UniProtKB - Q8TD19 (NEK9_HUMAN)
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Protein
Serine/threonine-protein kinase Nek9
Gene
NEK9
Organism
Homo sapiens (Human)
Status
Functioni
Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation. Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2. Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues. Important for G1/S transition and S phase progression. Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively.3 Publications
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.
Cofactori
Enzyme regulationi
Activated during mitosis by intramolecular autophosphorylation. Activity and autophosphorylation is activated by manganese >> magnesium ions. Sensitive to increasing concentration of detergents. It is not cell-cycle regulated but activity is higher in G0-arrested cells.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 81 | ATP | 1 | |
Active sitei | 176 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 58 – 66 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- protein kinase binding Source: UniProtKB
- protein serine/threonine kinase activity Source: UniProtKB-KW
GO - Biological processi
- cell division Source: UniProtKB-KW
- mitotic nuclear envelope disassembly Source: Reactome
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle, Cell division, Mitosis |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-HSA-2980767. Activation of NIMA Kinases NEK9, NEK6, NEK7. R-HSA-3301854. Nuclear Pore Complex (NPC) Disassembly. |
SignaLinki | Q8TD19. |
SIGNORi | Q8TD19. |
Protein family/group databases
TCDBi | 1.I.1.1.3. the eukaryotic nuclear pore complex (e-npc) family. |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein kinase Nek9 (EC:2.7.11.1)Alternative name(s): Nercc1 kinase Never in mitosis A-related kinase 9 Short name: NimA-related protein kinase 9 NimA-related kinase 8 Short name: Nek8 |
Gene namesi | Name:NEK9 Synonyms:KIAA1995, NEK8, NERCC |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000119638.12. |
HGNCi | HGNC:18591. NEK9. |
MIMi | 609798. gene. |
neXtProti | NX_Q8TD19. |
Pathology & Biotechi
Involvement in diseasei
Lethal congenital contracture syndrome 10 (LCCS10)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth.
See also OMIM:617022Nevus comedonicus (NC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare type of epidermal nevus characterized by closely arranged, dilated, plugged follicular ostia in a honeycomb pattern. The plugged ostia contain lamellated keratinaceous material, and their appearance resembles black dots. NC may be non-pyogenic with an acne-like appearance or associated with the formation of cysts, papules, pustules, and abscesses. Most commonly it affects the face and neck area and, by exception, other anatomical regions, including genital area, palms, and soles. NC lesions might present with various patterns of distribution: unilateral, bilateral, linear, interrupted, segmental, or blaschkoid.
See also OMIM:617025Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077801 | 167 | I → T in NC; increased autophosphorylation at T-210. 1 PublicationCorresponds to variant dbSNP:rs879253775Ensembl. | 1 | |
Natural variantiVAR_077802 | 573 | I → T in NC; increased autophosphorylation at T-210. 1 Publication | 1 |
Arthrogryposis, Perthes disease, and upward gaze palsy (APUG)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive, syndromic form of arthrogryposis, a disease characterized by persistent joints flexure or contracture. APUG patients manifest an unusual combination of arthrogryposis, upward gaze palsy, and avascular necrosis of the hip (Perthes disease).
See also OMIM:614262Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077803 | 681 | R → H in APUG. 1 PublicationCorresponds to variant dbSNP:rs142859694Ensembl. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 81 | K → M: Loss of activity and autophosphorylation. 1 Publication | 1 | |
Mutagenesisi | 210 | T → A: Significant reduction of autophosphorylation. 1 Publication | 1 | |
Mutagenesisi | 214 | T → A: No effect on autophosphorylation. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 91754. |
MalaCardsi | NEK9. |
MIMi | 614262. phenotype. 617022. phenotype. 617025. phenotype. |
OpenTargetsi | ENSG00000119638. |
PharmGKBi | PA38593. |
Chemistry databases
ChEMBLi | CHEMBL5257. |
GuidetoPHARMACOLOGYi | 2124. |
Polymorphism and mutation databases
BioMutai | NEK9. |
DMDMi | 116242675. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000086435 | 2 – 979 | Serine/threonine-protein kinase Nek9Add BLAST | 978 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineCombined sources | 1 | |
Modified residuei | 2 | PhosphoserineCombined sources | 1 | |
Modified residuei | 13 | PhosphoserineCombined sources | 1 | |
Modified residuei | 16 | PhosphoserineCombined sources | 1 | |
Modified residuei | 20 | PhosphoserineCombined sources | 1 | |
Modified residuei | 29 | PhosphoserineCombined sources | 1 | |
Modified residuei | 52 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 76 | PhosphoserineCombined sources | 1 | |
Modified residuei | 210 | Phosphothreonine; by autocatalysis1 Publication1 Publication | 1 | |
Modified residuei | 254 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 331 | PhosphoserineCombined sources | 1 | |
Modified residuei | 333 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 741 | PhosphoserineCombined sources | 1 | |
Modified residuei | 801 | PhosphoserineCombined sources | 1 | |
Modified residuei | 832 | PhosphoserineCombined sources | 1 | |
Modified residuei | 868 | PhosphoserineCombined sources | 1 | |
Modified residuei | 869 | PhosphoserineCombined sources | 1 | |
Modified residuei | 886 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 944 | PhosphoserineCombined sources | 1 | |
Modified residuei | 978 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Autophosphorylated on serine and threonine residues (PubMed:27153399). When complexed with FACT, exhibits markedly elevated phosphorylation on Thr-210. During mitosis, not phosphorylated on Thr-210. Phosphorylated by CDK1 in vitro.2 Publications
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q8TD19. |
MaxQBi | Q8TD19. |
PaxDbi | Q8TD19. |
PeptideAtlasi | Q8TD19. |
PRIDEi | Q8TD19. |
PTM databases
iPTMneti | Q8TD19. |
PhosphoSitePlusi | Q8TD19. |
Expressioni
Tissue specificityi
Most abundant in heart, liver, kidney and testis. Also expressed in smooth muscle cells and fibroblasts.
Developmental stagei
Expression varied mildly across the cell cycle, with highest expression observed in G1 and stationary-phase cells.
Gene expression databases
Bgeei | ENSG00000119638. |
CleanExi | HS_NEK8. HS_NEK9. |
ExpressionAtlasi | Q8TD19. baseline and differential. |
Genevisiblei | Q8TD19. HS. |
Organism-specific databases
HPAi | HPA001405. |
Interactioni
Subunit structurei
Homodimer. Binds to Ran GTPase. Has a greater affinity for Ran-GDP over Ran-GTP. Interacts with NEK6, NEK7 and BICD2. Interacts with SSRP1 and SUPT16H, the 2 subunits of the FACT complex. Interacts with DYNLL1; phosphorylation at Ser-944 strongly reduces DYNLL1 binding.3 Publications
Binary interactionsi
GO - Molecular functioni
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 124876. 35 interactors. |
CORUMi | Q8TD19. |
IntActi | Q8TD19. 27 interactors. |
MINTi | Q8TD19. |
STRINGi | 9606.ENSP00000238616. |
Chemistry databases
BindingDBi | Q8TD19. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 942 – 948 | Combined sources | 7 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3ZKE | X-ray | 2.20 | B/D/F/H/J/L | 940-950 | [»] | |
3ZKF | X-ray | 2.60 | B/D/F/H/J/L | 940-950 | [»] | |
ProteinModelPortali | Q8TD19. | |||||
SMRi | Q8TD19. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 52 – 308 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 257 | |
Repeati | 388 – 444 | RCC1 1Add BLAST | 57 | |
Repeati | 445 – 498 | RCC1 2Add BLAST | 54 | |
Repeati | 499 – 550 | RCC1 3Add BLAST | 52 | |
Repeati | 551 – 615 | RCC1 4Add BLAST | 65 | |
Repeati | 616 – 668 | RCC1 5Add BLAST | 53 | |
Repeati | 669 – 726 | RCC1 6Add BLAST | 58 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 732 – 891 | Interaction with NEK61 PublicationAdd BLAST | 160 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 892 – 939 | Sequence analysisAdd BLAST | 48 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 752 – 760 | Poly-Gly | 9 | |
Compositional biasi | 765 – 888 | Pro/Ser/Thr-richAdd BLAST | 124 |
Domaini
Dimerizes through its coiled-coil domain.
Sequence similaritiesi
Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.Curated
Keywords - Domaini
Coiled coil, RepeatPhylogenomic databases
eggNOGi | KOG0589. Eukaryota. KOG1426. Eukaryota. ENOG410Y7JF. LUCA. |
GeneTreei | ENSGT00760000118997. |
HOVERGENi | HBG039572. |
InParanoidi | Q8TD19. |
KOi | K20878. |
OMAi | EYERHCD. |
OrthoDBi | EOG091G0181. |
PhylomeDBi | Q8TD19. |
TreeFami | TF106472. |
Family and domain databases
Gene3Di | 2.130.10.30. 1 hit. |
InterProi | View protein in InterPro IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR009091. RCC1/BLIP-II. IPR000408. Reg_chr_condens. IPR008271. Ser/Thr_kinase_AS. |
Pfami | View protein in Pfam PF00069. Pkinase. 1 hit. PF00415. RCC1. 4 hits. |
SMARTi | View protein in SMART SM00220. S_TKc. 1 hit. |
SUPFAMi | SSF50985. SSF50985. 1 hit. SSF56112. SSF56112. 1 hit. |
PROSITEi | View protein in PROSITE PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50012. RCC1_3. 6 hits. |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q8TD19-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSVLGEYERH CDSINSDFGS ESGGCGDSSP GPSASQGPRA GGGAAEQEEL
60 70 80 90 100
HYIPIRVLGR GAFGEATLYR RTEDDSLVVW KEVDLTRLSE KERRDALNEI
110 120 130 140 150
VILALLQHDN IIAYYNHFMD NTTLLIELEY CNGGNLYDKI LRQKDKLFEE
160 170 180 190 200
EMVVWYLFQI VSAVSCIHKA GILHRDIKTL NIFLTKANLI KLGDYGLAKK
210 220 230 240 250
LNSEYSMAET LVGTPYYMSP ELCQGVKYNF KSDIWAVGCV IFELLTLKRT
260 270 280 290 300
FDATNPLNLC VKIVQGIRAM EVDSSQYSLE LIQMVHSCLD QDPEQRPTAD
310 320 330 340 350
ELLDRPLLRK RRREMEEKVT LLNAPTKRPR SSTVTEAPIA VVTSRTSEVY
360 370 380 390 400
VWGGGKSTPQ KLDVIKSGCS ARQVCAGNTH FAVVTVEKEL YTWVNMQGGT
410 420 430 440 450
KLHGQLGHGD KASYRQPKHV EKLQGKAIRQ VSCGDDFTVC VTDEGQLYAF
460 470 480 490 500
GSDYYGCMGV DKVAGPEVLE PMQLNFFLSN PVEQVSCGDN HVVVLTRNKE
510 520 530 540 550
VYSWGCGEYG RLGLDSEEDY YTPQKVDVPK ALIIVAVQCG CDGTFLLTQS
560 570 580 590 600
GKVLACGLNE FNKLGLNQCM SGIINHEAYH EVPYTTSFTL AKQLSFYKIR
610 620 630 640 650
TIAPGKTHTA AIDERGRLLT FGCNKCGQLG VGNYKKRLGI NLLGGPLGGK
660 670 680 690 700
QVIRVSCGDE FTIAATDDNH IFAWGNGGNG RLAMTPTERP HGSDICTSWP
710 720 730 740 750
RPIFGSLHHV PDLSCRGWHT ILIVEKVLNS KTIRSNSSGL SIGTVFQSSS
760 770 780 790 800
PGGGGGGGGG EEEDSQQESE TPDPSGGFRG TMEADRGMEG LISPTEAMGN
810 820 830 840 850
SNGASSSCPG WLRKELENAE FIPMPDSPSP LSAAFSESEK DTLPYEELQG
860 870 880 890 900
LKVASEAPLE HKPQVEASSP RLNPAVTCAG KGTPLTPPAC ACSSLQVEVE
910 920 930 940 950
RLQGLVLKCL AEQQKLQQEN LQIFTQLQKL NKKLEGGQQV GMHSKGTQTA
960 970
KEEMEMDPKP DLDSDSWCLL GTDSCRPSL
Sequence cautioni
The sequence AAD31936 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAC02704 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 351 | V → I in AAL87410 (PubMed:12101123).Curated | 1 | |
Sequence conflicti | 967 | W → G in AAL87410 (PubMed:12101123).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077801 | 167 | I → T in NC; increased autophosphorylation at T-210. 1 PublicationCorresponds to variant dbSNP:rs879253775Ensembl. | 1 | |
Natural variantiVAR_027900 | 429 | R → H3 PublicationsCorresponds to variant dbSNP:rs10146482Ensembl. | 1 | |
Natural variantiVAR_077802 | 573 | I → T in NC; increased autophosphorylation at T-210. 1 Publication | 1 | |
Natural variantiVAR_077803 | 681 | R → H in APUG. 1 PublicationCorresponds to variant dbSNP:rs142859694Ensembl. | 1 | |
Natural variantiVAR_040926 | 828 | P → T1 PublicationCorresponds to variant dbSNP:rs36014869Ensembl. | 1 | |
Natural variantiVAR_040927 | 870 | P → S in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY048580 mRNA. Translation: AAL05428.1. AY080896 mRNA. Translation: AAL87410.1. AB082526 mRNA. Translation: BAC02704.1. Different initiation. AC007055 Genomic DNA. Translation: AAD31936.1. Sequence problems. AC007055 Genomic DNA. Translation: AAD31938.1. AC007055 Genomic DNA. Translation: AAD31939.1. AC007055 Genomic DNA. Translation: AAD31940.1. BC009336 mRNA. Translation: AAH09336.2. BC093881 mRNA. Translation: AAH93881.1. BC112101 mRNA. Translation: AAI12102.1. |
CCDSi | CCDS9839.1. |
RefSeqi | NP_001316166.1. NM_001329237.1. NP_001316167.1. NM_001329238.1. NP_149107.4. NM_033116.5. |
UniGenei | Hs.624721. Hs.7200. |
Genome annotation databases
Ensembli | ENST00000238616; ENSP00000238616; ENSG00000119638. |
GeneIDi | 91754. |
KEGGi | hsa:91754. |
UCSCi | uc001xrl.4. human. |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Entry informationi
Entry namei | NEK9_HUMAN | |
Accessioni | Q8TD19Primary (citable) accession number: Q8TD19 Secondary accession number(s): Q52LK6 Q9Y6S6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 15, 2003 |
Last sequence update: | October 17, 2006 | |
Last modified: | March 28, 2018 | |
This is version 177 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |