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Q95UN8

- M3KSL_DROME

UniProt

Q95UN8 - M3KSL_DROME

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Protein
Mitogen-activated protein kinase kinase kinase
Gene
slpr, Mlk2, CG2272
Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.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 Publication
Active sitei264 – 2641Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi148 – 1569ATP By similarityBy similarity

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

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:slpr
Synonyms:Mlk2
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 kinase
PRO_0000086269Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei300 – 3001Phosphothreonine; by autocatalysis By similarityBy similarity
Modified residuei304 – 3041Phosphoserine; by autocatalysis By similarityBy similarity
Modified residuei525 – 5251PhosphoserineBy similarity1 Publication
Modified residuei560 – 5601Phosphoserine By similarityBy similarity
Modified residuei685 – 6851Phosphoserine By similarityBy similarity
Modified residuei773 – 7731Phosphoserine By similarityBy similarity
Modified residuei792 – 7921Phosphoserine By similarityBy similarity
Modified residuei862 – 8621Phosphothreonine1 Publication
Modified residuei993 – 9931Phosphoserine By similarityBy similarity

Post-translational modificationi

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

Protein-protein interaction databases

BioGridi68838. 5 interactions.

Structurei

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini56 – 12065SH3
Add
BLAST
Domaini142 – 402261Protein kinase
Add
BLAST

Region

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

Compositional bias

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

Sequence similaritiesi

Contains 1 SH3 domain.

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.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti327 – 3271D → Y in AAM50203. 1 Publication
Sequence conflicti670 – 6701S → P in AAL08011. 1 Publication
Sequence conflicti908 – 9081E → G in AAL08011. 1 Publication

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

« Hide 'large scale' publications
  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.
    , 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. Cited for: GENOME REANNOTATION.
    Strain: Berkeley.
  4. 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.

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: July 9, 2014
This is version 106 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

Similar proteinsi