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Q9U9Y8 (NLK_CAEEL) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine kinase NLK

EC=2.7.11.24
Alternative name(s):
Loss of intestine protein 1
Nemo-like kinase
Gene names
Name:lit-1
Synonyms:nlk
ORF Names:W06F12.1
OrganismCaenorhabditis elegans [Reference proteome]
Taxonomic identifier6239 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis

Protein attributes

Sequence length634 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Has a role in the Wnt signaling pathway controlling the asymmetry of cell divisions during embryogenesis. Operates in the AB and EMS cell lineages influencing cell specification. Required for body wall muscle development, endoderm development, pop-1 asymmetry and T-cell division asymmetry. Lit-1/wrm-1 complex regulates pop-1 localization and is required for pop-1/par-5 interaction. Ref.1 Ref.2 Ref.4 Ref.6 Ref.7

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. UniProtKB O54949

Cofactor

Magnesium By similarity. UniProtKB O54949

Subunit structure

Interacts with wrm-1 (via N-terminus); activates lit-1 kinase activity and the lit-1/wrm-1 dimer phosphorylates pop-1 which promotes pop-1 interaction with par-5 and translocation of pop-1 from the nucleus to the cytoplasm. Interacts with pop-1 (phosphorylated on 'Ser-118' and 'Ser-127'); dependent on lit-1/wrm-1 complex. Ref.1 Ref.2 Ref.7

Subcellular location

Cytoplasmcell cortex. Nucleus. Note: Located in the anterior cell cortex before and during asymmetric cell division. After division, located preferentially in the nucleus of the posterior daughter cell. Ref.7 Ref.9

Tissue specificity

Expressed in larval and adult pharynx and seam and vulval cells. Ref.5 Ref.8

Miscellaneous

Worms lacking nlk exhibit defects in body wall muscle, endoderm development and pop-1 asymmetry. Ref.2 Ref.4

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from genetic interaction Ref.1. Source: WormBase

anatomical structure morphogenesis

Inferred from genetic interaction PubMed 21857800. Source: WormBase

asymmetric cell division

Inferred from mutant phenotype Ref.2Ref.4. Source: WormBase

asymmetric protein localization involved in cell fate determination

Inferred from mutant phenotype Ref.2PubMed 15020416. Source: WormBase

embryo development

Inferred from mutant phenotype Ref.4. Source: WormBase

endoderm development

Inferred from mutant phenotype Ref.1. Source: UniProtKB

endodermal cell fate specification

Inferred from mutant phenotype Ref.2. Source: WormBase

muscle cell fate specification

Inferred from mutant phenotype Ref.2. Source: WormBase

polarity specification of proximal/distal axis

Inferred from mutant phenotype PubMed 15020416. Source: WormBase

protein phosphorylation

Inferred from direct assay Ref.1PubMed 12651889. Source: WormBase

   Cellular_componentcell cortex

Inferred from direct assay PubMed 17276345. Source: WormBase

cytoplasm

Inferred from direct assay Ref.7PubMed 20624379. Source: WormBase

nucleus

Inferred from direct assay Ref.7PubMed 17276345PubMed 20624379. Source: WormBase

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MAP kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein N-terminus binding

Inferred from physical interaction Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.1. Source: UniProtKB

protein kinase activity

Inferred from direct assay Ref.1PubMed 12651889. Source: WormBase

protein serine/threonine kinase activity

Inferred from sequence or structural similarity Ref.1. Source: WormBase

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform a Ref.2 (identifier: Q9U9Y8-1)

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 b Ref.2 (identifier: Q9U9Y8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: Missing.
     173-178: HHQQLV → MRDMIY
Isoform c Ref.3 (identifier: Q9U9Y8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-197: Missing.
     198-216: YEKNQQKQQQVQQIPTQPQ → MILIAIIESFIEYLRKIVW
Note: No experimental confirmation available.
Isoform d Ref.3 (identifier: Q9U9Y8-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.
     34-51: KDTEDEFCGCLFPDPEIP → MGRNQEGQFNGAGNSESA
Note: No experimental confirmation available.
Isoform e Ref.2 (identifier: Q9U9Y8-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-180: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 634634Serine/threonine kinase NLK
PRO_0000372802

Regions

Domain240 – 531292Protein kinase
Nucleotide binding246 – 2549ATP By similarity
Compositional bias80 – 216137Gln-rich
Compositional bias102 – 18887His-rich

Sites

Active site3661Proton acceptor By similarity
Binding site2691ATP By similarity

Natural variations

Alternative sequence1 – 197197Missing in isoform c. Ref.3
VSP_052845
Alternative sequence1 – 180180Missing in isoform e. Ref.2
VSP_052846
Alternative sequence1 – 172172Missing in isoform b. Ref.2
VSP_052847
Alternative sequence1 – 3333Missing in isoform d. Ref.3
VSP_052848
Alternative sequence34 – 5118KDTED…DPEIP → MGRNQEGQFNGAGNSESA in isoform d. Ref.3
VSP_052849
Alternative sequence173 – 1786HHQQLV → MRDMIY in isoform b. Ref.2
VSP_052850
Alternative sequence198 – 21619YEKNQ…PTQPQ → MILIAIIESFIEYLRKIVW in isoform c. Ref.3
VSP_052851

Experimental info

Mutagenesis3571L → S in t1512; intestine cells absent but have an excess of pharyngeal cells, symmetrical localization of pop-1 and symmetrical T-cell division. Ref.1 Ref.2 Ref.4
Mutagenesis4001T → A: No detectable kinase activity. Ref.5
Mutagenesis4021E → K in t1534; reduced body-wall muscle. Ref.4
Mutagenesis5411C → Y in or131; loss of pop-1 asymmetry and protruding vulva phenotype and defects in gonadal migration and development. Ref.2 Ref.5 Ref.8

Sequences

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

Last modified May 1, 2000. Version 1.
Checksum: A9F2EA7E3E2CE7F5

FASTA63471,777
        10         20         30         40         50         60 
MVSWGRGKDA YYLYISREQE EDDDDSLSFY SSQKDTEDEF CGCLFPDPEI PGSSSSSGCS 

        70         80         90        100        110        120 
SSSTELYDLA AAHAALISRQ QQILSQAIPI IPEHQLAAVA AHHQHHQQLH PSVQYQLVAA 

       130        140        150        160        170        180 
ATHHNHHQPQ AAQPHYSAVV PRSDVIQQPP HFALHHHLQN LVQQQQQQQA HHHHQQLVGE 

       190        200        210        220        230        240 
MALVSHTHPA AVGSTTCYEK NQQKQQQVQQ IPTQPQVAHV SSNAILAAAQ PFYPPPVQDS 

       250        260        270        280        290        300 
QPDRPIGYGA FGVVWSVTDP RSGKRVALKK MPNVFQNLAS CKRVFREIKM LSSFRHDNVL 

       310        320        330        340        350        360 
SLLDILQPAN PSFFQELYVL TELMQSDLHK IIVSPQALTP DHVKVFVYQI LRGLKYLHTA 

       370        380        390        400        410        420 
NILHRDIKPG NLLVNSNCIL KICDFGLART WDQRDRLNMT HEVVTQYYRA PELLMGARRY 

       430        440        450        460        470        480 
TGAVDIWSVG CIFAELLQRK ILFQAAGPIE QLQMIIDLLG TPSQEAMKYA CEGAKNHVLR 

       490        500        510        520        530        540 
AGLRAPDTQR LYKIASPDDK NHEAVDLLQK LLHFDPDKRI SVEEALQHRY LEEGRLRFHS 

       550        560        570        580        590        600 
CMCSCCYTKP NMPSRLFAQD LDPRHESPFD PKWEKDMSRL SMFELREKMY QFVMDRPALY 

       610        620        630 
GVALCINPQS AAYKNFASSS VAQASELPPS PQAW 

« Hide

Isoform b [UniParc].

Checksum: D030A48CA8F2968C
Show »

FASTA46252,603
Isoform c [UniParc].

Checksum: 21C9CF88553F20D3
Show »

FASTA43749,951
Isoform d [UniParc].

Checksum: 311EED6DED5AA170
Show »

FASTA60167,652
Isoform e [UniParc].

Checksum: D951AB8C0CAC9394
Show »

FASTA45451,607

References

« Hide 'large scale' references
[1]"WRM-1 activates the LIT-1 protein kinase to transduce anterior/posterior polarity signals in C. elegans."
Rocheleau C.E., Yasuda J., Shin T.H., Lin R., Sawa H., Okano H., Priess J.R., Davis R.J., Mello C.C.
Cell 97:717-726(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND E), FUNCTION, INTERACTION WITH WRM-1, MUTAGENESIS OF LEU-357.
[2]"MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans."
Meneghini M.D., Ishitani T., Carter J.C., Hisamoto N., Ninomiya-Tsuji J., Thorpe C.J., Hamill D.R., Matsumoto K., Bowerman B.
Nature 399:793-797(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, MUTAGENESIS OF CYS-541.
[3]"Genome sequence of the nematode C. elegans: a platform for investigating biology."
The C. elegans sequencing consortium
Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING.
Strain: Bristol N2.
[4]"Binary specification of the embryonic lineage in Caenorhabditis elegans."
Kaletta T., Schnabel H., Schnabel R.
Nature 390:294-298(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LEU-357 AND GLU-402.
[5]"MOM-4, a MAP kinase kinase kinase-related protein, activates WRM-1/LIT-1 kinase to transduce anterior/posterior polarity signals in C. elegans."
Shin T.H., Yasuda J., Rocheleau C.E., Lin R., Soto M., Bei Y., Davis R.J., Mello C.C.
Mol. Cell 4:275-280(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-400.
[6]"Left-right asymmetry in C. elegans intestine organogenesis involves a LIN-12/Notch signaling pathway."
Hermann G.J., Leung B., Priess J.R.
Development 127:3429-3440(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Phosphorylation by the beta-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans."
Lo M.-C., Gay F., Odom R., Shi Y., Lin R.
Cell 117:95-106(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH POP-1.
[8]"Identification of C. elegans DAF-12-binding sites, response elements, and target genes."
Shostak Y., Van Gilst M.R., Antebi A., Yamamoto K.R.
Genes Dev. 18:2529-2544(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF CYS-541.
[9]"Asymmetric cortical and nuclear localizations of WRM-1/beta-catenin during asymmetric cell division in C. elegans."
Takeshita H., Sawa H.
Genes Dev. 19:1743-1748(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF143243 mRNA. Translation: AAD37360.1.
AF143244 mRNA. Translation: AAD37361.1.
AF145376 mRNA. Translation: AAD39815.1.
Z83244 Genomic DNA. Translation: CAB05827.2.
Z83244 Genomic DNA. Translation: CAB60300.2.
Z83244 Genomic DNA. Translation: CAD18878.1.
Z83244 Genomic DNA. Translation: CAH10803.1.
Z83244, Z92822 Genomic DNA. Translation: CAH10804.1.
PIRT26240.
RefSeqNP_001022805.1. NM_001027634.2. [Q9U9Y8-1]
NP_001022806.1. NM_001027635.2. [Q9U9Y8-2]
NP_001022807.1. NM_001027636.2. [Q9U9Y8-3]
NP_001022808.1. NM_001027637.3. [Q9U9Y8-4]
NP_001022809.1. NM_001027638.3. [Q9U9Y8-5]
UniGeneCel.6733.

3D structure databases

ProteinModelPortalQ9U9Y8.
SMRQ9U9Y8. Positions 214-595.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid41974. 64 interactions.
DIPDIP-25624N.
IntActQ9U9Y8. 23 interactions.
MINTMINT-1045592.
STRING6239.W06F12.1a.

Proteomic databases

PaxDbQ9U9Y8.
PRIDEQ9U9Y8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaW06F12.1a; W06F12.1a; WBGene00003048. [Q9U9Y8-1]
GeneID176808.
KEGGcel:CELE_W06F12.1.
UCSCW06F12.1d. c. elegans.

Organism-specific databases

CTD176808.
WormBaseW06F12.1a; CE29476; WBGene00003048; lit-1.
W06F12.1b; CE29477; WBGene00003048; lit-1.
W06F12.1c; CE29478; WBGene00003048; lit-1.
W06F12.1d; CE37160; WBGene00003048; lit-1.
W06F12.1e; CE37161; WBGene00003048; lit-1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00730000110881.
InParanoidQ9U9Y8.
KOK04468.
OMAQHRYLEE.
OrthoDBEOG72RMZ3.
PhylomeDBQ9U9Y8.

Enzyme and pathway databases

SignaLinkQ9U9Y8.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio894088.
PROQ9U9Y8.

Entry information

Entry nameNLK_CAEEL
AccessionPrimary (citable) accession number: Q9U9Y8
Secondary accession number(s): O62395 expand/collapse secondary AC list , Q69YW9, Q8WQB7, Q9U343, Q9UA07, Q9Y198
Entry history
Integrated into UniProtKB/Swiss-Prot: May 5, 2009
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Caenorhabditis elegans

Caenorhabditis elegans: entries, gene names and cross-references to WormBase