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Reviewed, UniProtKB/Swiss-Prot O60285 (NUAK1_HUMAN)

Last modified February 9, 2010. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    NUAK family SNF1-like kinase 1
    EC=2.7.11.1
Alternative name(s):
    AMPK-related protein kinase 5
Gene names
Name: NUAK1
Synonyms: ARK5, KIAA0537
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length661 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Involved in tolerance to glucose starvation. Phosphorylates ATM. Suppresses Fas-induced apoptosis by phosphorylation of CASP6, thus suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Ref.1 Ref.4 Ref.5

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated by PKB/AKT1 during glucose starvation. Activated by phosphorylation on Thr-211 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39. Ref.1

Tissue specificity

Expressed at high levels in heart and brain, and at lower levels in skeletal muscle, kidney, ovary, placenta, lung and liver.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 protein kinase domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60285-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O60285-2)

The sequence of this isoform differs from the canonical sequence as follows:
     182-208: ENILLDDNCNIKIADFGLSNLYQKDKF → KKTSRENQVTTLPQSAVSLRSCWTVMM
     209-661: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 661661NUAK family SNF1-like kinase 1
PRO_0000086453

Regions

Domain55 – 306252Protein kinase
Nucleotide binding61 – 699ATP By similarity

Sites

Active site1781Proton acceptor By similarity
Binding site841ATP By similarity

Amino acid modifications

Modified residue221Phosphoserine
Modified residue2111Phosphothreonine Ref.1
Modified residue2151Phosphoserine By similarity
Modified residue3711Phosphoserine By similarity
Modified residue3801Phosphoserine By similarity
Modified residue3881Phosphoserine
Modified residue4441Phosphoserine
Modified residue4451Phosphoserine
Modified residue4551Phosphoserine
Modified residue6001Phosphoserine; by PKB/AKT1

Natural variations

Alternative sequence182 – 20827ENILL…QKDKF → KKTSRENQVTTLPQSAVSLR SCWTVMM in isoform 2.
VSP_014236
Alternative sequence209 – 661453Missing in isoform 2.
VSP_014237
Natural variant4191G → D: dbSNP rs55774704. Ref.7
VAR_040963
Natural variant5431P → R: dbSNP rs3741883. Ref.7
VAR_017246

Experimental info

Mutagenesis2111T → A: Prevents phosphorylation and activation by STK11 complex. Ref.1
Mutagenesis6001S → A: No phosphorylation. Ref.4
Sequence conflict861I → V in BAB55026. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 806F37D52CA4718F

FASTA66174,305
        10         20         30         40         50         60 
MEGAAAPVAG DRPDLGLGAP GSPREAVAGA TAALEPRKPH GVKRHHHKHN LKHRYELQET 

        70         80         90        100        110        120 
LGKGTYGKVK RATERFSGRV VAIKSIRKDK IKDEQDMVHI RREIEIMSSL NHPHIISIYE 

       130        140        150        160        170        180 
VFENKDKIVI IMEYASKGEL YDYISERRRL SERETRHFFR QIVSAVHYCH KNGVVHRDLK 

       190        200        210        220        230        240 
LENILLDDNC NIKIADFGLS NLYQKDKFLQ TFCGSPLYAS PEIVNGRPYR GPEVDSWALG 

       250        260        270        280        290        300 
VLLYTLVYGT MPFDGFDHKN LIRQISSGEY REPTQPSDAR GLIRWMLMVN PDRRATIEDI 

       310        320        330        340        350        360 
ANHWWVNWGY KSSVCDCDAL HDSESPLLAR IIDWHHRSTG LQADTEAKMK GLAKPTTSEV 

       370        380        390        400        410        420 
MLERQRSLKK SKKENDFAQS GQDAVPESPS KLSSKRPKGI LKKRSNSEHR SHSTGFIEGV 

       430        440        450        460        470        480 
VGPALPSTFK MEQDLCRTGV LLPSSPEAEV PGKLSPKQSA TMPKKGILKK TQQRESGYYS 

       490        500        510        520        530        540 
SPERSESSEL LDSNDVMGSS IPSPSPPDPA RVTSHSLSCR RKGILKHSSK YSAGTMDPAL 

       550        560        570        580        590        600 
VSPEMPTLES LSEPGVPAEG LSRSYSRPSS VISDDSVLSS DSFDLLDLQE NRPARQRIRS 

       610        620        630        640        650        660 
CVSAENFLQI QDFEGLQNRP RPQYLKRYRN RLADSSFSLL TDMDDVTQVY KQALEICSKL 


N 

« Hide

Isoform 2.

Checksum: 36E0B4FB479B16EF
Show »

FASTA20823,824

References

« Hide 'large scale' references
[1]"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1."
Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.
EMBO J. 23:833-843(2004) [PubMed: 14976552] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-211, MUTAGENESIS OF THR-211.
[2]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed: 9628581] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]"Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein."
Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F., Esumi H.
J. Biol. Chem. 278:48-53(2003) [PubMed: 12409306] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-600.
[5]"Regulation of caspase-6 and FLIP by the AMPK family member ARK5."
Suzuki A., Kusakai G., Kishimoto A., Shimojo Y., Miyamoto S., Ogura T., Ochiai A., Esumi H.
Oncogene 23:7067-7075(2004) [PubMed: 15273717] [Abstract]
Cited for: FUNCTION.
[6]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; THR-211; SER-388; SER-444; SER-445 AND SER-455, MASS SPECTROMETRY.
[7]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-419 AND ARG-543.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB011109 mRNA. Translation: BAA25463.2. Different initiation.
AK027302 mRNA. Translation: BAB55026.1.
IPIIPI00028566.
IPI00386903.
RefSeqNP_055655.1.

3D structure databases

SMRO60285. Positions 18-306, 49-338.
ModBaseSearch...

Protein-protein interaction databases

IntActO60285. 7 interactions.
STRINGO60285.

PTM databases

PhosphoSiteO60285.

Proteomic databases

PRIDEO60285.

Genome annotation databases

EnsemblENST00000261402; ENSP00000261402; ENSG00000074590; Homo sapiens. [Genome view]
GeneID9891.
KEGGhsa:9891.
UCSCuc001tlj.1. human.

Organism-specific databases

CTD9891.
GeneCardsGC12M104960.
H-InvDBHIX0010951.
HIX0021283.
HGNCHGNC:14311. NUAK1.
MIM608130. gene.
PharmGKBPA142671242.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG16403.
HOGENOMHBG445847.
HOVERGENO60285.
InParanoidO60285.
OMANRPRPQY.
OrthoDBEOG9D55J2.
PhylomeDBO60285.

Enzyme and pathway databases

BRENDA2.7.11.1. 247.

Gene expression databases

ArrayExpressO60285.
BgeeO60285.
CleanExHS_NUAK1.
GenevestigatorO60285.
GermOnlineENSG00000074590. Homo sapiens.

Family and domain databases

InterProIPR020636. Ca/CaM-dep_prot_kinase-like.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR008271. Ser/Thr_prot_kinase_AS.
IPR002290. Ser/Thr_prot_kinase_dom.
IPR020665. SNF1-like_kinase_NUAK-typ.
[Graphical view]
PANTHERPTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit.
PTHR22982:SF51. SNF1-like_kinase_NUAK-typ. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio37291.
SOURCESearch...

Entry information

Entry nameNUAK1_HUMAN
AccessionPrimary (citable) accession number: O60285
Secondary accession number(s): Q96KA8
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: August 1, 1998
Last modified: February 9, 2010
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents