O45818 (DKF2_CAEEL) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase dkf-2
EC=2.7.11.13

Alternative name(s):
D kinase family-2

Gene names

Name:	dkf-2
ORF Names:	T25E12.4

Organism

Caenorhabditis elegans [Reference proteome]

Taxonomic identifier

6239 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis

Protein attributes

Sequence length	1070 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Acts in the intestine to regulate both innate immunity by promoting activation of PMK-1 and also stress response and life span by acting as an upstream, negative regulator of the daf-16 transcription factor. Ref.1 Ref.3
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.3
Cofactor	Magnesium. Ref.1 Ref.3
Enzyme regulation	Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds phorbol ester with low affinity. Phorbol-ester/DAG-type domain 2 binds phorbol ester with high affinity and targets the kinase to the cell periphery, enabling phosphorylation and activation by co-localized tpa-1. Both domains 1 and 2 appear to bind DAG with equal affinity so may contribute equally to translocation and activation. Ref.1 Ref.3
Subcellular location	Cytoplasm. Membrane. Note: Translocation to the cell membrane is required for kinase activation. Ref.1
Tissue specificity	Expressed in the late embryo, all larval stages, and adult in the intestine and in cells positioned near the posterior bulb of the pharynx. Ref.1 Ref.3
Post-translational modification	Phosphorylation on Ser-925 by tpa-1 is the dominant regulator of catalysis, phosphorylation on Ser-929 by tpa-1 has a lesser effect. Prolonged phosphorylation results in ubiquitination and degradation.
Disruption phenotype	Increase in adult life span. Increased levels of daf-16 translocate into the nucleus in response to heat stress. Hypersensitive to killing by bacteria. Ref.1 Ref.3
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily. Contains 1 PH domain. Contains 2 phorbol-ester/DAG-type zinc fingers. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Immunity Innate immunity
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to Gram-negative bacterium Inferred from mutant phenotype Ref.3. Source: WormBase defense response to Gram-positive bacterium Inferred from mutant phenotype Ref.3. Source: WormBase innate immune response Inferred from electronic annotation. Source: UniProtKB-KW intracellular protein kinase cascade Inferred from mutant phenotype Ref.3. Source: WormBase peptidyl-serine phosphorylation Inferred from direct assay Ref.1. Source: WormBase positive regulation of innate immune response Inferred from mutant phenotype Ref.3. Source: WormBase
Cellular_component	cytoplasm Inferred from direct assay Ref.3. Source: WormBase membrane Inferred from direct assay Ref.3. Source: WormBase
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro protein kinase C activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: WormBase
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform a Ref.2 (identifier: O45818-1)

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.2 (identifier: O45818-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-533: Missing.
     534-701: LGSQADDGAS...RTGVCVYFIS → MILNILRLPH...TKRNGWSGDA
     750-755: ETGHLG → KTRPPY
     756-1070: Missing.

Note: No experimental confirmation available.

Isoform c Ref.2 (identifier: O45818-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-197: Missing.
     198-310: DHSDDEVWTP...GTLVEVVIGS → MTDRHPESKT...GRRTYIVIGA

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1070	1070	Serine/threonine-protein kinase dkf-2		PRO_0000385354
Regions
	Domain	624 – 726	103	PH
	Domain	770 – 1026	257	Protein kinase
	Zinc finger	321 – 371	51	Phorbol-ester/DAG-type 1
	Zinc finger	473 – 523	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	776 – 784	9	ATP By similarity UniProtKB P28523
	Compositional bias	217 – 220	4	Poly-Ser
Sites
	Active site	893	1	Proton acceptor By similarity UniProtKB P28523
	Binding site	799	1	ATP By similarity UniProtKB Q9XUJ7
Amino acid modifications
	Modified residue	925	1	Phosphoserine Ref.1
	Modified residue	929	1	Phosphoserine Ref.1
Natural variations
	Alternative sequence	1 – 533	533	Missing in isoform b. Ref.2		VSP_053150
	Alternative sequence	1 – 197	197	Missing in isoform c. Ref.2		VSP_053151
	Alternative sequence	198 – 310	113	DHSDD…VVIGS → MTDRHPESKTSTSSNSPSIS SSTSSSLKMMKKQQRAKSCA TPNSGRKSPRLEVKAMTISS SPTAQRFVFQQQASFQVLED FENLKVYEEKEKQRKKEKAP DVGRRTYIVIGA in isoform c. Ref.2		VSP_053152
	Alternative sequence	534 – 701	168	LGSQA…VYFIS → MILNILRLPHADEPTTSQSV QDYPLVHFSPRRHQKFRTII SVGDSDVIKDSSLTDEELYN IIHASPIARKSSTVSSTDSG YLGSSGASSSCVRSREGSTV SSTITVERTRRGGSTASSEP DSVADSEGAGSYSSFSSIAS TASRMLGRAADCLVLMTKRN GWSGDA in isoform b. Ref.2		VSP_053153
	Alternative sequence	750 – 755	6	ETGHLG → KTRPPY in isoform b. Ref.2		VSP_053154
	Alternative sequence	756 – 1070	315	Missing in isoform b. Ref.2		VSP_053155
Experimental info
	Mutagenesis	332	1	P → G: Loss of sensitivity to phorbol ester or DAG stimulation of kinase activity; when associated with G-484. No effect on sensitivity to phorbol ester, loss of DAG stimulation of kinase activity. Ref.1
	Mutagenesis	484	1	P → G: Loss of sensitivity to phorbol ester or DAG stimulation of kinase activity. Loss of sensitivity to phorbol ester or DAG stimulation of kinase activity; when associated with G-332. Ref.1
	Mutagenesis	643	1	K → A: Small increase in basal kinase activity, no effect on sensitivity to phorbol ester stimulation of kinase activity. Ref.1
	Mutagenesis	925	1	S → A: Loss of sensitivity to phorbol ester stimulation of kinase activity. Ref.1 Ref.3
	Mutagenesis	925	1	S → D: High basal kinase activity, loss of phorbol ester-stimulated kinase activity and ability to phosphorylate pmk-1; when associated with D-929. Ref.1 Ref.3
	Mutagenesis	929	1	S → A: Moderate loss of sensitivity to phorbol ester stimulation of kinase activity. Ref.1 Ref.3
	Mutagenesis	929	1	S → D: High basal kinase activity, loss of phorbol ester-stimulated kinase activity and ability to phosphorylate pmk-1; when associated with D-925. Ref.1 Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform a [UniParc]. Last modified May 20, 2008. Version 4. Checksum: 6A4891629C021973	FASTA	1,070	120,583
	10 20 30 40 50 60 MDANDYPRLY YTSMPSSSTS MVTTTRFSTS FSPSIPCHRQ ENFRRHSTSA LAKRNGSESE 70 80 90 100 110 120 KSAEIRENPD EIEVSRVSGR DSSLAFYTTA HETSSMLSRD SRDETLTPNE HIHQASSRRV 130 140 150 160 170 180 SANDSVFEDG YVDFVDEPRE HGSRRKSFEK FTDRNGEEKE GRVFELSTPQ PTREAAPGAH 190 200 210 220 230 240 QFQLPTLLVT STPTTVFDHS DDEVWTPYRP PPNREYSSSS EPMMGDLTFR LQSGIHKKSI 250 260 270 280 290 300 AVEGTEIALR DLRNEALQFI KEIYPEKGCS SLEDYILLYK HDLRSINILQ LITTSSDVTD 310 320 330 340 350 360 GTLVEVVIGS CPQNERIVVH PHTLFVHSYK VPTFCDFCGE LLFGLVKQGL KCFGCGLNYH 370 380 390 400 410 420 KRCASKIPNN CNGSKQRRPS AIPLSPSNSN ILNLNERRHS RRESCLEALD AARPSSTLGG 430 440 450 460 470 480 AATPNIFITS DDCGDAVGGN YLQMPRKDRS CSWSGRPLWM EIAEATRVKL QVPHTFQVHS 490 500 510 520 530 540 YKLPTVCQHC KKLLKGLIRQ GMQCRDCKYN CHKKCSEHVA KDCSGNTKAS QFFLGSQADD 550 560 570 580 590 600 GASEDRDDDL SLRSGSGAHK KAQNTPSAPL QGSEGSGSPG PVVSFAANAL SNMPDDDVIS 610 620 630 640 650 660 SESANIPLMR VVMSKKQTKR KNNKLLKEGW IVHYTDQQNM RKKHYWRLDT KGITMYQDEN 670 680 690 700 710 720 TTRYYKEIPL NEILNVSMSP PDKTADYLFE IRTGVCVYFI SGSPSDEKGS SLDAQSWTTA 730 740 750 760 770 780 IQSALMPVTP QSSVVGGKRI DKLKVPTEGE TGHLGAKIQT EHEFSQLYQI FAEEVLGSGQ 790 800 810 820 830 840 FGTVYGGIHR RNGQHVAVKL IDKLKFPPNK EDLLRAEVQI LEKVDHPGVV HFMQMLETTD 850 860 870 880 890 900 RIFVVMEKLK GDMLEMILSS EKGRLSERTT QFLVAQILEA LRYLHHLNIV HCDLKPENIL 910 920 930 940 950 960 LNSNSDFPQV KLCDFGFARI IGEKSFRRSV VGTPAYLAPE VLRNKGFNRS LDMWSVGVIV 970 980 990 1000 1010 1020 YVSLSGTFPF NEDEDINDQI QNAEFMYPPT PWKEISENAI EFINGLLQVK MSKRYTVTKA 1030 1040 1050 1060 1070 QSQIWMQNYT LWSDLRVLEK AVGQRFVTHE SDDVRWQAYE KEHNVTPVYV
	Isoform b [UniParc]. Checksum: B28D89D665CFEFC8	FASTA	220	23,291
	10 20 30 40 50 60 MILNILRLPH ADEPTTSQSV QDYPLVHFSP RRHQKFRTII SVGDSDVIKD SSLTDEELYN 70 80 90 100 110 120 IIHASPIARK SSTVSSTDSG YLGSSGASSS CVRSREGSTV SSTITVERTR RGGSTASSEP 130 140 150 160 170 180 DSVADSEGAG SYSSFSSIAS TASRMLGRAA DCLVLMTKRN GWSGDAGSPS DEKGSSLDAQ 190 200 210 220 SWTTAIQSAL MPVTPQSSVV GGKRIDKLKV PTEGKTRPPY
	Isoform c [UniParc]. Checksum: 12B2D7AFD5611AEF	FASTA	872	98,139
	10 20 30 40 50 60 MTDRHPESKT STSSNSPSIS SSTSSSLKMM KKQQRAKSCA TPNSGRKSPR LEVKAMTISS 70 80 90 100 110 120 SPTAQRFVFQ QQASFQVLED FENLKVYEEK EKQRKKEKAP DVGRRTYIVI GACPQNERIV 130 140 150 160 170 180 VHPHTLFVHS YKVPTFCDFC GELLFGLVKQ GLKCFGCGLN YHKRCASKIP NNCNGSKQRR 190 200 210 220 230 240 PSAIPLSPSN SNILNLNERR HSRRESCLEA LDAARPSSTL GGAATPNIFI TSDDCGDAVG 250 260 270 280 290 300 GNYLQMPRKD RSCSWSGRPL WMEIAEATRV KLQVPHTFQV HSYKLPTVCQ HCKKLLKGLI 310 320 330 340 350 360 RQGMQCRDCK YNCHKKCSEH VAKDCSGNTK ASQFFLGSQA DDGASEDRDD DLSLRSGSGA 370 380 390 400 410 420 HKKAQNTPSA PLQGSEGSGS PGPVVSFAAN ALSNMPDDDV ISSESANIPL MRVVMSKKQT 430 440 450 460 470 480 KRKNNKLLKE GWIVHYTDQQ NMRKKHYWRL DTKGITMYQD ENTTRYYKEI PLNEILNVSM 490 500 510 520 530 540 SPPDKTADYL FEIRTGVCVY FISGSPSDEK GSSLDAQSWT TAIQSALMPV TPQSSVVGGK 550 560 570 580 590 600 RIDKLKVPTE GETGHLGAKI QTEHEFSQLY QIFAEEVLGS GQFGTVYGGI HRRNGQHVAV 610 620 630 640 650 660 KLIDKLKFPP NKEDLLRAEV QILEKVDHPG VVHFMQMLET TDRIFVVMEK LKGDMLEMIL 670 680 690 700 710 720 SSEKGRLSER TTQFLVAQIL EALRYLHHLN IVHCDLKPEN ILLNSNSDFP QVKLCDFGFA 730 740 750 760 770 780 RIIGEKSFRR SVVGTPAYLA PEVLRNKGFN RSLDMWSVGV IVYVSLSGTF PFNEDEDIND 790 800 810 820 830 840 QIQNAEFMYP PTPWKEISEN AIEFINGLLQ VKMSKRYTVT KAQSQIWMQN YTLWSDLRVL 850 860 870 EKAVGQRFVT HESDDVRWQA YEKEHNVTPV YV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Properties, regulation, and in vivo functions of a novel protein kinase D: Caenorhabditis elegans DKF-2 links diacylglycerol second messenger to the regulation of stress responses and life span." Feng H., Ren M., Chen L., Rubin C.S. J. Biol. Chem. 282:31273-31288(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, MUTAGENESIS OF PRO-332; PRO-484; LYS-643; SER-925 AND SER-929, PHOSPHORYLATION AT SER-925 AND SER-929.
[2]	"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]. Strain: Bristol N2.
[3]	"Protein kinase D is an essential regulator of C. elegans innate immunity." Ren M., Feng H., Fu Y., Land M., Rubin C.S. Immunity 30:521-532(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, MUTAGENESIS OF SER-925 AND SER-929.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL021507 , AL021572, Z82052, Z92967 Genomic DNA. Translation: CAA16430.2. AL021507, AL021572, Z92967 Genomic DNA. Translation: CAQ35077.1. AL021572 , AL021507, Z82052, Z92967 Genomic DNA. Translation: CAA16519.2. AL021572, AL021507, Z92967 Genomic DNA. Translation: CAQ35060.1. Z82052 , AL021507, AL021572, Z92967 Genomic DNA. Translation: CAB04830.2. Z92967 Genomic DNA. Translation: CAB07477.1. Z92967 , AL021507, AL021572, Z82052 Genomic DNA. Translation: CAB07478.2. Z92967, AL021507, AL021572 Genomic DNA. Translation: CAQ35035.1.
RefSeq	NP_001123022.1. NM_001129550.1. NP_507239.2. NM_074838.5. NP_507240.1. NM_074839.3.
UniGene	Cel.17825.
3D structure databases
HSSP	HSSP built from PDB template 1PTQ based on UniProtKB P28867.
ProteinModelPortal	O45818.
SMR	O45818. Positions 322-371, 441-528, 625-1042.
ModBase	Search...
Protein-protein interaction databases
STRING	6239.T25E12.4a.
Proteomic databases
PaxDb	O45818.
PRIDE	O45818.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	T25E12.4a; T25E12.4a; T25E12.4.
GeneID	13217576. 180121.
KEGG	cel:CELE_T25E12.4. cel:CELE_T25E12.4a.
UCSC	T25E12.4a. c. elegans.
Organism-specific databases
CTD	180121.
WormBase	T25E12.4a; CE42484; WBGene00012019; dkf-2. T25E12.4b; CE18283; WBGene00012019; dkf-2. T25E12.4c; CE42507; WBGene00012019; dkf-2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00680000099894.
HOGENOM	HOG000015135.
InParanoid	O45818.
OMA	DERWENC.
Gene expression databases
ArrayExpress	O45818.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR020454. DAG/PE-bd. IPR011009. Kinase-like_dom. IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR015727. Protein_Kinase_C_mu-related. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
PANTHER	PTHR22968. PTHR22968. 1 hit.
Pfam	PF00130. C1_1. 2 hits. PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 2 hits. SM00233. PH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50003. PH_DOMAIN. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00479. ZF_DAG_PE_1. 2 hits. PS50081. ZF_DAG_PE_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	908162.

Entry information

Entry name

DKF2_CAEEL

Accession

Primary (citable) accession number: O45818
Secondary accession number(s): B1V8I6, O62166, O62167

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 22, 2009
Last sequence update:	May 20, 2008
Last modified:	May 1, 2013
This is version 122 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Caenorhabditis annotation project