FB2026_02 , released June 18, 2026
Gene: Dmel\Mkk4
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General Information
Symbol
Dmel\Mkk4
Species
D. melanogaster
Name
MAP kinase kinase 4
Annotation Symbol
CG9738
Feature Type
protein_coding_gene
FlyBase ID
FBgn0024326
Gene Model Status
Current
Stock Availability
14 publicly available
Enzyme Name (EC)
mitogen-activated protein kinase kinase (2.7.12.2)
Gene Summary
MAP kinase kinase 4 (Mkk4) encodes a mitogen activated protein kinase kinase (MAPKK) involved in the Jun kinase (JNK) pathway. It is directly activated by the MAPKKK encoded by Tak1. Mkk4 product roles include activation of intracellular JNK signalling upon the TNF family ligand encoded by egr and regulation of axon stability. [Date last reviewed: 2018-09-20] (FlyBase Gene Snapshot)
All Summaries
Also Known As

dMKK4, D-MKK4, JNKK2, SEK1/MKK4

Key Links
Genomic Location
Cytogenetic map
85A5-85A5
Sequence location
Recombination map
3-48
RefSeq locus
NT_033777 REGION:8646172..8650796
Sequence
Get Decorated FASTA
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
NCBI
UCSC
Ensembl
PopFly
Function
Gene Ontology (GO) Annotations (10 terms)
Molecular Function (3 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
enables ATP binding
inferred from electronic annotation with InterPro:IPR000719, InterPro:IPR017441
(InterPro Project Members, 2004-)
enables MAP kinase kinase activity
traceable author statement
(Martin-Blanco, 2000)
enables protein kinase activity
inferred from electronic annotation with InterPro:IPR000719, InterPro:IPR008271
(InterPro Project Members, 2004-)
Biological Process (6 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
involved_in JNK cascade
inferred from genetic interaction with FLYBASE:hep; FB:FBgn0010303
(Geuking et al., 2009)
inferred from genetic interaction with FLYBASE:egr; FB:FBgn0033483
(Geuking et al., 2009)
inferred from direct assay
(Han et al., 1998)
involved_in neuron development
inferred from mutant phenotype
(Rallis et al., 2010)
acts_upstream_of positive regulation of programmed cell death
inferred from genetic interaction with FLYBASE:egr; FB:FBgn0033483
(Geuking et al., 2009)
involved_in regulation of adult chitin-containing cuticle pigmentation
inferred from genetic interaction with FLYBASE:Ask1; FB:FBgn0014006
(Sekine et al., 2011)
involved_in tumor necrosis factor-mediated signaling pathway
inferred from genetic interaction with FLYBASE:egr; FB:FBgn0033483
(Geuking et al., 2009)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
involved_in MAPK cascade
inferred from biological aspect of ancestor with PANTHER:PTN000684494
(GO Reference Genome Project, 2011-)
Cellular Component (1 term)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
located_in axon
inferred from direct assay
(Rallis et al., 2010)
Terms Based on Predictions or Assertions (0 terms)
Gene Group (FlyBase)
Pathway (FlyBase)
Protein Family (UniProt)
-
Protein Signatures (InterPro)
Catalytic Activity (EC/Rhea)
MAP kinase kinase activity
(1) L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (2.7.12.2)
(2) L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (2.7.12.2)
(3) L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (2.7.12.2)
Summaries
Gene Snapshot
MAP kinase kinase 4 (Mkk4) encodes a mitogen activated protein kinase kinase (MAPKK) involved in the Jun kinase (JNK) pathway. It is directly activated by the MAPKKK encoded by Tak1. Mkk4 product roles include activation of intracellular JNK signalling upon the TNF family ligand encoded by egr and regulation of axon stability. [Date last reviewed: 2018-09-20]
Gene Group (FlyBase)
STE7 MAP KINASE KINASES -
STE7 MAP kinase kinases (MAPKKs) belong to the STE7 subfamily and are serine/threonine kinases that phosphorylate MAP kinases in MAPK signalling cascades. MAPKKs are activated by MAP kinase kinase kinases (MAPKKKs). (Adapted from FBrf0225276.)
Pathway (FlyBase)
TNFalpha-EIGER SIGNALING PATHWAY CORE COMPONENTS -
The Tumor Necrosis Factor α (TNFα) signaling pathway is activated by Eiger (egr) binding to a member of the TNF receptor superfamily. The signal is primarily transduced via the Jun N-terminal kinase (JNK) cascade, leading to cell death. (Adapted from FBrf0225608.)
Gene Model and Products
Number of Transcripts
3
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\Mkk4 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry O61444)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Gene model reviewed during 5.47

Tissue-specific extension of 3' UTRs observed during later stages (FBrf0218523, FBrf0219848); all variants may not be annotated

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
Mkk4-RA
FBtr0081892
NM_058005
2698
424
Mkk4-RB
FBtr0300443
NM_001170080
2525
424
Mkk4-RC
FBtr0334320
NM_001275446
4110
424
Additional Transcript Data and Comments
Reported size (kB)

2.515 (longest cDNA)

(Han et al., 1998)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
Mkk4-PA
FBpp0081378
47.5
424
7.47
O61444
NP_477353
AAF54258
Mkk4-PB
FBpp0289672
47.5
424
7.47
O61444
NP_001163551
ACZ94848
Mkk4-PC
FBpp0306434
47.5
424
7.47
O61444
NP_001262375
AGB95757
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

424 aa isoforms: Mkk4-PA, Mkk4-PB, Mkk4-PC
Additional Polypeptide Data and Comments
Reported size (kDa)

424 (aa)

(Han et al., 1998)
Comments
External Data
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Mkk4 using the Feature Mapper tool.

External Data
Crossreferences
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-1.55

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
embryonic stage
organism | ubiquitous
(Han et al., 1998)
larval ventral nerve cord
(Han et al., 1998)
embryonic stage 1 -- 3
organism

Comment: maternally deposited

(Fisher et al., 2012)
embryonic stage 4 -- 6
organism | ubiquitous
(Fisher et al., 2012)
embryonic stage 7 -- 8
anterior endoderm anlage
(Fisher et al., 2012)
head mesoderm
(Fisher et al., 2012)
organism | ubiquitous
(Fisher et al., 2012)
posterior endoderm
(Fisher et al., 2012)
trunk mesoderm
(Fisher et al., 2012)
embryonic stage 9 -- 10
anterior endoderm
(Fisher et al., 2012)
head mesoderm
(Fisher et al., 2012)
organism | ubiquitous
(Fisher et al., 2012)
posterior endoderm
(Fisher et al., 2012)
trunk mesoderm
(Fisher et al., 2012)
embryonic stage 11 -- 12
anterior midgut primordium
(Fisher et al., 2012)
central brain primordium
(Fisher et al., 2012)
organism | ubiquitous
(Fisher et al., 2012)
posterior midgut primordium
(Fisher et al., 2012)
ventral nerve cord primordium
(Fisher et al., 2012)
embryonic stage 13 -- 16
embryonic brain
(Fisher et al., 2012)
embryonic/larval midgut
(Fisher et al., 2012)
organism | faint | ubiquitous
(Fisher et al., 2012)
organism | ubiquitous
(Fisher et al., 2012)
larval ventral nerve cord
(Fisher et al., 2012)
Additional Descriptive Data

Mkk4 transcripts are detected throughout embryonic development by in situ hybridization. There is a high level of maternal deposition. Later, expression is observed in most tissues with elevated levels in the ventral nerve cord.

(Han et al., 1998)
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
adult stage
adult mushroom body
• axon
(Rallis et al., 2010)
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
adult stage
adult head
(Aradska et al., 2015)
Additional Descriptive Data

Mkk4 protein is detected in mushroom body axons (particularly in α'β' and αβ axons) and cell bodies.

(Rallis et al., 2010)
Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in axon
inferred from direct assay
(Rallis et al., 2010)
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Mkk4 in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Bulk Downloads
RNA-Seq RPKM values for all genes
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 4-6
  • Stages(s) 7-8
  • Stages(s) 9-10
  • Stages(s) 11-12
FlyBase Wiki
Image Based Resources
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 24 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 13 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Mkk4
Transgenic constructs containing regulatory region of Mkk4
Aberrations (Deficiencies and Duplications) ( 5 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
Orthologs
Downloads
Download All DIOPT Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
Domainoid
eggNOG
Hieranoid
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (29)
Hsap\MAP2K4
14 of 14
Yes
Yes
Hsap\MAP2K3
5 of 14
No
No
1  
Hsap\MAP2K6
5 of 14
No
No
1  
Hsap\MAP2K1
2 of 14
No
No
Hsap\MAP2K2
2 of 14
No
No
Hsap\MAP2K5
2 of 14
No
No
Hsap\MAP2K7
2 of 14
No
No
Hsap\STK39
2 of 14
No
No
Hsap\LOC407835
1 of 14
No
No
Hsap\LOC100996792
1 of 14
No
Yes
Hsap\MAP4K2
1 of 14
No
No
Hsap\MAP4K3
1 of 14
No
No
Hsap\MAP4K5
1 of 14
No
No
Hsap\MINK1
1 of 14
No
No
2  
Hsap\MYO3A
1 of 14
No
No
Hsap\MYO3B
1 of 14
No
No
Hsap\NRK
1 of 14
No
No
Hsap\OXSR1
1 of 14
No
No
Hsap\SLK
1 of 14
No
No
6  
Hsap\STK3
1 of 14
No
No
1  
Hsap\STK4
1 of 14
No
No
2  
Hsap\STK10
1 of 14
No
No
Hsap\STK24
1 of 14
No
No
Hsap\STK25
1 of 14
No
No
1  
Hsap\STK26
1 of 14
No
No
Hsap\STK32A
1 of 14
No
No
1  
Hsap\STK36
1 of 14
No
No
1  
Hsap\TAOK3
1 of 14
No
No
Hsap\TNIK
1 of 14
No
No
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
Domainoid
eggNOG
Hieranoid
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (11)
Rnor\Map2k4
14 of 14
Yes
Yes
Rnor\Map2k3
5 of 14
No
No
Rnor\Map2k6
5 of 14
No
No
Rnor\Map2k1
2 of 14
No
No
Rnor\Map2k2
2 of 14
No
No
Rnor\Map2k5
2 of 14
No
No
Rnor\Map2k7
2 of 14
No
No
Rnor\Stk3
1 of 14
No
No
Rnor\Stk4
1 of 14
No
No
Rnor\Stk25
1 of 14
No
No
Rnor\Stk39
1 of 14
No
No
Mus musculus (laboratory mouse) (10)
Mmus\Map2k4
14 of 14
Yes
Yes
Mmus\Map2k3
5 of 14
No
No
Mmus\Map2k6
5 of 14
No
No
Mmus\Map2k1
2 of 14
No
No
Mmus\Map2k2
2 of 14
No
No
Mmus\Map2k5
2 of 14
No
No
Mmus\Map2k7
2 of 14
No
No
Mmus\Stk3
1 of 14
No
No
Mmus\Stk4
1 of 14
No
No
Mmus\Stk25
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (12)
Xtro\map2k4
8 of 13
Yes
Yes
Xtro\map2k1
2 of 13
No
No
Xtro\map2k6
2 of 13
No
No
Xtro\stk39
2 of 13
No
No
Xtro\LOC100486125
1 of 13
No
No
Xtro\macroh2a1
1 of 13
No
No
Xtro\map2k5
1 of 13
No
No
Xtro\map2k7
1 of 13
No
No
Xtro\map4k3
1 of 13
No
No
Xtro\stk3
1 of 13
No
No
Xtro\stk4
1 of 13
No
No
Xtro\stk10
1 of 13
No
No
Danio rerio (Zebrafish) (14)
Drer\map2k4a
14 of 14
Yes
Yes
Drer\map2k4b
13 of 14
No
Yes
Drer\map2k6
5 of 14
No
No
Drer\map2k1
2 of 14
No
No
Drer\map2k2a
2 of 14
No
No
Drer\map2k2b
2 of 14
No
No
Drer\map2k5
2 of 14
No
No
Drer\map2k7
2 of 14
No
No
Drer\map3k19
1 of 14
No
No
Drer\stk3
1 of 14
No
No
Drer\stk25a
1 of 14
No
No
Drer\stk25b
1 of 14
No
No
Drer\stk26
1 of 14
No
No
Drer\stk39
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (19)
Cele\mkk-4
12 of 14
Yes
Yes
Cele\sek-6
11 of 14
No
Yes
Cele\sek-1
5 of 14
No
No
Cele\sek-3
3 of 14
No
No
Cele\cst-2
2 of 14
No
No
Cele\jkk-1
2 of 14
No
No
Cele\mek-1
2 of 14
No
No
Cele\mek-2
2 of 14
No
No
Cele\sek-5
2 of 14
No
No
Cele\cst-1
1 of 14
No
No
Cele\gck-1
1 of 14
No
No
Cele\gck-2
1 of 14
No
No
Cele\gck-3
1 of 14
No
No
Cele\mig-15
1 of 14
No
No
Cele\nekl-3
1 of 14
No
No
Cele\pak-1
1 of 14
No
No
Cele\pak-2
1 of 14
No
No
Cele\R03D7.5
1 of 14
No
No
Cele\sek-4
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (14)
Agam\AgaP_AGAP003365
12 of 12
Yes
Yes
Agam\AgaP_AGAP000310
4 of 12
No
No
Agam\AgaP_AGAP001103
2 of 12
No
No
Agam\AgaP_AGAP001867
2 of 12
No
No
Agam\AgaP_AGAP000477
1 of 12
No
No
Agam\AgaP_AGAP001790
1 of 12
No
No
Agam\AgaP_AGAP003180
1 of 12
No
No
Agam\AgaP_AGAP003202
1 of 12
No
No
Agam\AgaP_AGAP006044
1 of 12
No
No
Agam\AgaP_AGAP006340
1 of 12
No
No
Agam\AgaP_AGAP006715
1 of 12
No
No
Agam\AgaP_AGAP009961
1 of 12
No
No
Agam\AgaP_AGAP011099
1 of 12
No
No
Agam\AgaP_AGAP012963
1 of 12
No
No
Arabidopsis thaliana (thale-cress) (24)
Atha\MKK3
3 of 13
Yes
No
Atha\MEK1
2 of 13
No
No
Atha\MKK2
2 of 13
No
No
Atha\MKK4
2 of 13
No
No
Atha\MKK5
2 of 13
No
No
Atha\MKK6
2 of 13
No
No
Atha\MKK7
2 of 13
No
No
Atha\MKK8
2 of 13
No
No
Atha\MKK9
2 of 13
No
No
Atha\MKK10
2 of 13
No
No
Atha\AT1G79640
1 of 13
No
No
Atha\AT3G15220
1 of 13
No
No
Atha\AT4G10730
1 of 13
No
No
Atha\AT4G24100
1 of 13
No
No
Atha\AT5G14720
1 of 13
No
No
Atha\AT5G18700
1 of 13
No
No
Atha\ATMAP4K ALPHA1
1 of 13
No
No
Atha\MAP3KA
1 of 13
No
No
Atha\MAPKKK5
1 of 13
No
No
Atha\MAPKKK16
1 of 13
No
Yes
Atha\MAPKKK17
1 of 13
No
Yes
Atha\MAPKKK18
1 of 13
No
Yes
Atha\SIK1
1 of 13
No
No
Atha\YDA
1 of 13
No
No
Saccharomyces cerevisiae (Brewer's yeast) (6)
Scer\PBS2
4 of 13
Yes
No
Scer\MKK1
3 of 13
No
No
Scer\MKK2
3 of 13
No
No
Scer\STE7
2 of 13
No
No
Scer\KIC1
1 of 13
No
No
Scer\SPS1
1 of 13
No
No
Schizosaccharomyces pombe (Fission yeast) (4)
Spom\wis1
6 of 12
Yes
Yes
Spom\byr1
2 of 12
No
No
Spom\pek1
2 of 12
No
No
Spom\ppk11
1 of 12
No
No
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Mkk4. Refer to their site for version information.
Paralogs
Downloads
Download All DIOPT Paralogs
Paralogs (via DIOPT v9.1)
Gene Symbol
Score
Source
Compara
Domainoid
eggNOG
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Drosophila melanogaster (Fruit fly) (13)
lic
8 of 13
Dsor1
4 of 13
hep
2 of 13
for
1 of 13
fray
1 of 13
GckIII
1 of 13
hpo
1 of 13
hppy
1 of 13
Mekk1
1 of 13
msn
1 of 13
Pak3
1 of 13
Slik
1 of 13
Tao
1 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    DO term
    Complementation?
    Transgene?
    MAP2K4; mitogen-activated protein kinase kinase 4
    14 of 14
    601335
        MAP2K3; mitogen-activated protein kinase kinase 3
        5 of 14
        602315
             
            MAP2K6; mitogen-activated protein kinase kinase 6
            5 of 14
            601254
                 
                Functional Complementation Data
                Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
                Interactions
                Summary of Physical Interactions
                Summary of Genetic Interactions
                Interaction Browsers
                View in FlyBase Interactions Browser   View in MIST tool (external link)
                Please look at the allele data for full details of the genetic interactions
                Starting gene(s)
                Interaction type
                Interacting gene(s)
                Reference
                Mkk4
                suppressible
                hep
                (Rallis et al., 2010)
                Mkk4
                enhanceable
                hep
                (Rallis et al., 2010)
                Starting gene(s)
                Interaction type
                Interacting gene(s)
                Reference
                Ask1
                suppressible
                Mkk4
                (Sekine et al., 2011)
                egr
                suppressible
                Mkk4
                (Geuking et al., 2009)
                hep
                enhanceable
                Mkk4
                (Rallis et al., 2010)
                hep
                suppressible
                Mkk4
                (Geuking et al., 2009)
                MAPk-Ak2
                suppressible
                Mkk4
                (Seisenbacher et al., 2011)
                External Data
                Linkouts
                BioGRID - A database of protein and genetic interactions.
                DroID - A comprehensive database of gene and protein interactions.
                MIST (genetic) - An integrated Molecular Interaction Database
                MIST (protein-protein) - An integrated Molecular Interaction Database
                Pathways
                Signaling Pathways (FlyBase)
                Metabolic Pathways
                FlyBase
                External Links
                External Data
                Linkouts
                KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
                Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
                SignaLink - A signaling pathway resource with multi-layered regulatory networks.
                Class of Gene
                Genomic Location and Detailed Mapping Data
                Chromosome (arm)
                3R
                Recombination map
                3-48
                Cytogenetic map
                85A5-85A5
                Sequence location
                FlyBase Computed Cytological Location
                Cytogenetic map
                Evidence for location
                85A5-85A5
                Limits computationally determined from genome sequence between P{EP}EP833 and P{lacW}l(3)L4740L4740
                Experimentally Determined Cytological Location
                Cytogenetic map
                Notes
                References
                85A2-85A7
                (Han, 1997.11.21)
                85A2-85A7
                (determined by in situ hybridisation)
                (Han, 1998.4.1, Han et al., 1998)
                Experimentally Determined Recombination Data
                Location

                3-48

                (FlyBase, 2016)

                3-45.4

                (Comeron et al., 2012)
                Left of (cM)
                Right of (cM)
                Notes
                Stocks and Reagents
                Stocks (14)
                Genomic Clones (19)
                 

                Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

                cDNA Clones (120)
                 

                Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

                cDNA clones, fully sequenced
                BDGP DGC clones
                Other clones
                Drosophila Genomics Resource Center cDNA clones

                For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

                cDNA Clones, End Sequenced (ESTs)
                BDGP DGC clones
                Other clones
                RNAi and Array Information
                Linkouts
                DRSC - Results frm RNAi screens
                Antibody Information
                Laboratory Generated Antibodies
                 

                polyclonal

                (Rallis et al., 2010)
                Commercially Available Antibodies
                 
                Cell Line Information
                Publicly Available Cell Lines
                 
                  Other Stable Cell Lines
                   
                    Other Comments

                    When dsRNA constructs are made and transiently transfected into S2 cells in RNAi experiments, chromosome abnormalities and chromosome alignment defects are seen.

                    (Bettencourt-Dias et al., 2004)

                    dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.

                    (Kiger et al., 2003)

                    By using a drug SB203580 that specifically binds and inhibits p38 activity (lic and Mkk4), we demonstrated that Drosophila p38 is surprisingly involved in down-regulation of Drosophila immune response.

                    (Han et al., 1998)

                    Mkk4 is an activator of bsk kinase but not Mpk2 and p38b kinases.

                    (Han et al., 1998)
                    Relationship to Other Genes
                    Source for database merge of

                    Source for merge of: Mkk4 JNKK2

                    (Martinez Arias, 2000.4.12)
                    Additional comments
                    Nomenclature History
                    Source for database identify of

                    Source for identity of: Mkk4 CG9738

                    (Zhao, 1999.11)
                    Nomenclature comments
                    Etymology
                    Synonyms and Secondary IDs (21)
                    Reported As
                    Symbol Synonym
                    142758_at
                    (Kristensen et al., 2005)
                    CG9738
                    (Metwally et al., 2019, Hosono et al., 2015, Ni et al., 2011.7.19, Ni et al., 2010.12.1, Keleman et al., 2009.8.5, Sepp et al., 2008, Morrison et al., 2000)
                    CT27508
                    (Morrison et al., 2000)
                    D-MKK4
                    (Ryabinina et al., 2006, Martin-Blanco, 2000, Han et al., 1998, Han et al., 1998)
                    DMKK4
                    (Ip and Davis, 1998)
                    JNKK2
                    (Martinez Arias, 2000.4.12, Kim, 1998.4.22)
                    MAPKK4
                    (Guichard et al., 2006)
                    MKK4
                    (Harnish et al., 2021, Galenza and Foley, 2019, Lee et al., 2019, Ma et al., 2016, Das et al., 2013, Macdonald et al., 2013, Ríos-Barrera and Riesgo-Escovar, 2013, Serysheva et al., 2013, Vandenabeele and Bertrand, 2012, Seisenbacher et al., 2011, Suganuma et al., 2010, Mlodzik, 2002, Sokol and Cooley, 2001, Martinez Arias, 2000.4.12, Weber et al., 2000, Han, 1997.11.21, Han, 1997.11.21)
                    Mkk4
                    (He et al., 2025, Huang and Calvi, 2025, Balakireva et al., 2024, Pan et al., 2023, Havula et al., 2022, Bilder et al., 2021, Buhlman et al., 2021, Gan et al., 2021, Klemm et al., 2021, Ostalé et al., 2021, La Marca and Richardson, 2020, Wang et al., 2020, Meltzer et al., 2019, Metwally et al., 2019, Sun et al., 2019, Gene Disruption Project members, 2018-, Romey-Glüsing et al., 2018, Schimizzi et al., 2016, Dent et al., 2015, Kanoh et al., 2015, Faisal et al., 2014, Sopko et al., 2014, Wong et al., 2014, Carter, 2013, Das et al., 2013, Kwon et al., 2013, Yin et al., 2013, Felix et al., 2012, Igboin et al., 2012, Marchal et al., 2012, Friedman et al., 2011, Neisch et al., 2010, Rallis et al., 2010, Geuking et al., 2009, Sepp et al., 2008, Syrzycka et al., 2007, Gesellchen et al., 2005)
                    Mpk4
                    P-MKK4
                    (Hebbar et al., 2015)
                    SEK1/MKK4
                    (Bjorklund et al., 2006, Morrison et al., 2000)
                    dMKK4
                    (Mishra et al., 2021, Biteau et al., 2011, Bond and Foley, 2009, Zhuang et al., 2006, Sathyanarayana et al., 2003)
                    dMkk4
                    (Sekine et al., 2011)
                    mkk4
                    (Fabian et al., 2021, Hsu et al., 2021, Rallis et al., 2013, Tresch and Markowetz, 2008, Boutros et al., 2002)
                    Name Synonyms
                    Drosophila MAP kinase kinase 4
                    (Han et al., 1998)
                    JNK kinase 2
                    (Kim, 1998.4.22)
                    MAP kinase kinase 4
                    (Felix et al., 2012, Han et al., 1998, Han, 1997.11.21)
                    MAPK kinase 4
                    (Vandenabeele and Bertrand, 2012)
                    Map kinase kinase 4
                    (Neisch et al., 2010)
                    map kinase kinase 4
                    (Faisal et al., 2014)
                    Secondary FlyBase IDs
                    • FBgn0024950
                    • FBgn0040310
                    Datasets (0)
                    Study focus (0)
                    Experimental Role
                    Project
                    Project Type
                    Title
                    Study result (0)
                    Result
                    Result Type
                    Title
                    External Crossreferences and Linkouts ( 53 )
                    Sequence Crossreferences
                    NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
                    GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
                    GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
                    RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
                    UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
                    UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
                    Other crossreferences
                    AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
                    BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
                    DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
                    EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
                    FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
                    FlyMine - An integrated database for Drosophila genomics
                    InterPro - A database of protein families, domains and functional sites
                    KEGG Genes - Molecular building blocks of life in the genomic space.
                    MARRVEL_MODEL - MARRVEL (model organism gene)
                    Linkouts
                    BioGRID - A database of protein and genetic interactions.
                    Cell Signaling Technology - Commercial vendor for primary antibodies and antibody conjugates.
                    Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
                    DroID - A comprehensive database of gene and protein interactions.
                    DRSC - Results frm RNAi screens
                    FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
                    FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
                    Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
                    Flygut - An atlas of the Drosophila adult midgut
                    FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.
                    iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
                    KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
                    MIST (genetic) - An integrated Molecular Interaction Database
                    MIST (protein-protein) - An integrated Molecular Interaction Database
                    Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
                    SignaLink - A signaling pathway resource with multi-layered regulatory networks.
                    References (135)