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Q95UN8

- M3KSL_DROME

UniProt

Q95UN8 - M3KSL_DROME

Protein

Mitogen-activated protein kinase kinase kinase

Gene

slpr

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    Activates the JUN N-terminal pathway during dorsal closure.3 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.1 Publication

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation By similarity. Activated by C6-ceramide.By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei169 – 1691ATP1 PublicationPROSITE-ProRule annotation
    Active sitei264 – 2641Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi148 – 1569ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. JUN kinase kinase kinase activity Source: UniProtKB
    3. protein homodimerization activity Source: UniProtKB
    4. protein kinase activity Source: FlyBase

    GO - Biological processi

    1. activation of JNKK activity Source: FlyBase
    2. activation of JUN kinase activity Source: UniProtKB
    3. cellular response to ethanol Source: FlyBase
    4. dorsal appendage formation Source: FlyBase
    5. dorsal closure Source: FlyBase
    6. dorsal closure, elongation of leading edge cells Source: FlyBase
    7. imaginal disc-derived female genitalia morphogenesis Source: FlyBase
    8. imaginal disc-derived male genitalia morphogenesis Source: FlyBase
    9. imaginal disc fusion, thorax closure Source: FlyBase
    10. JNK cascade Source: UniProtKB
    11. positive regulation of JNK cascade Source: FlyBase
    12. protein autophosphorylation Source: UniProtKB
    13. protein phosphorylation Source: UniProtKB
    14. response to heat Source: FlyBase

    Keywords - Molecular functioni

    Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    SignaLinkiQ95UN8.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase kinase kinase (EC:2.7.11.25)
    Alternative name(s):
    Mixed lineage kinase
    Protein slipper
    dMLK
    Gene namesi
    Name:slprImported
    Synonyms:Mlk2Imported
    ORF Names:CG2272
    OrganismiDrosophila melanogaster (Fruit fly)
    Taxonomic identifieri7227 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
    ProteomesiUP000000803: Chromosome X

    Organism-specific databases

    FlyBaseiFBgn0030018. slpr.

    Pathology & Biotechi

    Disruption phenotypei

    Mutants display defects in dorsal closure, resulting in a cuticle that resembles an open shoe. Therefore the protein was given the name Slipper.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi169 – 1691K → A: Loss of kinase activity. Attenuates bsk activation. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11611161Mitogen-activated protein kinase kinase kinasePRO_0000086269Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei300 – 3001Phosphothreonine; by autocatalysisBy similarity
    Modified residuei304 – 3041Phosphoserine; by autocatalysisBy similarity
    Modified residuei525 – 5251Phosphoserine1 Publication
    Modified residuei560 – 5601PhosphoserineBy similarity
    Modified residuei685 – 6851PhosphoserineBy similarity
    Modified residuei773 – 7731PhosphoserineBy similarity
    Modified residuei792 – 7921PhosphoserineBy similarity
    Modified residuei862 – 8621Phosphothreonine1 Publication
    Modified residuei993 – 9931PhosphoserineBy similarity

    Post-translational modificationi

    Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ95UN8.
    PRIDEiQ95UN8.

    Expressioni

    Tissue specificityi

    Expressed both maternally and zygotically. Expressed uniformly in large quantities in the early embryo (stages 1-4). In the late embryo, expression is ubiquitous, but expression levels are dramatically reduced. Expressed in the adult head and thorax, and in S2 cells.1 Publication

    Gene expression databases

    BgeeiQ95UN8.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    BioGridi68838. 5 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ95UN8.
    SMRiQ95UN8. Positions 58-115, 136-466.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini56 – 12065SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini142 – 402261Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni426 – 44722Leucine-zipper 1Add
    BLAST
    Regioni461 – 48222Leucine-zipper 2Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi21 – 3919Gln-richSequence AnalysisAdd
    BLAST
    Compositional biasi637 – 71276Asn-richSequence AnalysisAdd
    BLAST
    Compositional biasi978 – 100932Ser-richSequence AnalysisAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    InParanoidiQ95UN8.
    OrthoDBiEOG7D85VN.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    PRINTSiPR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00326. SH3. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q95UN8-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPSQVSRGLD TTNMLPISEE QQLQQQQQQQ QLEQLHHPQI PEIPIPDLEQ     50
    VETQVGDGSL WTALYDYDAQ GEDELTLRRG EIVVVLSTDS EVSGDVGWWT 100
    GKIGDKVGVF PKDFVTDEDP LQLNVSSAIG DIQPHEIEYN ELDIKEVIGS 150
    GGFCKVHRGY YDGEEVAIKI AHQTGEDDMQ RMRDNVLQEA KLFWALKHEN 200
    IAALRGVCLN TKLCLVMEYA RGGSLNRILA GKIPPDVLVN WAIQIARGMN 250
    YLHNEAPMSI IHRDLKSSNV LIYEAIEGNH LQQKTLKITD FGLAREMYNT 300
    QRMSAAGTYA WMPPEVISVS TYSKFSDVWS YGVLLWELIT GETPYKGFDP 350
    LSVAYGVAVN TLTLPIPKTC PETWGALMKS CWQTDPHKRP GFKEILKQLE 400
    SIACSKFTLT PQESFHYMQE CWRKEIAGVL HDLREKEKEL RNKEEQLLRV 450
    QNEQREKANL LKIREQNLRE RERVLIEREL VMLQPVPSKR KHKKGKKNKP 500
    LQISLPTGFR HTITAVRDKA EQPGSPSFSG LRIVALTDGH KGKTWGPSTM 550
    HQRERSLLPS QLSGGQPEWP AQTSTHSSFS KSAPNLDKKQ QQQNQQQVAS 600
    LTPPPGLGIL GGSGGAGGTP ATPLLYPGIP IILTRPNNNN IGNCKAITTT 650
    ITTTTTTTTN NNNNNNNSIS ANNNNQLNNI STINSNNNNN QTNLTSQPNT 700
    IIVLQNGRNN SNSSTTSQSP AKIYHRARSQ EYGLDHPLAY QPPPLYLVTD 750
    DSSETDTVAS PTGCFHFLKS GNSSAASGAV HLHRFGGSLG NSPAVGRKKH 800
    SLDSSSHHPP ANGSNSFALP NQLTLPSEDN NTYDHAFYRD VIKKMSMASS 850
    ERVNSKSSGD LTMYNSSTPL TARDCDDAEE AFEGGRFQRN FSGSQFPRHC 900
    FFTRQEEEGE AEDEDAVAAE VDTADADADD ECQVPASQMR QNSTTSRKSS 950
    VTFQSVSFEE PDFVATPRTT ARSDLYTSSA SISFATYRSA SPSLSSSSTT 1000
    ASASPSIAST EAVNGYHMQE NSILNTRRMQ DVQPHPDVIK LRAQEQRQQT 1050
    KNQKKQRPKH ITKSKSVEAP VEGQHHEHDD HNDPQHQHHS AGSSKIRALF 1100
    NLFTRSRKKY SKLAEHNMVG GPEFCAIDPY QTDLAMGGSS RSLKRKGKKP 1150
    QTQSCEQLER C 1161
    Length:1,161
    Mass (Da):128,961
    Last modified:December 1, 2001 - v1
    Checksum:iDD6C7ABAC08EDA24
    GO

    Sequence cautioni

    The sequence AAF46344.3 differs from that shown. Reason: Erroneous gene model prediction.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti327 – 3271D → Y in AAM50203. (PubMed:12537569)Curated
    Sequence conflicti670 – 6701S → P in AAL08011. (PubMed:12676357)Curated
    Sequence conflicti908 – 9081E → G in AAL08011. (PubMed:12676357)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY045717 mRNA. Translation: AAK98795.1.
    AE014298 Genomic DNA. Translation: AAF46344.3. Sequence problems.
    AY119549 mRNA. Translation: AAM50203.1.
    AF416233 mRNA. Translation: AAL08011.1.
    RefSeqiNP_001188559.1. NM_001201630.1.
    NP_001188560.1. NM_001201631.1.
    NP_572458.3. NM_132230.3.
    UniGeneiDm.3504.

    Genome annotation databases

    GeneIDi44111.
    KEGGidme:Dmel_CG2272.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY045717 mRNA. Translation: AAK98795.1 .
    AE014298 Genomic DNA. Translation: AAF46344.3 . Sequence problems.
    AY119549 mRNA. Translation: AAM50203.1 .
    AF416233 mRNA. Translation: AAL08011.1 .
    RefSeqi NP_001188559.1. NM_001201630.1.
    NP_001188560.1. NM_001201631.1.
    NP_572458.3. NM_132230.3.
    UniGenei Dm.3504.

    3D structure databases

    ProteinModelPortali Q95UN8.
    SMRi Q95UN8. Positions 58-115, 136-466.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 68838. 5 interactions.

    Proteomic databases

    PaxDbi Q95UN8.
    PRIDEi Q95UN8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 44111.
    KEGGi dme:Dmel_CG2272.

    Organism-specific databases

    CTDi 44111.
    FlyBasei FBgn0030018. slpr.

    Phylogenomic databases

    eggNOGi COG0515.
    InParanoidi Q95UN8.
    OrthoDBi EOG7D85VN.

    Enzyme and pathway databases

    SignaLinki Q95UN8.

    Miscellaneous databases

    GenomeRNAii 44111.
    NextBioi 836785.
    PROi Q95UN8.

    Gene expression databases

    Bgeei Q95UN8.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR001452. SH3_domain.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00326. SH3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Activation of the JNK pathway during dorsal closure in Drosophila requires the mixed lineage kinase, slipper."
      Stronach B., Perrimon N.
      Genes Dev. 16:377-387(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE.
      Strain: Berkeley1 Publication.
      Tissue: HeadImported.
    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: Berkeley1 Publication.
    3. Cited for: GENOME REANNOTATION.
      Strain: Berkeley.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: BerkeleyImported.
      Tissue: Head1 Publication.
    5. "Drosophila mixed lineage kinase/slipper, a missing biochemical link in Drosophila JNK signaling."
      Sathyanarayana P., Barthwal M.K., Lane M.E., Acevedo S.F., Skoulakis E.M., Bergmann A., Rana A.
      Biochim. Biophys. Acta 1640:77-84(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-1161, FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
      Strain: Berkeley1 Publication.
      Tissue: Embryo1 Publication.
    6. "Activation of the Drosophila MLK by ceramide reveals TNF-alpha and ceramide as agonists of mammalian MLK3."
      Sathyanarayana P., Barthwal M.K., Kundu C.N., Lane M.E., Bergmann A., Tzivion G., Rana A.
      Mol. Cell 10:1527-1533(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF LYS-169.
    7. "Phosphoproteome analysis of Drosophila melanogaster embryos."
      Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.
      J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-525 AND THR-862, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Embryo.

    Entry informationi

    Entry nameiM3KSL_DROME
    AccessioniPrimary (citable) accession number: Q95UN8
    Secondary accession number(s): Q8MRK7, Q95VF6, Q9W3I3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2005
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 107 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programDrosophila annotation project

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Drosophila
      Drosophila: entries, gene names and cross-references to FlyBase
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3