Serine/threonine kinase NLK - Caenorhabditis elegans

Preferred order of sections

Names and origin

Protein names

Recommended 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

Organism

Caenorhabditis elegans [Reference proteome]

Taxonomic identifier

6239 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis

Protein attributes

Sequence length	634 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Cytoplasm › cell 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 process	Wnt signaling pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: GOC Wnt receptor signaling pathway Inferred from genetic interaction Ref.1. Source: WormBase asymmetric cell division Inferred from mutant phenotype Ref.2 Ref.4. Source: WormBase asymmetric protein localization involved in cell fate determination Inferred from mutant phenotype Ref.2 PubMed 15020416. Source: WormBase 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
Cellular_component	cell cortex Inferred from direct assay PubMed 17276345. Source: WormBase nucleus Inferred from direct assay Ref.7 PubMed 17276345 PubMed 20624379. Source: WormBase
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from sequence or structural similarity Ref.1. Source: WormBase
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct
gmeb-4	Q18171	3	EBI-318513,EBI-320157
R02D5.1	Q21636	5	EBI-318513,EBI-329142
wrm-1	Q10953	8	EBI-318513,EBI-2530558
ZK1055.7	O76449	3	EBI-318513,EBI-313622

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 634

634

Serine/threonine kinase NLK

PRO_0000372802

Regions

Domain

240 – 531

292

Protein kinase

Nucleotide binding

246 – 254

9

ATP By similarity

Compositional bias

80 – 216

137

Gln-rich

Compositional bias

102 – 188

87

His-rich

Sites

Active site

366

1

Proton acceptor By similarity

Binding site

269

1

ATP By similarity

Natural variations

Alternative sequence

1 – 197

197

Missing in isoform c. Ref.3

VSP_052845

Alternative sequence

1 – 180

180

Missing in isoform e. Ref.2

VSP_052846

Alternative sequence

1 – 172

172

Missing in isoform b. Ref.2

VSP_052847

Alternative sequence

1 – 33

33

Missing in isoform d. Ref.3

VSP_052848

Alternative sequence

34 – 51

18

KDTED…DPEIP → MGRNQEGQFNGAGNSESA in isoform d. Ref.3

VSP_052849

Alternative sequence

173 – 178

6

HHQQLV → MRDMIY in isoform b. Ref.2

VSP_052850

Alternative sequence

198 – 216

19

YEKNQ…PTQPQ → MILIAIIESFIEYLRKIVW in isoform c. Ref.3

VSP_052851

Experimental info

Mutagenesis

357

1

L → 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

Mutagenesis

400

1

T → A: No detectable kinase activity. Ref.5

Mutagenesis

402

1

E → K in t1534; reduced body-wall muscle. Ref.4

Mutagenesis

541

1

C → 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		Length	Mass (Da)
Isoform a [UniParc]. Last modified May 1, 2000. Version 1. Checksum: A9F2EA7E3E2CE7F5 Show »	FASTA	634	71,777
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 »	FASTA	462	52,603
10 20 30 40 50 60 MRDMIYGEMA LVSHTHPAAV GSTTCYEKNQ QKQQQVQQIP TQPQVAHVSS NAILAAAQPF 70 80 90 100 110 120 YPPPVQDSQP DRPIGYGAFG VVWSVTDPRS GKRVALKKMP NVFQNLASCK RVFREIKMLS 130 140 150 160 170 180 SFRHDNVLSL LDILQPANPS FFQELYVLTE LMQSDLHKII VSPQALTPDH VKVFVYQILR 190 200 210 220 230 240 GLKYLHTANI LHRDIKPGNL LVNSNCILKI CDFGLARTWD QRDRLNMTHE VVTQYYRAPE 250 260 270 280 290 300 LLMGARRYTG AVDIWSVGCI FAELLQRKIL FQAAGPIEQL QMIIDLLGTP SQEAMKYACE 310 320 330 340 350 360 GAKNHVLRAG LRAPDTQRLY KIASPDDKNH EAVDLLQKLL HFDPDKRISV EEALQHRYLE 370 380 390 400 410 420 EGRLRFHSCM CSCCYTKPNM PSRLFAQDLD PRHESPFDPK WEKDMSRLSM FELREKMYQF 430 440 450 460 VMDRPALYGV ALCINPQSAA YKNFASSSVA QASELPPSPQ AW « Hide
Isoform c [UniParc]. Checksum: 21C9CF88553F20D3 Show »	FASTA	437	49,951
10 20 30 40 50 60 MILIAIIESF IEYLRKIVWV AHVSSNAILA AAQPFYPPPV QDSQPDRPIG YGAFGVVWSV 70 80 90 100 110 120 TDPRSGKRVA LKKMPNVFQN LASCKRVFRE IKMLSSFRHD NVLSLLDILQ PANPSFFQEL 130 140 150 160 170 180 YVLTELMQSD LHKIIVSPQA LTPDHVKVFV YQILRGLKYL HTANILHRDI KPGNLLVNSN 190 200 210 220 230 240 CILKICDFGL ARTWDQRDRL NMTHEVVTQY YRAPELLMGA RRYTGAVDIW SVGCIFAELL 250 260 270 280 290 300 QRKILFQAAG PIEQLQMIID LLGTPSQEAM KYACEGAKNH VLRAGLRAPD TQRLYKIASP 310 320 330 340 350 360 DDKNHEAVDL LQKLLHFDPD KRISVEEALQ HRYLEEGRLR FHSCMCSCCY TKPNMPSRLF 370 380 390 400 410 420 AQDLDPRHES PFDPKWEKDM SRLSMFELRE KMYQFVMDRP ALYGVALCIN PQSAAYKNFA 430 SSSVAQASEL PPSPQAW « Hide
Isoform d [UniParc]. Checksum: 311EED6DED5AA170 Show »	FASTA	601	67,652
10 20 30 40 50 60 MGRNQEGQFN GAGNSESAGS SSSSGCSSSS TELYDLAAAH AALISRQQQI LSQAIPIIPE 70 80 90 100 110 120 HQLAAVAAHH QHHQQLHPSV QYQLVAAATH HNHHQPQAAQ PHYSAVVPRS DVIQQPPHFA 130 140 150 160 170 180 LHHHLQNLVQ QQQQQQAHHH HQQLVGEMAL VSHTHPAAVG STTCYEKNQQ KQQQVQQIPT 190 200 210 220 230 240 QPQVAHVSSN AILAAAQPFY PPPVQDSQPD RPIGYGAFGV VWSVTDPRSG KRVALKKMPN 250 260 270 280 290 300 VFQNLASCKR VFREIKMLSS FRHDNVLSLL DILQPANPSF FQELYVLTEL MQSDLHKIIV 310 320 330 340 350 360 SPQALTPDHV KVFVYQILRG LKYLHTANIL HRDIKPGNLL VNSNCILKIC DFGLARTWDQ 370 380 390 400 410 420 RDRLNMTHEV VTQYYRAPEL LMGARRYTGA VDIWSVGCIF AELLQRKILF QAAGPIEQLQ 430 440 450 460 470 480 MIIDLLGTPS QEAMKYACEG AKNHVLRAGL RAPDTQRLYK IASPDDKNHE AVDLLQKLLH 490 500 510 520 530 540 FDPDKRISVE EALQHRYLEE GRLRFHSCMC SCCYTKPNMP SRLFAQDLDP RHESPFDPKW 550 560 570 580 590 600 EKDMSRLSMF ELREKMYQFV MDRPALYGVA LCINPQSAAY KNFASSSVAQ ASELPPSPQA W « Hide
Isoform e [UniParc]. Checksum: D951AB8C0CAC9394 Show »	FASTA	454	51,607
10 20 30 40 50 60 MALVSHTHPA AVGSTTCYEK NQQKQQQVQQ IPTQPQVAHV SSNAILAAAQ PFYPPPVQDS 70 80 90 100 110 120 QPDRPIGYGA FGVVWSVTDP RSGKRVALKK MPNVFQNLAS CKRVFREIKM LSSFRHDNVL 130 140 150 160 170 180 SLLDILQPAN PSFFQELYVL TELMQSDLHK IIVSPQALTP DHVKVFVYQI LRGLKYLHTA 190 200 210 220 230 240 NILHRDIKPG NLLVNSNCIL KICDFGLART WDQRDRLNMT HEVVTQYYRA PELLMGARRY 250 260 270 280 290 300 TGAVDIWSVG CIFAELLQRK ILFQAAGPIE QLQMIIDLLG TPSQEAMKYA CEGAKNHVLR 310 320 330 340 350 360 AGLRAPDTQR LYKIASPDDK NHEAVDLLQK LLHFDPDKRI SVEEALQHRY LEEGRLRFHS 370 380 390 400 410 420 CMCSCCYTKP NMPSRLFAQD LDPRHESPFD PKWEKDMSRL SMFELREKMY QFVMDRPALY 430 440 450 GVALCINPQS AAYKNFASSS VAQASELPPS PQAW « Hide

References

	« Hide 'large scale' referencesShow '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.
PIR	T26240.
RefSeq	NP_001022805.1. NM_001027634.2. NP_001022806.1. NM_001027635.2. NP_001022807.1. NM_001027636.2. NP_001022808.1. NM_001027637.3. NP_001022809.1. NM_001027638.3.
UniGene	Cel.6733.
3D structure databases
HSSP	HSSP built from PDB template 1YWR based on UniProtKB P47811.
ProteinModelPortal	Q9U9Y8.
SMR	Q9U9Y8. Positions 214-533.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-25624N.
IntAct	Q9U9Y8. 23 interactions.
MINT	MINT-1045592.
STRING	6239.W06F12.1a.
Proteomic databases
PaxDb	Q9U9Y8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	W06F12.1a; W06F12.1a; W06F12.1.
GeneID	176808.
KEGG	cel:CELE_W06F12.1.
UCSC	W06F12.1d. c. elegans.
Organism-specific databases
CTD	176808.
WormBase	W06F12.1a; 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
eggNOG	COG0515.
GeneTree	ENSGT00550000074298.
InParanoid	Q9U9Y8.
KO	K04468.
OMA	NHATHEA.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR003527. MAP_kinase_CS. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS01351. MAPK. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	894088.

Entry information

Entry name

NLK_CAEEL

Accession

Primary (citable) accession number: Q9U9Y8
Secondary accession number(s): O62395

Q9Y198

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 5, 2009
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Caenorhabditis annotation project

Relevant documents

Caenorhabditis elegans

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

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Family and domain databases

Other

Entry information

Relevant documents