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Q9VVW5 (DUSK3_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length411 AA.
Sequence statusComplete.
Protein existenceEvidence 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 protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + 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

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 411411Dual specificity protein phosphatase Mpk3
PRO_0000408762

Regions

Domain22 – 149128Rhodanese
Domain215 – 357143Tyrosine-protein phosphatase
Compositional bias201 – 2099Poly-His

Sites

Active site3021Phosphocysteine intermediate By similarity

Natural variations

Alternative sequence1 – 170170Missing in isoform A.
VSP_041148

Experimental info

Mutagenesis56 – 572RR → AA: Reduces binding affinity to substrate by approximately 18-fold.
Mutagenesis3021C → A: Loss of activity. Ref.1
Mutagenesis3161Y → 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 conflict2081H → L in AAK85311. Ref.1
Sequence conflict2081H → L in AAL25511. Ref.4
Sequence conflict3841T → A in AAK85311. Ref.1
Sequence conflict3841T → A in AAL25511. Ref.4

Sequences

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

Last modified October 1, 2002. Version 2.
Checksum: D3C689BC953B29E3

FASTA41145,792
        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 

« Hide

Isoform A [UniParc].

Checksum: 4B1AD996FA631B2E
Show »

FASTA24126,639

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
RefSeqNP_001262032.1. NM_001275103.1. [Q9VVW5-1]
NP_649087.1. NM_140830.2. [Q9VVW5-1]
NP_730385.1. NM_168785.1. [Q9VVW5-2]
UniGeneDm.3967.

3D structure databases

ProteinModelPortalQ9VVW5.
SMRQ9VVW5. Positions 13-151, 215-358.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING7227.FBpp0074802.

Proteomic databases

PaxDbQ9VVW5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaFBtr0075035; FBpp0074802; FBgn0036844. [Q9VVW5-1]
FBtr0333220; FBpp0305422; FBgn0036844. [Q9VVW5-1]
GeneID40081.
KEGGdme:Dmel_CG14080.
UCSCCG14080-RB. d. melanogaster. [Q9VVW5-1]

Organism-specific databases

CTD40081.
FlyBaseFBgn0036844. Mkp3.

Phylogenomic databases

eggNOGCOG2453.
GeneTreeENSGT00750000117282.
InParanoidQ86P14.
KOK04459.
OrthoDBEOG793B7W.
PhylomeDBQ9VVW5.

Enzyme and pathway databases

SignaLinkQ9VVW5.

Gene expression databases

BgeeQ9VVW5.

Family and domain databases

Gene3D3.40.250.10. 1 hit.
3.90.190.10. 1 hit.
InterProIPR000340. Dual-sp_phosphatase_cat-dom.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR024950. DUSP.
IPR008343. MKP.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR001763. Rhodanese-like_dom.
IPR000387. Tyr/Dual-sp_Pase.
[Graphical view]
PANTHERPTHR10159. PTHR10159. 1 hit.
PfamPF00782. DSPc. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]
PIRSFPIRSF000939. MAPK_Ptase. 1 hit.
PRINTSPR01764. MAPKPHPHTASE.
SMARTSM00195. DSPc. 1 hit.
SM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMSSF52799. SSF52799. 1 hit.
SSF52821. SSF52821. 1 hit.
PROSITEPS50206. RHODANESE_3. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMkp3. drosophila.
GenomeRNAi40081.
NextBio816901.

Entry information

Entry nameDUSK3_DROME
AccessionPrimary (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: July 9, 2014
This is version 98 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase