O75449 (KTNA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Katanin p60 ATPase-containing subunit A1
Short name=Katanin p60 subunit A1
EC=3.6.4.3

Alternative name(s):
p60 katanin

Gene names

Name:

KATNA1

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	491 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytic subunit of a complex which severs microtubules in an ATP-dependent manner. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth By similarity. Ref.5 Ref.6 Ref.9
Catalytic activity	ATP + H2O = ADP + phosphate. HAMAP-Rule MF_03023
Enzyme regulation	ATPase activity is stimulated by microtubules, which promote homooligomerization By similarity. ATP dependent microtubule severing is stimulated by interaction with KATNB1. HAMAP-Rule MF_03023
Subunit structure	Can homooligomerize into hexameric rings, which may be promoted by interaction with microtubules By similarity. Interacts with KATNB1, which may serve as a targeting subunit. Interacts with dynein and NDEL1 By similarity. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and VPRBP proteins (EDVP complex). Interacts with KLHL42 (via the kelch domains). Interacts with CUL3; the interaction is enhanced by KLHL42. Ref.5 Ref.9
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton › centrosome. Cytoplasm › cytoskeleton › spindle. Cytoplasm › cytoskeleton › spindle pole. Midbody. Cytoplasm › cytoskeleton. Note: Predominantly cytoplasmic. Localized diffusely in the cytoplasm during the interphase. During metaphase is localized throughout the cell and more widely dispersed than the microtubules. In anaphase and telophase is localized at the midbody region. Also localized to the interphase centrosome and the mitotic spindle poles. Enhanced recruitment to the mitotic spindle poles requires microtubules and interaction with KATNB1. Ref.1 Ref.5
Domain	The N-terminus is sufficient for interaction with microtubules. However, high affinity binding to microtubules also requires an intact C-terminal domain and ATP, which promotes oligomerization By similarity. HAMAP-Rule MF_03023
Post-translational modification	Phosphorylation by DYRK2 triggers ubiquitination and subsequent degradation. HAMAP-Rule MF_03023 Ubiquitinated by the EDVP E3 ligase complex and subsequently targeted to proteasomal degradation. Ubiquitinated by the BCR(KLHL42) E3 ubiquitin ligase complex, leading to its proteasomal degradation. Ref.8
Sequence similarities	Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Cytoplasm Cytoskeleton Microtubule
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell division Inferred from electronic annotation. Source: UniProtKB-KW cytoplasmic microtubule organization Inferred from electronic annotation. Source: Compara interphase of mitotic cell cycle Inferred from mutant phenotype Ref.5. Source: UniProtKB microtubule bundle formation Inferred from electronic annotation. Source: Compara microtubule severing Inferred from electronic annotation. Source: Compara mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of neuron projection development Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara protein localization Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from electronic annotation. Source: Compara centrosome Inferred from direct assay. Source: HPA cytoplasm Inferred from direct assay Ref.8. Source: UniProtKB growth cone Inferred from electronic annotation. Source: Compara lipid particle Inferred from electronic annotation. Source: Compara microtubule Inferred from electronic annotation. Source: UniProtKB-KW midbody Inferred from direct assay Ref.8. Source: UniProtKB neuronal cell body Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from electronic annotation. Source: Compara spindle pole Inferred from direct assay Ref.5Ref.8. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW microtubule binding Inferred from direct assay Ref.5. Source: UniProtKB microtubule-severing ATPase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75449-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O75449-2)

The sequence of this isoform differs from the canonical sequence as follows:
     168-243: Missing.
     384-387: AKGR → GMRP
     388-491: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 491	491	Katanin p60 ATPase-containing subunit A1 HAMAP-Rule MF_03023		PRO_0000084594
Regions
	Nucleotide binding	249 – 256	8	ATP Potential
	Region	1 – 185	185	Interaction with microtubules HAMAP-Rule MF_03023
	Region	1 – 75	75	Interaction with dynein and NDEL1 By similarity
	Region	1 – 29	29	Interaction with KATNB1 HAMAP-Rule MF_03023
Amino acid modifications
	Modified residue	42	1	Phosphoserine; by DYRK2 Ref.9
	Modified residue	109	1	Phosphoserine; by DYRK2 Ref.9
	Modified residue	133	1	Phosphothreonine; by DYRK2 Ref.9
	Modified residue	170	1	Phosphoserine Ref.7 Ref.11
Natural variations
	Alternative sequence	168 – 243	76	Missing in isoform 2.		VSP_012948
	Alternative sequence	384 – 387	4	AKGR → GMRP in isoform 2.		VSP_012949
	Alternative sequence	388 – 491	104	Missing in isoform 2.		VSP_012950
Experimental info
	Mutagenesis	255	1	K → A: Abolishes ATP dependent microtubule severing activity and localization to spindle poles. Ref.5 Ref.6
	Mutagenesis	308	1	D → N: Abolishes ATP dependent microtubule severing activity and localization to spindle poles; when associated with N-309. Ref.5
	Mutagenesis	309	1	E → N: Abolishes ATP dependent microtubule severing activity and localization to spindle poles; when associated with N-308. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: F431594F478491DD	FASTA	491	55,965
	10 20 30 40 50 60 MSLLMISENV KLAREYALLG NYDSAMVYYQ GVLDQMNKYL YSVKDTYLQQ KWQQVWQEIN 70 80 90 100 110 120 VEAKHVKDIM KTLESFKLDS TPLKAAQHDL PASEGEVWSM PVPVERRPSP GPRKRQSSQY 130 140 150 160 170 180 SDPKSHGNRP STTVRVHRSS AQNVHNDRGK AVRCREKKEQ NKGREEKNKS PAAVTEPETN 190 200 210 220 230 240 KFDSTGYDKD LVEALERDII SQNPNVRWDD IADLVEAKKL LKEAVVLPMW MPEFFKGIRR 250 260 270 280 290 300 PWKGVLMVGP PGTGKTLLAK AVATECKTTF FNVSSSTLTS KYRGESEKLV RLLFEMARFY 310 320 330 340 350 360 SPATIFIDEI DSICSRRGTS EEHEASRRVK AELLVQMDGV GGTSENDDPS KMVMVLAATN 370 380 390 400 410 420 FPWDIDEALR RRLEKRIYIP LPSAKGREEL LRISLRELEL ADDVDLASIA ENMEGYSGAD 430 440 450 460 470 480 ITNVCRDASL MAMRRRIEGL TPEEIRNLSK EEMHMPTTME DFEMALKKVS KSVSAADIER 490 YEKWIFEFGS C
	Isoform 2 [UniParc]. Checksum: 9DF635C4E51147C7	FASTA	311	35,319
	10 20 30 40 50 60 MSLLMISENV KLAREYALLG NYDSAMVYYQ GVLDQMNKYL YSVKDTYLQQ KWQQVWQEIN 70 80 90 100 110 120 VEAKHVKDIM KTLESFKLDS TPLKAAQHDL PASEGEVWSM PVPVERRPSP GPRKRQSSQY 130 140 150 160 170 180 SDPKSHGNRP STTVRVHRSS AQNVHNDRGK AVRCREKKEQ NKGREEKGVL MVGPPGTGKT 190 200 210 220 230 240 LLAKAVATEC KTTFFNVSSS TLTSKYRGES EKLVRLLFEM ARFYSPATIF IDEIDSICSR 250 260 270 280 290 300 RGTSEEHEAS RRVKAELLVQ MDGVGGTSEN DDPSKMVMVL AATNFPWDID EALRRRLEKR 310 IYIPLPSGMR P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Katanin is responsible for the M-phase microtubule-severing activity in Xenopus eggs." McNally F.J., Thomas S. Mol. Biol. Cell 9:1847-1861(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 (SEP-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] (ISOFORM 2). Tissue: Brain.
[5]	"Two domains of p80 katanin regulate microtubule severing and spindle pole targeting by p60 katanin." McNally K.P., Bazirgan O.A., McNally F.J. J. Cell Sci. 113:1623-1633(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH KATNB1, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-255; ASP-308 AND GLU-309.
[6]	"Katanin inhibition prevents the redistribution of gamma-tubulin at mitosis." Buster D., McNally K., McNally F.J. J. Cell Sci. 115:1083-1092(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-255.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"The Cul3/Klhdc5 E3 ligase regulates p60/katanin and is required for normal mitosis in mammalian cells." Cummings C.M., Bentley C.A., Perdue S.A., Baas P.W., Singer J.D. J. Biol. Chem. 284:11663-11675(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY THE BCR(KLHL42) COMPLEX.
[9]	"Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase." Maddika S., Chen J. Nat. Cell Biol. 11:409-419(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-42; SER-109 AND THR-133 BY DYRK2, FUNCTION AS KATNA1 KINASE, INTERACTION WITH EDVP COMPLEX.
[10]	"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].
[11]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF056022 mRNA. Translation: AAC25114.1. AL078581, BX276089 Genomic DNA. Translation: CAI19504.1. AL078581, BX276089 Genomic DNA. Translation: CAI19505.1. BX276089, AL078581 Genomic DNA. Translation: CAI16431.1. BX276089, AL078581 Genomic DNA. Translation: CAI16432.1. CH471051 Genomic DNA. Translation: EAW47793.1. CH471051 Genomic DNA. Translation: EAW47795.1. BC050428 mRNA. Translation: AAH50428.1.
IPI	IPI00013075. IPI00384339.
RefSeq	NP_001191005.1. NM_001204076.1. NP_008975.1. NM_007044.3.
UniGene	Hs.450175.
3D structure databases
ProteinModelPortal	O75449.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000335106.
PTM databases
PhosphoSite	O75449.
Proteomic databases
PaxDb	O75449.
PRIDE	O75449.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000335643; ENSP00000335180; ENSG00000186625. ENST00000335647; ENSP00000335106; ENSG00000186625. ENST00000367411; ENSP00000356381; ENSG00000186625.
GeneID	11104.
KEGG	hsa:11104.
UCSC	uc003qmr.2. human. uc003qmt.3. human.
Organism-specific databases
CTD	11104.
GeneCards	GC06M149957.
HGNC	HGNC:6216. KATNA1.
HPA	HPA036207.
MIM	606696. gene.
neXtProt	NX_O75449.
PharmGKB	PA30017.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0464.
HOGENOM	HOG000225142.
HOVERGEN	HBG057074.
InParanoid	O75449.
KO	K07767.
OMA	SQYSDPK.
OrthoDB	EOG4CJVGZ.
Enzyme and pathway databases
Pathway_Interaction_DB	lis1pathway. Lissencephaly gene (LIS1) in neuronal migration and development.
Gene expression databases
ArrayExpress	O75449.
Bgee	O75449.
CleanEx	HS_KATNA1.
Genevestigator	O75449.
Family and domain databases
HAMAP	MF_03023. Katanin_p60_A1.
InterPro	IPR003593. AAA+_ATPase. IPR003959. ATPase_AAA_core. IPR003960. ATPase_AAA_CS. IPR015415. Vps4_C. [Graphical view]
Pfam	PF00004. AAA. 1 hit. PF09336. Vps4_C. 1 hit. [Graphical view]
SMART	SM00382. AAA. 1 hit. [Graphical view]
PROSITE	PS00674. AAA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	KATNA1. human.
GenomeRNAi	11104.
NextBio	42220.
SOURCE	Search...

Entry information

Entry name

KTNA1_HUMAN

Accession

Primary (citable) accession number: O75449
Secondary accession number(s): E1P5A3 , Q5TFA8, Q5TFA9, Q86VN2, Q9NU52

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2005
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 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.