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Protein

Serine/threonine-protein kinase Nek6

Gene

NEK6

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

Functioni

Protein kinase which plays an important role in mitotic cell cycle progression. Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis. Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3. Phosphorylates KIF11 to promote mitotic spindle formation. Involved in G2/M phase cell cycle arrest induced by DNA damage. Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Activity regulationi

Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-108.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei74ATPPROSITE-ProRule annotation1
Sitei108Autoinhibitory1
Active sitei172Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi51 – 59ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-2980767 Activation of NIMA Kinases NEK9, NEK6, NEK7
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly
SignaLinkiQ9HC98
SIGNORiQ9HC98

Protein family/group databases

TCDBi1.I.1.1.3 the eukaryotic nuclear pore complex (e-npc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase Nek6 (EC:2.7.11.1)
Alternative name(s):
Never in mitosis A-related kinase 6
Short name:
NimA-related protein kinase 6
Protein kinase SID6-1512
Gene namesi
Name:NEK6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000119408.16
HGNCiHGNC:7749 NEK6
MIMi604884 gene
neXtProtiNX_Q9HC98

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

Cytoplasm, Cytoskeleton, Microtubule, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi74K → M: Loss of autophosphorylation and of kinase activity and induction of apoptosis; when associated with M-75. 2 Publications1
Mutagenesisi75K → M: Loss of autophosphorylation and of kinase activity and induction of apoptosis; when associated with M-74. 2 Publications1
Mutagenesisi108Y → A: Increase in catalytic activity. 1 Publication1

Organism-specific databases

DisGeNETi10783
OpenTargetsiENSG00000119408
PharmGKBiPA31550

Chemistry databases

ChEMBLiCHEMBL4309

Polymorphism and mutation databases

BioMutaiNEK6
DMDMi37537993

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864271 – 313Serine/threonine-protein kinase Nek6Add BLAST313

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei37Phosphoserine1 Publication1
Modified residuei202Phosphothreonine1 Publication1
Modified residuei206Phosphoserine; by NEK9Combined sources2 Publications1
Modified residuei210Phosphothreonine1 Publication1

Post-translational modificationi

Autophosphorylated. Phosphorylation at Ser-206 is required for its activation. Phosphorylated upon IR or UV-induced DNA damage. Phosphorylated by CHEK1 and CHEK2. Interaction with APBB1 down-regulates phosphorylation at Thr-210.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9HC98
MaxQBiQ9HC98
PaxDbiQ9HC98
PeptideAtlasiQ9HC98
PRIDEiQ9HC98
ProteomicsDBi81659
81660 [Q9HC98-2]
81661 [Q9HC98-3]
81662 [Q9HC98-4]

PTM databases

iPTMnetiQ9HC98
PhosphoSitePlusiQ9HC98

Expressioni

Tissue specificityi

Ubiquitous, with highest expression in heart and skeletal muscle. Up-regulated in a variety of malignant cancers, such as breast, colon, lung, and gastric cancers.2 Publications

Inductioni

Up-regulated during the M phase of cell cycle progression. Down-regulated in both replicative and premature senescence of cancer cells.2 Publications

Gene expression databases

BgeeiENSG00000119408 Expressed in 176 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_NEK6
ExpressionAtlasiQ9HC98 baseline and differential
GenevisibleiQ9HC98 HS

Organism-specific databases

HPAiCAB045993
HPA056828

Interactioni

Subunit structurei

Interacts with STAT3 and RPS6KB1 (By similarity). Interacts with NEK9, predominantly in mitosis. Interacts with KIF11 (via C-terminus). Interacts with APBB1 (via WW domain). Interacts with ANKRA2, ATF4, ARHGAP33, CDC42, CIR1, PRAM1, PTN, PRDX3, PIN1, RAD26L, RBBP6, RPS7 and TRIP4.By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116000, 68 interactors
IntActiQ9HC98, 94 interactors
MINTiQ9HC98
STRINGi9606.ENSP00000362702

Chemistry databases

BindingDBiQ9HC98

Structurei

3D structure databases

ProteinModelPortaliQ9HC98
SMRiQ9HC98
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini45 – 310Protein kinasePROSITE-ProRule annotationAdd BLAST266

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 44Interaction with ARHGAP33, ANKRA2, CDC42, PRDX3, RAD26L, RBBP6, RPS7 and TRIP41 PublicationAdd BLAST44
Regioni267 – 270Interaction with APBB11 Publication4

Domaini

Displays an autoinhibited conformation: Tyr-108 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0591 Eukaryota
ENOG410XNQP LUCA
GeneTreeiENSGT00760000118997
HOVERGENiHBG105886
InParanoidiQ9HC98
KOiK20875
OMAiHQIAKQM
OrthoDBiEOG091G0AER
PhylomeDBiQ9HC98
TreeFamiTF101021

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR00109 TYRKINASE
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 (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9HC98-1) [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
MAGQPGHMPH GGSSNNLCHT LGPVHPPDPQ RHPNTLSFRC SLADFQIEKK
60 70 80 90 100
IGRGQFSEVY KATCLLDRKT VALKKVQIFE MMDAKARQDC VKEIGLLKQL
110 120 130 140 150
NHPNIIKYLD SFIEDNELNI VLELADAGDL SQMIKYFKKQ KRLIPERTVW
160 170 180 190 200
KYFVQLCSAV EHMHSRRVMH RDIKPANVFI TATGVVKLGD LGLGRFFSSE
210 220 230 240 250
TTAAHSLVGT PYYMSPERIH ENGYNFKSDI WSLGCLLYEM AALQSPFYGD
260 270 280 290 300
KMNLFSLCQK IEQCDYPPLP GEHYSEKLRE LVSMCICPDP HQRPDIGYVH
310
QVAKQMHIWM SST
Length:313
Mass (Da):35,714
Last modified:October 3, 2003 - v2
Checksum:iB898DC57407A8C16
GO
Isoform 2 (identifier: Q9HC98-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MPRREVCWEAAHFRQEEQSLPRPRVRALVRLACRM

Show »
Length:347
Mass (Da):39,844
Checksum:i2CA3B83E91024B8A
GO
Isoform 3 (identifier: Q9HC98-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGRRRPAPFRALVRLACRM

Show »
Length:331
Mass (Da):37,823
Checksum:iDF83ECFFE6F5B2F6
GO
Isoform 4 (identifier: Q9HC98-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MEATGWDSRCSPGTQVRALVRLACRM

Show »
Length:338
Mass (Da):38,460
Checksum:i2B680899AE6D5765
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5TBG7Q5TBG7_HUMAN
Serine/threonine-protein kinase Nek...
NEK6
219Annotation score:
Q5TBH2Q5TBH2_HUMAN
Serine/threonine-protein kinase Nek...
NEK6
220Annotation score:
Q5TBH1Q5TBH1_HUMAN
Serine/threonine-protein kinase Nek...
NEK6
222Annotation score:
Q5TBG1Q5TBG1_HUMAN
Serine/threonine-protein kinase Nek...
NEK6
207Annotation score:
Q5TBG4Q5TBG4_HUMAN
Serine/threonine-protein kinase Nek...
NEK6
194Annotation score:
Q5TBG2Q5TBG2_HUMAN
Serine/threonine-protein kinase Nek...
NEK6
171Annotation score:
Q5TBH0Q5TBH0_HUMAN
Serine/threonine-protein kinase Nek...
NEK6
200Annotation score:

Sequence cautioni

The sequence AAG13417 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence AAH00101 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH04174 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH04209 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA85045 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti88Q → W in CAG33372 (Ref. 7) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0417981M → MPRREVCWEAAHFRQEEQSL PRPRVRALVRLACRM in isoform 2. 1 Publication1
Alternative sequenceiVSP_0417991M → MGRRRPAPFRALVRLACRM in isoform 3. 1 Publication1
Alternative sequenceiVSP_0418001M → MEATGWDSRCSPGTQVRALV RLACRM in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF087909 mRNA Translation: AAG13417.1 Sequence problems.
AB026289 mRNA Translation: BAA85045.1 Different initiation.
AK294614 mRNA Translation: BAH11825.1
AK313071 mRNA Translation: BAG35899.1
AL162724 Genomic DNA No translation available.
AL137846 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW87579.1
CH471090 Genomic DNA Translation: EAW87581.1
BC000101 mRNA Translation: AAH00101.2 Different initiation.
BC004174 mRNA Translation: AAH04174.2 Different initiation.
BC004209 mRNA Translation: AAH04209.2 Different initiation.
BC012761 mRNA Translation: AAH12761.1
CR457091 mRNA Translation: CAG33372.1
CR542222 mRNA Translation: CAG47018.1
CCDSiCCDS48015.1 [Q9HC98-2]
CCDS55338.1 [Q9HC98-3]
CCDS55339.1 [Q9HC98-4]
CCDS6854.1 [Q9HC98-1]
PIRiJC7838
RefSeqiNP_001138473.1, NM_001145001.2 [Q9HC98-2]
NP_001159639.1, NM_001166167.1 [Q9HC98-3]
NP_001159640.1, NM_001166168.1 [Q9HC98-1]
NP_001159641.1, NM_001166169.1 [Q9HC98-4]
NP_001159642.1, NM_001166170.1 [Q9HC98-1]
NP_001159643.1, NM_001166171.1 [Q9HC98-2]
NP_055212.2, NM_014397.5 [Q9HC98-1]
XP_005251721.1, XM_005251664.1 [Q9HC98-1]
XP_006716999.1, XM_006716936.2 [Q9HC98-1]
XP_016869706.1, XM_017014217.1 [Q9HC98-2]
UniGeneiHs.197071

Genome annotation databases

EnsembliENST00000320246; ENSP00000319734; ENSG00000119408 [Q9HC98-1]
ENST00000373600; ENSP00000362702; ENSG00000119408 [Q9HC98-2]
ENST00000373603; ENSP00000362705; ENSG00000119408 [Q9HC98-1]
ENST00000394199; ENSP00000377749; ENSG00000119408 [Q9HC98-2]
ENST00000539416; ENSP00000439651; ENSG00000119408 [Q9HC98-4]
ENST00000540326; ENSP00000441469; ENSG00000119408 [Q9HC98-3]
ENST00000545174; ENSP00000442636; ENSG00000119408 [Q9HC98-1]
ENST00000546191; ENSP00000441426; ENSG00000119408 [Q9HC98-1]
GeneIDi10783
KEGGihsa:10783
UCSCiuc004bof.4 human [Q9HC98-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF087909 mRNA Translation: AAG13417.1 Sequence problems.
AB026289 mRNA Translation: BAA85045.1 Different initiation.
AK294614 mRNA Translation: BAH11825.1
AK313071 mRNA Translation: BAG35899.1
AL162724 Genomic DNA No translation available.
AL137846 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW87579.1
CH471090 Genomic DNA Translation: EAW87581.1
BC000101 mRNA Translation: AAH00101.2 Different initiation.
BC004174 mRNA Translation: AAH04174.2 Different initiation.
BC004209 mRNA Translation: AAH04209.2 Different initiation.
BC012761 mRNA Translation: AAH12761.1
CR457091 mRNA Translation: CAG33372.1
CR542222 mRNA Translation: CAG47018.1
CCDSiCCDS48015.1 [Q9HC98-2]
CCDS55338.1 [Q9HC98-3]
CCDS55339.1 [Q9HC98-4]
CCDS6854.1 [Q9HC98-1]
PIRiJC7838
RefSeqiNP_001138473.1, NM_001145001.2 [Q9HC98-2]
NP_001159639.1, NM_001166167.1 [Q9HC98-3]
NP_001159640.1, NM_001166168.1 [Q9HC98-1]
NP_001159641.1, NM_001166169.1 [Q9HC98-4]
NP_001159642.1, NM_001166170.1 [Q9HC98-1]
NP_001159643.1, NM_001166171.1 [Q9HC98-2]
NP_055212.2, NM_014397.5 [Q9HC98-1]
XP_005251721.1, XM_005251664.1 [Q9HC98-1]
XP_006716999.1, XM_006716936.2 [Q9HC98-1]
XP_016869706.1, XM_017014217.1 [Q9HC98-2]
UniGeneiHs.197071

3D structure databases

ProteinModelPortaliQ9HC98
SMRiQ9HC98
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116000, 68 interactors
IntActiQ9HC98, 94 interactors
MINTiQ9HC98
STRINGi9606.ENSP00000362702

Chemistry databases

BindingDBiQ9HC98
ChEMBLiCHEMBL4309

Protein family/group databases

TCDBi1.I.1.1.3 the eukaryotic nuclear pore complex (e-npc) family

PTM databases

iPTMnetiQ9HC98
PhosphoSitePlusiQ9HC98

Polymorphism and mutation databases

BioMutaiNEK6
DMDMi37537993

Proteomic databases

EPDiQ9HC98
MaxQBiQ9HC98
PaxDbiQ9HC98
PeptideAtlasiQ9HC98
PRIDEiQ9HC98
ProteomicsDBi81659
81660 [Q9HC98-2]
81661 [Q9HC98-3]
81662 [Q9HC98-4]

Protocols and materials databases

DNASUi10783
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000320246; ENSP00000319734; ENSG00000119408 [Q9HC98-1]
ENST00000373600; ENSP00000362702; ENSG00000119408 [Q9HC98-2]
ENST00000373603; ENSP00000362705; ENSG00000119408 [Q9HC98-1]
ENST00000394199; ENSP00000377749; ENSG00000119408 [Q9HC98-2]
ENST00000539416; ENSP00000439651; ENSG00000119408 [Q9HC98-4]
ENST00000540326; ENSP00000441469; ENSG00000119408 [Q9HC98-3]
ENST00000545174; ENSP00000442636; ENSG00000119408 [Q9HC98-1]
ENST00000546191; ENSP00000441426; ENSG00000119408 [Q9HC98-1]
GeneIDi10783
KEGGihsa:10783
UCSCiuc004bof.4 human [Q9HC98-1]

Organism-specific databases

CTDi10783
DisGeNETi10783
EuPathDBiHostDB:ENSG00000119408.16
GeneCardsiNEK6
HGNCiHGNC:7749 NEK6
HPAiCAB045993
HPA056828
MIMi604884 gene
neXtProtiNX_Q9HC98
OpenTargetsiENSG00000119408
PharmGKBiPA31550
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0591 Eukaryota
ENOG410XNQP LUCA
GeneTreeiENSGT00760000118997
HOVERGENiHBG105886
InParanoidiQ9HC98
KOiK20875
OMAiHQIAKQM
OrthoDBiEOG091G0AER
PhylomeDBiQ9HC98
TreeFamiTF101021

Enzyme and pathway databases

ReactomeiR-HSA-2980767 Activation of NIMA Kinases NEK9, NEK6, NEK7
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly
SignaLinkiQ9HC98
SIGNORiQ9HC98

Miscellaneous databases

ChiTaRSiNEK6 human
GeneWikiiNEK6
GenomeRNAii10783
PROiPR:Q9HC98
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119408 Expressed in 176 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_NEK6
ExpressionAtlasiQ9HC98 baseline and differential
GenevisibleiQ9HC98 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR00109 TYRKINASE
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
ProtoNetiSearch...

Entry informationi

Entry nameiNEK6_HUMAN
AccessioniPrimary (citable) accession number: Q9HC98
Secondary accession number(s): B7Z2D9
, Q5TBG3, Q5TBG9, Q6FG86, Q6IAR3, Q96E83, Q9ULX2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: November 7, 2018
This is version 168 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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