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Q95UN8 (M3KSL_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase kinase kinase

EC=2.7.11.25
Alternative name(s):
Mixed lineage kinase
Protein slipper
dMLK
Gene names
Name:slpr
Synonyms:Mlk2
ORF Names:CG2272
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length1161 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Activates the JUN N-terminal pathway during dorsal closure. Ref.1 Ref.5 Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.5

Cofactor

Magnesium By similarity. UniProtKB P80192

Enzyme regulation

Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation By similarity. Activated by C6-ceramide. Ref.6 UniProtKB Q16584

Subunit structure

Homodimer By similarity. UniProtKB Q16584

Tissue specificity

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. Ref.5

Post-translational modification

Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation By similarity. UniProtKB Q16584

Disruption phenotype

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

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.

Contains 1 protein kinase domain.

Contains 1 SH3 domain.

Sequence caution

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

Ontologies

Keywords
   DomainRepeat
SH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Inferred from mutant phenotype Ref.5. Source: UniProtKB

activation of JNKK activity

Traceable author statement PubMed 12000787. Source: FlyBase

activation of JUN kinase activity

Inferred from mutant phenotype Ref.6. Source: UniProtKB

cellular response to ethanol

Inferred from mutant phenotype PubMed 16451733. Source: FlyBase

dorsal appendage formation

Inferred from mutant phenotype PubMed 16888342. Source: FlyBase

dorsal closure

Inferred from mutant phenotype Ref.1PubMed 16888342PubMed 19064708. Source: FlyBase

dorsal closure, elongation of leading edge cells

Inferred from mutant phenotype Ref.1. Source: FlyBase

imaginal disc fusion, thorax closure

Inferred from mutant phenotype PubMed 16888342PubMed 19064708. Source: FlyBase

imaginal disc-derived female genitalia morphogenesis

Inferred from mutant phenotype PubMed 16888342. Source: FlyBase

imaginal disc-derived male genitalia morphogenesis

Inferred from mutant phenotype PubMed 16888342. Source: FlyBase

positive regulation of JNK cascade

Inferred from mutant phenotype PubMed 16451733PubMed 16888342. Source: FlyBase

protein autophosphorylation

Inferred from sequence or structural similarity Ref.1. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.5. Source: UniProtKB

response to heat

Inferred from mutant phenotype PubMed 22848763. Source: FlyBase

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

JUN kinase kinase kinase activity

Inferred from direct assay Ref.5. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity Ref.1. Source: UniProtKB

protein kinase activity

Inferred from direct assay Ref.5. Source: FlyBase

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11611161Mitogen-activated protein kinase kinase kinase
PRO_0000086269

Regions

Domain56 – 12065SH3
Domain142 – 402261Protein kinase
Nucleotide binding148 – 1569ATP By similarity UniProtKB Q02779
Region426 – 44722Leucine-zipper 1
Region461 – 48222Leucine-zipper 2
Compositional bias21 – 3919Gln-rich
Compositional bias637 – 71276Asn-rich
Compositional bias978 – 100932Ser-rich

Sites

Active site2641Proton acceptor By similarity UniProtKB Q02779
Binding site1691ATP Ref.6

Amino acid modifications

Modified residue3001Phosphothreonine; by autocatalysis By similarity UniProtKB Q16584
Modified residue3041Phosphoserine; by autocatalysis By similarity UniProtKB Q16584
Modified residue5251Phosphoserine Ref.7 UniProtKB Q16584
Modified residue5601Phosphoserine By similarity UniProtKB Q16584
Modified residue6851Phosphoserine By similarity UniProtKB Q16584
Modified residue7731Phosphoserine By similarity UniProtKB Q16584
Modified residue7921Phosphoserine By similarity UniProtKB Q16584
Modified residue8621Phosphothreonine Ref.7
Modified residue9931Phosphoserine By similarity UniProtKB Q16584

Experimental info

Mutagenesis1691K → A: Loss of kinase activity. Attenuates bsk activation. Ref.6
Sequence conflict3271D → Y in AAM50203. Ref.4
Sequence conflict6701S → P in AAL08011. Ref.5
Sequence conflict9081E → G in AAL08011. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q95UN8 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: DD6C7ABAC08EDA24

FASTA1,161128,961
        10         20         30         40         50         60 
MPSQVSRGLD TTNMLPISEE QQLQQQQQQQ QLEQLHHPQI PEIPIPDLEQ VETQVGDGSL 

        70         80         90        100        110        120 
WTALYDYDAQ GEDELTLRRG EIVVVLSTDS EVSGDVGWWT GKIGDKVGVF PKDFVTDEDP 

       130        140        150        160        170        180 
LQLNVSSAIG DIQPHEIEYN ELDIKEVIGS GGFCKVHRGY YDGEEVAIKI AHQTGEDDMQ 

       190        200        210        220        230        240 
RMRDNVLQEA KLFWALKHEN IAALRGVCLN TKLCLVMEYA RGGSLNRILA GKIPPDVLVN 

       250        260        270        280        290        300 
WAIQIARGMN YLHNEAPMSI IHRDLKSSNV LIYEAIEGNH LQQKTLKITD FGLAREMYNT 

       310        320        330        340        350        360 
QRMSAAGTYA WMPPEVISVS TYSKFSDVWS YGVLLWELIT GETPYKGFDP LSVAYGVAVN 

       370        380        390        400        410        420 
TLTLPIPKTC PETWGALMKS CWQTDPHKRP GFKEILKQLE SIACSKFTLT PQESFHYMQE 

       430        440        450        460        470        480 
CWRKEIAGVL HDLREKEKEL RNKEEQLLRV QNEQREKANL LKIREQNLRE RERVLIEREL 

       490        500        510        520        530        540 
VMLQPVPSKR KHKKGKKNKP LQISLPTGFR HTITAVRDKA EQPGSPSFSG LRIVALTDGH 

       550        560        570        580        590        600 
KGKTWGPSTM HQRERSLLPS QLSGGQPEWP AQTSTHSSFS KSAPNLDKKQ QQQNQQQVAS 

       610        620        630        640        650        660 
LTPPPGLGIL GGSGGAGGTP ATPLLYPGIP IILTRPNNNN IGNCKAITTT ITTTTTTTTN 

       670        680        690        700        710        720 
NNNNNNNSIS ANNNNQLNNI STINSNNNNN QTNLTSQPNT IIVLQNGRNN SNSSTTSQSP 

       730        740        750        760        770        780 
AKIYHRARSQ EYGLDHPLAY QPPPLYLVTD DSSETDTVAS PTGCFHFLKS GNSSAASGAV 

       790        800        810        820        830        840 
HLHRFGGSLG NSPAVGRKKH SLDSSSHHPP ANGSNSFALP NQLTLPSEDN NTYDHAFYRD 

       850        860        870        880        890        900 
VIKKMSMASS ERVNSKSSGD LTMYNSSTPL TARDCDDAEE AFEGGRFQRN FSGSQFPRHC 

       910        920        930        940        950        960 
FFTRQEEEGE AEDEDAVAAE VDTADADADD ECQVPASQMR QNSTTSRKSS VTFQSVSFEE 

       970        980        990       1000       1010       1020 
PDFVATPRTT ARSDLYTSSA SISFATYRSA SPSLSSSSTT ASASPSIAST EAVNGYHMQE 

      1030       1040       1050       1060       1070       1080 
NSILNTRRMQ DVQPHPDVIK LRAQEQRQQT KNQKKQRPKH ITKSKSVEAP VEGQHHEHDD 

      1090       1100       1110       1120       1130       1140 
HNDPQHQHHS AGSSKIRALF NLFTRSRKKY SKLAEHNMVG GPEFCAIDPY QTDLAMGGSS 

      1150       1160 
RSLKRKGKKP QTQSCEQLER C 

« Hide

References

« Hide 'large scale' references
[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: Berkeley.
Tissue: Head.
[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.
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].
Strain: Berkeley.
Tissue: Head.
[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: Berkeley.
Tissue: Embryo.
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY045717 mRNA. Translation: AAK98795.1.
AE014298 Genomic DNA. Translation: AAF46344.3. Sequence problems.
AY119549 mRNA. Translation: AAM50203.1.
AF416233 mRNA. Translation: AAL08011.1.
RefSeqNP_001188559.1. NM_001201630.1.
NP_001188560.1. NM_001201631.1.
NP_572458.3. NM_132230.3.
UniGeneDm.3504.

3D structure databases

ProteinModelPortalQ95UN8.
SMRQ95UN8. Positions 58-466.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid68838. 5 interactions.

Proteomic databases

PaxDbQ95UN8.
PRIDEQ95UN8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID44111.
KEGGdme:Dmel_CG2272.

Organism-specific databases

CTD44111.
FlyBaseFBgn0030018. slpr.

Phylogenomic databases

eggNOGCOG0515.
InParanoidQ95UN8.
OrthoDBEOG7D85VN.

Enzyme and pathway databases

SignaLinkQ95UN8.

Gene expression databases

BgeeQ95UN8.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR001452. SH3_domain.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi44111.
NextBio836785.
PROQ95UN8.

Entry information

Entry nameM3KSL_DROME
AccessionPrimary (citable) accession number: Q95UN8
Secondary accession number(s): Q8MRK7, Q95VF6, Q9W3I3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 104 of the entry and version 1 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