NEK8_DANRE
ID NEK8_DANRE Reviewed; 697 AA.
AC Q90XC2;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 136.
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;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 DISRUPTION PHENOTYPE.
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.
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Note=Predominantly
CC cytoplasmic. {ECO:0000250}.
CC -!- DISEASE: Note=Defects in nek8 are the cause of polycystic kidney
CC disease.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein in the embryo
CC causes ventral body curvature, pronephric cyst formation and laterality
CC defects, including reversed heart looping.
CC {ECO:0000269|PubMed:23793029}.
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; AF407580; AAL09676.1; -; mRNA.
DR RefSeq; NP_620776.1; NM_139077.1.
DR AlphaFoldDB; Q90XC2; -.
DR SMR; Q90XC2; -.
DR STRING; 7955.ENSDARP00000067094; -.
DR PaxDb; Q90XC2; -.
DR GeneID; 171094; -.
DR KEGG; dre:171094; -.
DR CTD; 284086; -.
DR ZFIN; ZDB-GENE-020509-1; nek8.
DR eggNOG; KOG0589; Eukaryota.
DR InParanoid; Q90XC2; -.
DR OrthoDB; 1062377at2759; -.
DR PhylomeDB; Q90XC2; -.
DR PRO; PR:Q90XC2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005813; C:centrosome; IBA:GO_Central.
DR GO; GO:0005929; C:cilium; IDA:ZFIN.
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; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
DR GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:ZFIN.
DR GO; GO:0001947; P:heart looping; IMP:ZFIN.
DR GO; GO:0048793; P:pronephros development; IGI:ZFIN.
DR GO; GO:0072116; P:pronephros formation; IGI:ZFIN.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0061326; P:renal tubule development; IMP:ZFIN.
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 2: Evidence at transcript level;
KW ATP-binding; Cell cycle; Cell division; Cytoplasm; Kinase; Magnesium;
KW Metal-binding; Mitosis; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..697
FT /note="Serine/threonine-protein kinase Nek8"
FT /id="PRO_0000086434"
FT DOMAIN 4..263
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 417..468
FT /note="RCC1 1"
FT REPEAT 469..520
FT /note="RCC1 2"
FT REPEAT 521..586
FT /note="RCC1 3"
FT REPEAT 587..636
FT /note="RCC1 4"
FT REPEAT 637..689
FT /note="RCC1 5"
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 697 AA; 76541 MW; 875A51D1F3831AA7 CRC64;
MEKYEKTKVV GRGAFGIVHL CRRRTDSALV ILKEIPVEQM TRDERLAAQN ECQVLKLLSH
PNIIEYYENF LEDKALMIAM EYAPGGTLAD YIQKRCNSLL DEDTILHSFV QILLALYHVH
NKLILHRDLK TQNILLDKHQ MIVKIGDFGI SKILVSKSKA YTVVGTPCYI SPELCEGKPY
NQKSDIWALG CVLYELASLK RAFEAANLPA LVLKIMSGTF APISDRYSPE LRQLILNMLN
LDPSKRPQLN EIMAHAICIR PLLNLYTDIG NVKMRRIEKP LSNVQAGPHG RPGGWITSTR
TRGGLSSLTS SKMMHPLPLF SVYTWGSGIS TPLRLPMLNT EVIQVSLGRT QKMGVTKSGR
LITWEAPSVG SGEPTLPGAV EQMQPQFISR FLEGQSGVTI KSVSCGDLFT TCLTDRGIIM
TFGSGSNGCL GHGNFNDVTQ PKIVEALLGY ELVQVSCGAS HVLAVTNERE VFSWGRGDNG
RLGLATQDSH NCPQQVSLPA DFEAQRVLCG VDCSMIMSTQ HQILACGNNR FNKLGLDKVS
GTEEPSSFCQ VEEVHLFQLV QSAPLNTEKI VYIDIGTAHS VAVTEKGQCF TFGSNQHGQL
GCSHRRSSRV PYQVSGLQGI TMAACGDAFT LAIGAEGEVY TWGKGARGRL GRKEEDFGIP
KPVQLDESHA FTVTSVACCH GNTLLAVKPF FEEPGPK
