Q86SG6 (NEK8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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
Nima-related protein kinase 12a

Gene names

Name:	NEK8
Synonyms:	JCK, NEK12A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	692 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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.
Subcellular location	Cytoplasm By similarity. Cytoplasm › cytoskeleton. Cell projection › cilium 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.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.

Ontologies

Keywords
Cellular component	Cell projection Cilium Cytoplasm Cytoskeleton
Disease	Ciliopathy Disease mutation Nephronophthisis
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell primary cilium Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 692	692	Serine/threonine-protein kinase Nek8		PRO_0000086432
Regions
	Domain	4 – 258	255	Protein kinase
	Repeat	312 – 350	39	RCC1 1
	Repeat	410 – 461	52	RCC1 2
	Repeat	462 – 513	52	RCC1 3
	Repeat	580 – 631	52	RCC1 4
	Repeat	632 – 684	53	RCC1 5
	Nucleotide binding	10 – 18	9	ATP By similarity
Sites
	Active site	128	1	Proton acceptor By similarity
	Binding site	33	1	ATP By similarity
Amino acid modifications
	Modified residue	162	1	Phosphothreonine; by autocatalysis By similarity
Natural variations
	Natural variant	330	1	L → 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.8		VAR_065769
	Natural variant	425	1	H → 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.8		VAR_065770
	Natural variant	497	1	A → 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.8		VAR_065771

Sequences

	Sequence		Length	Mass (Da)
	Q86SG6 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 9E09820DFB3D5CA1	FASTA	692	74,806
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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.
IPI	IPI00328397.
RefSeq	NP_835464.1. NM_178170.2.
UniGene	Hs.448468.
3D structure databases
ProteinModelPortal	Q86SG6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q86SG6. 5 interactions.
STRING	9606.ENSP00000268766.
PTM databases
PhosphoSite	Q86SG6.
Polymorphism databases
DMDM	34098463.
Proteomic databases
PaxDb	Q86SG6.
PRIDE	Q86SG6.
Protocols and materials databases
DNASU	284086.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000268766; ENSP00000268766; ENSG00000160602.
GeneID	284086.
KEGG	hsa:284086.
UCSC	uc002hcp.3. human.
Organism-specific databases
CTD	284086.
GeneCards	GC17P027055.
HGNC	HGNC:13387. NEK8.
HPA	HPA040661. HPA040679.
MIM	609799. gene. 613824. phenotype.
neXtProt	NX_Q86SG6.
Orphanet	655. Autosomal recessive medullary cystic kidney disease.
PharmGKB	PA38361.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000006908.
HOVERGEN	HBG098799.
InParanoid	Q86SG6.
KO	K08857.
OMA	EREVFAW.
OrthoDB	EOG4PZJ65.
Gene expression databases
ArrayExpress	Q86SG6.
Bgee	Q86SG6.
CleanEx	HS_NEK8.
Genevestigator	Q86SG6.
GermOnline	ENSG00000160602. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.30. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF00069. Pkinase. 1 hit. PF00415. RCC1. 4 hits. [Graphical view]
PRINTS	PR00633. RCCNDNSATION.
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50985. RCC1/BLIP-II. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00625. RCC1_1. False negative. PS00626. RCC1_2. False negative. PS50012. RCC1_3. 5 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	284086.
NextBio	94527.
SOURCE	Search...

Entry information

Entry name

NEK8_HUMAN

Accession

Primary (citable) accession number: Q86SG6
Secondary accession number(s): A6NIC5 , Q14CL7, Q2M1S6, Q8NDH1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 15, 2003
Last sequence update:	June 1, 2003
Last modified:	May 1, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.