule studies of motor proteins
moving along tau-decorated microtubules. Dynein tended to reverse
direction, whereas kinesin tended to detach at patches of bound tau.
Kinesin was inhibited at about a tenth of the tau concentration that
inhibited dynein, and the microtubule-binding domain of tau was
sufficient to inhibit motor activity. The differential modulation of
dynein and kinesin motility suggests that microtubule-associated
proteins (MAPs) can spatially regulate the balance of
microtubule-dependent axonal transport.
Metzger et al. (2012) identified the microtubule-associated protein MAP7
(604108) and KIF5B as essential, evolutionarily conserved regulators of
myonuclear positioning in Drosophila and cultured mammalian myotubes.
Metzger et al. (2012) found that these proteins interact physically and
that expression of the KIF5B motor domain fused to the MAP7
microtubule-binding domain rescues nuclear positioning defects in
MAP7-depleted cells. This suggested that MAP7 links KIF5B to the
microtubule cytoskeleton to promote nuclear positioning. Finally,
Metzger et al. (2012) showed that myonuclear positioning is
physiologically important. Drosophila ensconsin (ens; homolog of MAP7)
mutant larvae have decreased locomotion and incorrect myonuclear
positioning, and these phenotypes are rescued by muscle-specific
expression of ens. Metzger et al. (2012) concluded that improper nuclear
positioning contributes to muscle dysfunction in a cell-autonomous
fashion.
BIOCHEMICAL FEATURES
- Crystal Structure
Kull et al. (1996) reported the crystal structure of the human kinesin
motor domain with bound ADP. The motor consists primarily of a single
alpha/beta arrowhead-shaped domain. It has striking structural
similarity to the core of the catalytic domain of the actin-based motor
myosin, although kinesin and myosin have virtually no amino acid
sequence identity and exhibit distinct enzymatic and motile properties.
Mori et al. (2007) developed 2 different single-molecule fluorescence
resonance energy transfer sensors to detect whether kinesin is bound to
its microtubule track by 1 or 2 heads. Their FRET results indicated
that, while moving in the presence of saturating ATP, kinesin spends
most of its time bound to the microtubule with both heads. However, when
nucleotide binding becomes rate-limiting at low ATP concentrations,
kinesin waits for ATP in a one-head-bound state and makes brief
transitions to a 2-head-bound intermediate as it walks along the
microtubule. On the basis of these results, Mori et al. (2007) suggested
a model for how transitions in the ATPase cycle position the 2 kinesin
heads and drive their hand-over-hand motion.
Pernigo et al. (2013) presented the crystal structure of the
tetratricopeptide repeat domain of kinesin light chain-2 (611729) in
complex with a cargo peptide harboring a tryptophan-acidic motif derived
from SKIP (609613), a critical host determinant in Salmonella
pathogenesis and a regulator of lysosomal positioning. Structural data
together with biophysical, biochemical, and cellular assays allowed
Pernigo et al. (2013) to propose a framework for intracellular transport
based on the binding by kinesin-1 of W-acidic cargo motifs through a
combination of electrostatic interactions and sequence-specific
elements, providing direct molecular evidence of the mechanisms for
kinesin-1:cargo recognition.
ANIMAL MODEL
Tanaka et al. (1998) disrupted the mouse kif5B gene by homologous
recombination. The kif5B -/- mice were embryonic lethal with a severe
growth retardation at 9.5 to 11.5 days postcoitum. To analyze the
significance of this conventional kinesin heavy chain in organelle
transport, the authors studied the distribution of major organelles in
the extraembryonic cells. The null mutant cells impaired lysosomal
dispersion, while brefeldin A could normally induce the breakdown of
their Golgi apparatus. More prominently, their mitochondria abnormally
clustered in the perinuclear region. This mitochondrial phenotype was
reversed by an exogenous expression of KIF5B, and a subcellular
fractionation revealed that KIF5B was associated with mitochondria.
These data indicated that kinesin is essential for mitochondrial and
lysosomal dispersion rather than for the Golgi-to-endoplasmic reticulum
traffic in these cells.
*FIELD* RF
1. Dixit, R.; Ross, J. L.; Goldman, Y. E.; Holzbaur, E. L. F.: Differential
regulation of dynein and kinesin motor proteins by tau. Science 319:
1086-1089, 2008.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 9/18/2013.
3. Kamal, A.; Almenar-Queralt, A.; LeBlanc, J. F.; Roberts, E. A.;
Goldstein, L. S. B.: Kinesin-mediated axonal transport of a membrane
compartment containing beta-secretase and presenilin-1 requires APP. Nature 414:
643-648, 2001.
4. Kamal, A.; Stokin, G. B.; Yang, Z.; Xia, C.; Goldstein, L. S.:
Axonal transport of amyloid precursor protein is mediated by direct
binding to the kinesin light chain subunit of kinesin-I. Neuron 28:
449-459, 2000.
5. Kanai, Y.; Dohmae, N.; Hirokawa, N.: Kinesin transports RNA: isolation
and characterization of an RNA-transporting granule. Neuron 43:
513-525, 2004.
6. Kull, F. J.; Sablin, E. P.; Lau, R.; Fletterick, R. J.; Vale, R.
D.: Crystal structure of the kinesin motor domain reveals a structural
similarity to myosin. Nature 380: 550-555, 1996.
7. Kural, C.; Kim, H.; Syed, S.; Goshima, G.; Gelfand, V. I.; Selvin,
P. R.: Kinesin and dynein move a peroxisome in vivo: a tug-of-war
or coordinated movement? Science 308: 1469-1472, 2005.
8. Lawrence, C. J.; Dawe, R. K.; Christie, K. R.; Cleveland, D. W.;
Dawson, S. C.; Endow, S. A.; Goldstein, L. S. B.; Goodson, H. V.;
Hirokawa, N.; Howard, J.; Malmberg, R. L.; McIntosh, J. R.; and 10
others: A standardized kinesin nomenclature. J. Cell Biol. 167:
19-22, 2004.
9. Metzger, T.; Gache, V.; Xu, M.; Cadot, B.; Folker, E. S.; Richardson,
B. E.; Gomes, E. R.; Baylies, M. K.: MAP and kinesin-dependent nuclear
positioning is required for skeletal muscle function. Nature 484:
120-124, 2012.
10. Mori, T.; Vale, R. D.; Tomishige, M.: How kinesin waits between
steps. Nature 450: 750-754, 2007.
11. Navone, F.; Niclas, J.; Hom-Booher, N.; Sparks, L.; Bernstein,
H. D.; McCaffrey, G.; Vale, R. D.: Cloning and expression of a human
kinesin heavy chain gene: interaction of the COOH-terminal domain
with cytoplasmic microtubules in transfected CV-1 cells. J. Cell
Biol. 117: 1263-1275, 1992.
12. Niclas, J.; Navone, F.; Hom-Booher, N.; Vale, R. D.: Cloning
and localization of a conventional kinesin motor expressed exclusively
in neurons. Neuron 12: 1059-1072, 1994.
13. Pernigo, S.; Lamprecht, A.; Steiner, R. A.; Dodding, M. P.: Structural
basis for kinesin-1:cargo recognition. Science 340: 356-359, 2013.
14. Tanaka, Y.; Kanai, Y.; Okada, Y.; Nonaka, S.; Takeda, S.; Harada,
A.; Hirokawa, N.: Targeted disruption of mouse conventional kinesin
heavy chain, kif5B, results in abnormal perinuclear clustering of
mitochondria. Cell 93: 1147-1158, 1998.
*FIELD* CN
Matthew B. Gross - updated: 09/18/2013
Ada Hamosh - updated: 5/2/2013
Matthew B. Gross - updated: 6/21/2012
Ada Hamosh - updated: 4/24/2012
Patricia A. Hartz - updated: 5/4/2011
Ada Hamosh - updated: 4/4/2008
Ada Hamosh - updated: 1/22/2008
Ada Hamosh - updated: 8/2/2005
Ada Hamosh - updated: 1/2/2002
Stylianos E. Antonarakis - updated: 7/17/1998
*FIELD* CD
Patti M. Sherman: 7/9/1998
*FIELD* ED
mgross: 09/18/2013
alopez: 5/3/2013
alopez: 5/2/2013
mgross: 6/21/2012
alopez: 4/26/2012
terry: 4/24/2012
mgross: 5/20/2011
terry: 5/4/2011
alopez: 4/11/2008
terry: 4/4/2008
alopez: 1/24/2008
terry: 1/22/2008
alopez: 8/3/2005
terry: 8/2/2005
alopez: 10/3/2002
terry: 3/6/2002
alopez: 1/8/2002
terry: 1/2/2002
psherman: 2/22/2000
alopez: 5/18/1999
psherman: 4/16/1999
psherman: 12/2/1998
carol: 7/17/1998
carol: 7/16/1998
carol: 7/13/1998
*RECORD*
*FIELD* NO
602809
*FIELD* TI
*602809 KINESIN FAMILY MEMBER 5B; KIF5B
;;KINESIN 1 HEAVY CHAIN; KNS1;;
KINESIN, HEAVY CHAIN, UBIQUITOUS; UKHC;;
read moreKINH
*FIELD* TX
DESCRIPTION
Kinesins are microtubule-based motor proteins involved in the transport
of organelles in eukaryotic cells. They typically consist of 2
identical, approximately 110- to 120-kD heavy chains, such as KIF5B, and
2 identical, approximately 60- to 70-kD light chains. The heavy chain
contains 3 domains: a globular N-terminal motor domain, which converts
the chemical energy of ATP into a motile force along microtubules in 1
fixed direction; a central alpha-helical rod domain, which enables the 2
heavy chains to dimerize; and a globular C-terminal domain, which
interacts with light chains and possibly an organelle receptor (summary
by Navone et al. (1992) and Niclas et al. (1994)).
CLONING
By screening a human placenta cDNA library with a probe based on a
conserved region of the Drosophila and squid kinesin heavy chains
(KHCs), Navone et al. (1992) isolated cDNAs encoding KNS1. The predicted
963-amino acid protein has 63% sequence identity to the Drosophila KHC.
Immunoblot analysis using antibodies against squid KHC detected a 120-kD
protein in CV-1 monkey kidney epithelial cells. Immunofluorescence
studies showed that KNS1 expressed in CV-1 cells had both a diffuse
distribution and a filamentous staining pattern that coaligned with
microtubules but not vimentin (VIM; 193060) intermediate filaments; the
KNS1 N- and C-terminal domains, but not the alpha-helical rod domain,
also colocalized with microtubules.
By Northern blot analysis, Niclas et al. (1994) demonstrated that Ukhc
was expressed as multiple transcripts in all rat tissues examined.
Immunoblot analysis of rat tissue extracts using antibodies specific for
UKHC detected a 120-kD protein in all examined tissues. Niclas et al.
(1994) found that UKHC is distributed uniformly between the cell body
and processes of cultured hippocampal neurons.
MAPPING
Niclas et al. (1994) stated that the placenta UKHC cDNA isolated by
Navone et al. (1992) hybridizes to a region on mouse chromosome 18 that
shows homology of synteny with human 18q. However, Gross (2013) mapped
the human KIF5B gene to chromosome 10p11.22 based on an alignment of the
KIF5B sequence (GenBank GENBANK BC126279) with the genomic sequence
(GRCh37).
NOMENCLATURE
Lawrence et al. (2004) presented a standardized kinesin nomenclature
based on 14 family designations. Under this system, KIF5B belongs to the
kinesin-1 family.
GENE FUNCTION
Kamal et al. (2000) demonstrated that the axonal transport of APP in
neurons is mediated by the direct binding of APP to the kinesin light
chain (600025) subunit of kinesin-I. Kamal et al. (2001) identified an
axonal membrane compartment that contains APP, beta-secretase (604252),
and presenilin-1 (104311). The fast anterograde axonal transport of this
compartment is mediated by APP and kinesin-I. Proteolytic processing of
APP can occur in the compartment in vitro and in vivo in axons. This
proteolysis generates amyloid-beta and a carboxy-terminal fragment of
APP, and liberates kinesin-I from the membrane. Kamal et al. (2001)
concluded that APP functions as a kinesin-I membrane receptor, mediating
the axonal transport of beta-secretase and presenilin-1, and that
processing of APP to amyloid-beta by secretases can occur in an axonal
membrane compartment transported by kinesin-I.
Kanai et al. (2004) found that the hinge and C-terminal tail regions of
Kif5a (602821), Kif5b, and Kif5c (604593) bound a large
detergent-resistant RNase-sensitive granule from mouse brain. Mass
spectrometric analysis showed that the granule contained mRNAs for
Camk2-alpha (CAMK2A; 114078) and Arc (NOL3; 605235) and 42 proteins,
including those for RNA transport, protein synthesis, and translational
silencing. The granule localized to dendrites and underwent
bidirectional movement. Distally directed movement of the granule was
enhanced by Kif5 overexpression and reduced by Kif5 functional blockage.
Kanai et al. (2004) concluded that kinesins transport RNA in dendrites
via this large granule.
Kural et al. (2005) used fluorescence imaging with 1-nanometer accuracy
(FIONA) to analyze organelle movement by conventional kinesin and
cytoplasmic dynein (see 600112) in a cell. They located a green
fluorescent protein (GFP)-tagged peroxisome in cultured Drosophila S2
cells to within 1.5 nanometers in 1.1 milliseconds, a 400-fold
improvement in temporal resolution, sufficient to determine the average
step size to be approximately 8 nanometers for both dynein and kinesin.
Furthermore, Kural et al. (2005) found that dynein and kinesin do not
work against each other in vivo during peroxisome transport. Rather,
multiple kinesins or multiple dyneins work together, producing up to 10
times the in vitro speed.
To determine the effects of tau (157140) on dynein and kinesin motility,
Dixit et al. (2008) conducted single-molecule studies of motor proteins
moving along tau-decorated microtubules. Dynein tended to reverse
direction, whereas kinesin tended to detach at patches of bound tau.
Kinesin was inhibited at about a tenth of the tau concentration that
inhibited dynein, and the microtubule-binding domain of tau was
sufficient to inhibit motor activity. The differential modulation of
dynein and kinesin motility suggests that microtubule-associated
proteins (MAPs) can spatially regulate the balance of
microtubule-dependent axonal transport.
Metzger et al. (2012) identified the microtubule-associated protein MAP7
(604108) and KIF5B as essential, evolutionarily conserved regulators of
myonuclear positioning in Drosophila and cultured mammalian myotubes.
Metzger et al. (2012) found that these proteins interact physically and
that expression of the KIF5B motor domain fused to the MAP7
microtubule-binding domain rescues nuclear positioning defects in
MAP7-depleted cells. This suggested that MAP7 links KIF5B to the
microtubule cytoskeleton to promote nuclear positioning. Finally,
Metzger et al. (2012) showed that myonuclear positioning is
physiologically important. Drosophila ensconsin (ens; homolog of MAP7)
mutant larvae have decreased locomotion and incorrect myonuclear
positioning, and these phenotypes are rescued by muscle-specific
expression of ens. Metzger et al. (2012) concluded that improper nuclear
positioning contributes to muscle dysfunction in a cell-autonomous
fashion.
BIOCHEMICAL FEATURES
- Crystal Structure
Kull et al. (1996) reported the crystal structure of the human kinesin
motor domain with bound ADP. The motor consists primarily of a single
alpha/beta arrowhead-shaped domain. It has striking structural
similarity to the core of the catalytic domain of the actin-based motor
myosin, although kinesin and myosin have virtually no amino acid
sequence identity and exhibit distinct enzymatic and motile properties.
Mori et al. (2007) developed 2 different single-molecule fluorescence
resonance energy transfer sensors to detect whether kinesin is bound to
its microtubule track by 1 or 2 heads. Their FRET results indicated
that, while moving in the presence of saturating ATP, kinesin spends
most of its time bound to the microtubule with both heads. However, when
nucleotide binding becomes rate-limiting at low ATP concentrations,
kinesin waits for ATP in a one-head-bound state and makes brief
transitions to a 2-head-bound intermediate as it walks along the
microtubule. On the basis of these results, Mori et al. (2007) suggested
a model for how transitions in the ATPase cycle position the 2 kinesin
heads and drive their hand-over-hand motion.
Pernigo et al. (2013) presented the crystal structure of the
tetratricopeptide repeat domain of kinesin light chain-2 (611729) in
complex with a cargo peptide harboring a tryptophan-acidic motif derived
from SKIP (609613), a critical host determinant in Salmonella
pathogenesis and a regulator of lysosomal positioning. Structural data
together with biophysical, biochemical, and cellular assays allowed
Pernigo et al. (2013) to propose a framework for intracellular transport
based on the binding by kinesin-1 of W-acidic cargo motifs through a
combination of electrostatic interactions and sequence-specific
elements, providing direct molecular evidence of the mechanisms for
kinesin-1:cargo recognition.
ANIMAL MODEL
Tanaka et al. (1998) disrupted the mouse kif5B gene by homologous
recombination. The kif5B -/- mice were embryonic lethal with a severe
growth retardation at 9.5 to 11.5 days postcoitum. To analyze the
significance of this conventional kinesin heavy chain in organelle
transport, the authors studied the distribution of major organelles in
the extraembryonic cells. The null mutant cells impaired lysosomal
dispersion, while brefeldin A could normally induce the breakdown of
their Golgi apparatus. More prominently, their mitochondria abnormally
clustered in the perinuclear region. This mitochondrial phenotype was
reversed by an exogenous expression of KIF5B, and a subcellular
fractionation revealed that KIF5B was associated with mitochondria.
These data indicated that kinesin is essential for mitochondrial and
lysosomal dispersion rather than for the Golgi-to-endoplasmic reticulum
traffic in these cells.
*FIELD* RF
1. Dixit, R.; Ross, J. L.; Goldman, Y. E.; Holzbaur, E. L. F.: Differential
regulation of dynein and kinesin motor proteins by tau. Science 319:
1086-1089, 2008.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 9/18/2013.
3. Kamal, A.; Almenar-Queralt, A.; LeBlanc, J. F.; Roberts, E. A.;
Goldstein, L. S. B.: Kinesin-mediated axonal transport of a membrane
compartment containing beta-secretase and presenilin-1 requires APP. Nature 414:
643-648, 2001.
4. Kamal, A.; Stokin, G. B.; Yang, Z.; Xia, C.; Goldstein, L. S.:
Axonal transport of amyloid precursor protein is mediated by direct
binding to the kinesin light chain subunit of kinesin-I. Neuron 28:
449-459, 2000.
5. Kanai, Y.; Dohmae, N.; Hirokawa, N.: Kinesin transports RNA: isolation
and characterization of an RNA-transporting granule. Neuron 43:
513-525, 2004.
6. Kull, F. J.; Sablin, E. P.; Lau, R.; Fletterick, R. J.; Vale, R.
D.: Crystal structure of the kinesin motor domain reveals a structural
similarity to myosin. Nature 380: 550-555, 1996.
7. Kural, C.; Kim, H.; Syed, S.; Goshima, G.; Gelfand, V. I.; Selvin,
P. R.: Kinesin and dynein move a peroxisome in vivo: a tug-of-war
or coordinated movement? Science 308: 1469-1472, 2005.
8. Lawrence, C. J.; Dawe, R. K.; Christie, K. R.; Cleveland, D. W.;
Dawson, S. C.; Endow, S. A.; Goldstein, L. S. B.; Goodson, H. V.;
Hirokawa, N.; Howard, J.; Malmberg, R. L.; McIntosh, J. R.; and 10
others: A standardized kinesin nomenclature. J. Cell Biol. 167:
19-22, 2004.
9. Metzger, T.; Gache, V.; Xu, M.; Cadot, B.; Folker, E. S.; Richardson,
B. E.; Gomes, E. R.; Baylies, M. K.: MAP and kinesin-dependent nuclear
positioning is required for skeletal muscle function. Nature 484:
120-124, 2012.
10. Mori, T.; Vale, R. D.; Tomishige, M.: How kinesin waits between
steps. Nature 450: 750-754, 2007.
11. Navone, F.; Niclas, J.; Hom-Booher, N.; Sparks, L.; Bernstein,
H. D.; McCaffrey, G.; Vale, R. D.: Cloning and expression of a human
kinesin heavy chain gene: interaction of the COOH-terminal domain
with cytoplasmic microtubules in transfected CV-1 cells. J. Cell
Biol. 117: 1263-1275, 1992.
12. Niclas, J.; Navone, F.; Hom-Booher, N.; Vale, R. D.: Cloning
and localization of a conventional kinesin motor expressed exclusively
in neurons. Neuron 12: 1059-1072, 1994.
13. Pernigo, S.; Lamprecht, A.; Steiner, R. A.; Dodding, M. P.: Structural
basis for kinesin-1:cargo recognition. Science 340: 356-359, 2013.
14. Tanaka, Y.; Kanai, Y.; Okada, Y.; Nonaka, S.; Takeda, S.; Harada,
A.; Hirokawa, N.: Targeted disruption of mouse conventional kinesin
heavy chain, kif5B, results in abnormal perinuclear clustering of
mitochondria. Cell 93: 1147-1158, 1998.
*FIELD* CN
Matthew B. Gross - updated: 09/18/2013
Ada Hamosh - updated: 5/2/2013
Matthew B. Gross - updated: 6/21/2012
Ada Hamosh - updated: 4/24/2012
Patricia A. Hartz - updated: 5/4/2011
Ada Hamosh - updated: 4/4/2008
Ada Hamosh - updated: 1/22/2008
Ada Hamosh - updated: 8/2/2005
Ada Hamosh - updated: 1/2/2002
Stylianos E. Antonarakis - updated: 7/17/1998
*FIELD* CD
Patti M. Sherman: 7/9/1998
*FIELD* ED
mgross: 09/18/2013
alopez: 5/3/2013
alopez: 5/2/2013
mgross: 6/21/2012
alopez: 4/26/2012
terry: 4/24/2012
mgross: 5/20/2011
terry: 5/4/2011
alopez: 4/11/2008
terry: 4/4/2008
alopez: 1/24/2008
terry: 1/22/2008
alopez: 8/3/2005
terry: 8/2/2005
alopez: 10/3/2002
terry: 3/6/2002
alopez: 1/8/2002
terry: 1/2/2002
psherman: 2/22/2000
alopez: 5/18/1999
psherman: 4/16/1999
psherman: 12/2/1998
carol: 7/17/1998
carol: 7/16/1998
carol: 7/13/1998