Human Disease Model Report: cancer, multiple, MAP2K1,2-related

General Information

Name

cancer, multiple, MAP2K1,2-related

FlyBase ID

FBhh0001022

Disease Ontology Term

cancer

Parent Disease

OMIM

Overview

The human MAP2K (Mitogen-Activated Protein Kinase Kinase) genes, MAP2K1 and MAP2K2, are implicated in a variety of human cancers. MAP2K1 (also called MEK1) and MAP2K2 (also called MEK2) are dual-specificity protein kinases that are essential component of the MAP kinase signal transduction pathway. There is a single gene in flies, Dsor1, orthologous to both human genes. Multiple genetic reagents have been generated for Dmel\Dsor1, including amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis.

Neither human gene, MAP2K1 nor MAP2K2, has been introduced into flies.

Animals homozygous for loss-of-functions mutations of Dmel\Dsor1 typically die during embryogenesis. Phenotypes produced by overexpression of wild-type Dsor1 and of mutants analogous to disease-implicated variants have been assessed. Overexpression of wild-type produces no phenotypes detected in the assays used; for the disease-implicated variants, segmentation defects and minor defects of head structures are observed; a high percentage of animals fail to develop past the embryo state.

Variant(s) implicated in human disease tested (as analogous mutation in fly gene): F72L in the fly Dsor1 gene (corresponds to F53L in the human MAP2K1 gene and F57L in the MAP2K2 gene); E222K in the fly Dsor1 gene (corresponds to E203K in the human MAP2K1 gene and E207K in the human MAP2K2 gene). Based on the percentage of animals that fail to survive the embryonic stage, the relative severity of the disease-implicated variants has been assessed.

See also the Human Disease Model report 'RASopathies, MAP2K1,2-related' (FBhh0001509).

[updated Apr. 2023 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, multiple, MAP2K1,2-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

MAP2K1 is implicated in a variety of human cancers, including malignant melanoma of skin, lung adenocarcinoma, neoplasm of the large intestine, colorectal neoplasms, adenocarcinoma of stomach, and cutaneous melanoma. [ClinVar, 376445, 375982; 2019.05.13]

(FlyBase Curators, 2013-)

Genetics

Cellular phenotype and pathology

Molecular information

MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1) encodes a dual-specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway (also called the MAPK/ERK pathway). [Gene Cards, MAP2K1; 2019.05.13]

(FlyBase Curators, 2013-)

External links

COSMIC gene: MAP2K1
COSMIC gene: MAP2K2
Gene2Function (human gene): MAP2K1
Gene2Function (human gene): MAP2K2
Gene Cards: MAP2K1
Gene Cards: MAP2K2
MedlinePlus (gene): MAP2K2
MedlinePlus (gene): MAP2K1
KEGG Disease Pathways: Pathways in Cancer
MARRVEL (human gene): MAP2K1
MARRVEL (human gene): MAP2K2
NCBI (Entrez) gene: MAP2K1; mitogen-activated protein kinase kinase 1
NCBI (Entrez) gene: MAP2K2; mitogen-activated protein kinase kinase 2

Disease synonyms

cancer, multiple, MAP2K1-related

Related Diseases

Related human health report(s)

cardiofaciocutaneous syndrome 3

RASopathies, MAP2K1,2-related

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

MAP2K1; mitogen-activated protein kinase kinase 1

D. melanogaster ortholog (based on DIOPT)

Dmel\Dsor1

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila. The second human gene is MAP2K2.

Human gene (HGNC)

Symbol / Name

MAP2K2; mitogen-activated protein kinase kinase 2

D. melanogaster ortholog (based on DIOPT)

Dmel\Dsor1

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human genes to 1 Drosophila gene.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Dsor1

Gene Snapshot

Downstream of raf1 (Dsor1) encodes a serine/threonine kinase that phosphorylates MAP kinase. It is activated by the product of Raf and acts downstream of receptor tyrosine kinases such as those encoded by tor, Egfr, and sev. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human MAP2K1 and MAP2K2 (1 Drosophila to 2 human). Dmel\Dsor1 shares 55-64% identity and 69-78% similarity with the human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (78 groups)

Dsor1

protein-protein

Interacting group

Assay

References

Dsor1 - 14-3-3ε

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - 14-3-3ζ

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Akap200

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - αTub84D

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - arm

proximity ligation assay, fluorescence microscopy

(Hall and Verheyen, 2015)

Dsor1 - AspRS-m

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - ave

pull down, anti tag western blot, electron microscopy, molecular sieving, molecular weight estimation by staining

(Maisonneuve et al., 2024)

Dsor1 - βCOP

anti tag coimmunoprecipitation, anti tag western blot

(Friedman et al., 2011)

Dsor1 - blanks

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - brm

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - caz

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - CG1416

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - CG4972

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - CG12948

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - cindr

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - cnk

pull down, anti tag western blot, electron microscopy, molecular sieving, molecular weight estimation by staining, anti tag coimmunoprecipitation, peptide massfingerprinting

(Maisonneuve et al., 2024, Friedman et al., 2011)

Dsor1 - cpa

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - CSN8

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Dp1

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Droj2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - eIF3a

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - eIF3l

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - eIF4E1

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - GCS2β

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - glo

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Gmppb

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Golgin97

experimental knowledge based

(Guruharsha et al., 2011)

Dsor1 - HDAC1

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Hsp83

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Imp

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - krz

anti tag coimmunoprecipitation, anti tag western blot

(Tipping et al., 2010)

Dsor1 - ksr

molecular sieving, molecular weight estimation by staining, electron microscopy, anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting

(Maisonneuve et al., 2024, Friedman et al., 2011)

Dsor1 - kuk

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Lamtor3

pull down, autoradiography

(Mouchel-Vielh et al., 2008)

Dsor1 - larp

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Map60

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Mbs

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Mcad

anti tag coimmunoprecipitation, anti tag western blot

(Friedman et al., 2011)

Dsor1 - Mcm7

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Mec2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Mkk4

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Nepl3

experimental knowledge based

(Guruharsha et al., 2011)

Dsor1 - nesd

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Ostm1

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - ptch

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Pyk

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Raf

anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting, two hybrid

(Maisonneuve et al., 2024, Friedman et al., 2011, Therrien et al., 1998)

Dsor1 - Rbcn-3A

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RfC4

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RhoGAP18B

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - rl

anti tag coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy

(Hall and Verheyen, 2015, Tipping et al., 2010)

Dsor1 - RpL9

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpL10

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpL15

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpL24

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpL28

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpL32

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpS2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpS20

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpS28b

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - RpS30

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Rpt4

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Rpt6

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Saf-B

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - scny

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - ScsβA

anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting

(Friedman et al., 2011, Friedman et al., 2011)

Dsor1 - ScsβG

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - Sec13

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - SERCA

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - sesB

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - sip2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - SkpA

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - sqd

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - UQCR-C2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - vlc

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - vret

experimental knowledge based

(Guruharsha et al., 2011)

Dsor1 - wal

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Dsor1 - ZAP3

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (20 alleles)

Dsor1

Models Based on Experimental Evidence ( 12 )

Allele

Disease

Evidence

References

Dsor1^F53S.UASp

model of RASopathy

CEA

(Marmion et al., 2021)

model of cancer

CEA

(Jindal et al., 2017)

Dsor1^F53L.UASp

model of cancer

CEA

(Jindal et al., 2017)

Dsor1^E203K.UASp

model of cancer

CEA

(Jindal et al., 2017)

Dsor1^Y130C.UASp

model of cancer

CEA

(Jindal et al., 2017)

Dsor1^D44G.UASp

model of cancer

CEA

(Jindal et al., 2017)

Dsor1^F72S

model of RASopathy

CEA

(Marmion et al., 2023)

Dsor1^Y149C

model of RASopathy

CEA

(Marmion et al., 2023)

Dsor1^E222K

model of RASopathy

CEA

(Marmion et al., 2023)

Dsor1^{F53S.UASp.SSAA}

model of RASopathy

CEA

(Marmion et al., 2021)

Dsor1^F53Y.UASp

model of cancer

CEA

(Andrianova et al., 2023)

Dsor1^G128D.UASp

model of cancer

CEA

(Andrianova et al., 2023)

Dsor1^Q56P.UASp

model of cancer

CEA

(Andrianova et al., 2023)

Modifiers Based on Experimental Evidence ( 9 )

Allele

Disease

Interaction

References

Dsor1^HMS00037

ameliorates mitochondrial DNA depletion syndrome 15

modeled by TFAM^UAS.cCa

(Duncan et al., 2018)

Dsor1^JF01697

ameliorates mitochondrial DNA depletion syndrome 15

modeled by TFAM^UAS.cCa

(Duncan et al., 2018)

Dsor1^G79

ameliorates autosomal dominant cerebellar ataxia

modeled by Hsap\ATXN1^82Q.UAS

(Park et al., 2013)

Dsor1^LH110

ameliorates neurofibromatosis

modeled by Nf1^E2

(Walker et al., 2013)

ameliorates pancreatic ductal adenocarcinoma

modeled by CycE^{UAS.Tag:HA.Medsh}, Med^{RNAi.UAS.CycE-HA}, p53^{RNAi.UAS.RasG12D}

(Sekiya et al., 2023)

Dsor1^S-1221

ameliorates Huntington's disease

modeled by Hsap\HTT^NT.128Q.UAS

(Miller et al., 2012)

Dsor1^GD9123

ameliorates Huntington's disease

modeled by Hsap\HTT^NT.128Q.UAS

(Miller et al., 2012)

ameliorates neurofibromatosis

modeled by Nf1^E2

(Walker et al., 2013)

Dsor1^KK102276

ameliorates neurofibromatosis

modeled by Nf1^E2

(Walker et al., 2013)

ameliorates colorectal cancer

modeled by SH3PX1^JF02730

(Zhang et al., 2019)

ameliorates hematologic cancer

modeled by mxc¹

(Kurihara et al., 2020)

Dsor1^F72S

model of RASopathy

is ameliorated by grk^unspecified

(Marmion et al., 2023)

Dsor1^RNAi.UAS.cUa

ameliorates cardiomyopathy

modeled by Hsap\RAF1^gof.UAS

(Yu et al., 2013)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

Dsor1^D44G.UASp

P{UASp-Dsor1.D44G}

Dsor1^{F53S.UASp.SSAA}

P{UASp-Dsor1.F53S.SSAA}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸; P{GD9123}v40026

y¹ v¹; P{TRiP.JF03100}attP2

Dsor1^JF01697

P{TRiP.JF01697}

y¹ v¹; P{TRiP.JF01697}attP2

Dsor1^HMS00037

P{TRiP.HMS00037}

y¹ v¹; P{TRiP.HMS00037}attP2

Dsor1^HMS00710

P{TRiP.HMS00710}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00710}attP2/TM3, Sb¹

Dsor1^GL00096

P{TRiP.GL00096}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00096}attP2/TM3, Sb¹

Dsor1^GLV21003

P{TRiP.GLV21003}

y¹ sc^* v¹ sev²¹; P{TRiP.GLV21003}attP2

Dsor1^HMS00145

P{TRiP.HMS00145}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00145}attP2

Dsor1^GLC01824

P{TRiP.GLC01824}

y¹ sc^* v¹ sev²¹; P{TRiP.GLC01824}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Dsor1^K8C13

loss of function allele

CRISPR/Cas9

CRISPR/Cas9

CRISPR/Cas9

ethyl methanesulfonate

y¹ w^a Dsor1^S-1221/Basc

Dsor1^LH110

amorphic allele - genetic evidence

y¹ w^* Dsor1^LH110 P{FRT(w^hs)}101/FM7a

Dsor1^G79

ethyl methanesulfonate

w¹ Dsor1^G79/FM7c/Dp(1;Y)FF1, y⁺

References (7)

Report Sections

Open Close