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P51956 (NEK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length506 AA.
Sequence statusComplete.
Protein existenceEvidence 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 projectionaxon 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

VAV2P527353EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 506506Serine/threonine-protein kinase Nek3
PRO_0000086423

Regions

Domain4 – 257254Protein kinase
Nucleotide binding10 – 189ATP By similarity
Region1 – 285285Interaction with VAV2

Sites

Active site1271Proton acceptor By similarity
Binding site331ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.11
Modified residue1611Phosphothreonine; by autocatalysis By similarity
Modified residue4791Phosphothreonine Ref.10

Natural variations

Alternative sequence293 – 30917Missing in isoform 2.
VSP_035427
Natural variant231H → L. Ref.12
Corresponds to variant rs17482764 [ dbSNP | Ensembl ].
VAR_033906
Natural variant601P → R. Ref.12
Corresponds to variant rs55946204 [ dbSNP | Ensembl ].
VAR_040908
Natural variant1221R → H. Ref.12
Corresponds to variant rs56190615 [ dbSNP | Ensembl ].
VAR_040909
Natural variant1701P → L. Ref.12
Corresponds to variant rs56021040 [ dbSNP | Ensembl ].
VAR_040910
Natural variant2591R → G. Ref.12
Corresponds to variant rs34077016 [ dbSNP | Ensembl ].
VAR_040911
Natural variant3051E → D. Ref.12
Corresponds to variant rs55969405 [ dbSNP | Ensembl ].
VAR_040912
Natural variant4611D → N. Ref.12
Corresponds to variant rs34076988 [ dbSNP | Ensembl ].
VAR_040913
Natural variant4771E → K. Ref.12
Corresponds to variant rs34488913 [ dbSNP | Ensembl ].
VAR_040914

Experimental info

Sequence conflict141S → F in BAC15599. Ref.1
Sequence conflict541L → S in CAA82310. Ref.6
Sequence conflict77 – 782IV → LY in CAA80921. Ref.7
Sequence conflict187 – 1893SLG → PSV in CAA80921. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 16, 2002. Version 2.
Checksum: 4437EB4A41A44777

FASTA50657,705
        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 

« Hide

Isoform 2 [UniParc].

Checksum: BAF871DA589E7BD3
Show »

FASTA48955,924

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"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. expand/collapse author list , 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.
CCDSCCDS53871.1. [P51956-2]
PIRI38224.
RefSeqNP_001139571.1. NM_001146099.1. [P51956-2]
NP_002489.1. NM_002498.2. [P51956-1]
NP_689933.1. NM_152720.2. [P51956-1]
UniGeneHs.409989.

3D structure databases

ProteinModelPortalP51956.
SMRP51956. Positions 1-317.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110827. 4 interactions.
IntActP51956. 5 interactions.
STRING9606.ENSP00000383210.

Chemistry

BindingDBP51956.
ChEMBLCHEMBL5679.
GuidetoPHARMACOLOGY2118.

PTM databases

PhosphoSiteP51956.

Polymorphism databases

DMDM20178297.

Proteomic databases

MaxQBP51956.
PaxDbP51956.
PRIDEP51956.

Protocols and materials databases

DNASU4752.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000400357; ENSP00000383210; ENSG00000136098. [P51956-2]
GeneID4752.
KEGGhsa:4752.
UCSCuc001vgi.3. human. [P51956-1]
uc010tgy.2. human. [P51956-2]

Organism-specific databases

CTD4752.
GeneCardsGC13M052706.
HGNCHGNC:7746. NEK3.
HPAHPA019062.
HPA043230.
MIM604044. gene.
neXtProtNX_P51956.
PharmGKBPA31547.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000261617.
HOVERGENHBG003063.
KOK08857.
OrthoDBEOG7D59P5.
PhylomeDBP51956.
TreeFamTF106472.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
SignaLinkP51956.

Gene expression databases

ArrayExpressP51956.
BgeeP51956.
CleanExHS_NEK3.
GenevestigatorP51956.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNEK3.
GenomeRNAi4752.
NextBio18314.
PROP51956.
SOURCESearch...

Entry information

Entry nameNEK3_HUMAN
AccessionPrimary (citable) accession number: P51956
Secondary accession number(s): A8K2J4 expand/collapse secondary AC list , Q5TAP2, Q8J023, Q8WUN5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 16, 2002
Last modified: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM