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Protein

Serine/threonine-protein kinase Nek3

Gene

NEK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 VAV2.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Prolactin stimulates its activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei33ATPPROSITE-ProRule annotation1
Active sitei127Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 18ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, Mitosis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
SignaLinkiP51956

Names & Taxonomyi

Protein namesi
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 namesi
Name:NEK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000136098.16
HGNCiHGNC:7746 NEK3
MIMi604044 gene
neXtProtiNX_P51956

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi4752
OpenTargetsiENSG00000136098
PharmGKBiPA31547

Chemistry databases

ChEMBLiCHEMBL5679
GuidetoPHARMACOLOGYi2118

Polymorphism and mutation databases

BioMutaiNEK3
DMDMi20178297

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864231 – 506Serine/threonine-protein kinase Nek3Add BLAST506

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei161Phosphothreonine; by autocatalysisBy similarity1
Modified residuei479PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylation at Thr-479 regulates its catalytic activity.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP51956
MaxQBiP51956
PaxDbiP51956
PeptideAtlasiP51956
PRIDEiP51956
ProteomicsDBi56457
56458 [P51956-2]

PTM databases

iPTMnetiP51956
PhosphoSitePlusiP51956

Expressioni

Tissue specificityi

Up-regulated in malignant versus normal breast tissue. Isoform 2 shows a high level of expression in testis, ovary and brain.2 Publications

Gene expression databases

BgeeiENSG00000136098
CleanExiHS_NEK3
ExpressionAtlasiP51956 baseline and differential
GenevisibleiP51956 HS

Organism-specific databases

HPAiHPA019062
HPA043230

Interactioni

Subunit structurei

Interacts with PXN, PRLR, VAV1 and VAV2 and this interaction is prolactin-dependent.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
VAV2P527353EBI-476041,EBI-297549

Protein-protein interaction databases

BioGridi110827, 8 interactors
IntActiP51956, 6 interactors
STRINGi9606.ENSP00000383210

Chemistry databases

BindingDBiP51956

Structurei

3D structure databases

ProteinModelPortaliP51956
SMRiP51956
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 257Protein kinasePROSITE-ProRule annotationAdd BLAST254

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 285Interaction with VAV21 PublicationAdd BLAST285

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0589 Eukaryota
ENOG410Y7JF LUCA
GeneTreeiENSGT00760000118997
HOGENOMiHOG000261617
HOVERGENiHBG003063
InParanoidiP51956
KOiK20873
OMAiYTIYRPG
OrthoDBiEOG091G0GU4
PhylomeDBiP51956
TreeFamiTF106472

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51956-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDDYMVLRMI GEGSFGRALL VQHESSNQMF AMKEIRLPKS FSNTQNSRKE
60 70 80 90 100
AVLLAKMKHP NIVAFKESFE AEGHLYIVME YCDGGDLMQK IKQQKGKLFP
110 120 130 140 150
EDMILNWFTQ MCLGVNHIHK KRVLHRDIKS KNIFLTQNGK VKLGDFGSAR
160 170 180 190 200
LLSNPMAFAC TYVGTPYYVP PEIWENLPYN NKSDIWSLGC ILYELCTLKH
210 220 230 240 250
PFQANSWKNL ILKVCQGCIS PLPSHYSYEL QFLVKQMFKR NPSHRPSATT
260 270 280 290 300
LLSRGIVARL VQKCLPPEII MEYGEEVLEE IKNSKHNTPR KKTNPSRIRI
310 320 330 340 350
ALGNEASTVQ EEEQDRKGSH TDLESINENL VESALRRVNR EEKGNKSVHL
360 370 380 390 400
RKASSPNLHR RQWEKNVPNT ALTALENASI LTSSLTAEDD RGGSVIKYSK
410 420 430 440 450
NTTRKQWLKE TPDTLLNILK NADLSLAFQT YTIYRPGSEG FLKGPLSEET
460 470 480 490 500
EASDSVDGGH DSVILDPERL EPGLDEEDTD FEEEDDNPDW VSELKKRAGW

QGLCDR
Length:506
Mass (Da):57,705
Last modified:April 16, 2002 - v2
Checksum:i4437EB4A41A44777
GO
Isoform 2 (identifier: P51956-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:489
Mass (Da):55,924
Checksum:iBAF871DA589E7BD3
GO

Sequence cautioni

The sequence CAI12895 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAX08907 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14S → F in BAC15599 (PubMed:12063396).Curated1
Sequence conflicti54L → S in CAA82310 (PubMed:7522034).Curated1
Sequence conflicti77 – 78IV → LY in CAA80921 (PubMed:8274451).Curated2
Sequence conflicti187 – 189SLG → PSV in CAA80921 (PubMed:8274451).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03390623H → L1 PublicationCorresponds to variant dbSNP:rs17482764Ensembl.1
Natural variantiVAR_04090860P → R1 PublicationCorresponds to variant dbSNP:rs55946204Ensembl.1
Natural variantiVAR_040909122R → H1 PublicationCorresponds to variant dbSNP:rs56190615Ensembl.1
Natural variantiVAR_040910170P → L1 PublicationCorresponds to variant dbSNP:rs56021040Ensembl.1
Natural variantiVAR_040911259R → G1 PublicationCorresponds to variant dbSNP:rs34077016Ensembl.1
Natural variantiVAR_040912305E → D1 PublicationCorresponds to variant dbSNP:rs55969405Ensembl.1
Natural variantiVAR_040913461D → N1 PublicationCorresponds to variant dbSNP:rs34076988Ensembl.1
Natural variantiVAR_040914477E → K1 PublicationCorresponds to variant dbSNP:rs34488913Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_035427293 – 309Missing in isoform 2. 1 PublicationAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS73576.1 [P51956-1]
PIRiI38224
RefSeqiNP_001139571.1, NM_001146099.1 [P51956-2]
NP_002489.1, NM_002498.2 [P51956-1]
NP_689933.1, NM_152720.2 [P51956-1]
UniGeneiHs.409989

Genome annotation databases

EnsembliENST00000610828; ENSP00000480328; ENSG00000136098 [P51956-1]
ENST00000611833; ENSP00000484086; ENSG00000136098 [P51956-2]
ENST00000618534; ENSP00000484443; ENSG00000136098 [P51956-1]
GeneIDi4752
KEGGihsa:4752
UCSCiuc032agd.2 human [P51956-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNEK3_HUMAN
AccessioniPrimary (citable) accession number: P51956
Secondary accession number(s): A8K2J4
, Q5TAP2, Q8J023, Q8WUN5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 16, 2002
Last modified: June 20, 2018
This is version 177 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

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