KIF5C_HUMAN
ID KIF5C_HUMAN Reviewed; 957 AA.
AC O60282; O95079; Q2YDC5;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Kinesin heavy chain isoform 5C;
DE AltName: Full=Kinesin heavy chain neuron-specific 2;
GN Name=KIF5C; Synonyms=KIAA0531, NKHC2;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 355-585 (ISOFORMS 1/2).
RX PubMed=9361024; DOI=10.1093/hmg/6.13.2205;
RA Engelender S., Sharp A.H., Colomer V., Tokito M.K., Lanahan A., Worley P.,
RA Holzbaur E.L.F., Ross C.A.;
RT "Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued
RT subunit of dynactin.";
RL Hum. Mol. Genet. 6:2205-2212(1997).
RN [5]
RP INTERACTION WITH TRAK1.
RX PubMed=15644324; DOI=10.1074/jbc.m409095200;
RA Brickley K., Smith M.J., Beck M., Stephenson F.A.;
RT "GRIF-1 and OIP106, members of a novel gene family of coiled-coil domain
RT proteins: association in vivo and in vitro with kinesin.";
RL J. Biol. Chem. 280:14723-14732(2005).
RN [6]
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANT CDCBM2 LYS-237, AND
RP CHARACTERIZATION OF VARIANT CDCBM2 LYS-237.
RX PubMed=24812067; DOI=10.1136/jmedgenet-2013-102182;
RA Willemsen M.H., Ba W., Wissink-Lindhout W.M., de Brouwer A.P., Haas S.A.,
RA Bienek M., Hu H., Vissers L.E., van Bokhoven H., Kalscheuer V.,
RA Nadif Kasri N., Kleefstra T.;
RT "Involvement of the kinesin family members KIF4A and KIF5C in intellectual
RT disability and synaptic function.";
RL J. Med. Genet. 51:487-494(2014).
RN [8]
RP VARIANT CDCBM2 LYS-237.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [9]
RP VARIANT CDCBM2 VAL-237, AND CHARACTERIZATION OF VARIANT CDCBM2 VAL-237.
RX PubMed=23603762; DOI=10.1038/ng.2613;
RA Poirier K., Lebrun N., Broix L., Tian G., Saillour Y., Boscheron C.,
RA Parrini E., Valence S., Pierre B.S., Oger M., Lacombe D., Genevieve D.,
RA Fontana E., Darra F., Cances C., Barth M., Bonneau D., Bernadina B.D.,
RA N'guyen S., Gitiaux C., Parent P., des Portes V., Pedespan J.M., Legrez V.,
RA Castelnau-Ptakine L., Nitschke P., Hieu T., Masson C., Zelenika D.,
RA Andrieux A., Francis F., Guerrini R., Cowan N.J., Bahi-Buisson N.,
RA Chelly J.;
RT "Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of
RT cortical development and microcephaly.";
RL Nat. Genet. 45:639-647(2013).
RN [10]
RP VARIANT CDCBM2 LYS-237.
RX PubMed=29048727; DOI=10.1002/ajmg.a.38496;
RA Michels S., Foss K., Park K., Golden-Grant K., Saneto R., Lopez J.,
RA Mirzaa G.M.;
RT "Mutations of KIF5C cause a neurodevelopmental disorder of infantile-onset
RT epilepsy, absent language, and distinctive malformations of cortical
RT development.";
RL Am. J. Med. Genet. A 173:3127-3131(2017).
CC -!- FUNCTION: Involved in synaptic transmission (PubMed:24812067). Mediates
CC dendritic trafficking of mRNAs (By similarity). Kinesin is a
CC microtubule-associated force-producing protein that may play a role in
CC organelle transport. Required for anterograde axonal transportation of
CC MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon
CC elongation (By similarity). {ECO:0000250|UniProtKB:P28738,
CC ECO:0000250|UniProtKB:P56536, ECO:0000269|PubMed:24812067}.
CC -!- SUBUNIT: Oligomer composed of two heavy chains and two light chains.
CC Interacts with GRIP1 and KLC3 (By similarity). Interacts with TRAK1
CC (PubMed:15644324). Interacts with ZFYVE27 (By similarity).
CC {ECO:0000250|UniProtKB:P28738, ECO:0000250|UniProtKB:P56536,
CC ECO:0000269|PubMed:15644324}.
CC -!- INTERACTION:
CC O60282; P68400: CSNK2A1; NbExp=4; IntAct=EBI-717170, EBI-347804;
CC O60282; P19784: CSNK2A2; NbExp=4; IntAct=EBI-717170, EBI-347451;
CC O60282; Q8IXI2: RHOT1; NbExp=2; IntAct=EBI-717170, EBI-1396430;
CC O60282-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12334027, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000305}. Cell
CC projection, dendrite {ECO:0000269|PubMed:24812067}. Note=Abundant in
CC distal regions of dendrites. {ECO:0000269|PubMed:24812067}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60282-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60282-2; Sequence=VSP_035715, VSP_035716;
CC -!- TISSUE SPECIFICITY: Highest expression in brain, prostate and testis,
CC and moderate expression in kidney, small intestine and ovary.
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: Cortical dysplasia, complex, with other brain malformations 2
CC (CDCBM2) [MIM:615282]: A disorder of aberrant neuronal migration and
CC disturbed axonal guidance. Clinical features include intrauterine
CC growth retardation, fetal akinesia, seizures, microcephaly, lack of
CC psychomotor development, and arthrogryposis. Brain imaging shows
CC malformations of cortical development, including polymicrogyria, gyral
CC simplification, and thin corpus callosum. {ECO:0000269|PubMed:23033978,
CC ECO:0000269|PubMed:23603762, ECO:0000269|PubMed:24812067,
CC ECO:0000269|PubMed:29048727}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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=BAA25457.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB011103; BAA25457.2; ALT_INIT; mRNA.
DR EMBL; AC105402; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC144443; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC144611; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC110287; AAI10288.1; -; mRNA.
DR EMBL; AF010146; AAD01436.1; -; mRNA.
DR CCDS; CCDS74586.1; -. [O60282-1]
DR RefSeq; NP_004513.1; NM_004522.2. [O60282-1]
DR RefSeq; XP_011509459.1; XM_011511157.2. [O60282-2]
DR RefSeq; XP_016859551.1; XM_017004062.1. [O60282-1]
DR AlphaFoldDB; O60282; -.
DR SMR; O60282; -.
DR BioGRID; 110001; 54.
DR CORUM; O60282; -.
DR IntAct; O60282; 38.
DR MINT; O60282; -.
DR STRING; 9606.ENSP00000393379; -.
DR BindingDB; O60282; -.
DR ChEMBL; CHEMBL2029194; -.
DR iPTMnet; O60282; -.
DR PhosphoSitePlus; O60282; -.
DR SwissPalm; O60282; -.
DR BioMuta; KIF5C; -.
DR EPD; O60282; -.
DR jPOST; O60282; -.
DR MassIVE; O60282; -.
DR MaxQB; O60282; -.
DR PaxDb; O60282; -.
DR PeptideAtlas; O60282; -.
DR PRIDE; O60282; -.
DR ProteomicsDB; 49311; -. [O60282-1]
DR ProteomicsDB; 49312; -. [O60282-2]
DR Antibodypedia; 33631; 152 antibodies from 22 providers.
DR DNASU; 3800; -.
DR Ensembl; ENST00000435030.6; ENSP00000393379.1; ENSG00000168280.18. [O60282-1]
DR Ensembl; ENST00000676677.1; ENSP00000503401.1; ENSG00000168280.18. [O60282-2]
DR Ensembl; ENST00000677891.1; ENSP00000503013.1; ENSG00000168280.18. [O60282-1]
DR Ensembl; ENST00000679129.1; ENSP00000504291.1; ENSG00000168280.18. [O60282-2]
DR GeneID; 3800; -.
DR KEGG; hsa:3800; -.
DR MANE-Select; ENST00000435030.6; ENSP00000393379.1; NM_004522.3; NP_004513.1.
DR UCSC; uc010zbu.3; human. [O60282-1]
DR CTD; 3800; -.
DR DisGeNET; 3800; -.
DR GeneCards; KIF5C; -.
DR HGNC; HGNC:6325; KIF5C.
DR HPA; ENSG00000168280; Tissue enriched (brain).
DR MalaCards; KIF5C; -.
DR MIM; 604593; gene.
DR MIM; 615282; phenotype.
DR neXtProt; NX_O60282; -.
DR OpenTargets; ENSG00000168280; -.
DR PharmGKB; PA30109; -.
DR VEuPathDB; HostDB:ENSG00000168280; -.
DR eggNOG; KOG0240; Eukaryota.
DR GeneTree; ENSGT00940000158539; -.
DR HOGENOM; CLU_001485_11_1_1; -.
DR InParanoid; O60282; -.
DR OMA; AAKQHEM; -.
DR OrthoDB; 1334528at2759; -.
DR PhylomeDB; O60282; -.
DR TreeFam; TF105225; -.
DR PathwayCommons; O60282; -.
DR Reactome; R-HSA-264876; Insulin processing.
DR SignaLink; O60282; -.
DR SIGNOR; O60282; -.
DR BioGRID-ORCS; 3800; 6 hits in 315 CRISPR screens.
DR ChiTaRS; KIF5C; human.
DR GeneWiki; KIF5C; -.
DR GenomeRNAi; 3800; -.
DR Pharos; O60282; Tbio.
DR PRO; PR:O60282; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O60282; protein.
DR Bgee; ENSG00000168280; Expressed in Brodmann (1909) area 10 and 160 other tissues.
DR Genevisible; O60282; HS.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0044295; C:axonal growth cone; ISS:ARUK-UCL.
DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl.
DR GO; GO:0032839; C:dendrite cytoplasm; IEA:GOC.
DR GO; GO:0150034; C:distal axon; ISS:ARUK-UCL.
DR GO; GO:0005871; C:kinesin complex; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
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:0030705; P:cytoskeleton-dependent intracellular transport; IBA:GO_Central.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
DR GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl.
DR GO; GO:0051028; P:mRNA transport; ISS:UniProtKB.
DR GO; GO:0006996; P:organelle organization; TAS:ProtInc.
DR GO; GO:0048489; P:synaptic vesicle transport; IBA:GO_Central.
DR Gene3D; 3.40.850.10; -; 1.
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 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 Alternative splicing; ATP-binding; Cell projection; Coiled coil; Cytoplasm;
KW Cytoskeleton; Disease variant; Microtubule; Motor protein;
KW Nucleotide-binding; Reference proteome; Transport.
FT CHAIN 1..957
FT /note="Kinesin heavy chain isoform 5C"
FT /id="PRO_0000125355"
FT DOMAIN 8..327
FT /note="Kinesin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT REGION 174..315
FT /note="Microtubule-binding"
FT REGION 859..956
FT /note="Globular"
FT REGION 911..957
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 406..923
FT BINDING 86..93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT VAR_SEQ 1..232
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035715"
FT VAR_SEQ 233..238
FT /note="LAGSEK -> MATYIH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035716"
FT VARIANT 237
FT /note="E -> K (in CDCBM2; the mutation results in a
FT significant decrease of excitatory post-synaptic currents
FT when expressed in cultured primary hippocampal neurons;
FT decreased localization to distal regions of dendrites;
FT accumulates in dendrite cell body; dbSNP:rs587777570)"
FT /evidence="ECO:0000269|PubMed:23033978,
FT ECO:0000269|PubMed:24812067, ECO:0000269|PubMed:29048727"
FT /id="VAR_069389"
FT VARIANT 237
FT /note="E -> V (in CDCBM2; the mutant protein has a complete
FT loss of ATP hydrolysis activity; colocalizes with
FT microtubules throughout the cell but does not appear as
FT puncta or accumulates in cortical clusters as does the
FT wild-type protein; dbSNP:rs587777035)"
FT /evidence="ECO:0000269|PubMed:23603762"
FT /id="VAR_070574"
FT CONFLICT 355..360
FT /note="TLKNVI -> STHASV (in Ref. 4; AAD01436)"
FT /evidence="ECO:0000305"
FT CONFLICT 583..585
FT /note="EFT -> DRV (in Ref. 4; AAD01436)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 957 AA; 109495 MW; A9F25BB1C994322A CRC64;
MADPAECSIK VMCRFRPLNE AEILRGDKFI PKFKGDETVV IGQGKPYVFD RVLPPNTTQE
QVYNACAKQI VKDVLEGYNG TIFAYGQTSS GKTHTMEGKL HDPQLMGIIP RIAHDIFDHI
YSMDENLEFH IKVSYFEIYL DKIRDLLDVS KTNLAVHEDK NRVPYVKGCT ERFVSSPEEV
MDVIDEGKAN RHVAVTNMNE HSSRSHSIFL INIKQENVET EKKLSGKLYL VDLAGSEKVS
KTGAEGAVLD EAKNINKSLS ALGNVISALA EGTKTHVPYR DSKMTRILQD SLGGNCRTTI
VICCSPSVFN EAETKSTLMF GQRAKTIKNT VSVNLELTAE EWKKKYEKEK EKNKTLKNVI
QHLEMELNRW RNGEAVPEDE QISAKDQKNL EPCDNTPIID NIAPVVAGIS TEEKEKYDEE
ISSLYRQLDD KDDEINQQSQ LAEKLKQQML DQDELLASTR RDYEKIQEEL TRLQIENEAA
KDEVKEVLQA LEELAVNYDQ KSQEVEDKTR ANEQLTDELA QKTTTLTTTQ RELSQLQELS
NHQKKRATEI LNLLLKDLGE IGGIIGTNDV KTLADVNGVI EEEFTMARLY ISKMKSEVKS
LVNRSKQLES AQMDSNRKMN ASERELAACQ LLISQHEAKI KSLTDYMQNM EQKRRQLEES
QDSLSEELAK LRAQEKMHEV SFQDKEKEHL TRLQDAEEMK KALEQQMESH REAHQKQLSR
LRDEIEEKQK IIDEIRDLNQ KLQLEQEKLS SDYNKLKIED QEREMKLEKL LLLNDKREQA
REDLKGLEET VSRELQTLHN LRKLFVQDLT TRVKKSVELD NDDGGGSAAQ KQKISFLENN
LEQLTKVHKQ LVRDNADLRC ELPKLEKRLR ATAERVKALE SALKEAKENA MRDRKRYQQE
VDRIKEAVRA KNMARRAHSA QIAKPIRPGH YPASSPTAVH AIRGGGGSSS NSTHYQK
