NEK8_MOUSE
ID NEK8_MOUSE Reviewed; 698 AA.
AC Q91ZR4; Q3U498; Q9D685;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Serine/threonine-protein kinase Nek8;
DE EC=2.7.11.1;
DE AltName: Full=Never in mitosis A-related kinase 8;
DE Short=NimA-related protein kinase 8;
GN Name=Nek8; Synonyms=Jck;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-33, AND VARIANT ARJPKD
RP VAL-448.
RC STRAIN=C57BL/6J;
RX PubMed=12421721; DOI=10.1242/dev.00173;
RA Liu S., Lu W., Obara T., Kuida S., Lehoczky J., Dewar K., Drummond I.A.,
RA Beier D.R.;
RT "A defect in a novel Nek-family kinase causes cystic kidney disease in the
RT mouse and in zebrafish.";
RL Development 129:5839-5846(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Dendritic cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [4]
RP SUBCELLULAR LOCATION.
RX PubMed=16267153; DOI=10.1681/asn.2005080824;
RA Mahjoub M.R., Trapp M.L., Quarmby L.M.;
RT "NIMA-related kinases defective in murine models of polycystic kidney
RT diseases localize to primary cilia and centrosomes.";
RL J. Am. Soc. Nephrol. 16:3485-3489(2005).
RN [5]
RP INTERACTION WITH PKD2.
RX PubMed=18235101; DOI=10.1681/asn.2006090985;
RA Sohara E., Luo Y., Zhang J., Manning D.K., Beier D.R., Zhou J.;
RT "Nek8 regulates the expression and localization of polycystin-1 and
RT polycystin-2.";
RL J. Am. Soc. Nephrol. 19:469-476(2008).
RN [6]
RP MUTAGENESIS OF LEU-336; HIS-431 AND ALA-503, AND FUNCTION.
RX PubMed=18199800; DOI=10.1681/asn.2007040490;
RA Otto E.A., Trapp M.L., Schultheiss U.T., Helou J., Quarmby L.M.,
RA Hildebrandt F.;
RT "NEK8 mutations affect ciliary and centrosomal localization and may cause
RT nephronophthisis.";
RL J. Am. Soc. Nephrol. 19:587-592(2008).
RN [7]
RP INTERACTION WITH ANKS3.
RX PubMed=25671767; DOI=10.1038/ki.2015.17;
RA Yakulov T.A., Yasunaga T., Ramachandran H., Engel C., Mueller B., Hoff S.,
RA Dengjel J., Lienkamp S.S., Walz G.;
RT "Anks3 interacts with nephronophthisis proteins and is required for normal
RT renal development.";
RL Kidney Int. 87:1191-1200(2015).
CC -!- FUNCTION: Required for renal tubular integrity. May regulate local
CC cytoskeletal structure in kidney tubule epithelial cells. May regulate
CC ciliary biogenesis through targeting of proteins to the cilia. Plays a
CC role in organogenesis and is involved in the regulation of the Hippo
CC signaling pathway. {ECO:0000269|PubMed:18199800}.
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; Evidence={ECO:0000250};
CC -!- SUBUNIT: Interacts with PKD2; may regulate PKD2 targeting to the cilium
CC (PubMed:18235101). Component of a complex containing at least ANKS6,
CC INVS, NEK8 and NPHP3 (By similarity). ANKS6 may organize complex
CC assembly by linking INVS and NPHP3 to NEK8 and INVS may target the
CC complex to the proximal ciliary axoneme (By similarity). Interacts with
CC ANKS3 (PubMed:25671767). {ECO:0000250|UniProtKB:Q86SG6,
CC ECO:0000269|PubMed:18235101, ECO:0000269|PubMed:25671767}.
CC -!- INTERACTION:
CC Q91ZR4; O89019: Invs; NbExp=2; IntAct=EBI-4282339, EBI-4281337;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16267153}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:16267153}. Cell projection,
CC cilium {ECO:0000269|PubMed:16267153}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:Q86SG6}. Note=Predominantly cytoplasmic.
CC Localizes to the proximal region of the primary cilium and is not
CC observed in dividing cells. {ECO:0000269|PubMed:16267153}.
CC -!- TISSUE SPECIFICITY: Kidney, liver, and testis.
CC -!- DISEASE: Note=Defects in Nek8 are the cause of autosomal recessive
CC juvenile polycystic kidney disease (ARJPKD).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. NEK Ser/Thr
CC protein kinase family. NIMA subfamily. {ECO:0000305}.
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DR EMBL; AF407579; AAL09675.1; -; mRNA.
DR EMBL; AK154358; BAE32535.1; -; mRNA.
DR EMBL; BC070457; AAH70457.1; -; mRNA.
DR CCDS; CCDS25091.1; -.
DR RefSeq; NP_543125.1; NM_080849.3.
DR AlphaFoldDB; Q91ZR4; -.
DR SMR; Q91ZR4; -.
DR BioGRID; 228327; 2.
DR CORUM; Q91ZR4; -.
DR IntAct; Q91ZR4; 1.
DR MINT; Q91ZR4; -.
DR STRING; 10090.ENSMUSP00000017549; -.
DR PhosphoSitePlus; Q91ZR4; -.
DR EPD; Q91ZR4; -.
DR MaxQB; Q91ZR4; -.
DR PaxDb; Q91ZR4; -.
DR PRIDE; Q91ZR4; -.
DR ProteomicsDB; 252804; -.
DR Antibodypedia; 26547; 295 antibodies from 26 providers.
DR DNASU; 140859; -.
DR Ensembl; ENSMUST00000017549; ENSMUSP00000017549; ENSMUSG00000017405.
DR GeneID; 140859; -.
DR KEGG; mmu:140859; -.
DR UCSC; uc007kih.2; mouse.
DR CTD; 284086; -.
DR MGI; MGI:1890646; Nek8.
DR VEuPathDB; HostDB:ENSMUSG00000017405; -.
DR eggNOG; KOG0589; Eukaryota.
DR GeneTree; ENSGT00940000159297; -.
DR HOGENOM; CLU_000288_123_1_1; -.
DR InParanoid; Q91ZR4; -.
DR OMA; GIKMVMV; -.
DR OrthoDB; 1062377at2759; -.
DR PhylomeDB; Q91ZR4; -.
DR TreeFam; TF106472; -.
DR BioGRID-ORCS; 140859; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Nek8; mouse.
DR PRO; PR:Q91ZR4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q91ZR4; protein.
DR Bgee; ENSMUSG00000017405; Expressed in saccule of membranous labyrinth and 146 other tissues.
DR ExpressionAtlas; Q91ZR4; baseline and differential.
DR Genevisible; Q91ZR4; MM.
DR GO; GO:0005813; C:centrosome; IBA:GO_Central.
DR GO; GO:0097546; C:ciliary base; IDA:MGI.
DR GO; GO:0097543; C:ciliary inversin compartment; IDA:MGI.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:MGI.
DR GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0035330; P:regulation of hippo signaling; ISO:MGI.
DR CDD; cd08220; STKc_Nek8; 1.
DR Gene3D; 2.130.10.30; -; 2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR044120; STKc_Nek8.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00415; RCC1; 4.
DR PRINTS; PR00633; RCCNDNSATION.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50012; RCC1_3; 5.
PE 1: Evidence at protein level;
KW ATP-binding; Cell projection; Cilium; Cytoplasm; Cytoskeleton;
KW Disease variant; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..698
FT /note="Serine/threonine-protein kinase Nek8"
FT /id="PRO_0000086433"
FT DOMAIN 4..258
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 416..467
FT /note="RCC1 1"
FT REPEAT 468..519
FT /note="RCC1 2"
FT REPEAT 520..585
FT /note="RCC1 3"
FT REPEAT 586..637
FT /note="RCC1 4"
FT REPEAT 638..690
FT /note="RCC1 5"
FT REGION 278..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 128
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 162
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT VARIANT 448
FT /note="G -> V (in ARJPKD)"
FT /evidence="ECO:0000269|PubMed:12421721"
FT MUTAGEN 33
FT /note="K->M: Results in enlarged multinucleated cells."
FT /evidence="ECO:0000269|PubMed:12421721"
FT MUTAGEN 336
FT /note="L->F: Shows a defect in ciliary localization with no
FT apparent effect on ciliation, mitosis or centriole number."
FT /evidence="ECO:0000269|PubMed:18199800"
FT MUTAGEN 431
FT /note="H->Y: Shows a defect in ciliary localization with no
FT apparent effect on ciliation, mitosis or centriole number."
FT /evidence="ECO:0000269|PubMed:18199800"
FT MUTAGEN 503
FT /note="A->P: Shows a defect in ciliary localization with no
FT apparent effect on ciliation, mitosis or centriole number."
FT /evidence="ECO:0000269|PubMed:18199800"
FT CONFLICT 326
FT /note="G -> D (in Ref. 2; BAE32535)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="N -> D (in Ref. 2; BAE32535)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 698 AA; 75265 MW; 686B29A8CF180E94 CRC64;
MEKYERIRVV GRGAFGIVHL CLRKADQKLV ILKQIPVEQM TKEERQAAQN ECQVLKLLNH
PNVIEYYENF LEDKALMIAM EYAPGGTLAE FIQKRCNSLL EEETILHFFV QILLALHHVH
THLILHRDLK TQNILLDKHR MVVKIGDFGI SKILSSKSKA YTVVGTPCYI SPELCEGKPY
NQKSDIWALG CVLYELASLK RAFEAANLPA LVLKIMSGTF APISDRYSPE LRQLVLSLLS
LEPAQRPPLS HIMAQPLCIR ALLNIHTDVG SVRMRRAEKS LTPGPPIASG STGSRATSAR
CRGVPRGPVR PAIPPPLSSV YAWGGGLSSP LRLPMLNTEV VQVAAGRTQK AGVTRSGRLI
LWEAPPLGAG GGTLLPGAVE LPQPQFVSRF LEGQSGVTIK HVACGDLFTA CLTDRGIIMT
FGSGSNGCLG HGNLTDISQP TIVEALLGYE MVQVACGASH VLALSTDGEL FAWGRGDGGR
LGLGTRESHN CPQQVPVAPG QEAQRVVCGI DSSMILTSPG RVLACGSNRF NKLGLDHLSL
DEEPVPYQQV EEALSFTPLG SAPLDQEPLL CVDLGTAHSA AITASGDCYT FGSNQHGQLG
TSSRRVSRAP CRVQGLEGIK MVMVACGDAF TVAVGAEGEV YSWGKGTRGR LGRRDEDAGL
PRPVQLDETH PYMVTSVSCC HGNTLLAVRS VTDEPVPP
