InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NEK2

Summary

InnateDB Protein

IDBP-106518.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NEK2

Protein Name

NIMA (never in mitosis gene a)-related kinase 2

Synonyms

HsPK21; NEK2A; NLK1; PPP1R111; RP67;

Species

Homo sapiens

Ensembl Protein

ENSP00000355966

InnateDB Gene

IDBG-106516 (NEK2)

Protein Structure

UniProt Annotation

Function

Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Isoform 1 phosphorylates and activates NEK11 in G1/S- arrested cells. Isoform 2, which is not present in the nucleolus, does not. {ECO:0000269PubMed:11742531, ECO:0000269PubMed:12857871, ECO:0000269PubMed:14978040, ECO:0000269PubMed:15161910, ECO:0000269PubMed:15358203, ECO:0000269PubMed:15388344, ECO:0000269PubMed:17283141, ECO:0000269PubMed:17621308, ECO:0000269PubMed:17626005, ECO:0000269PubMed:18086858, ECO:0000269PubMed:18297113, ECO:0000269PubMed:20034488, ECO:0000269PubMed:21076410}.

Subcellular Localization

Isoform 1: Nucleus. Nucleus, nucleolus. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle pole. Chromosome, centromere, kinetochore. Chromosome, centromere {ECO:0000250}. Note=STK3/MST2 and SAV1 are required for its targeting to the centrosome. Colocalizes with SGOL1 and MAD1L1 at the kinetochore. Not associated with kinetochore in the interphase but becomes associated with it upon the breakdown of the nuclear envelope. Has a nucleolar targeting/ retention activity via a coiled-coil domain at the C-terminal end.Isoform 2: Cytoplasm. Note=Predominantly cytoplasmic.Isoform 4: Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Predominantly nuclear.

Disease Associations

Retinitis pigmentosa 67 (RP67) [MIM:615565]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269PubMed:24043777}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Isoform 1 and isoform 2 are expressed in peripheral blood T-cells and a wide variety of transformed cell types. Isoform 1 and isoform 4 are expressed in the testis. Up- regulated in various cancer cell lines, as well as primary breast tumors. {ECO:0000269PubMed:11742531, ECO:0000269PubMed:15659832}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 75 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	75 [view]
Protein-Protein	71 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019903	protein phosphatase binding
GO:0046872	metal ion binding

Biological Process

GO:0000070	mitotic sister chromatid segregation
GO:0000086	G2/M transition of mitotic cell cycle
GO:0000278	mitotic cell cycle
GO:0001824	blastocyst development
GO:0006468	protein phosphorylation
GO:0007059	chromosome segregation
GO:0007067	mitotic nuclear division
GO:0007088	regulation of mitosis
GO:0007126	meiotic nuclear division
GO:0043392	negative regulation of DNA binding
GO:0046602	regulation of mitotic centrosome separation
GO:0046777	protein autophosphorylation
GO:0051225	spindle assembly
GO:0051299	centrosome separation
GO:0051988	regulation of attachment of spindle microtubules to kinetochore
GO:0090307	spindle assembly involved in mitosis
GO:1903126	negative regulation of centriole-centriole cohesion

Cellular Component

GO:0000776	kinetochore
GO:0000777	condensed chromosome kinetochore
GO:0000794	condensed nuclear chromosome
GO:0000922	spindle pole
GO:0005634	nucleus
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005829	cytosol
GO:0005874	microtubule
GO:0030496	midbody
GO:0043234	protein complex
GO:0045171	intercellular bridge

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt