Reviewed, UniProtKB/Swiss-Prot O01700 (DLK1_CAEEL)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase kinase kinase dlk-1
    EC=2.7.11.25
Alternative name(s):
    Death-associated protein kinase-like kinase
    DAP kinase-like kinase

Gene names

Name:	dlk-1
ORF Names:	F33E2.2

Organism

Caenorhabditis elegans [Complete proteome]

Taxonomic identifier

6239 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	928 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of a MAP kinase pathway that functions presynaptically to regulate synaptic architecture and presynaptic differentiation. Phosphorylates and activates mkk-4. Ref.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB O43283
Cofactor	Magnesium By similarity. UniProtKB O43283
Subcellular location	Cell junction › synapse Ref.2 Ref.4.
Tissue specificity	Expressed in neurons and pharynx. Ref.2
Post-translational modification	Ubiquitinated by rpm-1. Negatively regulated by ubiquitination by fsn-1 bound rpm-1, followed by degradation. Ref.2
Disruption phenotype	Worms overcome the lack of synaptogenesis caused by of the loss of rpm-1 ubiquitin ligase activity. Ref.3
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell junction Synapse
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	nematode larval development Inferred from mutant phenotype. Source: WormBase protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW synapse Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
gei-16	Q22534	1	EBI-327135,EBI-327642
mig-5	Q22227	1	EBI-327135,EBI-316403

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform a Ref.1 (identifier: O01700-1)

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.

Note: No experimental confirmation available.

Isoform b Ref.1 (identifier: O01700-2)

The sequence of this isoform differs from the canonical sequence as follows:
     674-681: GVISCSSP → A

Note: No experimental confirmation available.

Isoform c Ref.1 (identifier: O01700-3)

The sequence of this isoform differs from the canonical sequence as follows:
     567-577: KILRNDAIRHS → SEYIFPEKLNI
     578-928: Missing.

Note: No experimental confirmation available.

Isoform d Ref.1 (identifier: O01700-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 928	928	Mitogen-activated protein kinase kinase kinase dlk-1		PRO_0000353198
Regions
	Domain	135 – 377	243	Protein kinase
	Nucleotide binding	141 – 149	9	ATP By similarity UniProtKB O43283
	Compositional bias	530 – 552	23	Ser-rich
Sites
	Active site	246	1	Proton acceptor By similarity UniProtKB O43283
	Binding site	162	1	ATP By similarity UniProtKB O43283
Natural variations
	Alternative sequence	1 – 73	73	Missing in isoform d. Ref.1		VSP_052964
	Alternative sequence	567 – 577	11	KILRNDAIRHS → SEYIFPEKLNI in isoform c. Ref.1		VSP_052965
	Alternative sequence	578 – 928	351	Missing in isoform c. Ref.1		VSP_052966
	Alternative sequence	674 – 681	8	GVISCSSP → A in isoform b. Ref.1		VSP_052967

Sequences

	Sequence		Length	Mass (Da)
	Isoform a [UniParc]. Last modified July 5, 2004. Version 4. Checksum: EE071636ACAADBD4	FASTA	928	103,483
	10 20 30 40 50 60 MTSTTMVTTL DLVTPTSEEQ PGPAPESSDF STVVLSPDGS ELVTQSAPNT PIQHREQANA 70 80 90 100 110 120 EFGQKEGSPD PKNMVAATGN ASKPSLNSFY ADGLGQLRNG LFSCFQPVFG YFGTKTTVEI 130 140 150 160 170 180 EKSEDELWEI PFDAISELEW LGSGSQGAVF RGQLENRTVA VKKVNQLKET EIKHLRHLRH 190 200 210 220 230 240 QNIIEFLGVC SKSPCYCIVM EYCSKGQLCT VLKSRNTITR ELFAQWVKEI ADGMHYLHQN 250 260 270 280 290 300 KVIHRDLKSP NILISAEDSI KICDFGTSHM QKKMDSTMMS FCGTVSWMAP EMIKKQPCNE 310 320 330 340 350 360 KVDVYSFGVV LWEMLTRETP YANIAQMAII FGVGTNILSL PMPEEAPKGL VLLIKQCLSQ 370 380 390 400 410 420 KGRNRPSFSH IRQHWEIFKP ELFEMTEEEW QLAWDSYREF AKCIQYPSTV TRDHGGPKSA 430 440 450 460 470 480 FAMEEEIQRK RHEQLNHIKD IRNMYEMKLK RTNKMYDKLQ GCFTELKLKE SELAEWEKDL 490 500 510 520 530 540 TEREQWHNQN SPKAVAAPRA QLRGYPNEGY DDMSSDEDVQ PCRGSPYRCS NTSSSSGVQS 550 560 570 580 590 600 SPFSRQSSSR SSAGQQTRRS EGANPPKILR NDAIRHSGSY WETLGGARGS PARDSGFSQD 610 620 630 640 650 660 SGMWSAGAGS CTAINGGGQQ VCYSQTLYRN GDGRWSDGRI ASRRRVSTSV NKSTAVPGQP 670 680 690 700 710 720 VFFTRDSPSR VPHGVISCSS PRSSSKLNRS SYPSRNAPHQ LEDGCCCAHA RAPRAKSIAV 730 740 750 760 770 780 PMTSSSRARS PTPYDNDFEN AESFVDPESP KNLKNLEKIV NLPESTSYDE ALCNSDVTMN 790 800 810 820 830 840 PIYTSPITTY SNPCHVELVD EENANDVDLT SSMDSRRSRS DDADVESSEE DEGNGNNILN 850 860 870 880 890 900 TSMESEDLRY RIDTSQSTMM SSLERSLEIG ATRSDGLSDN EMRVQAVKMS IKTHRRTGSN 910 920 PQALIHQCID EYTTSATDDS DDAGAVRI
	Isoform b. Checksum: 302577E5324813B4	FASTA	921	102,824
	10 20 30 40 50 60 MTSTTMVTTL DLVTPTSEEQ PGPAPESSDF STVVLSPDGS ELVTQSAPNT PIQHREQANA 70 80 90 100 110 120 EFGQKEGSPD PKNMVAATGN ASKPSLNSFY ADGLGQLRNG LFSCFQPVFG YFGTKTTVEI 130 140 150 160 170 180 EKSEDELWEI PFDAISELEW LGSGSQGAVF RGQLENRTVA VKKVNQLKET EIKHLRHLRH 190 200 210 220 230 240 QNIIEFLGVC SKSPCYCIVM EYCSKGQLCT VLKSRNTITR ELFAQWVKEI ADGMHYLHQN 250 260 270 280 290 300 KVIHRDLKSP NILISAEDSI KICDFGTSHM QKKMDSTMMS FCGTVSWMAP EMIKKQPCNE 310 320 330 340 350 360 KVDVYSFGVV LWEMLTRETP YANIAQMAII FGVGTNILSL PMPEEAPKGL VLLIKQCLSQ 370 380 390 400 410 420 KGRNRPSFSH IRQHWEIFKP ELFEMTEEEW QLAWDSYREF AKCIQYPSTV TRDHGGPKSA 430 440 450 460 470 480 FAMEEEIQRK RHEQLNHIKD IRNMYEMKLK RTNKMYDKLQ GCFTELKLKE SELAEWEKDL 490 500 510 520 530 540 TEREQWHNQN SPKAVAAPRA QLRGYPNEGY DDMSSDEDVQ PCRGSPYRCS NTSSSSGVQS 550 560 570 580 590 600 SPFSRQSSSR SSAGQQTRRS EGANPPKILR NDAIRHSGSY WETLGGARGS PARDSGFSQD 610 620 630 640 650 660 SGMWSAGAGS CTAINGGGQQ VCYSQTLYRN GDGRWSDGRI ASRRRVSTSV NKSTAVPGQP 670 680 690 700 710 720 VFFTRDSPSR VPHARSSSKL NRSSYPSRNA PHQLEDGCCC AHARAPRAKS IAVPMTSSSR 730 740 750 760 770 780 ARSPTPYDND FENAESFVDP ESPKNLKNLE KIVNLPESTS YDEALCNSDV TMNPIYTSPI 790 800 810 820 830 840 TTYSNPCHVE LVDEENANDV DLTSSMDSRR SRSDDADVES SEEDEGNGNN ILNTSMESED 850 860 870 880 890 900 LRYRIDTSQS TMMSSLERSL EIGATRSDGL SDNEMRVQAV KMSIKTHRRT GSNPQALIHQ 910 920 CIDEYTTSAT DDSDDAGAVR I
	Isoform c. Checksum: BEDDDCCA10DB525A	FASTA	577	65,401
	10 20 30 40 50 60 MTSTTMVTTL DLVTPTSEEQ PGPAPESSDF STVVLSPDGS ELVTQSAPNT PIQHREQANA 70 80 90 100 110 120 EFGQKEGSPD PKNMVAATGN ASKPSLNSFY ADGLGQLRNG LFSCFQPVFG YFGTKTTVEI 130 140 150 160 170 180 EKSEDELWEI PFDAISELEW LGSGSQGAVF RGQLENRTVA VKKVNQLKET EIKHLRHLRH 190 200 210 220 230 240 QNIIEFLGVC SKSPCYCIVM EYCSKGQLCT VLKSRNTITR ELFAQWVKEI ADGMHYLHQN 250 260 270 280 290 300 KVIHRDLKSP NILISAEDSI KICDFGTSHM QKKMDSTMMS FCGTVSWMAP EMIKKQPCNE 310 320 330 340 350 360 KVDVYSFGVV LWEMLTRETP YANIAQMAII FGVGTNILSL PMPEEAPKGL VLLIKQCLSQ 370 380 390 400 410 420 KGRNRPSFSH IRQHWEIFKP ELFEMTEEEW QLAWDSYREF AKCIQYPSTV TRDHGGPKSA 430 440 450 460 470 480 FAMEEEIQRK RHEQLNHIKD IRNMYEMKLK RTNKMYDKLQ GCFTELKLKE SELAEWEKDL 490 500 510 520 530 540 TEREQWHNQN SPKAVAAPRA QLRGYPNEGY DDMSSDEDVQ PCRGSPYRCS NTSSSSGVQS 550 560 570 SPFSRQSSSR SSAGQQTRRS EGANPPSEYI FPEKLNI
	Isoform d. Checksum: F44DD2538CB7D95A	FASTA	855	95,787
	10 20 30 40 50 60 MVAATGNASK PSLNSFYADG LGQLRNGLFS CFQPVFGYFG TKTTVEIEKS EDELWEIPFD 70 80 90 100 110 120 AISELEWLGS GSQGAVFRGQ LENRTVAVKK VNQLKETEIK HLRHLRHQNI IEFLGVCSKS 130 140 150 160 170 180 PCYCIVMEYC SKGQLCTVLK SRNTITRELF AQWVKEIADG MHYLHQNKVI HRDLKSPNIL 190 200 210 220 230 240 ISAEDSIKIC DFGTSHMQKK MDSTMMSFCG TVSWMAPEMI KKQPCNEKVD VYSFGVVLWE 250 260 270 280 290 300 MLTRETPYAN IAQMAIIFGV GTNILSLPMP EEAPKGLVLL IKQCLSQKGR NRPSFSHIRQ 310 320 330 340 350 360 HWEIFKPELF EMTEEEWQLA WDSYREFAKC IQYPSTVTRD HGGPKSAFAM EEEIQRKRHE 370 380 390 400 410 420 QLNHIKDIRN MYEMKLKRTN KMYDKLQGCF TELKLKESEL AEWEKDLTER EQWHNQNSPK 430 440 450 460 470 480 AVAAPRAQLR GYPNEGYDDM SSDEDVQPCR GSPYRCSNTS SSSGVQSSPF SRQSSSRSSA 490 500 510 520 530 540 GQQTRRSEGA NPPKILRNDA IRHSGSYWET LGGARGSPAR DSGFSQDSGM WSAGAGSCTA 550 560 570 580 590 600 INGGGQQVCY SQTLYRNGDG RWSDGRIASR RRVSTSVNKS TAVPGQPVFF TRDSPSRVPH 610 620 630 640 650 660 GVISCSSPRS SSKLNRSSYP SRNAPHQLED GCCCAHARAP RAKSIAVPMT SSSRARSPTP 670 680 690 700 710 720 YDNDFENAES FVDPESPKNL KNLEKIVNLP ESTSYDEALC NSDVTMNPIY TSPITTYSNP 730 740 750 760 770 780 CHVELVDEEN ANDVDLTSSM DSRRSRSDDA DVESSEEDEG NGNNILNTSM ESEDLRYRID 790 800 810 820 830 840 TSQSTMMSSL ERSLEIGATR SDGLSDNEMR VQAVKMSIKT HRRTGSNPQA LIHQCIDEYT 850 TSATDDSDDA GAVRI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genome sequence of the nematode C. elegans: a platform for investigating biology." The C. elegans sequencing consortium Science 282:2012-2018(1998) [PubMed: 9851916] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Bristol N2.
[2]	"Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development." Nakata K., Abrams B., Grill B., Goncharov A., Huang X., Chisholm A.D., Jin Y. Cell 120:407-420(2005) [PubMed: 15707898] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, UBIQUITINATION.
[3]	"C. elegans RPM-1 regulates axon termination and synaptogenesis through the Rab GEF GLO-4 and the Rab GTPase GLO-1." Grill B., Bienvenut W.V., Brown H.M., Ackley B.D., Quadroni M., Jin Y. Neuron 55:587-601(2007) [PubMed: 17698012] [Abstract] Cited for: ENZYME REGULATION, DISRUPTION PHENOTYPE.
[4]	"Cellular and molecular determinants targeting the Caenorhabditis elegans PHR protein RPM-1 to perisynaptic regions." Abrams B., Grill B., Huang X., Jin Y. Dev. Dyn. 237:630-639(2008) [PubMed: 18224716] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL022593, Z84574 Genomic DNA. Translation: CAA18635.3. AL022593, Z84574 Genomic DNA. Translation: CAE54889.1. Z84574, AL022593 Genomic DNA. Translation: CAB06544.3. Z84574 Genomic DNA. Translation: CAE54890.1. Z84574, AL022593 Genomic DNA. Translation: CAE54891.1. AL022593, Z84574 Genomic DNA. Translation: CAQ76463.1. Z84574, AL022593 Genomic DNA. Translation: CAQ76474.1.
PIR	B87950. T20082.
RefSeq	NP_001021443.1. NP_001021444.1. NP_001021445.1. NP_001129769.1.
UniGene	Cel.24063
3D structure databases
HSSP	HSSP built from PDB template 1UWJ based on UniProtKB P15056.
SMR	O01700. Positions 60-267, 94-375.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-26475N.
IntAct	O01700. 2 interactions.
Proteomic databases
PRIDE	O01700.
Genome annotation databases
Ensembl	F33E2.2a; F33E2.2a; F33E2.2; Caenorhabditis elegans. [Genome view]
GeneID	173128.
KEGG	cel:F33E2.2.
UCSC	F33E2.2b. c. elegans.
Organism-specific databases
CTD	173128.
WormBase	WBGene00001008. dlk-1.
WormPep	F33E2.2a. CE36153. [WorfDB] F33E2.2b. CE36154. [WorfDB] F33E2.2c. CE36155. [WorfDB] F33E2.2d. CE23702. [WorfDB]
Phylogenomic databases
eggNOG	meNOG04663.
HOGENOM	HBG378601.
InParanoid	O01700.
OMA	SAFAMEE.
PhylomeDB	O01700.
Gene expression databases
ArrayExpress	O01700.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	878375.

Entry information

Entry name

DLK1_CAEEL

Accession

Primary (citable) accession number: O01700
Secondary accession number(s): B3KYB4, Q7JKE7, Q7JKE9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 4, 2008
Last sequence update:	July 5, 2004
Last modified:	January 19, 2010
This is version 90 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Caenorhabditis annotation project