Q9VVW5 (DUSK3_DROME) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 98. History...
Names and origin
|Protein names||Recommended name:|
Dual specificity protein phosphatase Mpk3
Mitogen-activated protein kinase phosphatase 3
Short name=MAP kinase phosphatase 3
|Organism||Drosophila melanogaster (Fruit fly) [Reference proteome]|
|Taxonomic identifier||7227 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora ›|
|Sequence length||411 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
Interacts (via N-terminal region) with phosphorylated rl. Ref.1
Ubiquitous expression in eye and wing imaginal disks. Enriched in ovary. Ref.8
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
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
Contains 1 rhodanese domain.
Contains 1 tyrosine-protein phosphatase domain.
The sequence AAO39540.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
|Coding sequence diversity||Alternative splicing|
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||imaginal disc-derived wing vein specificationmaintenance of epithelial integrity, open tracheal systemmucosal immune responsenegative regulation of MAPK cascadeprimary branching, open tracheal systemprotein dephosphorylationregulation of cell proliferationsingle organismal cell-cell adhesion|
|Molecular_function||MAP kinase tyrosine/serine/threonine phosphatase activity|
Inferred from electronic annotation. Source: InterProphosphatase activityprotein tyrosine phosphatase activity
Inferred from electronic annotation. Source: UniProtKB-ECprotein tyrosine/serine/threonine phosphatase activity
|Complete GO annotation...|
|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:
|Note: No experimental confirmation available.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 411||411||Dual specificity protein phosphatase Mpk3||PRO_0000408762|
|Domain||22 – 149||128||Rhodanese|
|Domain||215 – 357||143||Tyrosine-protein phosphatase|
|Compositional bias||201 – 209||9||Poly-His|
|Active site||302||1||Phosphocysteine intermediate By similarity|
|Alternative sequence||1 – 170||170||Missing in isoform A.||VSP_041148|
|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|
|||"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.
|||"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. Venter J.C.
Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||"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. Lewis S.E.
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
|||"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).
|||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. Celniker S.|
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.|
|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. [Q9VVW5-1]|
NP_649087.1. NM_140830.2. [Q9VVW5-1]
NP_730385.1. NM_168785.1. [Q9VVW5-2]
3D structure databases
|SMR||Q9VVW5. Positions 13-151, 215-358. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|EnsemblMetazoa||FBtr0075035; FBpp0074802; FBgn0036844. [Q9VVW5-1]|
FBtr0333220; FBpp0305422; FBgn0036844. [Q9VVW5-1]
|UCSC||CG14080-RB. d. melanogaster. [Q9VVW5-1]|
|FlyBase||FBgn0036844. Mkp3. |
Enzyme and pathway databases
Gene expression databases
Family and domain databases
|Gene3D||184.108.40.206. 1 hit. |
220.127.116.11. 1 hit.
|InterPro||IPR000340. Dual-sp_phosphatase_cat-dom. |
|PANTHER||PTHR10159. PTHR10159. 1 hit. |
|Pfam||PF00782. DSPc. 1 hit. |
PF00581. Rhodanese. 1 hit.
|PIRSF||PIRSF000939. MAPK_Ptase. 1 hit. |
|PRINTS||PR01764. MAPKPHPHTASE. |
|SMART||SM00195. DSPc. 1 hit. |
SM00450. RHOD. 1 hit.
|SUPFAM||SSF52799. SSF52799. 1 hit. |
SSF52821. SSF52821. 1 hit.
|PROSITE||PS50206. RHODANESE_3. 1 hit. |
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
|ChiTaRS||Mkp3. drosophila. |
|Accession||Primary (citable) accession number: Q9VVW5|
Secondary accession number(s): Q86P14, Q95SV1, Q9VVW4
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Drosophila annotation project|