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Protein

Mitogen-activated protein kinase kinase kinase

Gene

slpr

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: 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

Mg2+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 – 1691ATPPROSITE-ProRule annotation1 Publication
Active sitei264 – 2641Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi148 – 1569ATPPROSITE-ProRule annotationBy 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. 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
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:slprImported
Synonyms:Mlk2Imported
ORF Names:CG2272
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
ProteomesiUP000000803 Componenti: 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.
IntActiQ95UN8. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ95UN8.
SMRiQ95UN8. Positions 136-401.
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.
KOiK04417.
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

        10         20         30         40         50
MPSQVSRGLD TTNMLPISEE QQLQQQQQQQ QLEQLHHPQI PEIPIPDLEQ
60 70 80 90 100
VETQVGDGSL WTALYDYDAQ GEDELTLRRG EIVVVLSTDS EVSGDVGWWT
110 120 130 140 150
GKIGDKVGVF PKDFVTDEDP LQLNVSSAIG DIQPHEIEYN ELDIKEVIGS
160 170 180 190 200
GGFCKVHRGY YDGEEVAIKI AHQTGEDDMQ RMRDNVLQEA KLFWALKHEN
210 220 230 240 250
IAALRGVCLN TKLCLVMEYA RGGSLNRILA GKIPPDVLVN WAIQIARGMN
260 270 280 290 300
YLHNEAPMSI IHRDLKSSNV LIYEAIEGNH LQQKTLKITD FGLAREMYNT
310 320 330 340 350
QRMSAAGTYA WMPPEVISVS TYSKFSDVWS YGVLLWELIT GETPYKGFDP
360 370 380 390 400
LSVAYGVAVN TLTLPIPKTC PETWGALMKS CWQTDPHKRP GFKEILKQLE
410 420 430 440 450
SIACSKFTLT PQESFHYMQE CWRKEIAGVL HDLREKEKEL RNKEEQLLRV
460 470 480 490 500
QNEQREKANL LKIREQNLRE RERVLIEREL VMLQPVPSKR KHKKGKKNKP
510 520 530 540 550
LQISLPTGFR HTITAVRDKA EQPGSPSFSG LRIVALTDGH KGKTWGPSTM
560 570 580 590 600
HQRERSLLPS QLSGGQPEWP AQTSTHSSFS KSAPNLDKKQ QQQNQQQVAS
610 620 630 640 650
LTPPPGLGIL GGSGGAGGTP ATPLLYPGIP IILTRPNNNN IGNCKAITTT
660 670 680 690 700
ITTTTTTTTN NNNNNNNSIS ANNNNQLNNI STINSNNNNN QTNLTSQPNT
710 720 730 740 750
IIVLQNGRNN SNSSTTSQSP AKIYHRARSQ EYGLDHPLAY QPPPLYLVTD
760 770 780 790 800
DSSETDTVAS PTGCFHFLKS GNSSAASGAV HLHRFGGSLG NSPAVGRKKH
810 820 830 840 850
SLDSSSHHPP ANGSNSFALP NQLTLPSEDN NTYDHAFYRD VIKKMSMASS
860 870 880 890 900
ERVNSKSSGD LTMYNSSTPL TARDCDDAEE AFEGGRFQRN FSGSQFPRHC
910 920 930 940 950
FFTRQEEEGE AEDEDAVAAE VDTADADADD ECQVPASQMR QNSTTSRKSS
960 970 980 990 1000
VTFQSVSFEE PDFVATPRTT ARSDLYTSSA SISFATYRSA SPSLSSSSTT
1010 1020 1030 1040 1050
ASASPSIAST EAVNGYHMQE NSILNTRRMQ DVQPHPDVIK LRAQEQRQQT
1060 1070 1080 1090 1100
KNQKKQRPKH ITKSKSVEAP VEGQHHEHDD HNDPQHQHHS AGSSKIRALF
1110 1120 1130 1140 1150
NLFTRSRKKY SKLAEHNMVG GPEFCAIDPY QTDLAMGGSS RSLKRKGKKP
1160
QTQSCEQLER C
Length:1,161
Mass (Da):128,961
Last modified:November 30, 2001 - v1
Checksum:iDD6C7ABAC08EDA24
GO

Sequence cautioni

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

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:
EMBLi
GenBanki
DDBJi
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_001201630.2.
NP_001188560.1. NM_001201631.2.
NP_572458.3. NM_132230.4.

Genome annotation databases

GeneIDi44111.
KEGGidme:Dmel_CG2272.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_001201630.2.
NP_001188560.1. NM_001201631.2.
NP_572458.3. NM_132230.4.

3D structure databases

ProteinModelPortaliQ95UN8.
SMRiQ95UN8. Positions 136-401.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi68838. 5 interactions.
IntActiQ95UN8. 1 interaction.

Proteomic databases

PaxDbiQ95UN8.
PRIDEiQ95UN8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi44111.
KEGGidme:Dmel_CG2272.

Organism-specific databases

CTDi44111.
FlyBaseiFBgn0030018. slpr.

Phylogenomic databases

eggNOGiCOG0515.
InParanoidiQ95UN8.
KOiK04417.
OrthoDBiEOG7D85VN.

Enzyme and pathway databases

SignaLinkiQ95UN8.

Miscellaneous databases

GenomeRNAii44111.
NextBioi836785.
PROiQ95UN8.

Gene expression databases

BgeeiQ95UN8.

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]
ProtoNetiSearch...

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(2001) [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(1999) [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(2002) [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(2001) [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(2007) [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 18, 2005
Last sequence update: November 30, 2001
Last modified: March 31, 2015
This is version 112 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.