P51956 (NEK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase Nek3
EC=2.7.11.1

Alternative name(s):
HSPK 36
Never in mitosis A-related kinase 3
Short name=NimA-related protein kinase 3

Gene names

Name:

NEK3

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

General annotation (Comments)

Function	Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2. Implicated in prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2. Ref.8 Ref.9
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Prolactin stimulates its activity. Ref.8
Subunit structure	Interacts with PXN, PRLR, VAV1 and VAV2 and this interaction is prolactin-dependent. Ref.8 Ref.9
Subcellular location	Cytoplasm By similarity. Cell projection › axon By similarity.
Tissue specificity	Up-regulated in malignant versus normal breast tissue. Isoform 2 shows a high level of expression in testis, ovary and brain. Ref.1 Ref.9
Post-translational modification	Phosphorylation at Thr-479 regulates its catalytic activity By similarity.
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 CAI12895.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence EAX08907.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis
Cellular component	Cell projection Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
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	cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Non-traceable author statement Ref.6. Source: UniProtKB
Cellular_component	axon Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Non-traceable author statement Ref.6. Source: UniProtKB
Molecular_function	ATP binding Non-traceable author statement. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Non-traceable author statement Ref.6. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VAV2	P52735	3	EBI-476041,EBI-297549

Alternative products

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

Isoform 1 (identifier: P51956-1)

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: P51956-2)

The sequence of this isoform differs from the canonical sequence as follows:
     293-309: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 506	506	Serine/threonine-protein kinase Nek3		PRO_0000086423
Regions
	Domain	4 – 257	254	Protein kinase
	Nucleotide binding	10 – 18	9	ATP By similarity
	Region	1 – 285	285	Interaction with VAV2
Sites
	Active site	127	1	Proton acceptor By similarity
	Binding site	33	1	ATP By similarity
Amino acid modifications
	Modified residue	161	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	479	1	Phosphothreonine Ref.10
Natural variations
	Alternative sequence	293 – 309	17	Missing in isoform 2.		VSP_035427
	Natural variant	23	1	H → L. Ref.11 Corresponds to variant rs17482764 [ dbSNP | Ensembl ].		VAR_033906
	Natural variant	60	1	P → R. Ref.11 Corresponds to variant rs55946204 [ dbSNP | Ensembl ].		VAR_040908
	Natural variant	122	1	R → H. Ref.11 Corresponds to variant rs56190615 [ dbSNP | Ensembl ].		VAR_040909
	Natural variant	170	1	P → L. Ref.11 Corresponds to variant rs56021040 [ dbSNP | Ensembl ].		VAR_040910
	Natural variant	259	1	R → G. Ref.11 Corresponds to variant rs34077016 [ dbSNP | Ensembl ].		VAR_040911
	Natural variant	305	1	E → D. Ref.11 Corresponds to variant rs55969405 [ dbSNP | Ensembl ].		VAR_040912
	Natural variant	461	1	D → N. Ref.11 Corresponds to variant rs34076988 [ dbSNP | Ensembl ].		VAR_040913
	Natural variant	477	1	E → K. Ref.11 Corresponds to variant rs34488913 [ dbSNP | Ensembl ].		VAR_040914
Experimental info
	Sequence conflict	14	1	S → F in BAC15599. Ref.1
	Sequence conflict	54	1	L → S in CAA82310. Ref.6
	Sequence conflict	77 – 78	2	IV → LY in CAA80921. Ref.7
	Sequence conflict	187 – 189	3	SLG → PSV in CAA80921. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: 4437EB4A41A44777	FASTA	506	57,705
	10 20 30 40 50 60 MDDYMVLRMI GEGSFGRALL VQHESSNQMF AMKEIRLPKS FSNTQNSRKE AVLLAKMKHP 70 80 90 100 110 120 NIVAFKESFE AEGHLYIVME YCDGGDLMQK IKQQKGKLFP EDMILNWFTQ MCLGVNHIHK 130 140 150 160 170 180 KRVLHRDIKS KNIFLTQNGK VKLGDFGSAR LLSNPMAFAC TYVGTPYYVP PEIWENLPYN 190 200 210 220 230 240 NKSDIWSLGC ILYELCTLKH PFQANSWKNL ILKVCQGCIS PLPSHYSYEL QFLVKQMFKR 250 260 270 280 290 300 NPSHRPSATT LLSRGIVARL VQKCLPPEII MEYGEEVLEE IKNSKHNTPR KKTNPSRIRI 310 320 330 340 350 360 ALGNEASTVQ EEEQDRKGSH TDLESINENL VESALRRVNR EEKGNKSVHL RKASSPNLHR 370 380 390 400 410 420 RQWEKNVPNT ALTALENASI LTSSLTAEDD RGGSVIKYSK NTTRKQWLKE TPDTLLNILK 430 440 450 460 470 480 NADLSLAFQT YTIYRPGSEG FLKGPLSEET EASDSVDGGH DSVILDPERL EPGLDEEDTD 490 500 FEEEDDNPDW VSELKKRAGW QGLCDR
	Isoform 2 [UniParc]. Checksum: BAF871DA589E7BD3	FASTA	489	55,924
	10 20 30 40 50 60 MDDYMVLRMI GEGSFGRALL VQHESSNQMF AMKEIRLPKS FSNTQNSRKE AVLLAKMKHP 70 80 90 100 110 120 NIVAFKESFE AEGHLYIVME YCDGGDLMQK IKQQKGKLFP EDMILNWFTQ MCLGVNHIHK 130 140 150 160 170 180 KRVLHRDIKS KNIFLTQNGK VKLGDFGSAR LLSNPMAFAC TYVGTPYYVP PEIWENLPYN 190 200 210 220 230 240 NKSDIWSLGC ILYELCTLKH PFQANSWKNL ILKVCQGCIS PLPSHYSYEL QFLVKQMFKR 250 260 270 280 290 300 NPSHRPSATT LLSRGIVARL VQKCLPPEII MEYGEEVLEE IKNSKHNTPR KKQEEEQDRK 310 320 330 340 350 360 GSHTDLESIN ENLVESALRR VNREEKGNKS VHLRKASSPN LHRRQWEKNV PNTALTALEN 370 380 390 400 410 420 ASILTSSLTA EDDRGGSVIK YSKNTTRKQW LKETPDTLLN ILKNADLSLA FQTYTIYRPG 430 440 450 460 470 480 SEGFLKGPLS EETEASDSVD GGHDSVILDP ERLEPGLDEE DTDFEEEDDN PDWVSELKKR AGWQGLCDR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of the human NIMA-related protein kinase 3 gene (NEK3)." Kimura M., Okano Y. Cytogenet. Cell Genet. 95:177-182(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[2]	"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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon.
[3]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"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 1). Tissue: Placenta.
[6]	"Cell cycle-dependent expression of Nek2, a novel human protein kinase related to the NIMA mitotic regulator of Aspergillus nidulans." Schultz S.J., Fry A.M., Suetterlin C., Ried T., Nigg E.A. Cell Growth Differ. 5:625-635(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 48-506 (ISOFORM 1). Tissue: Placenta.
[7]	"Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans." Schultz S.J., Nigg E.A. Cell Growth Differ. 4:821-830(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 76-189.
[8]	"Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor." Miller S.L., DeMaria J.E., Freier D.O., Riegel A.M., Clevenger C.V. Mol. Endocrinol. 19:939-949(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PRLR; VAV1 AND VAV2, ENZYME REGULATION.
[9]	"Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells." Miller S.L., Antico G., Raghunath P.N., Tomaszewski J.E., Clevenger C.V. Oncogene 26:4668-4678(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH PXN.
[10]	"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 THR-479, MASS SPECTROMETRY.
[11]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-23; ARG-60; HIS-122; LEU-170; GLY-259; ASP-305; ASN-461 AND LYS-477.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB072828 mRNA. Translation: BAC15599.1. AK290259 mRNA. Translation: BAF82948.1. AL139082 Genomic DNA. Translation: CAI12895.1. Sequence problems. CH471075 Genomic DNA. Translation: EAX08907.1. Sequence problems. BC019916 mRNA. Translation: AAH19916.2. Z29067 mRNA. Translation: CAA82310.1. Z25434 mRNA. Translation: CAA80921.1.
IPI	IPI00943072. IPI01020856.
PIR	I38224.
RefSeq	NP_001139571.1. NM_001146099.1. NP_002489.1. NM_002498.2. NP_689933.1. NM_152720.2.
UniGene	Hs.409989.
3D structure databases
ProteinModelPortal	P51956.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51956. 5 interactions.
STRING	9606.ENSP00000383210.
PTM databases
PhosphoSite	P51956.
Polymorphism databases
DMDM	20178297.
Proteomic databases
PaxDb	P51956.
PRIDE	P51956.
Protocols and materials databases
DNASU	4752.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000400357; ENSP00000383210; ENSG00000136098.
GeneID	4752.
KEGG	hsa:4752.
UCSC	uc001vgi.3. human. uc010tgy.2. human.
Organism-specific databases
CTD	4752.
GeneCards	GC13M052706.
HGNC	HGNC:7746. NEK3.
HPA	HPA019062. HPA043230.
MIM	604044. gene.
neXtProt	NX_P51956.
PharmGKB	PA31547.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000261617.
HOVERGEN	HBG003063.
KO	K08857.
Enzyme and pathway databases
BRENDA	2.7.11.1. 2681.
SignaLink	P51956.
Gene expression databases
ArrayExpress	P51956.
Bgee	P51956.
CleanEx	HS_NEK3.
Genevestigator	P51956.
GermOnline	ENSG00000136098. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
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	P51956.
ChEMBL	CHEMBL5679.
GenomeRNAi	4752.
NextBio	18314.
SOURCE	Search...

Entry information

Entry name

NEK3_HUMAN

Accession

Primary (citable) accession number: P51956
Secondary accession number(s): A8K2J4 , Q5TAP2, Q8J023, Q8WUN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	April 16, 2002
Last modified:	May 29, 2013
This is version 134 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.