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UniProtKB - Q12840 (KIF5A_HUMAN)

Protein

Kinesin heavy chain isoform 5A

Gene

KIF5A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL). Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner. The ZFYVE27-KIF5A complex contributes to the vesicular transport of VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 proteins in neurons. Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi86 – 93ATPPROSITE-ProRule annotation8

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionMotor protein
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-2132295 MHC class II antigen presentation
R-HSA-264876 Insulin processing
R-HSA-5625970 RHO GTPases activate KTN1
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-983189 Kinesins
SignaLinkiQ12840

Names & Taxonomyi

Protein namesi
Recommended name:
Kinesin heavy chain isoform 5A
Alternative name(s):
Kinesin heavy chain neuron-specific 1
Neuronal kinesin heavy chain
Short name:
NKHC
Gene namesi
Name:KIF5A
Synonyms:NKHC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000155980.11
HGNCiHGNC:6323 KIF5A
MIMi602821 gene
neXtProtiNX_Q12840

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Microtubule

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 10, autosomal dominant (SPG10)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:604187
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05874163Y → C in SPG10; complicated form. 1 Publication1
Natural variantiVAR_058742198M → T in SPG10; complicated form. 1 Publication1
Natural variantiVAR_066616203S → C in SPG10. 1 Publication1
Natural variantiVAR_058743204R → Q in SPG10; complicated form. 1 PublicationCorresponds to variant dbSNP:rs387907287EnsemblClinVar.1
Natural variantiVAR_058744251E → K in SPG10; complicated form. 1 PublicationCorresponds to variant dbSNP:rs387907285EnsemblClinVar.1
Natural variantiVAR_046744253K → N in SPG10; decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover. 2 Publications1
Natural variantiVAR_032842256N → S in SPG10; slightly decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover. 2 PublicationsCorresponds to variant dbSNP:rs121434441EnsemblClinVar.1
Natural variantiVAR_058745256Missing in SPG10. 1 Publication1
Natural variantiVAR_058746257K → N in SPG10; complicated form. 1 Publication1
Natural variantiVAR_033108276Y → C in SPG10. 1 PublicationCorresponds to variant dbSNP:rs121434443EnsemblClinVar.1
Natural variantiVAR_032843280R → C in SPG10. 2 PublicationsCorresponds to variant dbSNP:rs121434442EnsemblClinVar.1
Natural variantiVAR_058747280R → H in SPG10; complicated form. 1 PublicationCorresponds to variant dbSNP:rs387907288EnsemblClinVar.1
Natural variantiVAR_058748280R → L in SPG10; pure form. 1 Publication1
Natural variantiVAR_032844361A → V in SPG10; does not affect microtubule affinity; does not affect gliding velocity; does not affect microtubule-dependent ATP turnover. 2 PublicationsCorresponds to variant dbSNP:rs121434444EnsemblClinVar.1
Myoclonus, intractable, neonatal (NEIMY)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurologic disorder characterized by severe, infantile-onset myoclonic seizures, hypotonia, optic nerve abnormalities, dysphagia, apnea, and early developmental arrest. Brain imaging shows a progressive leukoencephalopathy. Some patients may die in infancy.
See also OMIM:617235
Amyotrophic lateral sclerosis 25 (ALS25)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. The mutation NM_004984.2:c.33019A>G encoding the predicted missence variant p.Arg1007Gly, may also affect splicing and induce the skipping of exon 27, resulting in a frameshift and a premature stop codon producing a truncated protein p.Asn999Valfs*39.1 Publication
Disease descriptionA form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS25 is an autosomal dominant form with variable adult onset and incomplete penetrance.
See also OMIM:617921
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080647413E → G in ALS25; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1399145820Ensembl.1
Natural variantiVAR_080648474Q → H in ALS25; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1183553852Ensembl.1
Natural variantiVAR_080649544 – 1032Missing in ALS25. 1 PublicationAdd BLAST489
Natural variantiVAR_080650577S → G in ALS25; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs754373609Ensembl.1
Natural variantiVAR_080651986P → L in ALS25; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs113247976EnsemblClinVar.1
Natural variantiVAR_0806521007R → G in ALS25. 2 Publications1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi280R → S: Strongly reduces microtubule affinity; slightly reduces gliding velocity. 1 Publication1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Disease mutation, Epilepsy, Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

DisGeNETi3798
MalaCardsiKIF5A
MIMi604187 phenotype
617235 phenotype
617921 phenotype
OpenTargetsiENSG00000155980
Orphaneti324611 Autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation
100991 Autosomal dominant spastic paraplegia type 10
PharmGKBiPA30107

Chemistry databases

ChEMBLiCHEMBL5295

Polymorphism and mutation databases

BioMutaiKIF5A
DMDMi143811412

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001253532 – 1032Kinesin heavy chain isoform 5AAdd BLAST1031

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei397PhosphothreonineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ12840
MaxQBiQ12840
PaxDbiQ12840
PeptideAtlasiQ12840
PRIDEiQ12840
ProteomicsDBi58979

PTM databases

iPTMnetiQ12840
PhosphoSitePlusiQ12840
SwissPalmiQ12840

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000155980 Expressed in 123 organ(s), highest expression level in right frontal lobe
CleanExiHS_KIF5A
ExpressionAtlasiQ12840 baseline and differential
GenevisibleiQ12840 HS

Organism-specific databases

HPAiHPA004469
HPA073448

Interactioni

Subunit structurei

Oligomer composed of two heavy chains and two light chains. Interacts with GRIP1. Interacts with FMR1 (via C-terminus); this interaction is increased in a mGluR-dependent manner. Interacts with ZFYVE27. Interacts with VAPA, VAPB, SURF4, RAB11A (GDP-bound form), RAB11B (GDP-bound form) and RTN3 in a ZFYVE27-dependent manner (By similarity). Interacts with BORCS5 (PubMed:25898167). Interacts with BICD2 (PubMed:20386726).By similarity2 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi109999, 32 interactors
CORUMiQ12840
DIPiDIP-37584N
IntActiQ12840, 24 interactors
MINTiQ12840
STRINGi9606.ENSP00000408979

Chemistry databases

BindingDBiQ12840

Structurei

3D structure databases

ProteinModelPortaliQ12840
SMRiQ12840
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 327Kinesin motorPROSITE-ProRule annotationAdd BLAST319

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni174 – 315Microtubule-bindingAdd BLAST142
Regioni271 – 361Necessary for interaction with ZFYVE27By similarityAdd BLAST91
Regioni353 – 1032Interaction with BICD21 PublicationAdd BLAST680
Regioni907 – 1032GlobularAdd BLAST126

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili331 – 906Add BLAST576

Domaini

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.

Sequence similaritiesi

Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0240 Eukaryota
COG5059 LUCA
GeneTreeiENSGT00910000143992
HOGENOMiHOG000216718
HOVERGENiHBG006210
InParanoidiQ12840
KOiK10396
OMAiEEDFTMA
OrthoDBiEOG091G02A2
PhylomeDBiQ12840
TreeFamiTF105225

Family and domain databases

Gene3Di3.40.850.10, 1 hit
InterProiView protein in InterPro
IPR027640 Kinesin-like_fam
IPR019821 Kinesin_motor_CS
IPR001752 Kinesin_motor_dom
IPR036961 Kinesin_motor_dom_sf
IPR027417 P-loop_NTPase
PANTHERiPTHR24115 PTHR24115, 1 hit
PfamiView protein in Pfam
PF00225 Kinesin, 1 hit
PRINTSiPR00380 KINESINHEAVY
SMARTiView protein in SMART
SM00129 KISc, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00411 KINESIN_MOTOR_1, 1 hit
PS50067 KINESIN_MOTOR_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

Q12840-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAETNNECSI KVLCRFRPLN QAEILRGDKF IPIFQGDDSV VIGGKPYVFD 
        60         70         80         90        100
RVFPPNTTQE QVYHACAMQI VKDVLAGYNG TIFAYGQTSS GKTHTMEGKL 
       110        120        130        140        150
HDPQLMGIIP RIARDIFNHI YSMDENLEFH IKVSYFEIYL DKIRDLLDVT 
       160        170        180        190        200
KTNLSVHEDK NRVPFVKGCT ERFVSSPEEI LDVIDEGKSN RHVAVTNMNE 
       210        220        230        240        250
HSSRSHSIFL INIKQENMET EQKLSGKLYL VDLAGSEKVS KTGAEGAVLD 
       260        270        280        290        300
EAKNINKSLS ALGNVISALA EGTKSYVPYR DSKMTRILQD SLGGNCRTTM 
       310        320        330        340        350
FICCSPSSYN DAETKSTLMF GQRAKTIKNT ASVNLELTAE QWKKKYEKEK 
       360        370        380        390        400
EKTKAQKETI AKLEAELSRW RNGENVPETE RLAGEEAALG AELCEETPVN 
       410        420        430        440        450
DNSSIVVRIA PEERQKYEEE IRRLYKQLDD KDDEINQQSQ LIEKLKQQML 
       460        470        480        490        500
DQEELLVSTR GDNEKVQREL SHLQSENDAA KDEVKEVLQA LEELAVNYDQ 
       510        520        530        540        550
KSQEVEEKSQ QNQLLVDELS QKVATMLSLE SELQRLQEVS GHQRKRIAEV 
       560        570        580        590        600
LNGLMKDLSE FSVIVGNGEI KLPVEISGAI EEEFTVARLY ISKIKSEVKS 
       610        620        630        640        650
VVKRCRQLEN LQVECHRKME VTGRELSSCQ LLISQHEAKI RSLTEYMQSV 
       660        670        680        690        700
ELKKRHLEES YDSLSDELAK LQAQETVHEV ALKDKEPDTQ DADEVKKALE 
       710        720        730        740        750
LQMESHREAH HRQLARLRDE INEKQKTIDE LKDLNQKLQL ELEKLQADYE 
       760        770        780        790        800
KLKSEEHEKS TKLQELTFLY ERHEQSKQDL KGLEETVARE LQTLHNLRKL 
       810        820        830        840        850
FVQDVTTRVK KSAEMEPEDS GGIHSQKQKI SFLENNLEQL TKVHKQLVRD 
       860        870        880        890        900
NADLRCELPK LEKRLRATAE RVKALEGALK EAKEGAMKDK RRYQQEVDRI 
       910        920        930        940        950
KEAVRYKSSG KRGHSAQIAK PVRPGHYPAS SPTNPYGTRS PECISYTNSL 
       960        970        980        990       1000
FQNYQNLYLQ ATPSSTSDMY FANSCTSSGA TSSGGPLASY QKANMDNGNA 
      1010       1020       1030 
TDINDNRSDL PCGYEAEDQA KLFPLHQETA AS
Length:1,032
Mass (Da):117,378
Last modified:April 3, 2007 - v2
Checksum:iC4C6C12342040796
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KNA1J3KNA1_HUMAN
Kinesin-like protein
KIF5A
943Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti490A → V in BAE06127 (Ref. 2) Curated1
Sequence conflicti913G → A in AAA20231 (PubMed:7514426).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05874163Y → C in SPG10; complicated form. 1 Publication1
Natural variantiVAR_058742198M → T in SPG10; complicated form. 1 Publication1
Natural variantiVAR_066616203S → C in SPG10. 1 Publication1
Natural variantiVAR_058743204R → Q in SPG10; complicated form. 1 PublicationCorresponds to variant dbSNP:rs387907287EnsemblClinVar.1
Natural variantiVAR_058744251E → K in SPG10; complicated form. 1 PublicationCorresponds to variant dbSNP:rs387907285EnsemblClinVar.1
Natural variantiVAR_046744253K → N in SPG10; decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover. 2 Publications1
Natural variantiVAR_032842256N → S in SPG10; slightly decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover. 2 PublicationsCorresponds to variant dbSNP:rs121434441EnsemblClinVar.1
Natural variantiVAR_058745256Missing in SPG10. 1 Publication1
Natural variantiVAR_058746257K → N in SPG10; complicated form. 1 Publication1
Natural variantiVAR_033108276Y → C in SPG10. 1 PublicationCorresponds to variant dbSNP:rs121434443EnsemblClinVar.1
Natural variantiVAR_032843280R → C in SPG10. 2 PublicationsCorresponds to variant dbSNP:rs121434442EnsemblClinVar.1
Natural variantiVAR_058747280R → H in SPG10; complicated form. 1 PublicationCorresponds to variant dbSNP:rs387907288EnsemblClinVar.1
Natural variantiVAR_058748280R → L in SPG10; pure form. 1 Publication1
Natural variantiVAR_032844361A → V in SPG10; does not affect microtubule affinity; does not affect gliding velocity; does not affect microtubule-dependent ATP turnover. 2 PublicationsCorresponds to variant dbSNP:rs121434444EnsemblClinVar.1
Natural variantiVAR_080647413E → G in ALS25; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1399145820Ensembl.1
Natural variantiVAR_080648474Q → H in ALS25; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1183553852Ensembl.1
Natural variantiVAR_080649544 – 1032Missing in ALS25. 1 PublicationAdd BLAST489
Natural variantiVAR_080650577S → G in ALS25; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs754373609Ensembl.1
Natural variantiVAR_080651986P → L in ALS25; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs113247976EnsemblClinVar.1
Natural variantiVAR_0806521007R → G in ALS25. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS8945.1
PIRiI38510
RefSeqiNP_004975.2, NM_004984.2
UniGeneiHs.151219

Genome annotation databases

EnsembliENST00000455537; ENSP00000408979; ENSG00000155980
GeneIDi3798
KEGGihsa:3798
UCSCiuc001sor.2 human

Similar proteinsi

Entry informationi

Entry nameiKIF5A_HUMAN
AccessioniPrimary (citable) accession number: Q12840
Secondary accession number(s): A6H8M5, Q4LE26
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 3, 2007
Last modified: September 12, 2018
This is version 165 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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