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Protein

Serine/threonine-protein kinase Nek8

Gene

Nek8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for renal tubular integrity. May regulate local cytoskeletal structure in kidney tubule epithelial cells. May regulate ciliary biogenesis through targeting of proteins to the cilia. Plays a role in organogenesis and is involved in the regulation of the Hippo signaling pathway.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei33 – 331ATPPROSITE-ProRule annotation
Active sitei128 – 1281Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi10 – 189ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • determination of left/right symmetry Source: MGI
  • heart development Source: MGI
  • organ morphogenesis Source: MGI
  • regulation of hippo signaling Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase Nek8 (EC:2.7.11.1)
Alternative name(s):
Never in mitosis A-related kinase 8
Short name:
NimA-related protein kinase 8
Gene namesi
Name:Nek8
Synonyms:Jck
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1890646. Nek8.

Subcellular locationi

GO - Cellular componenti

  • ciliary base Source: MGI
  • ciliary inversin compartment Source: MGI
  • cilium Source: MGI
  • cytoplasm Source: UniProtKB-SubCell
  • cytoskeleton Source: UniProtKB-SubCell
  • primary cilium Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Defects in Nek8 are the cause of autosomal recessive juvenile polycystic kidney disease (ARJPKD).

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi33 – 331K → M: Results in enlarged multinucleated cells. 1 Publication
Mutagenesisi336 – 3361L → F: Shows a defect in ciliary localization with no apparent effect on ciliation, mitosis or centriole number. 1 Publication
Mutagenesisi431 – 4311H → Y: Shows a defect in ciliary localization with no apparent effect on ciliation, mitosis or centriole number. 1 Publication
Mutagenesisi503 – 5031A → P: Shows a defect in ciliary localization with no apparent effect on ciliation, mitosis or centriole number. 1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 698698Serine/threonine-protein kinase Nek8PRO_0000086433Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei162 – 1621Phosphothreonine; by autocatalysisBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ91ZR4.
PaxDbiQ91ZR4.
PRIDEiQ91ZR4.

PTM databases

PhosphoSiteiQ91ZR4.

Expressioni

Tissue specificityi

Kidney, liver, and testis.

Gene expression databases

BgeeiQ91ZR4.
ExpressionAtlasiQ91ZR4. baseline and differential.
GenevisibleiQ91ZR4. MM.

Interactioni

Subunit structurei

Interacts with PKD2; may regulate PKD2 targeting to the cilium. Component of a complex containing at least ANKS6, INVS, NEK8 and NPHP3. ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary axoneme (By similarity). Interacts with ANKS3 (PubMed:25671767).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
InvsO890192EBI-4282339,EBI-4281337

Protein-protein interaction databases

BioGridi228327. 2 interactions.
IntActiQ91ZR4. 1 interaction.
MINTiMINT-1341145.
STRINGi10090.ENSMUSP00000017549.

Structurei

3D structure databases

ProteinModelPortaliQ91ZR4.
SMRiQ91ZR4. Positions 1-689.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 258255Protein kinasePROSITE-ProRule annotationAdd
BLAST
Repeati416 – 46752RCC1 1Add
BLAST
Repeati468 – 51952RCC1 2Add
BLAST
Repeati520 – 58566RCC1 3Add
BLAST
Repeati586 – 63752RCC1 4Add
BLAST
Repeati638 – 69053RCC1 5Add
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 5 RCC1 repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0589. Eukaryota.
ENOG410Y7JF. LUCA.
GeneTreeiENSGT00760000118997.
HOGENOMiHOG000006908.
HOVERGENiHBG098799.
InParanoidiQ91ZR4.
KOiK08857.
OMAiTSARCRG.
OrthoDBiEOG7D59P5.
PhylomeDBiQ91ZR4.
TreeFamiTF106472.

Family and domain databases

Gene3Di2.130.10.30. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR009091. RCC1/BLIP-II.
IPR000408. Reg_chr_condens.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00415. RCC1. 4 hits.
[Graphical view]
PRINTSiPR00633. RCCNDNSATION.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50985. SSF50985. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50012. RCC1_3. 5 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q91ZR4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKYERIRVV GRGAFGIVHL CLRKADQKLV ILKQIPVEQM TKEERQAAQN
60 70 80 90 100
ECQVLKLLNH PNVIEYYENF LEDKALMIAM EYAPGGTLAE FIQKRCNSLL
110 120 130 140 150
EEETILHFFV QILLALHHVH THLILHRDLK TQNILLDKHR MVVKIGDFGI
160 170 180 190 200
SKILSSKSKA YTVVGTPCYI SPELCEGKPY NQKSDIWALG CVLYELASLK
210 220 230 240 250
RAFEAANLPA LVLKIMSGTF APISDRYSPE LRQLVLSLLS LEPAQRPPLS
260 270 280 290 300
HIMAQPLCIR ALLNIHTDVG SVRMRRAEKS LTPGPPIASG STGSRATSAR
310 320 330 340 350
CRGVPRGPVR PAIPPPLSSV YAWGGGLSSP LRLPMLNTEV VQVAAGRTQK
360 370 380 390 400
AGVTRSGRLI LWEAPPLGAG GGTLLPGAVE LPQPQFVSRF LEGQSGVTIK
410 420 430 440 450
HVACGDLFTA CLTDRGIIMT FGSGSNGCLG HGNLTDISQP TIVEALLGYE
460 470 480 490 500
MVQVACGASH VLALSTDGEL FAWGRGDGGR LGLGTRESHN CPQQVPVAPG
510 520 530 540 550
QEAQRVVCGI DSSMILTSPG RVLACGSNRF NKLGLDHLSL DEEPVPYQQV
560 570 580 590 600
EEALSFTPLG SAPLDQEPLL CVDLGTAHSA AITASGDCYT FGSNQHGQLG
610 620 630 640 650
TSSRRVSRAP CRVQGLEGIK MVMVACGDAF TVAVGAEGEV YSWGKGTRGR
660 670 680 690
LGRRDEDAGL PRPVQLDETH PYMVTSVSCC HGNTLLAVRS VTDEPVPP
Length:698
Mass (Da):75,265
Last modified:December 1, 2001 - v1
Checksum:i686B29A8CF180E94
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti326 – 3261G → D in BAE32535 (PubMed:16141072).Curated
Sequence conflicti528 – 5281N → D in BAE32535 (PubMed:16141072).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti448 – 4481G → V in ARJPKD. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF407579 mRNA. Translation: AAL09675.1.
AK154358 mRNA. Translation: BAE32535.1.
BC070457 mRNA. Translation: AAH70457.1.
CCDSiCCDS25091.1.
RefSeqiNP_543125.1. NM_080849.3.
UniGeneiMm.23788.

Genome annotation databases

EnsembliENSMUST00000017549; ENSMUSP00000017549; ENSMUSG00000017405.
GeneIDi140859.
KEGGimmu:140859.
UCSCiuc007kih.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF407579 mRNA. Translation: AAL09675.1.
AK154358 mRNA. Translation: BAE32535.1.
BC070457 mRNA. Translation: AAH70457.1.
CCDSiCCDS25091.1.
RefSeqiNP_543125.1. NM_080849.3.
UniGeneiMm.23788.

3D structure databases

ProteinModelPortaliQ91ZR4.
SMRiQ91ZR4. Positions 1-689.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi228327. 2 interactions.
IntActiQ91ZR4. 1 interaction.
MINTiMINT-1341145.
STRINGi10090.ENSMUSP00000017549.

PTM databases

PhosphoSiteiQ91ZR4.

Proteomic databases

MaxQBiQ91ZR4.
PaxDbiQ91ZR4.
PRIDEiQ91ZR4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000017549; ENSMUSP00000017549; ENSMUSG00000017405.
GeneIDi140859.
KEGGimmu:140859.
UCSCiuc007kih.2. mouse.

Organism-specific databases

CTDi284086.
MGIiMGI:1890646. Nek8.

Phylogenomic databases

eggNOGiKOG0589. Eukaryota.
ENOG410Y7JF. LUCA.
GeneTreeiENSGT00760000118997.
HOGENOMiHOG000006908.
HOVERGENiHBG098799.
InParanoidiQ91ZR4.
KOiK08857.
OMAiTSARCRG.
OrthoDBiEOG7D59P5.
PhylomeDBiQ91ZR4.
TreeFamiTF106472.

Miscellaneous databases

NextBioi370021.
PROiQ91ZR4.
SOURCEiSearch...

Gene expression databases

BgeeiQ91ZR4.
ExpressionAtlasiQ91ZR4. baseline and differential.
GenevisibleiQ91ZR4. MM.

Family and domain databases

Gene3Di2.130.10.30. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR009091. RCC1/BLIP-II.
IPR000408. Reg_chr_condens.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00415. RCC1. 4 hits.
[Graphical view]
PRINTSiPR00633. RCCNDNSATION.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50985. SSF50985. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50012. RCC1_3. 5 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish."
    Liu S., Lu W., Obara T., Kuida S., Lehoczky J., Dewar K., Drummond I.A., Beier D.R.
    Development 129:5839-5846(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-33, VARIANT ARJPKD VAL-448.
    Strain: C57BL/6J.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NOD.
    Tissue: Dendritic cell.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Eye.
  4. "NIMA-related kinases defective in murine models of polycystic kidney diseases localize to primary cilia and centrosomes."
    Mahjoub M.R., Trapp M.L., Quarmby L.M.
    J. Am. Soc. Nephrol. 16:3485-3489(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  5. "Nek8 regulates the expression and localization of polycystin-1 and polycystin-2."
    Sohara E., Luo Y., Zhang J., Manning D.K., Beier D.R., Zhou J.
    J. Am. Soc. Nephrol. 19:469-476(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PKD2.
  6. "NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis."
    Otto E.A., Trapp M.L., Schultheiss U.T., Helou J., Quarmby L.M., Hildebrandt F.
    J. Am. Soc. Nephrol. 19:587-592(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF LEU-336; HIS-431 AND ALA-503, FUNCTION.
  7. "Anks3 interacts with nephronophthisis proteins and is required for normal renal development."
    Yakulov T.A., Yasunaga T., Ramachandran H., Engel C., Mueller B., Hoff S., Dengjel J., Lienkamp S.S., Walz G.
    Kidney Int. 87:1191-1200(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ANKS3.

Entry informationi

Entry nameiNEK8_MOUSE
AccessioniPrimary (citable) accession number: Q91ZR4
Secondary accession number(s): Q3U498, Q9D685
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: December 1, 2001
Last modified: May 11, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.