Q9VVW5 (DUSK3_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual specificity protein phosphatase Mpk3
EC=3.1.3.16
EC=3.1.3.48

Alternative name(s):
Drosophila MKP3
Short name=DMKP3
Mitogen-activated protein kinase phosphatase 3
Short name=MAP kinase phosphatase 3
Short name=MKP-3

Gene names

Name:	Mkp3
ORF Names:	CG14080

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Negatively regulates the activity of members of the MAP kinase family in response to changes in the cellular environment. Has a specificity for the ERK family. Acts as negative regulator in a variety of developmental processes including cell differentiation and proliferation controlled by the Ras/ERK pathway. Suppresses the photoreceptor cell differentiation and wing vein formation. Required for proper oogenesis and early embryogenesis. Functions autonomously in a subset of photoreceptor progenitor cells in eye imaginal disks. Appears also to be required in surrounding non-neuronal cells for ommatidial patterning and photoreceptor differentiation. Plays a role in the maintenance of epithelial integrity during tracheal development. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.1 Ref.6 A phosphoprotein + H2O = a protein + phosphate. Ref.1 Ref.6
Enzyme regulation	Activity abolished by tyrosine phosphatase inhibitor sodium vanadate. Activated by rl. Ref.1 Ref.6
Subunit structure	Interacts (via N-terminal region) with phosphorylated rl. Ref.1
Subcellular location	Cytoplasm Ref.1.
Tissue specificity	Ubiquitous expression in eye and wing imaginal disks. Enriched in ovary. Ref.8
Developmental stage	Low expression in the various developmental stages, although relatively high levels detected in 8 to 12 h embryos, as well as in pupae and adults, particularly in the head region. Expressed in third-instar eye imaginal disks posterior to the morphogenetic furrow where photoreceptor differentiation occurs. Preferentially detected in wing imaginal disks in two stripes of cells interrupted at the dorsoventral boundary, which correspond to the developing veins L3 and L4. In pupal wings the maximal levels of expression are present in all longitudinal veins, with low levels detected in most intervein cells. Uniformly distributed in the syncytial blastoderm (stage 4). At early stage 5, accumulates at the embryonic poles and is absent from the central region. This pattern evolves very rapidly with the formation of a third central domain of expression from 85% to 40% egg length. In older embryos, the main places where high levels accumulate correspond to the invaginating mesoderm, the tracheal pits at stage 11, the visceral mesoderm at stage 13, the heart, the midline and the apodema. Expression in tracheal branches at later stages. Ref.1 Ref.7 Ref.9 Ref.10
Disruption phenotype	Homozygous embryonic lethal, while hypomorphic alleles (reduction in gene dosage) lead to extra photoreceptor cells in the eye, ectopic veins in wings and severe defects in oogenesis in females. Females with the germ line mutation lay only a small number of eggs. The laid eggs are abnormal, approximately 77% of the laid eggs are shorter and some display severe defects in chorion formation. These embryos could not escape the embryonic stage and progress beyond the two-nuclei stage. Null mutants are viable and fertile exhibiting a mild, but significant increase in wing vein material. They are slightly rough eyed. Null mutation affects the R3 and R4 photoreceptors with a low penetrance resulting in either the loss of one cell of the R3/R4 pair or in the misdifferentiation of these photoreceptors. R3 and R4 are often symmetrically arranged in the eye in opposite to the asymmetrical positions they adopt in wild-type ommatidium. Ommatidia of the null mutants often contain a mystery cell having differentiated as a photoreceptor. Null mutants also exhibit mild delay in tracheal branching. Delay in 12% dorsal branches (DBs) compared with 0.3% in wild-type between metameres 4 to 8 that have reached the dorsal midline at stage 14-15. Null mutants have defects in cell intercalation. Ref.7 Ref.8 Ref.10
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily. Contains 1 rhodanese domain. Contains 1 tyrosine-protein phosphatase domain.
Sequence caution	The sequence AAO39540.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protein phosphatase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell adhesion Inferred from mutant phenotype Ref.10. Source: FlyBase imaginal disc-derived wing vein specification Inferred from mutant phenotype Ref.9. Source: FlyBase maintenance of epithelial integrity, open tracheal system Inferred from mutant phenotype Ref.10. Source: FlyBase mucosal immune response Inferred from mutant phenotype PubMed 19668222. Source: FlyBase peptidyl-tyrosine dephosphorylation Inferred from electronic annotation. Source: GOC primary branching, open tracheal system Inferred from mutant phenotype Ref.10. Source: FlyBase regulation of cell proliferation Inferred from genetic interaction PubMed 19141677. Source: FlyBase
Cellular_component	cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	MAP kinase tyrosine/serine/threonine phosphatase activity Inferred from Biological aspect of Ancestor. Source: RefGenome protein tyrosine phosphatase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform B (identifier: Q9VVW5-1)

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 A (identifier: Q9VVW5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-170: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 411	411	Dual specificity protein phosphatase Mpk3		PRO_0000408762
Regions
	Domain	22 – 149	128	Rhodanese
	Domain	215 – 357	143	Tyrosine-protein phosphatase
	Compositional bias	201 – 209	9	Poly-His
Sites
	Active site	302	1	Phosphocysteine intermediate By similarity
Natural variations
	Alternative sequence	1 – 170	170	Missing in isoform A.		VSP_041148
Experimental info
	Mutagenesis	56 – 57	2	RR → AA: Reduces binding affinity to substrate by approximately 18-fold.
	Mutagenesis	302	1	C → A: Loss of activity. Ref.1
	Mutagenesis	316	1	Y → N: Causes the differentiation of ectopic vein stretches in several regions of the wing. Shows elimination of distal stretches of longitunal veins L2-L5. Causes substitution of the wing by proximal hinge tissue. Affects the development of macrochaetae or the formation of the thorax. Ref.9
	Sequence conflict	208	1	H → L in AAK85311. Ref.1
	Sequence conflict	208	1	H → L in AAL25511. Ref.4
	Sequence conflict	384	1	T → A in AAK85311. Ref.1
	Sequence conflict	384	1	T → A in AAL25511. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform B [UniParc]. Last modified October 1, 2002. Version 2. Checksum: D3C689BC953B29E3	FASTA	411	45,792
	10 20 30 40 50 60 MPETEHETCS KEWLQSQLRS LDSKDLILLD CRGSHEYSES HIRGAVNLCI PSIVLRRLAV 70 80 90 100 110 120 GKIDLASTIK SPELKQRIQS GYKLCWFILY NGEGVPGQNQ EIAGAGSLAV AMDSIISILH 130 140 150 160 170 180 RRLKQDGCRV VALQDGFNNF RQAFPEWCED DNQTHSKEIE SSRNVQTDQL MGLRSLRIST 190 200 210 220 230 240 TQSDSACSSS AESSDCESSS HHHHHHSHHN YNEAPVEIIP GLLFLGNATH SCDSEALKKY 250 260 270 280 290 300 NIKYVLNVTP DLPNKFKESG DIKYLQIPIT DHYSQDLAIH FPDAIQFIEE ARSASSVVLV 310 320 330 340 350 360 HCLAGVSRSV TVTLAYLMHT RGLSLNDAFA MVRDRKPDVS PNFHFMQQLL SFESQLRLRP 370 380 390 400 410 GSRFSCSCIA PDCNCMQTTG FMATHLANAT GVSPDSGIEF DRWTPSDTGL K
	Isoform A [UniParc]. Checksum: 4B1AD996FA631B2E	FASTA	241	26,639
	10 20 30 40 50 60 MGLRSLRIST TQSDSACSSS AESSDCESSS HHHHHHSHHN YNEAPVEIIP GLLFLGNATH 70 80 90 100 110 120 SCDSEALKKY NIKYVLNVTP DLPNKFKESG DIKYLQIPIT DHYSQDLAIH FPDAIQFIEE 130 140 150 160 170 180 ARSASSVVLV HCLAGVSRSV TVTLAYLMHT RGLSLNDAFA MVRDRKPDVS PNFHFMQQLL 190 200 210 220 230 240 SFESQLRLRP GSRFSCSCIA PDCNCMQTTG FMATHLANAT GVSPDSGIEF DRWTPSDTGL K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a Drosophila homologue of mitogen-activated protein kinase phosphatase-3 which has a high substrate specificity towards extracellular-signal-regulated kinase." Kim S.H., Kwon H.B., Kim Y.S., Ryu J.H., Kim K.S., Ahn Y., Lee W.J., Choi K.Y. Biochem. J. 361:143-151(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, INTERACTION WITH RL, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, MUTAGENESIS OF 56-ARG-ARG-57 AND CYS-302.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING. Strain: Berkeley.
[4]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). Strain: Berkeley. Tissue: Embryo.
[5]	Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R., Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A. , Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S., Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Strain: Berkeley. Tissue: Embryo.
[6]	"Regulation of Drosophila MKP-3 by Drosophila ERK." Kim S.E., Kim S.H., Choi K.Y. Ann. N. Y. Acad. Sci. 1010:51-61(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION.
[7]	"The Drosophila dual-specificity ERK phosphatase DMKP3 cooperates with the ERK tyrosine phosphatase PTP-ER." Rintelen F., Hafen E., Nairz K. Development 130:3479-3490(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
[8]	"MKP-3 has essential roles as a negative regulator of the Ras/mitogen-activated protein kinase pathway during Drosophila development." Kim M., Cha G.H., Kim S., Lee J.H., Park J., Koh H., Choi K.Y., Chung J. Mol. Cell. Biol. 24:573-583(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[9]	"Conserved cross-interactions in Drosophila and Xenopus between Ras/MAPK signaling and the dual-specificity phosphatase MKP3." Gomez A.R., Lopez-Varea A., Molnar C., de la Calle-Mustienes E., Ruiz-Gomez M., Gomez-Skarmeta J.L., de Celis J.F. Dev. Dyn. 232:695-708(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF TYR-316.
[10]	"Egfr is essential for maintaining epithelial integrity during tracheal remodelling in Drosophila." Cela C., Llimargas M. Development 133:3115-3125(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY043264 mRNA. Translation: AAK85311.1. AE014296 Genomic DNA. Translation: AAF49192.2. AE014296 Genomic DNA. Translation: AAF49193.2. AY060472 mRNA. Translation: AAL25511.1. BT003536 mRNA. Translation: AAO39540.1. Different initiation.
RefSeq	NP_001262032.1. NM_001275103.1. NP_649087.1. NM_140830.2. NP_730385.1. NM_168785.1.
UniGene	Dm.3967.
3D structure databases
ProteinModelPortal	Q9VVW5.
SMR	Q9VVW5. Positions 13-151, 215-358.
ModBase	Search...
Protein-protein interaction databases
STRING	7227.FBpp0074802.
Proteomic databases
PaxDb	Q9VVW5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0075035; FBpp0074802; FBgn0036844. FBtr0333220; FBpp0305422; FBgn0036844.
GeneID	40081.
KEGG	dme:Dmel_CG14080.
UCSC	CG14080-RA. d. melanogaster. CG14080-RB. d. melanogaster.
Organism-specific databases
CTD	40081.
FlyBase	FBgn0036844. Mkp3.
Phylogenomic databases
eggNOG	COG2453.
GeneTree	ENSGT00700000104093.
InParanoid	Q86P14.
KO	K04459.
OMA	RLKQDGC.
OrthoDB	EOG4B2RCR.
PhylomeDB	Q9VVW5.
Enzyme and pathway databases
SignaLink	Q9VVW5.
Gene expression databases
Bgee	Q9VVW5.
Family and domain databases
Gene3D	3.40.250.10. 1 hit.
InterPro	IPR000340. Dual-sp_phosphatase_cat-dom. IPR020422. Dual-sp_phosphatase_subgr_cat. IPR024950. DUSP. IPR008343. MKP. IPR001763. Rhodanese-like_dom. IPR000387. Tyr/Dual-sp_Pase. [Graphical view]
PANTHER	PTHR10159. PTHR10159. 1 hit.
Pfam	PF00782. DSPc. 1 hit. PF00581. Rhodanese. 1 hit. [Graphical view]
PIRSF	PIRSF000939. MAPK_Ptase. 1 hit.
PRINTS	PR01764. MAPKPHPHTASE.
SMART	SM00195. DSPc. 1 hit. SM00450. RHOD. 1 hit. [Graphical view]
SUPFAM	SSF52821. Rhodanese-like. 1 hit.
PROSITE	PS50206. RHODANESE_3. 1 hit. PS50056. TYR_PHOSPHATASE_2. 1 hit. PS50054. TYR_PHOSPHATASE_DUAL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	Mkp3. drosophila.
GenomeRNAi	40081.
NextBio	816901.

Entry information

Entry name

DUSK3_DROME

Accession

Primary (citable) accession number: Q9VVW5
Secondary accession number(s): Q86P14, Q95SV1, Q9VVW4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 31, 2011
Last sequence update:	October 1, 2002
Last modified:	May 29, 2013
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project