Q9HC98 (NEK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 113.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames 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 Protein kinase SID6-1512 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Reference proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
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, RPS6KB1, 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. Ref.1 Ref.9 Ref.12 Ref.13 Ref.15 Ref.17 Ref.18 Ref.19 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. Ref.13 |
| Cofactor | Magnesium. |
| Enzyme regulation | Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-108. Ref.14 |
| Subunit structure | Interacts with STAT3 and RPS6KB1 By similarity. 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 and TRIP4. Ref.10 Ref.11 Ref.13 Ref.15 Ref.18 |
| Subcellular location | Cytoplasm. Nucleus. Nucleus speckle. Cytoplasm › cytoskeleton › centrosome. Cytoplasm › cytoskeleton › spindle pole. 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. Ref.1 Ref.10 Ref.11 Ref.15 |
| Tissue specificity | Ubiquitous, with highest expression in heart and skeletal muscle. Up-regulated in a variety of malignant cancers, such as breast, colon, lung, and gastric cancers. Ref.1 Ref.19 |
| Induction | Up-regulated during the M phase of cell cycle progression. Down-regulated in both replicative and premature senescence of cancer cells. Ref.9 Ref.14 Ref.17 |
| 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. Ref.14 |
| 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. Ref.8 Ref.9 Ref.11 Ref.12 Ref.18 |
| Sequence similarities | Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily. Contains 1 protein kinase domain. |
| Sequence caution | The sequence AAG13417.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part. The sequence AAH00101.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH04174.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH04209.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAA85045.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| PIN1 | Q13526 | 3 | EBI-740364,EBI-714158 |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9HC98-1) 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: Q9HC98-2) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MPRREVCWEAAHFRQEEQSLPRPRVRALVRLACRM | ||||||
| Isoform 3 (identifier: Q9HC98-3) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MGRRRPAPFRALVRLACRM | ||||||
| Isoform 4 (identifier: Q9HC98-4) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MEATGWDSRCSPGTQVRALVRLACRM |
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_0000086427 | |||||
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 | ||||||
| Region | 267 – 270 | 4 | Interaction with APBB1 | ||||||
Sites | |||||||||
| Active site | 172 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 74 | 1 | ATP By similarity | ||||||
| Site | 108 | 1 | Autoinhibitory | ||||||
Amino acid modifications | |||||||||
| Modified residue | 37 | 1 | Phosphoserine Ref.8 | ||||||
| Modified residue | 202 | 1 | Phosphothreonine Ref.8 | ||||||
| Modified residue | 206 | 1 | Phosphoserine; by NEK9 Ref.8 Ref.16 Ref.18 | ||||||
| Modified residue | 210 | 1 | Phosphothreonine Ref.11 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 | 1 | M → MPRREVCWEAAHFRQEEQSL PRPRVRALVRLACRM in isoform 2. | VSP_041798 | |||||
| Alternative sequence | 1 | 1 | M → MGRRRPAPFRALVRLACRM in isoform 3. | VSP_041799 | |||||
| Alternative sequence | 1 | 1 | M → MEATGWDSRCSPGTQVRALV RLACRM in isoform 4. | VSP_041800 | |||||
Experimental info | |||||||||
| Mutagenesis | 74 | 1 | K → M: Loss of autophosphorylation and of kinase activity and induction of apoptosis; when associated with M-75. Ref.9 Ref.13 | ||||||
| Mutagenesis | 75 | 1 | K → M: Loss of autophosphorylation and of kinase activity and induction of apoptosis; when associated with M-74. Ref.9 Ref.13 | ||||||
| Mutagenesis | 108 | 1 | Y → A: Increase in catalytic activity. Ref.14 | ||||||
| Sequence conflict | 88 | 1 | Q → W in CAG33372. Ref.7 | ||||||
Sequences
| ||||||||||||||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Identification and characterization of Nek6 protein kinase, a potential human homolog of NIMA histone H3 kinase." Hashimoto Y., Akita H., Hibino M., Kohri K., Nakanishi M. Biochem. Biophys. Res. Commun. 293:753-758(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. |
| [2] | "A protein kinase weakly similar to nek1." Saito T., Saito R., Saito S. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). Tissue: Brain and Hippocampus. |
| [4] | "DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. Dunham I.Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | 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. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "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] (ISOFORMS 1; 2 AND 3). Tissue: Kidney and Pancreas. |
| [7] | "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-313 (ISOFORMS 1/2/3/4). |
| [8] | "A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases." Belham C., Roig J., Caldwell J.A., Aoyama Y., Kemp B.E., Comb M., Avruch J. J. Biol. Chem. 278:34897-34909(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-37; THR-202 AND SER-206. |
| [9] | "The serine/threonine kinase Nek6 is required for cell cycle progression through mitosis." Yin M.J., Shao L., Voehringer D., Smeal T., Jallal B. J. Biol. Chem. 278:52454-52460(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-74 AND LYS-75, INDUCTION. |
| [10] | "Interaction of Pin1 with Nek6 and characterization of their expression correlation in Chinese hepatocellular carcinoma patients." Chen J., Li L., Zhang Y., Yang H., Wei Y., Zhang L., Liu X., Yu L. Biochem. Biophys. Res. Commun. 341:1059-1065(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PIN1. |
| [11] | "Human NIMA-related kinase 6 is one of the Fe65 WW domain binding proteins." Lee E.J., Hyun S.H., Chun J., Kang S.S. Biochem. Biophys. Res. Commun. 358:783-788(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH APBB1, PHOSPHORYLATION AT THR-210. |
| [12] | "Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation." Lee M.Y., Kim H.J., Kim M.A., Jee H.J., Kim A.J., Bae Y.S., Park J.I., Chung J.H., Yun J. Cell Cycle 7:2705-2709(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION. |
| [13] | "The NIMA-family kinase Nek6 phosphorylates the kinesin Eg5 at a novel site necessary for mitotic spindle formation." Rapley J., Nicolas M., Groen A., Regue L., Bertran M.T., Caelles C., Avruch J., Roig J. J. Cell Sci. 121:3912-3921(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH KIF11 AND NEK9, MUTAGENESIS OF LYS-74 AND LYS-75. |
| [14] | "An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9." Richards M.W., O'Regan L., Mas-Droux C., Blot J.M., Cheung J., Hoelder S., Fry A.M., Bayliss R. Mol. Cell 36:560-570(2009) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN, ENZYME REGULATION, MUTAGENESIS OF TYR-108. |
| [15] | "The Nek6 and Nek7 protein kinases are required for robust mitotic spindle formation and cytokinesis." O'Regan L., Fry A.M. Mol. Cell. Biol. 29:3975-3990(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NEK9. |
| [16] | "Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206, MASS SPECTROMETRY. |
| [17] | "Nek6 overexpression antagonizes p53-induced senescence in human cancer cells." Jee H.J., Kim A.J., Song N., Kim H.J., Kim M., Koh H., Yun J. Cell Cycle 9:4703-4710(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION. |
| [18] | "Characterization of hNek6 interactome reveals an important role for its short N-terminal domain and colocalization with proteins at the centrosome." Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J., Paes Leme A.F., Kobarg J. J. Proteome Res. 9:6298-6316(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ANKRA2; ATF4; ARHGAP33; CDC42; CIR1; NEK9; PRAM1; PTN; PRDX3; RAD26L; RBBP6; RPS7 AND TRIP4, PHOSPHORYLATION AT SER-206, AUTOPHOSPHORYLATION. |
| [19] | "Nek6 mediates human cancer cell transformation and is a potential cancer therapeutic target." Nassirpour R., Shao L., Flanagan P., Abrams T., Jallal B., Smeal T., Yin M.J. Mol. Cancer Res. 8:717-728(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY. |
| [20] | "Caught Nek-ing: cilia and centrioles." Quarmby L.M., Mahjoub M.R. J. Cell Sci. 118:5161-5169(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW. |
| [21] | "A role for Nek6 kinase activity in preventing senescence?" Fry A.M. Cell Cycle 10:19-20(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF087909 mRNA. Translation: AAG13417.1. Sequence problems. AB026289 mRNA. Translation: BAA85045.1. Different initiation. AK294614 mRNA. Translation: BAH11825.1. AK313071 mRNA. Translation: BAG35899.1. AL162724, AL137846 Genomic DNA. Translation: CAH70247.1. AL162724, AL137846 Genomic DNA. Translation: CAH70254.1. AL137846, AL162724 Genomic DNA. Translation: CAI10876.1. AL137846, AL162724 Genomic DNA. Translation: CAI10883.1. CH471090 Genomic DNA. Translation: EAW87579.1. CH471090 Genomic DNA. Translation: EAW87581.1. BC000101 mRNA. Translation: AAH00101.2. Different initiation. BC004174 mRNA. Translation: AAH04174.2. Different initiation. BC004209 mRNA. Translation: AAH04209.2. Different initiation. BC012761 mRNA. Translation: AAH12761.1. CR457091 mRNA. Translation: CAG33372.1. CR542222 mRNA. Translation: CAG47018.1. |
| IPI | IPI00396662. IPI00550738. IPI00946494. IPI00946980. |
| PIR | JC7838. |
| RefSeq | NP_001138473.1. NM_001145001.2. NP_001159639.1. NM_001166167.1. NP_001159640.1. NM_001166168.1. NP_001159641.1. NM_001166169.1. NP_001159642.1. NM_001166170.1. NP_001159643.1. NM_001166171.1. NP_055212.2. NM_014397.5. |
| UniGene | Hs.197071. |
3D structure databases | |
| ProteinModelPortal | Q9HC98. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9HC98. 5 interactions. |
| STRING | 9606.ENSP00000362702. |
PTM databases | |
| PhosphoSite | Q9HC98. |
Polymorphism databases | |
| DMDM | 37537993. |
Proteomic databases | |
| PaxDb | Q9HC98. |
| PRIDE | Q9HC98. |
Protocols and materials databases | |
| DNASU | 10783. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000320246; ENSP00000319734; ENSG00000119408. ENST00000373600; ENSP00000362702; ENSG00000119408. ENST00000373603; ENSP00000362705; ENSG00000119408. ENST00000394199; ENSP00000377749; ENSG00000119408. ENST00000539416; ENSP00000439651; ENSG00000119408. ENST00000540326; ENSP00000441469; ENSG00000119408. ENST00000545174; ENSP00000442636; ENSG00000119408. ENST00000546191; ENSP00000441426; ENSG00000119408. |
| GeneID | 10783. |
| KEGG | hsa:10783. |
| UCSC | uc004bof.3. human. uc004bog.3. human. uc004boh.3. human. uc022bng.1. human. |
Organism-specific databases | |
| CTD | 10783. |
| GeneCards | GC09P127019. |
| HGNC | HGNC:7749. NEK6. |
| HPA | CAB045993. |
| MIM | 604884. gene. |
| neXtProt | NX_Q9HC98. |
| PharmGKB | PA31550. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG0515. |
| HOVERGEN | HBG105886. |
| InParanoid | Q9HC98. |
| KO | K08857. |
| OMA | TLADFQI. |
| OrthoDB | EOG4NVZKN. |
| PhylomeDB | Q9HC98. |
Gene expression databases | |
| ArrayExpress | Q9HC98. |
| Bgee | Q9HC98. |
| CleanEx | HS_NEK6. |
| Genevestigator | Q9HC98. |
| GermOnline | ENSG00000119408. Homo sapiens. |
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 | |
| BindingDB | Q9HC98. |
| ChEMBL | CHEMBL4309. |
| ChiTaRS | NEK6. human. |
| GenomeRNAi | 10783. |
| NextBio | 40956. |
| SOURCE | Search... |
Entry information
| Entry name | NEK6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9HC98 Secondary accession number(s): B7Z2D9 Q9ULX2 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| Human chromosome 9 Human chromosome 9: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
