Q12840 (KIF5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1032 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Cytoplasm › perinuclear region By similarity. Cytoplasm › cytoskeleton 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 autosomal dominant 10 (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.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
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.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Microtubule
Disease	Disease mutation Hereditary spastic paraplegia Neurodegeneration
Domain	Coiled coil
Ligand	ATP-binding Nucleotide-binding
Molecular function	Motor protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of exogenous peptide antigen via MHC class II Traceable author statement. Source: Reactome blood coagulation Traceable author statement. Source: Reactome cell death Inferred from electronic annotation. Source: UniProtKB-KW microtubule-based movement Traceable author statement. Source: Reactome synaptic transmission Traceable author statement Ref.1. Source: ProtInc
Cellular_component	ciliary rootlet Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome kinesin complex Traceable author statement Ref.1. Source: ProtInc membrane Traceable author statement Ref.1. Source: ProtInc microtubule Inferred from electronic annotation. Source: UniProtKB-KW neuron projection Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW microtubule motor activity Inferred from electronic annotation. Source: InterPro motor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ANKRD27	Q96NW4	4	EBI-713468,EBI-6125599

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1032	1032	Kinesin heavy chain isoform 5A		PRO_0000125353
Regions
	Domain	2 – 330	329	Kinesin-motor
	Nucleotide binding	86 – 93	8	ATP By similarity
	Region	174 – 315	142	Microtubule-binding
	Region	907 – 1032	126	Globular
	Coiled coil	331 – 906	576
Natural variations
	Natural variant	63	1	Y → C in SPG10; complicated form. Ref.12		VAR_058741
	Natural variant	198	1	M → T in SPG10; complicated form. Ref.12		VAR_058742
	Natural variant	203	1	S → C in SPG10. Ref.13		VAR_066616
	Natural variant	204	1	R → Q in SPG10; complicated form. Ref.12		VAR_058743
	Natural variant	251	1	E → K in SPG10; complicated form. Ref.12		VAR_058744
	Natural variant	253	1	K → N in SPG10; decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover. Ref.10 Ref.11		VAR_046744
	Natural variant	256	1	N → S in SPG10; slightly decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover. Ref.6 Ref.10		VAR_032842
	Natural variant	256	1	Missing in SPG10. Ref.11		VAR_058745
	Natural variant	257	1	K → N in SPG10; complicated form. Ref.12		VAR_058746
	Natural variant	276	1	Y → C in SPG10. Ref.9		VAR_033108
	Natural variant	280	1	R → C in SPG10. Ref.7 Ref.12		VAR_032843
	Natural variant	280	1	R → H in SPG10; complicated form. Ref.12		VAR_058747
	Natural variant	280	1	R → L in SPG10; pure form. Ref.12		VAR_058748
	Natural variant	361	1	A → V in SPG10; does not affect microtubule affinity; does not affect gliding velocity; does not affect microtubule-dependent ATP turnover. Ref.8 Ref.10		VAR_032844
Experimental info
	Mutagenesis	280	1	R → S: Strongly reduces microtubule affinity; slightly reduces gliding velocity. Ref.10
	Sequence conflict	490	1	A → V in BAE06127. Ref.2
	Sequence conflict	913	1	G → A in AAA20231. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q12840 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: C4C6C12342040796	FASTA	1,032	117,378
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"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].
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
IPI	IPI00029722.
PIR	I38510.
RefSeq	NP_004975.2. NM_004984.2.
UniGene	Hs.151219.
3D structure databases
ProteinModelPortal	Q12840.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-37584N.
IntAct	Q12840. 9 interactions.
MINT	MINT-1370533.
STRING	9606.ENSP00000286452.
PTM databases
PhosphoSite	Q12840.
Polymorphism databases
DMDM	143811412.
Proteomic databases
PaxDb	Q12840.
PRIDE	Q12840.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000455537; ENSP00000408979; ENSG00000155980.
GeneID	3798.
KEGG	hsa:3798.
UCSC	uc001sor.1. human.
Organism-specific databases
CTD	3798.
GeneCards	GC12P057943.
H-InvDB	HIX0036852.
HGNC	HGNC:6323. KIF5A.
HPA	CAB015157. HPA004469.
MIM	602821. gene. 604187. phenotype.
neXtProt	NX_Q12840.
Orphanet	100991. Autosomal dominant spastic paraplegia type 10.
PharmGKB	PA30107.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5059.
HOGENOM	HOG000216718.
HOVERGEN	HBG006210.
InParanoid	Q12840.
KO	K10396.
OMA	EVQMESH.
OrthoDB	EOG4Q2DDS.
PhylomeDB	Q12840.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q12840.
Bgee	Q12840.
CleanEx	HS_KIF5A.
Genevestigator	Q12840.
GermOnline	ENSG00000155980. Homo sapiens.
Family and domain databases
Gene3D	3.40.850.10. 1 hit.
InterPro	IPR019821. Kinesin_motor_CS. IPR001752. Kinesin_motor_dom. [Graphical view]
Pfam	PF00225. Kinesin. 1 hit. [Graphical view]
PRINTS	PR00380. KINESINHEAVY.
SMART	SM00129. KISc. 1 hit. [Graphical view]
PROSITE	PS00411. KINESIN_MOTOR_DOMAIN1. 1 hit. PS50067. KINESIN_MOTOR_DOMAIN2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q12840.
ChEMBL	CHEMBL5295.
ChiTaRS	KIF5A. human.
GenomeRNAi	3798.
NextBio	14913.
SOURCE	Search...

Entry information

Entry name

KIF5A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.