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Protein

Serine/threonine-protein kinase Nek4

Gene

NEK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage.By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mn2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei35ATPPROSITE-ProRule annotation1
Active sitei131Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi12 – 20ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • mitotic cell cycle Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • positive regulation of transcription, DNA-templated Source: CACAO
  • protein phosphorylation Source: UniProtKB
  • regulation of cellular senescence Source: UniProtKB
  • regulation of replicative cell aging Source: UniProtKB
  • regulation of response to DNA damage stimulus Source: CACAO
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS03815-MONOMER.
SignaLinkiP51957.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase Nek4 (EC:2.7.11.1By similarity)
Alternative name(s):
Never in mitosis A-related kinase 4
Short name:
NimA-related protein kinase 4
Serine/threonine-protein kinase 2
Serine/threonine-protein kinase NRK2
Gene namesi
Name:NEK4
Synonyms:STK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:11399. NEK4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi6787.
OpenTargetsiENSG00000114904.
PharmGKBiPA31548.

Chemistry databases

ChEMBLiCHEMBL5819.
GuidetoPHARMACOLOGYi2119.

Polymorphism and mutation databases

BioMutaiNEK4.
DMDMi229462924.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864251 – 841Serine/threonine-protein kinase Nek4Add BLAST841

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei165Phosphothreonine; by autocatalysisBy similarity1
Modified residuei340PhosphoserineCombined sources1
Modified residuei343PhosphoserineCombined sources1
Modified residuei461PhosphoserineCombined sources1
Modified residuei563PhosphoserineCombined sources1
Modified residuei622N6-methyllysineCombined sources1
Modified residuei723PhosphoserineBy similarity1

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiP51957.
MaxQBiP51957.
PaxDbiP51957.
PeptideAtlasiP51957.
PRIDEiP51957.

PTM databases

iPTMnetiP51957.
PhosphoSitePlusiP51957.

Miscellaneous databases

PMAP-CutDBP51957.

Expressioni

Tissue specificityi

Highest expression in adult heart, followed by pancreas, skeletal muscle, brain, testis, retina, liver, kidney, lung and placenta. Present in most primary carcinomas.2 Publications

Gene expression databases

BgeeiENSG00000114904.
CleanExiHS_NEK4.
ExpressionAtlasiP51957. baseline and differential.
GenevisibleiP51957. HS.

Organism-specific databases

HPAiHPA015750.

Interactioni

Subunit structurei

Interacts with RPGRIP1 and RPGRIP1L.1 Publication

Protein-protein interaction databases

BioGridi112663. 27 interactors.
IntActiP51957. 10 interactors.
STRINGi9606.ENSP00000233027.

Chemistry databases

BindingDBiP51957.

Structurei

3D structure databases

ProteinModelPortaliP51957.
SMRiP51957.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 261Protein kinasePROSITE-ProRule annotationAdd BLAST256

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0589. Eukaryota.
ENOG410Y7JF. LUCA.
GeneTreeiENSGT00760000118997.
HOGENOMiHOG000294177.
HOVERGENiHBG031740.
InParanoidiP51957.
KOiK08857.
OMAiSELESCW.
OrthoDBiEOG091G0GU4.
PhylomeDBiP51957.
TreeFamiTF106472.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51957-1) [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
MPLAAYCYLR VVGKGSYGEV TLVKHRRDGK QYVIKKLNLR NASSRERRAA
60 70 80 90 100
EQEAQLLSQL KHPNIVTYKE SWEGGDGLLY IVMGFCEGGD LYRKLKEQKG
110 120 130 140 150
QLLPENQVVE WFVQIAMALQ YLHEKHILHR DLKTQNVFLT RTNIIKVGDL
160 170 180 190 200
GIARVLENHC DMASTLIGTP YYMSPELFSN KPYNYKSDVW ALGCCVYEMA
210 220 230 240 250
TLKHAFNAKD MNSLVYRIIE GKLPPMPRDY SPELAELIRT MLSKRPEERP
260 270 280 290 300
SVRSILRQPY IKRQISFFLE ATKIKTSKNN IKNGDSQSKP FATVVSGEAE
310 320 330 340 350
SNHEVIHPQP LSSEGSQTYI MGEGKCLSQE KPRASGLLKS PASLKAHTCK
360 370 380 390 400
QDLSNTTELA TISSVNIDIL PAKGRDSVSD GFVQENQPRY LDASNELGGI
410 420 430 440 450
CSISQVEEEM LQDNTKSSAQ PENLIPMWSS DIVTGEKNEP VKPLQPLIKE
460 470 480 490 500
QKPKDQSLAL SPKLECSGTI LAHSNLRLLG SSDSPASASR VAGITGVCHH
510 520 530 540 550
AQDQVAGECI IEKQGRIHPD LQPHNSGSEP SLSRQRRQKR REQTEHRGEK
560 570 580 590 600
RQVRRDLFAF QESPPRFLPS HPIVGKVDVT STQKEAENQR RVVTGSVSSS
610 620 630 640 650
RSSEMSSSKD RPLSARERRR LKQSQEEMSS SGPSVRKASL SVAGPGKPQE
660 670 680 690 700
EDQPLPARRL SSDCSVTQER KQIHCLSEDE LSSSTSSTDK SDGDYGEGKG
710 720 730 740 750
QTNEINALVQ LMTQTLKLDS KESCEDVPVA NPVSEFKLHR KYRDTLILHG
760 770 780 790 800
KVAEEAEEIH FKELPSAIMP GSEKIRRLVE VLRTDVIRGL GVQLLEQVYD
810 820 830 840
LLEEEDEFDR EVRLREHMGE KYTTYSVKAR QLKFFEENMN F
Length:841
Mass (Da):94,597
Last modified:May 5, 2009 - v2
Checksum:i43E8F11BA4007263
GO
Isoform 2 (identifier: P51957-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     457-502: Missing.
     813-841: RLREHMGEKYTTYSVKARQLKFFEENMNF → SVSLTVSRCLCYRIF

Note: No experimental confirmation available.
Show »
Length:781
Mass (Da):88,094
Checksum:iB251D19895A2AD44
GO
Isoform 3 (identifier: P51957-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     32-120: Missing.

Note: No experimental confirmation available.
Show »
Length:752
Mass (Da):84,348
Checksum:i9518EF5A24A1795A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti63P → L in BAG35330 (PubMed:14702039).Curated1
Sequence conflicti64N → D in ABQ59054 (Ref. 2) Curated1
Sequence conflicti333R → K in BAG35330 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040915225P → A.4 PublicationsCorresponds to variant rs1029871dbSNPEnsembl.1
Natural variantiVAR_040916239R → G.1 PublicationCorresponds to variant rs35778416dbSNPEnsembl.1
Natural variantiVAR_040917250P → L.1 PublicationCorresponds to variant rs56408749dbSNPEnsembl.1
Natural variantiVAR_040918357T → I.1 PublicationCorresponds to variant rs2230537dbSNPEnsembl.1
Natural variantiVAR_040919456Q → E.1 PublicationCorresponds to variant rs56019351dbSNPEnsembl.1
Natural variantiVAR_040920567F → L.1 PublicationCorresponds to variant rs34986855dbSNPEnsembl.1
Natural variantiVAR_040921777R → K in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04333432 – 120Missing in isoform 3. 1 PublicationAdd BLAST89
Alternative sequenceiVSP_037123457 – 502Missing in isoform 2. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_037124813 – 841RLREH…ENMNF → SVSLTVSRCLCYRIF in isoform 2. 1 PublicationAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L20321 mRNA. Translation: AAA36658.1.
EF560744 mRNA. Translation: ABQ59054.1.
AK294165 mRNA. Translation: BAH11686.1.
AK312420 mRNA. Translation: BAG35330.1.
AC006254 Genomic DNA. No translation available.
AC104446 Genomic DNA. No translation available.
BC063044 mRNA. Translation: AAH63044.1.
CCDSiCCDS2863.1. [P51957-1]
CCDS54593.1. [P51957-3]
PIRiI78885.
RefSeqiNP_001180462.1. NM_001193533.1. [P51957-3]
NP_003148.2. NM_003157.4. [P51957-1]
UniGeneiHs.631921.

Genome annotation databases

EnsembliENST00000233027; ENSP00000233027; ENSG00000114904. [P51957-1]
ENST00000383721; ENSP00000373227; ENSG00000114904. [P51957-2]
ENST00000535191; ENSP00000437703; ENSG00000114904. [P51957-3]
GeneIDi6787.
KEGGihsa:6787.
UCSCiuc003dfq.5. human. [P51957-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L20321 mRNA. Translation: AAA36658.1.
EF560744 mRNA. Translation: ABQ59054.1.
AK294165 mRNA. Translation: BAH11686.1.
AK312420 mRNA. Translation: BAG35330.1.
AC006254 Genomic DNA. No translation available.
AC104446 Genomic DNA. No translation available.
BC063044 mRNA. Translation: AAH63044.1.
CCDSiCCDS2863.1. [P51957-1]
CCDS54593.1. [P51957-3]
PIRiI78885.
RefSeqiNP_001180462.1. NM_001193533.1. [P51957-3]
NP_003148.2. NM_003157.4. [P51957-1]
UniGeneiHs.631921.

3D structure databases

ProteinModelPortaliP51957.
SMRiP51957.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112663. 27 interactors.
IntActiP51957. 10 interactors.
STRINGi9606.ENSP00000233027.

Chemistry databases

BindingDBiP51957.
ChEMBLiCHEMBL5819.
GuidetoPHARMACOLOGYi2119.

PTM databases

iPTMnetiP51957.
PhosphoSitePlusiP51957.

Polymorphism and mutation databases

BioMutaiNEK4.
DMDMi229462924.

Proteomic databases

EPDiP51957.
MaxQBiP51957.
PaxDbiP51957.
PeptideAtlasiP51957.
PRIDEiP51957.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233027; ENSP00000233027; ENSG00000114904. [P51957-1]
ENST00000383721; ENSP00000373227; ENSG00000114904. [P51957-2]
ENST00000535191; ENSP00000437703; ENSG00000114904. [P51957-3]
GeneIDi6787.
KEGGihsa:6787.
UCSCiuc003dfq.5. human. [P51957-1]

Organism-specific databases

CTDi6787.
DisGeNETi6787.
GeneCardsiNEK4.
H-InvDBHIX0030800.
HGNCiHGNC:11399. NEK4.
HPAiHPA015750.
MIMi601959. gene.
neXtProtiNX_P51957.
OpenTargetsiENSG00000114904.
PharmGKBiPA31548.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0589. Eukaryota.
ENOG410Y7JF. LUCA.
GeneTreeiENSGT00760000118997.
HOGENOMiHOG000294177.
HOVERGENiHBG031740.
InParanoidiP51957.
KOiK08857.
OMAiSELESCW.
OrthoDBiEOG091G0GU4.
PhylomeDBiP51957.
TreeFamiTF106472.

Enzyme and pathway databases

BioCyciZFISH:HS03815-MONOMER.
SignaLinkiP51957.

Miscellaneous databases

ChiTaRSiNEK4. human.
GenomeRNAii6787.
PMAP-CutDBP51957.
PROiP51957.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114904.
CleanExiHS_NEK4.
ExpressionAtlasiP51957. baseline and differential.
GenevisibleiP51957. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNEK4_HUMAN
AccessioniPrimary (citable) accession number: P51957
Secondary accession number(s): A5YM70
, B2R633, B7Z200, Q6P576
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 5, 2009
Last modified: November 30, 2016
This is version 156 of the entry and version 2 of the sequence. [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 3
    Human chromosome 3: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.