P59895 (NEK6_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase Nek6
EC=2.7.11.1

Alternative name(s):
Never in mitosis A-related kinase 6
Short name=NimA-related protein kinase 6

Gene names

Name:

Nek6

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	313 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein kinase which plays an important role in mitotic cell cycle progression. Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis. Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, TRIP4, STAT3 and histones H1 and H3. Phosphorylates KIF11 to promote mitotic spindle formation. Involved in G2/M phase cell cycle arrest induced by DNA damage. Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence By similarity. Phosphorylates RPS6KB1. Ref.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-108 By similarity.
Subunit structure	Interacts with NEK9, predominantly in mitosis. Interacts with KIF11 (via C-terminus). Interacts with APBB1 (via WW domain). Interacts with ANKRA2, ATF4, ARHGAP33, CDC42, CIR1, PRAM1, PTN, PRDX3, PIN1, RAD26L, RBBP6, RPS7, STAT3 and TRIP4 By similarity. Interacts with RPS6KB1.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Nucleus speckle By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Cytoplasm › cytoskeleton › spindle pole By similarity. Note: Co-localizes with APBB1 at the nuclear speckles. Co-localizes with PIN1 in the nucleus. Co-localizes with ATF4, CIR1, ARHGAP33, ANKRA2, CDC42, NEK9, RAD26L, RBBP6, RPS7, TRIP4, RELB and PHF1 in the centrosome. Localizes to spindle microtubules in metaphase and anaphase and to the midbody during cytokinesis By similarity.
Tissue specificity	Highly expressed in the liver. Ref.2
Domain	Displays an autoinhibited conformation: Tyr-108 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9 By similarity.
Post-translational modification	Autophosphorylated. Phosphorylation at Ser-206 is required for its activation. Phosphorylated upon IR or UV-induced DNA damage. Phosphorylated by CHEK1 and CHEK2. Interaction with APBB1 down-regulates phosphorylation at Thr-210 By similarity. Ref.2
Sequence similarities	Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Cell division Chromosome partition Mitosis
Cellular component	Cytoplasm Cytoskeleton Nucleus
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G2 DNA damage checkpoint Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW chromosome segregation Inferred from sequence or structural similarity. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of mitotic metaphase/anaphase transition Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell spindle pole Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 313	313	Serine/threonine-protein kinase Nek6		PRO_0000086429
Regions
	Domain	45 – 310	266	Protein kinase
	Nucleotide binding	51 – 59	9	ATP By similarity
	Region	1 – 44	44	Interaction with ARHGAP33, ANKRA2, CDC42, PRDX3, RAD26L, RBBP6, RPS7 and TRIP4 By similarity
	Region	267 – 270	4	Interaction with APBB1 By similarity
Sites
	Active site	172	1	Proton acceptor By similarity
	Binding site	74	1	ATP By similarity
	Site	108	1	Autoinhibitory By similarity
Amino acid modifications
	Modified residue	37	1	Phosphoserine By similarity
	Modified residue	202	1	Phosphothreonine By similarity
	Modified residue	206	1	Phosphoserine; by NEK9 By similarity
	Modified residue	210	1	Phosphothreonine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P59895 [UniParc]. Last modified October 3, 2003. Version 1. Checksum: 4CC398D70916021F	FASTA	313	35,835
	10 20 30 40 50 60 MAGQPSHMPH GGSPNHLCHV LGPAHPPDPQ RHPNTLSFRC SLADFQIEKK IGRGQFSEVY 70 80 90 100 110 120 KATCLLDRKT VALKKVQIFE MMDAKARQDC VKEIGLLKQL NHPNIIKYLD SFIEDNELNI 130 140 150 160 170 180 VLELADAGDL SQMIKYFKKQ KRLIPERTVW KYFVQLCSAV EHMHSRRVMH RDIKPANVFI 190 200 210 220 230 240 TATGIVKLGD LGLGRFFSSE TTAAHSLVGT PYYMSPERIH ENGYNFKSDI WSLGCLLYEM 250 260 270 280 290 300 AALQSPFYGD KMNLFSLCQK IEQCDYPPLP GEHYSEKLRE LVSMCIYPDP NHRPDIEYVH 310 QVAKQMHVWT SST

References

[1]	"Cloning of Rattus norvegicus NIMA (never in mitosis gene a)-related expressed kinase 6 (Nek6)." Zhou G., Zhang Y., Ni J. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification of the NIMA family kinases NEK6/7 as regulators of the p70 ribosomal S6 kinase." Belham C., Comb M.J., Avruch J. Curr. Biol. 11:1155-1167(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, TISSUE SPECIFICITY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY334013 mRNA. Translation: AAP97428.1.
IPI	IPI00215059.
RefSeq	NP_001264161.1. NM_001277232.1. NP_891998.1. NM_182953.2.
UniGene	Rn.18744.
3D structure databases
ProteinModelPortal	P59895.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000014630; ENSRNOP00000014631; ENSRNOG00000010897.
GeneID	360161.
KEGG	rno:360161.
UCSC	RGD:727779. rat.
Organism-specific databases
CTD	10783.
RGD	727779. Nek6.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104074.
HOGENOM	HOG000233029.
HOVERGEN	HBG105886.
InParanoid	P59895.
KO	K08857.
OMA	TLADFQI.
OrthoDB	EOG4NVZKN.
Gene expression databases
ArrayExpress	P59895.
Genevestigator	P59895.
GermOnline	ENSRNOG00000010897. Rattus norvegicus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	672720.

Entry information

Entry name

NEK6_RAT

Accession

Primary (citable) accession number: P59895

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
Last sequence update:	October 3, 2003
Last modified:	May 29, 2013
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program