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Q86SG6 (NEK8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Nima-related protein kinase 12a
Gene names
Name:NEK8
Synonyms:JCK, NEK12A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length692 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Plays a role in organogenesis and is involved in the regulation of the Hippo signaling pathway. Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Subunit structure

Interacts with PKD2; may regulate PKD2 targeting to the cilium By similarity. 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. Ref.8 Ref.9

Subcellular location

Cytoplasm By similarity. Cytoplasmcytoskeleton. Cell projectioncilium By similarity. Note: Predominantly cytoplasmic. Localizes to the proximal region of the primary cilium and is not observed in dividing cells.

Tissue specificity

Highest expression in thyroid, adrenal gland and skin. Low levels in spleen, colon and uterus. Overexpressed in breast tumors, with highest expression in infiltrating ductal carcinomas and moderate levels in mucinous adenocarcinoma. Ref.7

Involvement in disease

Nephronophthisis 9 (NPHP9) [MIM:613824]: An autosomal recessive disorder resulting in end-stage renal disease. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Renal-hepatic-pancreatic dysplasia 2 (RHPD2) [MIM:615415]: A form of renal-hepatic-pancreatic dysplasia, a disease characterized by cystic malformations of the kidneys, liver, and pancreas. The pathological findings consist of multicystic dysplastic kidneys, dilated and dysgenetic bile ducts, a dysplastic pancreas with dilated ducts, cysts, fibrosis and inflammatory infiltrates.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.

Contains 1 protein kinase domain.

Contains 5 RCC1 repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 692692Serine/threonine-protein kinase Nek8
PRO_0000086432

Regions

Domain4 – 258255Protein kinase
Repeat312 – 35039RCC1 1
Repeat410 – 46152RCC1 2
Repeat462 – 51352RCC1 3
Repeat580 – 63152RCC1 4
Repeat632 – 68453RCC1 5
Nucleotide binding10 – 189ATP By similarity

Sites

Active site1281Proton acceptor By similarity
Binding site331ATP By similarity

Amino acid modifications

Modified residue1621Phosphothreonine; by autocatalysis By similarity

Natural variations

Natural variant3301L → F in NPHP9; a full-length mouse NEK8 construct containing the mutation shows a defect in ciliary localization with no apparent effect on ciliation, mitosis or centriole number. Ref.10
VAR_065769
Natural variant4251H → Y in NPHP9; a full-length mouse NEK8 construct containing the mutation shows a defect in ciliary localization with no apparent effect on ciliation, mitosis or centriole number. Ref.10
VAR_065770
Natural variant4971A → P in NPHP9; a full-length mouse NEK8 construct containing the mutation shows a defect in ciliary localization with no apparent effect on ciliation, mitosis or centriole number. Ref.10
VAR_065771

Sequences

Sequence LengthMass (Da)Tools
Q86SG6 [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: 9E09820DFB3D5CA1

FASTA69274,806
        10         20         30         40         50         60 
MEKYERIRVV GRGAFGIVHL CLRKADQKLV IIKQIPVEQM TKEERQAAQN ECQVLKLLNH 

        70         80         90        100        110        120 
PNVIEYYENF LEDKALMIAM EYAPGGTLAE FIQKRCNSLL EEETILHFFV QILLALHHVH 

       130        140        150        160        170        180 
THLILHRDLK TQNILLDKHR MVVKIGDFGI SKILSSKSKA YTVVGTPCYI SPELCEGKPY 

       190        200        210        220        230        240 
NQKSDIWALG CVLYELASLK RAFEAANLPA LVLKIMSGTF APISDRYSPE LRQLVLSLLS 

       250        260        270        280        290        300 
LEPAQRPPLS HIMAQPLCIR ALLNLHTDVG SVRMRRAEKS VAPSNTGSRT TSVRCRGIPR 

       310        320        330        340        350        360 
GPVRPAIPPP LSSVYAWGGG LGTPLRLPML NTEVVQVAAG RTQKAGVTRS GRLILWEAPP 

       370        380        390        400        410        420 
LGAGGGSLLP GAVEQPQPQF ISRFLEGQSG VTIKHVACGD FFTACLTDRG IIMTFGSGSN 

       430        440        450        460        470        480 
GCLGHGSLTD ISQPTIVEAL LGYEMVQVAC GASHVLALST ERELFAWGRG DSGRLGLGTR 

       490        500        510        520        530        540 
ESHSCPQQVP MPPGQEAQRV VCGIDSSMIL TVPGQALACG SNRFNKLGLD HLSLGEEPVP 

       550        560        570        580        590        600 
HQQVEEALSF TLLGSAPLDQ EPLLSIDLGT AHSAAVTASG DCYTFGSNQH GQLGTNTRRG 

       610        620        630        640        650        660 
SRAPCKVQGL EGIKMAMVAC GDAFTVAIGA ESEVYSWGKG ARGRLGRRDE DAGLPRPVQL 

       670        680        690 
DETHPYTVTS VSCCHGNTLL AVRSVTDEPV PP 

« Hide

References

« Hide 'large scale' references
[1]Huang C.Q., Wu S.L., Yu L.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"NIMA-family kinase Nek8 complete human coding region."
Nedwidek M.N., Roig J., Lenz G., Avruch J.
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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].
Tissue: Brain.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 445-692.
Tissue: Testis.
[7]"Nek8, a NIMA family kinase member, is overexpressed in primary human breast tumors."
Bowers A.J., Boylan J.F.
Gene 328:135-142(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Mutations in NEK8 link multiple organ dysplasia with altered Hippo signalling and increased c-MYC expression."
Frank V., Habbig S., Bartram M.P., Eisenberger T., Veenstra-Knol H.E., Decker C., Boorsma R.A., Goebel H., Nuernberg G., Griessmann A., Franke M., Borgal L., Kohli P., Voelker L.A., Doetsch J., Nuernberg P., Benzing T., Bolz H.J. expand/collapse author list , Johnson C., Gerkes E.H., Schermer B., Bergmann C.
Hum. Mol. Genet. 22:2177-2185(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN RHPD2, FUNCTION, INTERACTION WITH NPHP3.
[9]"ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3."
Hoff S., Halbritter J., Epting D., Frank V., Nguyen T.M., van Reeuwijk J., Boehlke C., Schell C., Yasunaga T., Helmstadter M., Mergen M., Filhol E., Boldt K., Horn N., Ueffing M., Otto E.A., Eisenberger T., Elting M.W. expand/collapse author list , van Wijk J.A., Bockenhauer D., Sebire N.J., Rittig S., Vyberg M., Ring T., Pohl M., Pape L., Neuhaus T.J., Elshakhs N.A., Koon S.J., Harris P.C., Grahammer F., Huber T.B., Kuehn E.W., Kramer-Zucker A., Bolz H.J., Roepman R., Saunier S., Walz G., Hildebrandt F., Bergmann C., Lienkamp S.S.
Nat. Genet. 45:951-956(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ANKS6; INVS AND NPHP3.
[10]"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: VARIANTS NPHP9 PHE-330; TYR-425 AND PRO-497, CHARACTERIZATION OF VARIANTS NPHP9 PHE-330; TYR-425 AND PRO-497.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY242354 mRNA. Translation: AAO88243.1.
AY267371 mRNA. Translation: AAP04006.1.
AC010761 Genomic DNA. No translation available.
CH471159 Genomic DNA. Translation: EAW51136.1.
BC112240 mRNA. Translation: AAI12241.1.
BC113705 mRNA. Translation: AAI13706.1.
AL833909 mRNA. Translation: CAD38765.1.
RefSeqNP_835464.1. NM_178170.2.
UniGeneHs.448468.

3D structure databases

ProteinModelPortalQ86SG6.
SMRQ86SG6. Positions 1-255, 270-680.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid129755. 6 interactions.
IntActQ86SG6. 5 interactions.
STRING9606.ENSP00000268766.

Chemistry

GuidetoPHARMACOLOGY2123.

PTM databases

PhosphoSiteQ86SG6.

Polymorphism databases

DMDM34098463.

Proteomic databases

PaxDbQ86SG6.
PRIDEQ86SG6.

Protocols and materials databases

DNASU284086.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268766; ENSP00000268766; ENSG00000160602.
GeneID284086.
KEGGhsa:284086.
UCSCuc002hcp.3. human.

Organism-specific databases

CTD284086.
GeneCardsGC17P027068.
HGNCHGNC:13387. NEK8.
HPAHPA040661.
HPA040679.
MIM609799. gene.
613824. phenotype.
615415. phenotype.
neXtProtNX_Q86SG6.
Orphanet93591. Infantile autosomal recessive medullary cystic kidney disease.
294415. Renal-hepatic-pancreatic dysplasia.
PharmGKBPA38361.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000006908.
HOVERGENHBG098799.
InParanoidQ86SG6.
KOK08857.
OMATSARCRG.
OrthoDBEOG7D59P5.
PhylomeDBQ86SG6.
TreeFamTF106472.

Enzyme and pathway databases

SignaLinkQ86SG6.

Gene expression databases

ArrayExpressQ86SG6.
BgeeQ86SG6.
CleanExHS_NEK8.
GenevestigatorQ86SG6.

Family and domain databases

Gene3D2.130.10.30. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR009091. RCC1/BLIP-II.
IPR000408. Reg_chr_condens.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
PF00415. RCC1. 4 hits.
[Graphical view]
PRINTSPR00633. RCCNDNSATION.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF50985. SSF50985. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50012. RCC1_3. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNEK8.
GenomeRNAi284086.
NextBio94527.
PROQ86SG6.
SOURCESearch...

Entry information

Entry nameNEK8_HUMAN
AccessionPrimary (citable) accession number: Q86SG6
Secondary accession number(s): A6NIC5 expand/collapse secondary AC list , Q14CL7, Q2M1S6, Q8NDH1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: June 1, 2003
Last modified: April 16, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM