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Q12840 (KIF5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kinesin heavy chain isoform 5A
Alternative name(s):
Kinesin heavy chain neuron-specific 1
Neuronal kinesin heavy chain
Short name=NKHC
Gene names
Name:KIF5A
Synonyms:NKHC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1032 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL) By similarity.

Subunit structure

Oligomer composed of two heavy chains and two light chains. Interacts with GRIP1 By similarity.

Subcellular location

Cytoplasmperinuclear region By similarity. Cytoplasmcytoskeleton By similarity. Note: Concentrated in the cell body of the neurons, particularly in the perinuclear region By similarity.

Tissue specificity

Distributed throughout the CNS but is highly enriched in subsets of neurons.

Domain

Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.

Involvement in disease

Spastic paraplegia 10, autosomal dominant (SPG10) [MIM:604187]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Sequence similarities

Belongs to the kinesin-like protein family. Kinesin subfamily.

Contains 1 kinesin-motor domain.

Sequence caution

The sequence BAE06127.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ANKRD27Q96NW44EBI-713468,EBI-6125599
Trak2Q8R2H72EBI-713468,EBI-1396483From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 10321031Kinesin heavy chain isoform 5A
PRO_0000125353

Regions

Domain2 – 330329Kinesin-motor
Nucleotide binding86 – 938ATP By similarity
Region174 – 315142Microtubule-binding
Region907 – 1032126Globular
Coiled coil331 – 906576

Amino acid modifications

Modified residue21N-acetylalanine Ref.5

Natural variations

Natural variant631Y → C in SPG10; complicated form. Ref.13
VAR_058741
Natural variant1981M → T in SPG10; complicated form. Ref.13
VAR_058742
Natural variant2031S → C in SPG10. Ref.14
VAR_066616
Natural variant2041R → Q in SPG10; complicated form. Ref.13
VAR_058743
Natural variant2511E → K in SPG10; complicated form. Ref.13
VAR_058744
Natural variant2531K → N in SPG10; decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover. Ref.11 Ref.12
VAR_046744
Natural variant2561N → S in SPG10; slightly decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover. Ref.7 Ref.11
VAR_032842
Natural variant2561Missing in SPG10. Ref.12
VAR_058745
Natural variant2571K → N in SPG10; complicated form. Ref.13
VAR_058746
Natural variant2761Y → C in SPG10. Ref.10
VAR_033108
Natural variant2801R → C in SPG10. Ref.8 Ref.13
VAR_032843
Natural variant2801R → H in SPG10; complicated form. Ref.13
VAR_058747
Natural variant2801R → L in SPG10; pure form. Ref.13
VAR_058748
Natural variant3611A → V in SPG10; does not affect microtubule affinity; does not affect gliding velocity; does not affect microtubule-dependent ATP turnover. Ref.9 Ref.11
Corresponds to variant rs121434444 [ dbSNP | Ensembl ].
VAR_032844

Experimental info

Mutagenesis2801R → S: Strongly reduces microtubule affinity; slightly reduces gliding velocity. Ref.11
Sequence conflict4901A → V in BAE06127. Ref.2
Sequence conflict9131G → A in AAA20231. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q12840 [UniParc].

Last modified April 3, 2007. Version 2.
Checksum: C4C6C12342040796

FASTA1,032117,378
        10         20         30         40         50         60 
MAETNNECSI KVLCRFRPLN QAEILRGDKF IPIFQGDDSV VIGGKPYVFD RVFPPNTTQE 

        70         80         90        100        110        120 
QVYHACAMQI VKDVLAGYNG TIFAYGQTSS GKTHTMEGKL HDPQLMGIIP RIARDIFNHI 

       130        140        150        160        170        180 
YSMDENLEFH IKVSYFEIYL DKIRDLLDVT KTNLSVHEDK NRVPFVKGCT ERFVSSPEEI 

       190        200        210        220        230        240 
LDVIDEGKSN RHVAVTNMNE HSSRSHSIFL INIKQENMET EQKLSGKLYL VDLAGSEKVS 

       250        260        270        280        290        300 
KTGAEGAVLD EAKNINKSLS ALGNVISALA EGTKSYVPYR DSKMTRILQD SLGGNCRTTM 

       310        320        330        340        350        360 
FICCSPSSYN DAETKSTLMF GQRAKTIKNT ASVNLELTAE QWKKKYEKEK EKTKAQKETI 

       370        380        390        400        410        420 
AKLEAELSRW RNGENVPETE RLAGEEAALG AELCEETPVN DNSSIVVRIA PEERQKYEEE 

       430        440        450        460        470        480 
IRRLYKQLDD KDDEINQQSQ LIEKLKQQML DQEELLVSTR GDNEKVQREL SHLQSENDAA 

       490        500        510        520        530        540 
KDEVKEVLQA LEELAVNYDQ KSQEVEEKSQ QNQLLVDELS QKVATMLSLE SELQRLQEVS 

       550        560        570        580        590        600 
GHQRKRIAEV LNGLMKDLSE FSVIVGNGEI KLPVEISGAI EEEFTVARLY ISKIKSEVKS 

       610        620        630        640        650        660 
VVKRCRQLEN LQVECHRKME VTGRELSSCQ LLISQHEAKI RSLTEYMQSV ELKKRHLEES 

       670        680        690        700        710        720 
YDSLSDELAK LQAQETVHEV ALKDKEPDTQ DADEVKKALE LQMESHREAH HRQLARLRDE 

       730        740        750        760        770        780 
INEKQKTIDE LKDLNQKLQL ELEKLQADYE KLKSEEHEKS TKLQELTFLY ERHEQSKQDL 

       790        800        810        820        830        840 
KGLEETVARE LQTLHNLRKL FVQDVTTRVK KSAEMEPEDS GGIHSQKQKI SFLENNLEQL 

       850        860        870        880        890        900 
TKVHKQLVRD NADLRCELPK LEKRLRATAE RVKALEGALK EAKEGAMKDK RRYQQEVDRI 

       910        920        930        940        950        960 
KEAVRYKSSG KRGHSAQIAK PVRPGHYPAS SPTNPYGTRS PECISYTNSL FQNYQNLYLQ 

       970        980        990       1000       1010       1020 
ATPSSTSDMY FANSCTSSGA TSSGGPLASY QKANMDNGNA TDINDNRSDL PCGYEAEDQA 

      1030 
KLFPLHQETA AS 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and localization of a conventional kinesin motor expressed exclusively in neurons."
Niclas J., Navone F., Hom-Booher N., Vale R.D.
Neuron 12:1059-1072(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Hippocampus.
[2]"Preparation of a set of expression-ready clones of mammalian long cDNAs encoding large proteins by the ORF trap cloning method."
Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., Okazaki N., Koga H., Nagase T., Ohara O.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10)."
Reid E., Kloos M., Ashley-Koch A., Hughes L., Bevan S., Svenson I.K., Graham F.L., Gaskell P.C., Dearlove A., Pericak-Vance M.A., Rubinsztein D.C., Marchuk D.A.
Am. J. Hum. Genet. 71:1189-1194(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG10 SER-256.
[8]"Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic paraplegia."
Fichera M., Lo Giudice M., Falco M., Sturnio M., Amata S., Calabrese O., Bigoni S., Calzolari E., Neri M.
Neurology 63:1108-1110(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG10 CYS-280.
[9]"A missense mutation in the coiled-coil domain of the KIF5A gene and late-onset hereditary spastic paraplegia."
Lo Giudice M., Neri M., Falco M., Sturnio M., Calzolari E., Di Benedetto D., Fichera M.
Arch. Neurol. 63:284-287(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG10 VAL-361.
[10]"Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia."
Blair M.A., Ma S., Hedera P.
Neurogenetics 7:47-50(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG10 CYS-276.
[11]"Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity."
Ebbing B., Mann K., Starosta A., Jaud J., Schoels L., Schuele R., Woehlke G.
Hum. Mol. Genet. 17:1245-1252(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-253, CHARACTERIZATION OF VARIANT ASN-253, CHARACTERIZATION OF VARIANTS SPG10 SER-256 AND VAL-361, MUTAGENESIS OF ARG-280.
[12]"SPG10 is a rare cause of spastic paraplegia in European families."
Schuele R., Kremer B.P.H., Kassubek J., Auer-Grumbach M., Kostic V., Klopstock T., Klimpe S., Otto S., Boesch S., van de Warrenburg B.P., Schoels L.
J. Neurol. Neurosurg. Psych. 79:584-587(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SPG10 ASN-253 AND ASN-256 DEL.
[13]"Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10."
Goizet C., Boukhris A., Mundwiller E., Tallaksen C., Forlani S., Toutain A., Carriere N., Paquis V., Depienne C., Durr A., Stevanin G., Brice A.
Hum. Mutat. 30:E376-E385(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SPG10 CYS-63; THR-198; GLN-204; LYS-251; ASN-257; CYS-280; LEU-280 AND HIS-280.
[14]"A novel mutation in KIF5A gene causing hereditary spastic paraplegia with axonal neuropathy."
Musumeci O., Bassi M.T., Mazzeo A., Grandis M., Crimella C., Martinuzzi A., Toscano A.
Neurol. Sci. 32:665-668(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG10 CYS-203.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U06698 mRNA. Translation: AAA20231.1.
AB210045 mRNA. Translation: BAE06127.1. Different initiation.
CH471054 Genomic DNA. Translation: EAW97030.1.
BC146670 mRNA. Translation: AAI46671.1.
BC150208 mRNA. Translation: AAI50209.1.
PIRI38510.
RefSeqNP_004975.2. NM_004984.2.
UniGeneHs.151219.

3D structure databases

ProteinModelPortalQ12840.
SMRQ12840. Positions 7-339.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109999. 18 interactions.
DIPDIP-37584N.
IntActQ12840. 15 interactions.
MINTMINT-1370533.
STRING9606.ENSP00000286452.

Chemistry

BindingDBQ12840.
ChEMBLCHEMBL5295.

PTM databases

PhosphoSiteQ12840.

Polymorphism databases

DMDM143811412.

Proteomic databases

PaxDbQ12840.
PRIDEQ12840.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000455537; ENSP00000408979; ENSG00000155980.
GeneID3798.
KEGGhsa:3798.
UCSCuc001sor.1. human.

Organism-specific databases

CTD3798.
GeneCardsGC12P057943.
H-InvDBHIX0036852.
HGNCHGNC:6323. KIF5A.
HPACAB015157.
HPA004469.
MIM602821. gene.
604187. phenotype.
neXtProtNX_Q12840.
Orphanet324611. Autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation.
100991. Autosomal dominant spastic paraplegia type 10.
PharmGKBPA30107.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5059.
HOGENOMHOG000216718.
HOVERGENHBG006210.
InParanoidQ12840.
KOK10396.
OMAEVQMESH.
OrthoDBEOG7T4MJD.
PhylomeDBQ12840.
TreeFamTF105225.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkQ12840.

Gene expression databases

ArrayExpressQ12840.
BgeeQ12840.
CleanExHS_KIF5A.
GenevestigatorQ12840.

Family and domain databases

Gene3D3.40.850.10. 1 hit.
InterProIPR027640. Kinesin-like_fam.
IPR019821. Kinesin_motor_CS.
IPR001752. Kinesin_motor_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR24115. PTHR24115. 1 hit.
PfamPF00225. Kinesin. 1 hit.
[Graphical view]
PRINTSPR00380. KINESINHEAVY.
SMARTSM00129. KISc. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS00411. KINESIN_MOTOR_DOMAIN1. 1 hit.
PS50067. KINESIN_MOTOR_DOMAIN2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSKIF5A. human.
GeneWikiKIF5A.
GenomeRNAi3798.
NextBio14913.
PROQ12840.
SOURCESearch...

Entry information

Entry nameKIF5A_HUMAN
AccessionPrimary (citable) accession number: Q12840
Secondary accession number(s): A6H8M5, Q4LE26
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 3, 2007
Last modified: April 16, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM