KIF5A_HUMAN
ID KIF5A_HUMAN Reviewed; 1032 AA.
AC Q12840; A6H8M5; Q4LE26;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Kinesin heavy chain isoform 5A;
DE AltName: Full=Kinesin heavy chain neuron-specific 1;
DE AltName: Full=Neuronal kinesin heavy chain;
DE Short=NKHC;
GN Name=KIF5A; Synonyms=NKHC1;
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].
RC TISSUE=Hippocampus;
RX PubMed=7514426; DOI=10.1016/0896-6273(94)90314-x;
RA Niclas J., Navone F., Hom-Booher N., Vale R.D.;
RT "Cloning and localization of a conventional kinesin motor expressed
RT exclusively in neurons.";
RL Neuron 12:1059-1072(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R.,
RA Okazaki N., Koga H., Nagase T., Ohara O.;
RT "Preparation of a set of expression-ready clones of mammalian long cDNAs
RT encoding large proteins by the ORF trap cloning method.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP INTERACTION WITH BICD2.
RX PubMed=20386726; DOI=10.1371/journal.pbio.1000350;
RA Splinter D., Tanenbaum M.E., Lindqvist A., Jaarsma D., Flotho A., Yu K.L.,
RA Grigoriev I., Engelsma D., Haasdijk E.D., Keijzer N., Demmers J.,
RA Fornerod M., Melchior F., Hoogenraad C.C., Medema R.H., Akhmanova A.;
RT "Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes
RT and regulate centrosome and nuclear positioning during mitotic entry.";
RL PLoS Biol. 8:E1000350-E1000350(2010).
RN [7]
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., Buerckstuemmer T.,
RA 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 [8]
RP INTERACTION WITH BORCS5.
RX PubMed=25898167; DOI=10.1016/j.devcel.2015.02.011;
RA Pu J., Schindler C., Jia R., Jarnik M., Backlund P., Bonifacino J.S.;
RT "BORC, a multisubunit complex that regulates lysosome positioning.";
RL Dev. Cell 33:176-188(2015).
RN [9]
RP VARIANT SPG10 SER-256.
RX PubMed=12355402; DOI=10.1086/344210;
RA Reid E., Kloos M., Ashley-Koch A., Hughes L., Bevan S., Svenson I.K.,
RA Graham F.L., Gaskell P.C., Dearlove A., Pericak-Vance M.A.,
RA Rubinsztein D.C., Marchuk D.A.;
RT "A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia
RT (SPG10).";
RL Am. J. Hum. Genet. 71:1189-1194(2002).
RN [10]
RP VARIANT SPG10 CYS-280.
RX PubMed=15452312; DOI=10.1212/01.wnl.0000138731.60693.d2;
RA Fichera M., Lo Giudice M., Falco M., Sturnio M., Amata S., Calabrese O.,
RA Bigoni S., Calzolari E., Neri M.;
RT "Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary
RT spastic paraplegia.";
RL Neurology 63:1108-1110(2004).
RN [11]
RP VARIANT SPG10 VAL-361.
RX PubMed=16476820; DOI=10.1001/archneur.63.2.284;
RA Lo Giudice M., Neri M., Falco M., Sturnio M., Calzolari E.,
RA Di Benedetto D., Fichera M.;
RT "A missense mutation in the coiled-coil domain of the KIF5A gene and late-
RT onset hereditary spastic paraplegia.";
RL Arch. Neurol. 63:284-287(2006).
RN [12]
RP VARIANT SPG10 CYS-276.
RX PubMed=16489470; DOI=10.1007/s10048-005-0027-8;
RA Blair M.A., Ma S., Hedera P.;
RT "Mutation in KIF5A can also cause adult-onset hereditary spastic
RT paraplegia.";
RL Neurogenetics 7:47-50(2006).
RN [13]
RP VARIANT ASN-253, CHARACTERIZATION OF VARIANT ASN-253, CHARACTERIZATION OF
RP VARIANTS SPG10 SER-256 AND VAL-361, AND MUTAGENESIS OF ARG-280.
RX PubMed=18203753; DOI=10.1093/hmg/ddn014;
RA Ebbing B., Mann K., Starosta A., Jaud J., Schoels L., Schuele R.,
RA Woehlke G.;
RT "Effect of spastic paraplegia mutations in KIF5A kinesin on transport
RT activity.";
RL Hum. Mol. Genet. 17:1245-1252(2008).
RN [14]
RP VARIANTS SPG10 ASN-253 AND ASN-256 DEL.
RX PubMed=18245137; DOI=10.1136/jnnp.2007.137596;
RA Schuele R., Kremer B.P.H., Kassubek J., Auer-Grumbach M., Kostic V.,
RA Klopstock T., Klimpe S., Otto S., Boesch S., van de Warrenburg B.P.,
RA Schoels L.;
RT "SPG10 is a rare cause of spastic paraplegia in European families.";
RL J. Neurol. Neurosurg. Psych. 79:584-587(2008).
RN [15]
RP VARIANTS SPG10 CYS-63; THR-198; GLN-204; LYS-251; ASN-257; CYS-280; LEU-280
RP AND HIS-280.
RX PubMed=18853458; DOI=10.1002/humu.20920;
RA Goizet C., Boukhris A., Mundwiller E., Tallaksen C., Forlani S.,
RA Toutain A., Carriere N., Paquis V., Depienne C., Durr A., Stevanin G.,
RA Brice A.;
RT "Complicated forms of autosomal dominant hereditary spastic paraplegia are
RT frequent in SPG10.";
RL Hum. Mutat. 30:E376-E385(2009).
RN [16]
RP VARIANT SPG10 CYS-203.
RX PubMed=21107874; DOI=10.1007/s10072-010-0445-8;
RA Musumeci O., Bassi M.T., Mazzeo A., Grandis M., Crimella C., Martinuzzi A.,
RA Toscano A.;
RT "A novel mutation in KIF5A gene causing hereditary spastic paraplegia with
RT axonal neuropathy.";
RL Neurol. Sci. 32:665-668(2011).
RN [17]
RP INVOLVEMENT IN NEIMY.
RX PubMed=24215330; DOI=10.1186/1471-2350-14-118;
RA DaRe J.T., Vasta V., Penn J., Tran N.T., Hahn S.H.;
RT "Targeted exome sequencing for mitochondrial disorders reveals high genetic
RT heterogeneity.";
RL BMC Med. Genet. 14:118-118(2013).
RN [18]
RP INVOLVEMENT IN NEIMY.
RX PubMed=27463701; DOI=10.1002/ana.24744;
RA Duis J., Dean S., Applegate C., Harper A., Xiao R., He W., Dollar J.D.,
RA Sun L.R., Waberski M.B., Crawford T.O., Hamosh A., Stafstrom C.E.;
RT "KIF5A mutations cause an infantile onset phenotype including severe
RT myoclonus with evidence of mitochondrial dysfunction.";
RL Ann. Neurol. 80:633-637(2016).
RN [19]
RP INVOLVEMENT IN NEIMY.
RX PubMed=27414745; DOI=10.1111/cge.12831;
RA Rydzanicz M., Jagla M., Kosinska J., Tomasik T., Sobczak A., Pollak A.,
RA Herman-Sucharska I., Walczak A., Kwinta P., Ploski R.;
RT "KIF5A de novo mutation associated with myoclonic seizures and neonatal
RT onset progressive leukoencephalopathy.";
RL Clin. Genet. 91:769-773(2017).
RN [20]
RP INVOLVEMENT IN ALS25, AND VARIANTS ALS25 GLY-413; HIS-474; GLY-577; LEU-986
RP AND GLY-1007.
RX PubMed=29342275; DOI=10.1093/brain/awx370;
RA Brenner D., Yilmaz R., Mueller K., Grehl T., Petri S., Meyer T.,
RA Grosskreutz J., Weydt P., Ruf W., Neuwirth C., Weber M., Pinto S.,
RA Claeys K.G., Schrank B., Jordan B., Knehr A., Guenther K., Huebers A.,
RA Zeller D., Kubisch C., Jablonka S., Sendtner M., Klopstock T.,
RA de Carvalho M., Sperfeld A., Borck G., Volk A.E., Dorst J., Weis J.,
RA Otto M., Schuster J., Del Tredici K., Braak H., Danzer K.M.,
RA Freischmidt A., Meitinger T., Strom T.M., Ludolph A.C., Andersen P.M.,
RA Weishaupt J.H.;
RT "Hot-spot KIF5A mutations cause familial ALS.";
RL Brain 141:688-697(2018).
RN [21]
RP INVOLVEMENT IN ALS25, AND VARIANTS ALS25 544-ARG--SER-1032 DEL; LEU-986 AND
RP GLY-1007.
RX PubMed=29566793; DOI=10.1016/j.neuron.2018.02.027;
RA Nicolas A., Kenna K.P., Renton A.E., Ticozzi N., Faghri F., Chia R.,
RA Dominov J.A., Kenna B.J., Nalls M.A., Keagle P., Rivera A.M.,
RA van Rheenen W., Murphy N.A., van Vugt J.J.F.A., Geiger J.T.,
RA Van der Spek R.A., Pliner H.A., Shankaracharya X., Smith B.N., Marangi G.,
RA Topp S.D., Abramzon Y., Gkazi A.S., Eicher J.D., Kenna A., Mora G.,
RA Calvo A., Mazzini L., Riva N., Mandrioli J., Caponnetto C., Battistini S.,
RA Volanti P., La Bella V., Conforti F.L., Borghero G., Messina S.,
RA Simone I.L., Trojsi F., Salvi F., Logullo F.O., D'Alfonso S., Corrado L.,
RA Capasso M., Ferrucci L., Moreno C.A.M., Kamalakaran S., Goldstein D.B.,
RA Gitler A.D., Harris T., Myers R.M., Phatnani H., Musunuri R.L., Evani U.S.,
RA Abhyankar A., Zody M.C., Kaye J., Finkbeiner S., Wyman S.K., LeNail A.,
RA Lima L., Fraenkel E., Svendsen C.N., Thompson L.M., Van Eyk J.E.,
RA Berry J.D., Miller T.M., Kolb S.J., Cudkowicz M., Baxi E., Benatar M.,
RA Taylor J.P., Rampersaud E., Wu G., Wuu J., Lauria G., Verde F., Fogh I.,
RA Tiloca C., Comi G.P., Soraru G., Cereda C., Corcia P., Laaksovirta H.,
RA Myllykangas L., Jansson L., Valori M., Ealing J., Hamdalla H.,
RA Rollinson S., Pickering-Brown S., Orrell R.W., Sidle K.C., Malaspina A.,
RA Hardy J., Singleton A.B., Johnson J.O., Arepalli S., Sapp P.C.,
RA McKenna-Yasek D., Polak M., Asress S., Al-Sarraj S., King A., Troakes C.,
RA Vance C., de Belleroche J., Baas F., Ten Asbroek A.L.M.A.,
RA Munoz-Blanco J.L., Hernandez D.G., Ding J., Gibbs J.R., Scholz S.W.,
RA Floeter M.K., Campbell R.H., Landi F., Bowser R., Pulst S.M., Ravits J.M.,
RA MacGowan D.J.L., Kirby J., Pioro E.P., Pamphlett R., Broach J., Gerhard G.,
RA Dunckley T.L., Brady C.B., Kowall N.W., Troncoso J.C., Le Ber I.,
RA Mouzat K., Lumbroso S., Heiman-Patterson T.D., Kamel F., Van Den Bosch L.,
RA Baloh R.H., Strom T.M., Meitinger T., Shatunov A., Van Eijk K.R.,
RA de Carvalho M., Kooyman M., Middelkoop B., Moisse M., McLaughlin R.L.,
RA Van Es M.A., Weber M., Boylan K.B., Van Blitterswijk M., Rademakers R.,
RA Morrison K.E., Basak A.N., Mora J.S., Drory V.E., Shaw P.J., Turner M.R.,
RA Talbot K., Hardiman O., Williams K.L., Fifita J.A., Nicholson G.A.,
RA Blair I.P., Rouleau G.A., Esteban-Perez J., Garcia-Redondo A.,
RA Al-Chalabi A., Rogaeva E., Zinman L., Ostrow L.W., Maragakis N.J.,
RA Rothstein J.D., Simmons Z., Cooper-Knock J., Brice A., Goutman S.A.,
RA Feldman E.L., Gibson S.B., Taroni F., Ratti A., Gellera C., Van Damme P.,
RA Robberecht W., Fratta P., Sabatelli M., Lunetta C., Ludolph A.C.,
RA Andersen P.M., Weishaupt J.H., Camu W., Trojanowski J.Q., Van Deerlin V.M.,
RA Brown R.H. Jr., van den Berg L.H., Veldink J.H., Harms M.B., Glass J.D.,
RA Stone D.J., Tienari P., Silani V., Chio A., Shaw C.E., Traynor B.J.,
RA Landers J.E.;
RT "Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.";
RL Neuron 97:1268-1283(2018).
CC -!- FUNCTION: Microtubule-dependent motor required for slow axonal
CC transport of neurofilament proteins (NFH, NFM and NFL). Can induce
CC formation of neurite-like membrane protrusions in non-neuronal cells in
CC a ZFYVE27-dependent manner. The ZFYVE27-KIF5A complex contributes to
CC the vesicular transport of VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3
CC proteins in neurons. Required for anterograde axonal transportation of
CC MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon
CC elongation. {ECO:0000250|UniProtKB:P33175,
CC ECO:0000250|UniProtKB:Q6QLM7}.
CC -!- SUBUNIT: Oligomer composed of two heavy chains and two light chains.
CC Interacts with GRIP1. Interacts with FMR1 (via C-terminus); this
CC interaction is increased in a mGluR-dependent manner. Interacts with
CC ZFYVE27. Interacts with VAPA, VAPB, SURF4, RAB11A (GDP-bound form),
CC RAB11B (GDP-bound form) and RTN3 in a ZFYVE27-dependent manner (By
CC similarity). Interacts with BORCS5 (PubMed:25898167). Interacts with
CC BICD2 (PubMed:20386726). Interacts with DTNB (By similarity).
CC {ECO:0000250|UniProtKB:P33175, ECO:0000269|PubMed:20386726,
CC ECO:0000269|PubMed:25898167}.
CC -!- INTERACTION:
CC Q12840; Q96NW4: ANKRD27; NbExp=4; IntAct=EBI-713468, EBI-6125599;
CC Q12840; Q8R2H7: Trak2; Xeno; NbExp=2; IntAct=EBI-713468, EBI-1396483;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q6QLM7}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q6QLM7}. Perikaryon
CC {ECO:0000250|UniProtKB:Q6QLM7}. Note=Concentrated in the cell body of
CC the neurons, particularly in the perinuclear region.
CC {ECO:0000250|UniProtKB:Q6QLM7}.
CC -!- TISSUE SPECIFICITY: Distributed throughout the CNS but is highly
CC enriched in subsets of neurons.
CC -!- DOMAIN: Composed of three structural domains: a large globular N-
CC terminal domain which is responsible for the motor activity of kinesin
CC (it hydrolyzes ATP and binds microtubule), a central alpha-helical
CC coiled coil domain that mediates the heavy chain dimerization; and a
CC small globular C-terminal domain which interacts with other proteins
CC (such as the kinesin light chains), vesicles and membranous organelles.
CC -!- DISEASE: Spastic paraplegia 10, autosomal dominant (SPG10)
CC [MIM:604187]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body.
CC {ECO:0000269|PubMed:12355402, ECO:0000269|PubMed:15452312,
CC ECO:0000269|PubMed:16476820, ECO:0000269|PubMed:16489470,
CC ECO:0000269|PubMed:18203753, ECO:0000269|PubMed:18245137,
CC ECO:0000269|PubMed:18853458, ECO:0000269|PubMed:21107874}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Myoclonus, intractable, neonatal (NEIMY) [MIM:617235]: An
CC autosomal dominant neurologic disorder characterized by severe,
CC infantile-onset myoclonic seizures, hypotonia, optic nerve
CC abnormalities, dysphagia, apnea, and early developmental arrest. Brain
CC imaging shows a progressive leukoencephalopathy. Some patients may die
CC in infancy. {ECO:0000269|PubMed:24215330, ECO:0000269|PubMed:27414745,
CC ECO:0000269|PubMed:27463701}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Amyotrophic lateral sclerosis 25 (ALS25) [MIM:617921]: A form
CC of amyotrophic lateral sclerosis, a neurodegenerative disorder
CC affecting upper motor neurons in the brain and lower motor neurons in
CC the brain stem and spinal cord, resulting in fatal paralysis. Sensory
CC abnormalities are absent. The pathologic hallmarks of the disease
CC include pallor of the corticospinal tract due to loss of motor neurons,
CC presence of ubiquitin-positive inclusions within surviving motor
CC neurons, and deposition of pathologic aggregates. The etiology of
CC amyotrophic lateral sclerosis is likely to be multifactorial, involving
CC both genetic and environmental factors. The disease is inherited in 5-
CC 10% of the cases. ALS25 is an autosomal dominant form with variable
CC adult onset and incomplete penetrance. {ECO:0000269|PubMed:29342275,
CC ECO:0000269|PubMed:29566793}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry. The
CC mutation NM_004984.2:c.33019A>G encoding the predicted missence variant
CC p.Arg1007Gly, may also affect splicing and induce the skipping of exon
CC 27, resulting in a frameshift and a premature stop codon producing a
CC truncated protein p.Asn999Valfs*39. {ECO:0000269|PubMed:29342275}.
CC -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase
CC superfamily. Kinesin family. Kinesin subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00283}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE06127.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U06698; AAA20231.1; -; mRNA.
DR EMBL; AB210045; BAE06127.1; ALT_INIT; mRNA.
DR EMBL; CH471054; EAW97030.1; -; Genomic_DNA.
DR EMBL; BC146670; AAI46671.1; -; mRNA.
DR EMBL; BC150208; AAI50209.1; -; mRNA.
DR CCDS; CCDS8945.1; -.
DR PIR; I38510; I38510.
DR RefSeq; NP_004975.2; NM_004984.2.
DR PDB; 4UXT; EM; 7.40 A; C=1-340.
DR PDB; 4UXY; EM; 6.50 A; C=1-340.
DR PDB; 4UY0; EM; 7.70 A; C=1-340.
DR PDBsum; 4UXT; -.
DR PDBsum; 4UXY; -.
DR PDBsum; 4UY0; -.
DR AlphaFoldDB; Q12840; -.
DR SMR; Q12840; -.
DR BioGRID; 109999; 73.
DR CORUM; Q12840; -.
DR DIP; DIP-37584N; -.
DR IntAct; Q12840; 45.
DR MINT; Q12840; -.
DR STRING; 9606.ENSP00000408979; -.
DR BindingDB; Q12840; -.
DR ChEMBL; CHEMBL5295; -.
DR iPTMnet; Q12840; -.
DR PhosphoSitePlus; Q12840; -.
DR SwissPalm; Q12840; -.
DR BioMuta; KIF5A; -.
DR DMDM; 143811412; -.
DR EPD; Q12840; -.
DR jPOST; Q12840; -.
DR MassIVE; Q12840; -.
DR MaxQB; Q12840; -.
DR PaxDb; Q12840; -.
DR PeptideAtlas; Q12840; -.
DR PRIDE; Q12840; -.
DR ProteomicsDB; 58979; -.
DR Antibodypedia; 1390; 270 antibodies from 36 providers.
DR DNASU; 3798; -.
DR Ensembl; ENST00000455537.7; ENSP00000408979.2; ENSG00000155980.13.
DR GeneID; 3798; -.
DR KEGG; hsa:3798; -.
DR MANE-Select; ENST00000455537.7; ENSP00000408979.2; NM_004984.4; NP_004975.2.
DR UCSC; uc001sor.2; human.
DR CTD; 3798; -.
DR DisGeNET; 3798; -.
DR GeneCards; KIF5A; -.
DR GeneReviews; KIF5A; -.
DR HGNC; HGNC:6323; KIF5A.
DR HPA; ENSG00000155980; Group enriched (brain, choroid plexus).
DR MalaCards; KIF5A; -.
DR MIM; 602821; gene.
DR MIM; 604187; phenotype.
DR MIM; 617235; phenotype.
DR MIM; 617921; phenotype.
DR neXtProt; NX_Q12840; -.
DR OpenTargets; ENSG00000155980; -.
DR Orphanet; 324611; Autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation.
DR Orphanet; 100991; Autosomal dominant spastic paraplegia type 10.
DR PharmGKB; PA30107; -.
DR VEuPathDB; HostDB:ENSG00000155980; -.
DR eggNOG; KOG0240; Eukaryota.
DR GeneTree; ENSGT00940000159439; -.
DR HOGENOM; CLU_001485_11_1_1; -.
DR InParanoid; Q12840; -.
DR OrthoDB; 1334528at2759; -.
DR PhylomeDB; Q12840; -.
DR TreeFam; TF105225; -.
DR PathwayCommons; Q12840; -.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-264876; Insulin processing.
DR Reactome; R-HSA-5625970; RHO GTPases activate KTN1.
DR Reactome; R-HSA-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR Reactome; R-HSA-983189; Kinesins.
DR SignaLink; Q12840; -.
DR SIGNOR; Q12840; -.
DR BioGRID-ORCS; 3798; 18 hits in 1074 CRISPR screens.
DR ChiTaRS; KIF5A; human.
DR GeneWiki; KIF5A; -.
DR GenomeRNAi; 3798; -.
DR Pharos; Q12840; Tbio.
DR PRO; PR:Q12840; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q12840; protein.
DR Bgee; ENSG00000155980; Expressed in right frontal lobe and 128 other tissues.
DR ExpressionAtlas; Q12840; baseline and differential.
DR Genevisible; Q12840; HS.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032839; C:dendrite cytoplasm; IEA:GOC.
DR GO; GO:0005871; C:kinesin complex; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0003774; F:cytoskeletal motor activity; TAS:ProtInc.
DR GO; GO:0019894; F:kinesin binding; IEA:Ensembl.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0003777; F:microtubule motor activity; IBA:GO_Central.
DR GO; GO:0008574; F:plus-end-directed microtubule motor activity; IBA:GO_Central.
DR GO; GO:0099641; P:anterograde axonal protein transport; ISS:UniProtKB.
DR GO; GO:0098971; P:anterograde dendritic transport of neurotransmitter receptor complex; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0030705; P:cytoskeleton-dependent intracellular transport; IBA:GO_Central.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
DR GO; GO:1990049; P:retrograde neuronal dense core vesicle transport; ISS:ARUK-UCL.
DR GO; GO:0048489; P:synaptic vesicle transport; IBA:GO_Central.
DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB.
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; IPR036961; Kinesin_motor_dom_sf.
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_1; 1.
DR PROSITE; PS50067; KINESIN_MOTOR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Amyotrophic lateral sclerosis; ATP-binding;
KW Coiled coil; Cytoplasm; Cytoskeleton; Disease variant; Epilepsy;
KW Hereditary spastic paraplegia; Microtubule; Motor protein;
KW Neurodegeneration; Nucleotide-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..1032
FT /note="Kinesin heavy chain isoform 5A"
FT /id="PRO_0000125353"
FT DOMAIN 9..327
FT /note="Kinesin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT REGION 174..315
FT /note="Microtubule-binding"
FT REGION 271..361
FT /note="Necessary for interaction with ZFYVE27"
FT /evidence="ECO:0000250|UniProtKB:P33175"
FT REGION 353..1032
FT /note="Interaction with BICD2"
FT /evidence="ECO:0000269|PubMed:20386726"
FT REGION 906..939
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 907..1032
FT /note="Globular"
FT REGION 978..1010
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 331..906
FT COMPBIAS 978..1006
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 86..93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 397
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P33175"
FT VARIANT 63
FT /note="Y -> C (in SPG10; complicated form)"
FT /evidence="ECO:0000269|PubMed:18853458"
FT /id="VAR_058741"
FT VARIANT 198
FT /note="M -> T (in SPG10; complicated form)"
FT /evidence="ECO:0000269|PubMed:18853458"
FT /id="VAR_058742"
FT VARIANT 203
FT /note="S -> C (in SPG10)"
FT /evidence="ECO:0000269|PubMed:21107874"
FT /id="VAR_066616"
FT VARIANT 204
FT /note="R -> Q (in SPG10; complicated form;
FT dbSNP:rs387907287)"
FT /evidence="ECO:0000269|PubMed:18853458"
FT /id="VAR_058743"
FT VARIANT 251
FT /note="E -> K (in SPG10; complicated form;
FT dbSNP:rs387907285)"
FT /evidence="ECO:0000269|PubMed:18853458"
FT /id="VAR_058744"
FT VARIANT 253
FT /note="K -> N (in SPG10; decreases microtubule affinity;
FT reduces gliding velocity; reduces microtubule-dependent ATP
FT turnover)"
FT /evidence="ECO:0000269|PubMed:18203753,
FT ECO:0000269|PubMed:18245137"
FT /id="VAR_046744"
FT VARIANT 256
FT /note="N -> S (in SPG10; slightly decreases microtubule
FT affinity; reduces gliding velocity; reduces microtubule-
FT dependent ATP turnover; dbSNP:rs121434441)"
FT /evidence="ECO:0000269|PubMed:12355402,
FT ECO:0000269|PubMed:18203753"
FT /id="VAR_032842"
FT VARIANT 256
FT /note="Missing (in SPG10)"
FT /evidence="ECO:0000269|PubMed:18245137"
FT /id="VAR_058745"
FT VARIANT 257
FT /note="K -> N (in SPG10; complicated form)"
FT /evidence="ECO:0000269|PubMed:18853458"
FT /id="VAR_058746"
FT VARIANT 276
FT /note="Y -> C (in SPG10; dbSNP:rs121434443)"
FT /evidence="ECO:0000269|PubMed:16489470"
FT /id="VAR_033108"
FT VARIANT 280
FT /note="R -> C (in SPG10; dbSNP:rs121434442)"
FT /evidence="ECO:0000269|PubMed:15452312,
FT ECO:0000269|PubMed:18853458"
FT /id="VAR_032843"
FT VARIANT 280
FT /note="R -> H (in SPG10; complicated form;
FT dbSNP:rs387907288)"
FT /evidence="ECO:0000269|PubMed:18853458"
FT /id="VAR_058747"
FT VARIANT 280
FT /note="R -> L (in SPG10; pure form)"
FT /evidence="ECO:0000269|PubMed:18853458"
FT /id="VAR_058748"
FT VARIANT 361
FT /note="A -> V (in SPG10; does not affect microtubule
FT affinity; does not affect gliding velocity; does not affect
FT microtubule-dependent ATP turnover; dbSNP:rs121434444)"
FT /evidence="ECO:0000269|PubMed:16476820,
FT ECO:0000269|PubMed:18203753"
FT /id="VAR_032844"
FT VARIANT 413
FT /note="E -> G (in ALS25; unknown pathological significance;
FT dbSNP:rs1399145820)"
FT /evidence="ECO:0000269|PubMed:29342275"
FT /id="VAR_080647"
FT VARIANT 474
FT /note="Q -> H (in ALS25; unknown pathological significance;
FT dbSNP:rs1373971092)"
FT /evidence="ECO:0000269|PubMed:29342275"
FT /id="VAR_080648"
FT VARIANT 544..1032
FT /note="Missing (in ALS25)"
FT /evidence="ECO:0000269|PubMed:29566793"
FT /id="VAR_080649"
FT VARIANT 577
FT /note="S -> G (in ALS25; unknown pathological significance;
FT dbSNP:rs754373609)"
FT /evidence="ECO:0000269|PubMed:29342275"
FT /id="VAR_080650"
FT VARIANT 986
FT /note="P -> L (in ALS25; unknown pathological significance;
FT dbSNP:rs113247976)"
FT /evidence="ECO:0000269|PubMed:29342275,
FT ECO:0000269|PubMed:29566793"
FT /id="VAR_080651"
FT VARIANT 1007
FT /note="R -> G (in ALS25; dbSNP:rs1555179087)"
FT /evidence="ECO:0000269|PubMed:29342275,
FT ECO:0000269|PubMed:29566793"
FT /id="VAR_080652"
FT MUTAGEN 280
FT /note="R->S: Strongly reduces microtubule affinity;
FT slightly reduces gliding velocity."
FT /evidence="ECO:0000269|PubMed:18203753"
FT CONFLICT 490
FT /note="A -> V (in Ref. 2; BAE06127)"
FT /evidence="ECO:0000305"
FT CONFLICT 913
FT /note="G -> A (in Ref. 1; AAA20231)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1032 AA; 117378 MW; C4C6C12342040796 CRC64;
MAETNNECSI KVLCRFRPLN QAEILRGDKF IPIFQGDDSV VIGGKPYVFD RVFPPNTTQE
QVYHACAMQI VKDVLAGYNG TIFAYGQTSS GKTHTMEGKL HDPQLMGIIP RIARDIFNHI
YSMDENLEFH IKVSYFEIYL DKIRDLLDVT KTNLSVHEDK NRVPFVKGCT ERFVSSPEEI
LDVIDEGKSN RHVAVTNMNE HSSRSHSIFL INIKQENMET EQKLSGKLYL VDLAGSEKVS
KTGAEGAVLD EAKNINKSLS ALGNVISALA EGTKSYVPYR DSKMTRILQD SLGGNCRTTM
FICCSPSSYN DAETKSTLMF GQRAKTIKNT ASVNLELTAE QWKKKYEKEK EKTKAQKETI
AKLEAELSRW RNGENVPETE RLAGEEAALG AELCEETPVN DNSSIVVRIA PEERQKYEEE
IRRLYKQLDD KDDEINQQSQ LIEKLKQQML DQEELLVSTR GDNEKVQREL SHLQSENDAA
KDEVKEVLQA LEELAVNYDQ KSQEVEEKSQ QNQLLVDELS QKVATMLSLE SELQRLQEVS
GHQRKRIAEV LNGLMKDLSE FSVIVGNGEI KLPVEISGAI EEEFTVARLY ISKIKSEVKS
VVKRCRQLEN LQVECHRKME VTGRELSSCQ LLISQHEAKI RSLTEYMQSV ELKKRHLEES
YDSLSDELAK LQAQETVHEV ALKDKEPDTQ DADEVKKALE LQMESHREAH HRQLARLRDE
INEKQKTIDE LKDLNQKLQL ELEKLQADYE KLKSEEHEKS TKLQELTFLY ERHEQSKQDL
KGLEETVARE LQTLHNLRKL FVQDVTTRVK KSAEMEPEDS GGIHSQKQKI SFLENNLEQL
TKVHKQLVRD NADLRCELPK LEKRLRATAE RVKALEGALK EAKEGAMKDK RRYQQEVDRI
KEAVRYKSSG KRGHSAQIAK PVRPGHYPAS SPTNPYGTRS PECISYTNSL FQNYQNLYLQ
ATPSSTSDMY FANSCTSSGA TSSGGPLASY QKANMDNGNA TDINDNRSDL PCGYEAEDQA
KLFPLHQETA AS
