NEK8_RAT
ID NEK8_RAT Reviewed; 698 AA.
AC D3ZGQ5;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 86.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH ANKS6; INVS AND NPHP3.
RX PubMed=23793029; DOI=10.1038/ng.2681;
RA Hoff S., Halbritter J., Epting D., Frank V., Nguyen T.M., van Reeuwijk J.,
RA Boehlke C., Schell C., Yasunaga T., Helmstadter M., Mergen M., Filhol E.,
RA Boldt K., Horn N., Ueffing M., Otto E.A., Eisenberger T., Elting M.W.,
RA van Wijk J.A., Bockenhauer D., Sebire N.J., Rittig S., Vyberg M., Ring T.,
RA Pohl M., Pape L., Neuhaus T.J., Elshakhs N.A., Koon S.J., Harris P.C.,
RA Grahammer F., Huber T.B., Kuehn E.W., Kramer-Zucker A., Bolz H.J.,
RA Roepman R., Saunier S., Walz G., Hildebrandt F., Bergmann C.,
RA Lienkamp S.S.;
RT "ANKS6 is a central component of a nephronophthisis module linking NEK8 to
RT INVS and NPHP3.";
RL Nat. Genet. 45:951-956(2013).
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 (By similarity). {ECO:0000250}.
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 (By similarity). Component of a complex containing at least ANKS6,
CC INVS, NEK8 and NPHP3 (PubMed:23793029). ANKS6 may organize complex
CC assembly by linking INVS and NPHP3 to NEK8 and INVS may target it to
CC the proximal ciliary axoneme (PubMed:23793029). Interacts with ANKS3
CC (By similarity). {ECO:0000250|UniProtKB:Q91ZR4,
CC ECO:0000269|PubMed:23793029}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q91ZR4}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q91ZR4}. Cell
CC projection, cilium {ECO:0000250|UniProtKB:Q91ZR4}. Cytoplasm,
CC cytoskeleton, 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q91ZR4}.
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; AABR06064754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473948; EDM05318.1; -; Genomic_DNA.
DR RefSeq; NP_001099274.1; NM_001105804.1.
DR RefSeq; XP_006246995.1; XM_006246933.2.
DR AlphaFoldDB; D3ZGQ5; -.
DR SMR; D3ZGQ5; -.
DR STRING; 10116.ENSRNOP00000017264; -.
DR PaxDb; D3ZGQ5; -.
DR Ensembl; ENSRNOT00000017264; ENSRNOP00000017264; ENSRNOG00000012866.
DR GeneID; 287473; -.
DR KEGG; rno:287473; -.
DR CTD; 284086; -.
DR RGD; 1306897; Nek8.
DR eggNOG; KOG0589; Eukaryota.
DR GeneTree; ENSGT00940000159297; -.
DR HOGENOM; CLU_000288_123_1_1; -.
DR InParanoid; D3ZGQ5; -.
DR OMA; GIKMVMV; -.
DR OrthoDB; 379104at2759; -.
DR PhylomeDB; D3ZGQ5; -.
DR TreeFam; TF106472; -.
DR PRO; PR:D3ZGQ5; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Proteomes; UP000234681; Chromosome 10.
DR Bgee; ENSRNOG00000012866; Expressed in adult mammalian kidney and 17 other tissues.
DR GO; GO:0005813; C:centrosome; IBA:GO_Central.
DR GO; GO:0097546; C:ciliary base; ISO:RGD.
DR GO; GO:0097543; C:ciliary inversin compartment; ISO:RGD.
DR GO; GO:0005929; C:cilium; ISO:RGD.
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:RGD.
DR GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
DR GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0035330; P:regulation of hippo signaling; ISO:RGD.
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; 4.
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_0000424415"
FT DOMAIN 4..258
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 415..466
FT /note="RCC1 1"
FT REPEAT 467..518
FT /note="RCC1 2"
FT REPEAT 520..571
FT /note="RCC1 3"
FT REPEAT 585..636
FT /note="RCC1 4"
FT REPEAT 638..689
FT /note="RCC1 5"
FT REGION 281..307
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"
SQ SEQUENCE 698 AA; 75254 MW; 3846FCE2E3E53A0D CRC64;
MEKYERIRVV GRGAFGIVHL CLRKADQKLV IIKQIPVEQM TKEERQAAQN ECQVLKLLNH
PNVIEYYENF LEDKALMIAM EYAPGGTLAE FIQKRCNSLL EEETILHFFV QILLALHHVH
THLILHRDLK TQNILLDKHR MVVKIGDFGI SKILSSKSKA YTVVGTPCYI SPELCEGKPY
NQKSDIWALG CVLYELASLK RAFEAANLPA LVLKIMSGTF APISDRYSPE LRQLVLSLLS
LEPAQRPPLS HIMAQPLCIR ALLNIHTDVG SVRMRRAEKC LTPGTPMAPG STGSRATSAR
CRGVPRGPVR PAIPPPLSSV YAWGGGLSIP LRLPMPNTEV VQVAAGRTQK AGVTRSGRLI
LWEAPPLGTG GGTLLPGAVE LPQPQFVSRF LEGQSGVTIK HVACGDLFTA CLTDRGIIMT
FGSGSNGCLG HGSLTDISQP TIVEALLGYE MVQVACGASH VLALSADGEL FAWGRGDGGR
LGLGTRESHN CPQQVPMVPG QEAQRVVCGI DCSMILTSPG RVLACGSNRF NKLGLDCLSL
EEEPVPHQQV EEALSFTPLG SAPLDRETLL CVDLGTAHSA AVTASGACYT FGSNQHGQLG
TSSRRVSRAP CRVQGLEGIK MVMVACGDAF TVAIGAEGEV YSWGKGARGR LGRRDEDAGL
PRPVQLDETH PYTVTSVSCC HGNTLLAVRS VTDEPVPP
