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Protein

NUAK family SNF1-like kinase 2

Gene

NUAK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Able to phosphorylate 'Ser-464' of LATS1.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.2 Publications

Cofactori

Mg2+2 Publications

Enzyme regulationi

Activated by phosphorylation on Thr-208.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei81 – 811ATPPROSITE-ProRule annotation1 Publication
Active sitei175 – 1751Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi59 – 679ATPPROSITE-ProRule annotationBy similarity

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton organization Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • cellular response to glucose starvation Source: UniProtKB
  • intracellular signal transduction Source: GO_Central
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of TOR signaling Source: GO_Central
  • protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

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

Enzyme and pathway databases

SignaLinkiQ9H093.

Names & Taxonomyi

Protein namesi
Recommended name:
NUAK family SNF1-like kinase 2 (EC:2.7.11.1)
Alternative name(s):
Omphalocele kinase 2
SNF1/AMP kinase-related kinase
Short name:
SNARK
Gene namesi
Name:NUAK2Imported
Synonyms:OMPHK2, SNARK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:29558. NUAK2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi81 – 811K → R: Loss of autophosphorylation, kinase activity and of anti-apoptotic activity. 1 Publication
Mutagenesisi208 – 2081T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. 1 Publication

Organism-specific databases

PharmGKBiPA142671243.

Polymorphism and mutation databases

BioMutaiNUAK2.
DMDMi74761376.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 628628NUAK family SNF1-like kinase 2PRO_0000247756Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication
Modified residuei208 – 2081Phosphothreonine; by LKB11 Publication
Modified residuei435 – 4351Phosphoserine1 Publication
Modified residuei523 – 5231Phosphoserine1 Publication
Modified residuei544 – 5441Phosphoserine1 Publication
Modified residuei547 – 5471Phosphoserine1 Publication
Modified residuei573 – 5731PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Autophosphorylated in vitro.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ9H093.
PaxDbiQ9H093.
PRIDEiQ9H093.

PTM databases

PhosphoSiteiQ9H093.

Expressioni

Gene expression databases

BgeeiQ9H093.
CleanExiHS_NUAK2.
GenevisibleiQ9H093. HS.

Organism-specific databases

HPAiHPA008958.

Interactioni

Protein-protein interaction databases

BioGridi123581. 17 interactions.
IntActiQ9H093. 3 interactions.
MINTiMINT-4719062.
STRINGi9606.ENSP00000356125.

Structurei

3D structure databases

ProteinModelPortaliQ9H093.
SMRiQ9H093. Positions 23-327.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini53 – 303251Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00790000123055.
HOGENOMiHOG000004864.
HOVERGENiHBG007160.
InParanoidiQ9H093.
KOiK08800.
OMAiTDCQEVT.
OrthoDBiEOG7MD4PN.
PhylomeDBiQ9H093.
TreeFamiTF324572.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9H093-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESLVFARRS GPTPSAAELA RPLAEGLIKS PKPLMKKQAV KRHHHKHNLR
60 70 80 90 100
HRYEFLETLG KGTYGKVKKA RESSGRLVAI KSIRKDKIKD EQDLMHIRRE
110 120 130 140 150
IEIMSSLNHP HIIAIHEVFE NSSKIVIVME YASRGDLYDY ISERQQLSER
160 170 180 190 200
EARHFFRQIV SAVHYCHQNR VVHRDLKLEN ILLDANGNIK IADFGLSNLY
210 220 230 240 250
HQGKFLQTFC GSPLYASPEI VNGKPYTGPE VDSWSLGVLL YILVHGTMPF
260 270 280 290 300
DGHDHKILVK QISNGAYREP PKPSDACGLI RWLLMVNPTR RATLEDVASH
310 320 330 340 350
WWVNWGYATR VGEQEAPHEG GHPGSDSARA SMADWLRRSS RPLLENGAKV
360 370 380 390 400
CSFFKQHAPG GGSTTPGLER QHSLKKSRKE NDMAQSLHSD TADDTAHRPG
410 420 430 440 450
KSNLKLPKGI LKKKVSASAE GVQEDPPELS PIPASPGQAA PLLPKKGILK
460 470 480 490 500
KPRQRESGYY SSPEPSESGE LLDAGDVFVS GDPKEQKPPQ ASGLLLHRKG
510 520 530 540 550
ILKLNGKFSQ TALELAAPTT FGSLDELAPP RPLARASRPS GAVSEDSILS
560 570 580 590 600
SESFDQLDLP ERLPEPPLRG CVSVDNLTGL EEPPSEGPGS CLRRWRQDPL
610 620
GDSCFSLTDC QEVTATYRQA LRVCSKLT
Length:628
Mass (Da):69,612
Last modified:March 1, 2001 - v1
Checksum:iF76F8B1BF94F4C87
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti309 – 3091T → S.1 Publication
Corresponds to variant rs55745939 [ dbSNP | Ensembl ].
VAR_040964
Natural varianti341 – 3411R → L.1 Publication
Corresponds to variant rs35208615 [ dbSNP | Ensembl ].
VAR_040965
Natural varianti503 – 5031K → R in an ovarian Endometrioid carcinoma sample; somatic mutation. 1 Publication
VAR_040966
Natural varianti516 – 5161A → V.1 Publication
Corresponds to variant rs35070935 [ dbSNP | Ensembl ].
VAR_040967
Natural varianti541 – 5411G → E in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication
VAR_040968

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136891 mRNA. Translation: CAB66825.1.
AK074830 mRNA. Translation: BAC11234.1.
BC017306 mRNA. Translation: AAH17306.1.
RefSeqiNP_112214.2. NM_030952.2.
UniGeneiHs.497512.

Genome annotation databases

EnsembliENST00000367157; ENSP00000356125; ENSG00000163545.
GeneIDi81788.
KEGGihsa:81788.
UCSCiuc001hce.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136891 mRNA. Translation: CAB66825.1.
AK074830 mRNA. Translation: BAC11234.1.
BC017306 mRNA. Translation: AAH17306.1.
RefSeqiNP_112214.2. NM_030952.2.
UniGeneiHs.497512.

3D structure databases

ProteinModelPortaliQ9H093.
SMRiQ9H093. Positions 23-327.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123581. 17 interactions.
IntActiQ9H093. 3 interactions.
MINTiMINT-4719062.
STRINGi9606.ENSP00000356125.

Chemistry

BindingDBiQ9H093.
ChEMBLiCHEMBL5698.
GuidetoPHARMACOLOGYi2130.

PTM databases

PhosphoSiteiQ9H093.

Polymorphism and mutation databases

BioMutaiNUAK2.
DMDMi74761376.

Proteomic databases

MaxQBiQ9H093.
PaxDbiQ9H093.
PRIDEiQ9H093.

Protocols and materials databases

DNASUi81788.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367157; ENSP00000356125; ENSG00000163545.
GeneIDi81788.
KEGGihsa:81788.
UCSCiuc001hce.3. human.

Organism-specific databases

CTDi81788.
GeneCardsiGC01M205271.
HGNCiHGNC:29558. NUAK2.
HPAiHPA008958.
MIMi608131. gene.
neXtProtiNX_Q9H093.
PharmGKBiPA142671243.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00790000123055.
HOGENOMiHOG000004864.
HOVERGENiHBG007160.
InParanoidiQ9H093.
KOiK08800.
OMAiTDCQEVT.
OrthoDBiEOG7MD4PN.
PhylomeDBiQ9H093.
TreeFamiTF324572.

Enzyme and pathway databases

SignaLinkiQ9H093.

Miscellaneous databases

GeneWikiiNUAK2.
GenomeRNAii81788.
NextBioi72088.
PROiQ9H093.
SOURCEiSearch...

Gene expression databases

BgeeiQ9H093.
CleanExiHS_NUAK2.
GenevisibleiQ9H093. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 205-224, FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-208, MUTAGENESIS OF THR-208.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: TestisImported.
  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.
    , 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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: TeratocarcinomaImported.
  4. "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: LymphImported.
  5. "Induction of cell-cell detachment during glucose starvation through F-actin conversion by SNARK, the fourth member of the AMP-activated protein kinase catalytic subunit family."
    Suzuki A., Kusakai G., Kishimoto A., Minegichi Y., Ogura T., Esumi H.
    Biochem. Biophys. Res. Commun. 311:156-161(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Identification of SNF1/AMP kinase-related kinase as an NF-kappaB-regulated anti-apoptotic kinase involved in CD95-induced motility and invasiveness."
    Legembre P., Schickel R., Barnhart B.C., Peter M.E.
    J. Biol. Chem. 279:46742-46747(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-81.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-523; SER-544 AND SER-547, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. Cited for: FUNCTION.
  9. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "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.
    , 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] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-309; LEU-341; ARG-503; VAL-516 AND GLU-541.

Entry informationi

Entry nameiNUAK2_HUMAN
AccessioniPrimary (citable) accession number: Q9H093
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: March 1, 2001
Last modified: June 24, 2015
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.