NEK9_HUMAN
ID NEK9_HUMAN Reviewed; 979 AA.
AC Q8TD19; Q52LK6; Q8NCN0; Q8TCY4; Q9UPI4; Q9Y6S4; Q9Y6S5; Q9Y6S6;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Serine/threonine-protein kinase Nek9;
DE EC=2.7.11.1;
DE AltName: Full=Nercc1 kinase;
DE AltName: Full=Never in mitosis A-related kinase 9;
DE Short=NimA-related protein kinase 9;
DE AltName: Full=NimA-related kinase 8;
DE Short=Nek8;
GN Name=NEK9; Synonyms=KIAA1995, NEK8, NERCC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, PROTEIN SEQUENCE OF 61-70;
RP 318-327; 331-352 AND 511-530, MUTAGENESIS OF THR-210 AND THR-214, AND
RP VARIANT HIS-429.
RC TISSUE=Dendritic cell, and Fibroblast;
RX PubMed=11864968; DOI=10.1074/jbc.m108662200;
RA Holland P.M., Milne A., Garka K., Johnson R.S., Willis C., Sims J.E.,
RA Rauch C.T., Bird T.A., Virca G.D.;
RT "Purification, cloning, and characterization of Nek8, a novel NIMA-related
RT kinase, and its candidate substrate Bicd2.";
RL J. Biol. Chem. 277:16229-16240(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, PARTIAL PROTEIN SEQUENCE, AND
RP MUTAGENESIS OF LYS-81.
RX PubMed=12101123; DOI=10.1101/gad.972202;
RA Roig J., Mikhailov A., Belham C., Avruch J.;
RT "Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates
RT mitotic progression.";
RL Genes Dev. 16:1640-1658(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-429.
RC TISSUE=Brain;
RX PubMed=12056414; DOI=10.1093/dnares/9.2.47;
RA Ohara O., Nagase T., Mitsui G., Kohga H., Kikuno R., Hiraoka S.,
RA Takahashi Y., Kitajima S., Saga Y., Koseki H.;
RT "Characterization of size-fractionated cDNA libraries generated by the in
RT vitro recombination-assisted method.";
RL DNA Res. 9:47-57(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION.
RX PubMed=12840024; DOI=10.1074/jbc.m303663200;
RA Belham C., Roig J., Caldwell J.A., Aoyama Y., Kemp B.E., Comb M.,
RA Avruch J.;
RT "A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6
RT and Nek7 kinases.";
RL J. Biol. Chem. 278:34897-34909(2003).
RN [7]
RP FUNCTION, INTERACTION WITH SSRP1 AND SUPT16H, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION AT THR-210.
RX PubMed=14660563; DOI=10.1074/jbc.m311477200;
RA Tan B.C.-M., Lee S.-C.;
RT "Nek9, a novel FACT-associated protein, modulates interphase progression.";
RL J. Biol. Chem. 279:9321-9330(2004).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP INTERACTION WITH NEK6.
RX PubMed=19001501; DOI=10.1242/jcs.035360;
RA Rapley J., Nicolas M., Groen A., Regue L., Bertran M.T., Caelles C.,
RA Avruch J., Roig J.;
RT "The NIMA-family kinase Nek6 phosphorylates the kinesin Eg5 at a novel site
RT necessary for mitotic spindle formation.";
RL J. Cell Sci. 121:3912-3921(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-76; THR-254; SER-741;
RP SER-801; THR-886; SER-944 AND SER-978, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-333, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP FUNCTION.
RX PubMed=19941817; DOI=10.1016/j.molcel.2009.09.038;
RA Richards M.W., O'Regan L., Mas-Droux C., Blot J.M., Cheung J., Hoelder S.,
RA Fry A.M., Bayliss R.;
RT "An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase
RT is released through binding of Nek9.";
RL Mol. Cell 36:560-570(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-2; SER-13; SER-16; TYR-52; SER-76; THR-254; SER-801;
RP SER-832; THR-886 AND SER-944, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-333, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20; THR-254; SER-331;
RP THR-333; SER-868 AND SER-869, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13 AND SER-29, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP INVOLVEMENT IN NC, VARIANTS NC THR-167 AND THR-573, CHARACTERIZATION OF
RP VARIANTS NC THR-167 AND THR-573, AND PHOSPHORYLATION AT THR-210.
RX PubMed=27153399; DOI=10.1016/j.ajhg.2016.03.019;
RG Yale Center for Mendelian Genomics;
RA Levinsohn J.L., Sugarman J.L., McNiff J.M., Antaya R.J., Choate K.A.;
RT "Somatic mutations in NEK9 cause nevus comedonicus.";
RL Am. J. Hum. Genet. 98:1030-1037(2016).
RN [21]
RP INVOLVEMENT IN APUG, AND VARIANT APUG HIS-681.
RX PubMed=26633546; DOI=10.1038/gim.2015.147;
RA Shaheen R., Patel N., Shamseldin H., Alzahrani F., Al-Yamany R.,
RA Almoisheer A., Ewida N., Anazi S., Alnemer M., Elsheikh M., Alfaleh K.,
RA Alshammari M., Alhashem A., Alangari A.A., Salih M.A., Kircher M.,
RA Daza R.M., Ibrahim N., Wakil S.M., Alaqeel A., Altowaijri I., Shendure J.,
RA Al-Habib A., Faqieh E., Alkuraya F.S.;
RT "Accelerating matchmaking of novel dysmorphology syndromes through clinical
RT and genomic characterization of a large cohort.";
RL Genet. Med. 18:686-695(2016).
RN [22]
RP INVOLVEMENT IN LCCS10.
RX PubMed=26908619; DOI=10.1093/hmg/ddw054;
RA Casey J.P., Brennan K., Scheidel N., McGettigan P., Lavin P.T., Carter S.,
RA Ennis S., Dorkins H., Ghali N., Blacque O.E., Mc Gee M.M., Murphy H.,
RA Lynch S.A.;
RT "Recessive NEK9 mutation causes a lethal skeletal dysplasia with evidence
RT of cell cycle and ciliary defects.";
RL Hum. Mol. Genet. 25:1824-1835(2016).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 940-950 IN COMPLEXES WITH DYNLL1,
RP AND INTERACTION WITH DYNLL1.
RX PubMed=23482567; DOI=10.1074/jbc.m113.459149;
RA Gallego P., Velazquez-Campoy A., Regue L., Roig J., Reverter D.;
RT "Structural analysis of the regulation of the DYNLL/LC8 binding to Nek9 by
RT phosphorylation.";
RL J. Biol. Chem. 288:12283-12294(2013).
RN [24]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-429; THR-828 AND SER-870.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Pleiotropic regulator of mitotic progression, participating
CC in the control of spindle dynamics and chromosome separation.
CC Phosphorylates different histones, myelin basic protein, beta-casein,
CC and BICD2. Phosphorylates histone H3 on serine and threonine residues
CC and beta-casein on serine residues. Important for G1/S transition and S
CC phase progression. Phosphorylates NEK6 and NEK7 and stimulates their
CC activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-
CC 97 respectively. {ECO:0000269|PubMed:12840024,
CC ECO:0000269|PubMed:14660563, ECO:0000269|PubMed:19941817}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated during mitosis by intramolecular
CC autophosphorylation. Activity and autophosphorylation is activated by
CC manganese >> magnesium ions. Sensitive to increasing concentration of
CC detergents. It is not cell-cycle regulated but activity is higher in
CC G0-arrested cells.
CC -!- SUBUNIT: Homodimer. Binds to Ran GTPase. Has a greater affinity for
CC Ran-GDP over Ran-GTP. Interacts with NEK6, NEK7 and BICD2. Interacts
CC with SSRP1 and SUPT16H, the 2 subunits of the FACT complex. Interacts
CC with DYNLL1; phosphorylation at Ser-944 strongly reduces DYNLL1
CC binding. {ECO:0000269|PubMed:14660563, ECO:0000269|PubMed:19001501,
CC ECO:0000269|PubMed:23482567}.
CC -!- INTERACTION:
CC Q8TD19; P63167: DYNLL1; NbExp=4; IntAct=EBI-1044009, EBI-349105;
CC Q8TD19; O95166: GABARAP; NbExp=5; IntAct=EBI-1044009, EBI-712001;
CC Q8TD19; Q9H0R8: GABARAPL1; NbExp=6; IntAct=EBI-1044009, EBI-746969;
CC Q8TD19; P60520: GABARAPL2; NbExp=7; IntAct=EBI-1044009, EBI-720116;
CC Q8TD19; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1044009, EBI-352572;
CC Q8TD19; Q9H492: MAP1LC3A; NbExp=2; IntAct=EBI-1044009, EBI-720768;
CC Q8TD19; Q9GZQ8: MAP1LC3B; NbExp=3; IntAct=EBI-1044009, EBI-373144;
CC Q8TD19; Q9BXW4: MAP1LC3C; NbExp=2; IntAct=EBI-1044009, EBI-2603996;
CC Q8TD19; P53350: PLK1; NbExp=5; IntAct=EBI-1044009, EBI-476768;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14660563}. Nucleus
CC {ECO:0000269|PubMed:14660563}.
CC -!- TISSUE SPECIFICITY: Most abundant in heart, liver, kidney and testis.
CC Also expressed in smooth muscle cells and fibroblasts.
CC -!- DEVELOPMENTAL STAGE: Expression varied mildly across the cell cycle,
CC with highest expression observed in G1 and stationary-phase cells.
CC -!- DOMAIN: Dimerizes through its coiled-coil domain.
CC -!- PTM: Autophosphorylated on serine and threonine residues
CC (PubMed:27153399). When complexed with FACT, exhibits markedly elevated
CC phosphorylation on Thr-210. During mitosis, not phosphorylated on Thr-
CC 210. Phosphorylated by CDK1 in vitro. {ECO:0000269|PubMed:14660563,
CC ECO:0000269|PubMed:27153399}.
CC -!- DISEASE: Lethal congenital contracture syndrome 10 (LCCS10)
CC [MIM:617022]: A form of lethal congenital contracture syndrome, an
CC autosomal recessive disorder characterized by degeneration of anterior
CC horn neurons, extreme skeletal muscle atrophy and congenital non-
CC progressive joint contractures. The contractures can involve the upper
CC or lower limbs and/or the vertebral column, leading to various degrees
CC of flexion or extension limitations evident at birth.
CC {ECO:0000269|PubMed:26908619}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Nevus comedonicus (NC) [MIM:617025]: A rare type of epidermal
CC nevus characterized by closely arranged, dilated, plugged follicular
CC ostia in a honeycomb pattern. The plugged ostia contain lamellated
CC keratinaceous material, and their appearance resembles black dots. NC
CC may be non-pyogenic with an acne-like appearance or associated with the
CC formation of cysts, papules, pustules, and abscesses. Most commonly it
CC affects the face and neck area and, by exception, other anatomical
CC regions, including genital area, palms, and soles. NC lesions might
CC present with various patterns of distribution: unilateral, bilateral,
CC linear, interrupted, segmental, or blaschkoid.
CC {ECO:0000269|PubMed:27153399}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Arthrogryposis, Perthes disease, and upward gaze palsy (APUG)
CC [MIM:614262]: An autosomal recessive, syndromic form of arthrogryposis,
CC a disease characterized by persistent joints flexure or contracture.
CC APUG patients manifest an unusual combination of arthrogryposis, upward
CC gaze palsy, and avascular necrosis of the hip (Perthes disease).
CC {ECO:0000269|PubMed:26633546}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. NEK Ser/Thr
CC protein kinase family. NIMA subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD31936.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAC02704.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY048580; AAL05428.1; -; mRNA.
DR EMBL; AY080896; AAL87410.1; -; mRNA.
DR EMBL; AB082526; BAC02704.1; ALT_INIT; mRNA.
DR EMBL; AC007055; AAD31936.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC007055; AAD31938.1; -; Genomic_DNA.
DR EMBL; AC007055; AAD31939.1; -; Genomic_DNA.
DR EMBL; AC007055; AAD31940.1; -; Genomic_DNA.
DR EMBL; BC009336; AAH09336.2; -; mRNA.
DR EMBL; BC093881; AAH93881.1; -; mRNA.
DR EMBL; BC112101; AAI12102.1; -; mRNA.
DR CCDS; CCDS9839.1; -.
DR RefSeq; NP_001316166.1; NM_001329237.1.
DR RefSeq; NP_001316167.1; NM_001329238.1.
DR RefSeq; NP_149107.4; NM_033116.5.
DR PDB; 3ZKE; X-ray; 2.20 A; B/D/F/H/J/L=940-950.
DR PDB; 3ZKF; X-ray; 2.60 A; B/D/F/H/J/L=940-950.
DR PDBsum; 3ZKE; -.
DR PDBsum; 3ZKF; -.
DR AlphaFoldDB; Q8TD19; -.
DR SMR; Q8TD19; -.
DR BioGRID; 124876; 106.
DR CORUM; Q8TD19; -.
DR IntAct; Q8TD19; 38.
DR MINT; Q8TD19; -.
DR STRING; 9606.ENSP00000238616; -.
DR BindingDB; Q8TD19; -.
DR ChEMBL; CHEMBL5257; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q8TD19; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyGen; Q8TD19; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TD19; -.
DR MetOSite; Q8TD19; -.
DR PhosphoSitePlus; Q8TD19; -.
DR BioMuta; NEK9; -.
DR DMDM; 116242675; -.
DR EPD; Q8TD19; -.
DR jPOST; Q8TD19; -.
DR MassIVE; Q8TD19; -.
DR MaxQB; Q8TD19; -.
DR PaxDb; Q8TD19; -.
DR PeptideAtlas; Q8TD19; -.
DR PRIDE; Q8TD19; -.
DR ProteomicsDB; 74219; -.
DR Antibodypedia; 104; 503 antibodies from 33 providers.
DR DNASU; 91754; -.
DR Ensembl; ENST00000238616.10; ENSP00000238616.5; ENSG00000119638.14.
DR GeneID; 91754; -.
DR KEGG; hsa:91754; -.
DR MANE-Select; ENST00000238616.10; ENSP00000238616.5; NM_033116.6; NP_149107.4.
DR UCSC; uc001xrl.4; human.
DR CTD; 91754; -.
DR DisGeNET; 91754; -.
DR GeneCards; NEK9; -.
DR HGNC; HGNC:18591; NEK9.
DR HPA; ENSG00000119638; Low tissue specificity.
DR MalaCards; NEK9; -.
DR MIM; 609798; gene.
DR MIM; 614262; phenotype.
DR MIM; 617022; phenotype.
DR MIM; 617025; phenotype.
DR neXtProt; NX_Q8TD19; -.
DR OpenTargets; ENSG00000119638; -.
DR Orphanet; 464366; NEK9-related lethal skeletal dysplasia.
DR Orphanet; 64754; Nevus comedonicus syndrome.
DR PharmGKB; PA38593; -.
DR VEuPathDB; HostDB:ENSG00000119638; -.
DR eggNOG; KOG0589; Eukaryota.
DR eggNOG; KOG1426; Eukaryota.
DR GeneTree; ENSGT00940000156145; -.
DR HOGENOM; CLU_000288_123_1_1; -.
DR InParanoid; Q8TD19; -.
DR OrthoDB; 1062377at2759; -.
DR PhylomeDB; Q8TD19; -.
DR TreeFam; TF106472; -.
DR PathwayCommons; Q8TD19; -.
DR Reactome; R-HSA-2980767; Activation of NIMA Kinases NEK9, NEK6, NEK7.
DR Reactome; R-HSA-3301854; Nuclear Pore Complex (NPC) Disassembly.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; Q8TD19; -.
DR SIGNOR; Q8TD19; -.
DR BioGRID-ORCS; 91754; 7 hits in 1117 CRISPR screens.
DR ChiTaRS; NEK9; human.
DR GeneWiki; NEK9; -.
DR GenomeRNAi; 91754; -.
DR Pharos; Q8TD19; Tchem.
DR PRO; PR:Q8TD19; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8TD19; protein.
DR Bgee; ENSG00000119638; Expressed in tibia and 205 other tissues.
DR ExpressionAtlas; Q8TD19; baseline and differential.
DR Genevisible; Q8TD19; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR CDD; cd08221; STKc_Nek9; 1.
DR Gene3D; 2.130.10.30; -; 2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR042767; Nek9_STKc.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00415; RCC1; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50012; RCC1_3; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division;
KW Coiled coil; Cytoplasm; Direct protein sequencing; Disease variant; Kinase;
KW Magnesium; Metal-binding; Mitosis; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..979
FT /note="Serine/threonine-protein kinase Nek9"
FT /id="PRO_0000086435"
FT DOMAIN 52..308
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 388..444
FT /note="RCC1 1"
FT REPEAT 445..498
FT /note="RCC1 2"
FT REPEAT 499..550
FT /note="RCC1 3"
FT REPEAT 551..615
FT /note="RCC1 4"
FT REPEAT 616..668
FT /note="RCC1 5"
FT REPEAT 669..726
FT /note="RCC1 6"
FT REGION 18..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..891
FT /note="Interaction with NEK6"
FT /evidence="ECO:0000269|PubMed:19001501"
FT REGION 740..783
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 821..841
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 935..979
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 892..939
FT /evidence="ECO:0000255"
FT COMPBIAS 18..35
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 948..962
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 58..66
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 81
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 52
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 210
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:27153399,
FT ECO:0000305|PubMed:14660563"
FT MOD_RES 254
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 333
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 741
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 801
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 832
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 868
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 869
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 886
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 944
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 978
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT VARIANT 167
FT /note="I -> T (in NC; increased autophosphorylation at T-
FT 210; dbSNP:rs879253775)"
FT /evidence="ECO:0000269|PubMed:27153399"
FT /id="VAR_077801"
FT VARIANT 429
FT /note="R -> H (in dbSNP:rs10146482)"
FT /evidence="ECO:0000269|PubMed:11864968,
FT ECO:0000269|PubMed:12056414, ECO:0000269|PubMed:17344846"
FT /id="VAR_027900"
FT VARIANT 573
FT /note="I -> T (in NC; increased autophosphorylation at T-
FT 210; dbSNP:rs1555352529)"
FT /evidence="ECO:0000269|PubMed:27153399"
FT /id="VAR_077802"
FT VARIANT 681
FT /note="R -> H (in APUG; dbSNP:rs142859694)"
FT /evidence="ECO:0000269|PubMed:26633546"
FT /id="VAR_077803"
FT VARIANT 828
FT /note="P -> T (in dbSNP:rs36014869)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040926"
FT VARIANT 870
FT /note="P -> S (in a lung neuroendocrine carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040927"
FT MUTAGEN 81
FT /note="K->M: Loss of activity and autophosphorylation."
FT /evidence="ECO:0000269|PubMed:12101123"
FT MUTAGEN 210
FT /note="T->A: Significant reduction of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:11864968"
FT MUTAGEN 214
FT /note="T->A: No effect on autophosphorylation."
FT /evidence="ECO:0000269|PubMed:11864968"
FT CONFLICT 351
FT /note="V -> I (in Ref. 2; AAL87410)"
FT /evidence="ECO:0000305"
FT CONFLICT 967
FT /note="W -> G (in Ref. 2; AAL87410)"
FT /evidence="ECO:0000305"
FT STRAND 942..948
FT /evidence="ECO:0007829|PDB:3ZKE"
SQ SEQUENCE 979 AA; 107168 MW; 8583FDDE599324A2 CRC64;
MSVLGEYERH CDSINSDFGS ESGGCGDSSP GPSASQGPRA GGGAAEQEEL HYIPIRVLGR
GAFGEATLYR RTEDDSLVVW KEVDLTRLSE KERRDALNEI VILALLQHDN IIAYYNHFMD
NTTLLIELEY CNGGNLYDKI LRQKDKLFEE EMVVWYLFQI VSAVSCIHKA GILHRDIKTL
NIFLTKANLI KLGDYGLAKK LNSEYSMAET LVGTPYYMSP ELCQGVKYNF KSDIWAVGCV
IFELLTLKRT FDATNPLNLC VKIVQGIRAM EVDSSQYSLE LIQMVHSCLD QDPEQRPTAD
ELLDRPLLRK RRREMEEKVT LLNAPTKRPR SSTVTEAPIA VVTSRTSEVY VWGGGKSTPQ
KLDVIKSGCS ARQVCAGNTH FAVVTVEKEL YTWVNMQGGT KLHGQLGHGD KASYRQPKHV
EKLQGKAIRQ VSCGDDFTVC VTDEGQLYAF GSDYYGCMGV DKVAGPEVLE PMQLNFFLSN
PVEQVSCGDN HVVVLTRNKE VYSWGCGEYG RLGLDSEEDY YTPQKVDVPK ALIIVAVQCG
CDGTFLLTQS GKVLACGLNE FNKLGLNQCM SGIINHEAYH EVPYTTSFTL AKQLSFYKIR
TIAPGKTHTA AIDERGRLLT FGCNKCGQLG VGNYKKRLGI NLLGGPLGGK QVIRVSCGDE
FTIAATDDNH IFAWGNGGNG RLAMTPTERP HGSDICTSWP RPIFGSLHHV PDLSCRGWHT
ILIVEKVLNS KTIRSNSSGL SIGTVFQSSS PGGGGGGGGG EEEDSQQESE TPDPSGGFRG
TMEADRGMEG LISPTEAMGN SNGASSSCPG WLRKELENAE FIPMPDSPSP LSAAFSESEK
DTLPYEELQG LKVASEAPLE HKPQVEASSP RLNPAVTCAG KGTPLTPPAC ACSSLQVEVE
RLQGLVLKCL AEQQKLQQEN LQIFTQLQKL NKKLEGGQQV GMHSKGTQTA KEEMEMDPKP
DLDSDSWCLL GTDSCRPSL
