MADD MAP-kinase activating death domain [Homo sapiens] - Gene

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Summary

Official Symbol: MADDprovided by HGNC
Official Full Name: MAP-kinase activating death domainprovided by HGNC
Primary source: HGNC:6766
See related: Ensembl:ENSG00000110514; HPRD:04664; MIM:603584; Vega:OTTHUMG00000150350
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DENN; IG20; RAB3GEP; FLJ35600; FLJ36300; KIAA0358
Summary: Tumor necrosis factor alpha (TNF-alpha) is a signaling molecule that interacts with one of two receptors on cells targeted for apoptosis. The apoptotic signal is transduced inside these cells by cytoplasmic adaptor proteins. The protein encoded by this gene is a death domain-containing adaptor protein that interacts with the death domain of TNF-alpha receptor 1 to activate mitogen-activated protein kinase (MAPK) and propagate the apoptotic signal. It is membrane-bound and expressed at a higher level in neoplastic cells than in normal cells. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 11p11.2

Sequence :: Chromosome: 11; NC_000011.9 (47290927..47351582)

See MADD in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

The SNP in ADCY5 is implicated in defective proinsulin-to-insulin conversion and previous findings on the role of a genetic variant in MADD on proinsulin-to-insulin conversion, were confirmed.
Title: Glucose-raising genetic variants in MADD and ADCY5 impair conversion of proinsulin to insulin.
Data show that SNPs from MADD, PROX1, and SLC30A8 were associated with type 2 diabetes.
Title: Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 are associated with glucose metabolism in the Chinese.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population.
Endogenous MADD is phosphorylated at three highly conserved sites by Akt, and only the phosphorylated MADD can directly interact with the TRAIL receptor DR4 thereby preventing Fas-associated death domain recruitment.
Title: Akt-phosphorylated mitogen-activated kinase-activating death domain protein (MADD) inhibits TRAIL-induced apoptosis by blocking Fas-associated death domain (FADD) association with death receptor 4.
Observational study of gene-disease association. (HuGE Navigator)
Title: Variants at DGKB/TMEM195, ADRA2A, GLIS3 and C2CD4B loci are associated with reduced glucose-stimulated beta cell function in middle-aged Danish people.
Meta-analysis and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Loss of MADD expression resulted in reduced Grb2 and Sos1/2 recruitment to the TNFR1 complex and decreased Ras and MEKK1/2 activation
Title: MADD, a splice variant of IG20, is indispensable for MAPK activation and protection against apoptosis upon tumor necrosis factor-alpha treatment.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
KIF1Bbeta- and KIF1A-mediated axonal transport of presynaptic regulator Rab3 occurs in a GTP-dependent manner through MADD.
Title: KIF1Bbeta- and KIF1A-mediated axonal transport of presynaptic regulator Rab3 occurs in a GTP-dependent manner through DENN/MADD.

Submit: New GeneRIF Correction See all (20)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	The mRNA expression levels for alpha-tubulin, TRADD, IFN-gamma R2, GAS1, MADD, NF-kappaB, I-kappa B, 14-3-3 protein, APaf1, PARP, IGF-1 receptor, RB1, Rb2/p130, ARC, and caspase 6 are upregulated in human neuronal cells after treatment with HIV-1 gp120	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
Q8WXG6	Q8WXG6	MADD	HPRD	PubMed
Q8WXG6	Q9NQX5	NPDC1	HPRD	PubMed
Q8WXG6	Q9HB75	PIDD	HPRD	PubMed
Q8WXG6	Q16849	PTPRN	HPRD	PubMed
Q8WXG6	O00220	TNFRSF10A	HPRD	PubMed
Q8WXG6	O14763	TNFRSF10B	HPRD	PubMed
Q8WXG6	P19438	TNFRSF1A	HPRD	PubMed
Q8WXG6	Q5THJ4	VPS13D	HPRD	PubMed
BioGRID:114136	BioGRID:120645	PIDD	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114136	BioGRID:112986	TNFRSF1A	BioGRID	PubMed	Reconstituted Complex
BioGRID:114136	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114136	BioGRID:120485	VPS13D	BioGRID	PubMed	Two-hybrid
BioGRID:114136	BioGRID:113366	YWHAZ	BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
Rab guanyl-nucleotide exchange factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
death receptor binding	TAS Traceable Author Statement more info	PubMed
guanyl-nucleotide exchange factor activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activator activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
activation of MAPK activity	IMP Inferred from Mutant Phenotype more info	PubMed
cell surface receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
positive regulation of protein phosphorylation	TAS Traceable Author Statement more info	PubMed
regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	TAS Traceable Author Statement more info	PubMed
integral to membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: MAP kinase-activating death domain protein

Names: MAP kinase-activating death domain protein; Rab3 GDP/GTP exchange factor; insulinoma glucagonoma clone 20; differentially expressed in normal and neoplastic cells

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029462.1 RefSeqGene

Range

5001..65656

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001135943.1 → NP_001129415.1 MAP kinase-activating death domain protein isoform i

Status: REVIEWED

Description

Transcript Variant: This variant (9) differs in the 5' UTR, and uses two alternate in-frame splice sites and lacks three alternate in-frame exons in the mid coding region, compared to variant 4. The resulting isoform (i) is shorter than isoform d.

Source sequence(s)

AF440100, BC040484, DA759613, U77352

UniProtKB/Swiss-Prot

Q8WXG6

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 142

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 246

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 485

DENN; DENN (AEX-3) domain
NM_001135944.1 → NP_001129416.1 MAP kinase-activating death domain protein isoform j

Status: REVIEWED

Description

Transcript Variant: This variant (9) uses two alternate in-frame splice sites and lacks three alternate in-frame exons in the mid coding region, compared to variant 4. The resulting isoform (j) is shorter than isoform d.

Source sequence(s)

AF440103, AK292442, AU077339, U77352

Consensus CDS

CCDS44589.1

UniProtKB/TrEMBL

A8K8S7

UniProtKB/TrEMBL

B5MEE5

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000378753, OTTHUMP00000237191, ENST00000395344, OTTHUMT00000396842

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 142

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 246

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 485

DENN; DENN (AEX-3) domain
NM_003682.3 → NP_003673.3 MAP kinase-activating death domain protein isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (d).

Source sequence(s)

AF440100, AU077339, U77352

Consensus CDS

CCDS7930.1

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000310933, OTTHUMP00000197136, ENST00000311027, OTTHUMT00000317746

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 141

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 246

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 489

DENN; DENN (AEX-3) domain
NM_130470.2 → NP_569826.2 MAP kinase-activating death domain protein isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) has a different exon 1 sequence and lacks exons 16, 21 and 26, as compared to transcript variant 4. The resulting isoform (a) is shorter than isoform d.

Source sequence(s)

AC018410, AF440101, AF440103, DA187733, U77352

Consensus CDS

CCDS7931.1

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000343902, OTTHUMP00000197131, ENST00000342922, OTTHUMT00000317741

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 141

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 245

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 486

DENN; DENN (AEX-3) domain
NM_130471.2 → NP_569827.2 MAP kinase-activating death domain protein isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks exons 21, 26, and a portion of exon 13 as compared to transcript variant 4. The resulting isoform (b) is missing regions of 43 aa, 18 aa, and 21 aa but has identical N- and C-termini as those of isoform (d) encoded by transcript variant 4.

Source sequence(s)

AF440102, AU077339, U77352

Consensus CDS

CCDS44587.1

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000384204, OTTHUMP00000197137, ENST00000407859, OTTHUMT00000317747

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 142

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 246

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 486

DENN; DENN (AEX-3) domain
NM_130472.2 → NP_569828.2 MAP kinase-activating death domain protein isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks exons 16, 21, 26, and a portion of exon 13 as compared to transcript variant 4. The resulting isoform (c) is missing regions of 43 aa, 20 aa, 18 aa, and 21 aa but has identical N- and C-termini as those of isoform (d) encoded by transcript variant 4.

Source sequence(s)

AF440103, AU077339, U77352

Consensus CDS

CCDS44588.1

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000385585, OTTHUMP00000197132, ENST00000402799, OTTHUMT00000317742

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 142

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 246

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 485

DENN; DENN (AEX-3) domain
NM_130473.2 → NP_569829.2 MAP kinase-activating death domain protein isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks exons 21 and 26 as compared to transcript variant 4. The resulting isoform (e) is missing regions of 18 aa and 21 aa but has identical N- and C-termini as those of isoform (d) encoded by transcript variant 4.

Source sequence(s)

AF440101, AU077339, U77352

Consensus CDS

CCDS7932.1

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000304505, OTTHUMP00000197135, ENST00000349238, OTTHUMT00000317745

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 141

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 245

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 487

DENN; DENN (AEX-3) domain
NM_130474.2 → NP_569830.2 MAP kinase-activating death domain protein isoform f

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks exons 16, 21, 26, 34, and part of exon 13 but maintains the same reading frame up through exon 33 as compared to transcript variant 4. The resulting isoform (f) is missing regions of 43 aa, 20 aa, 18 aa, and 21 aa and has a different carboxyl terminus as compared to isoform d.

Source sequence(s)

AF440434, AU077339, U77352

Consensus CDS

CCDS44590.1

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000384435, OTTHUMP00000197133, ENST00000406482, OTTHUMT00000317743

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 142

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 247

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 488

DENN; DENN (AEX-3) domain
NM_130475.2 → NP_569831.1 MAP kinase-activating death domain protein isoform g

Status: REVIEWED

Description

Transcript Variant: This variant (7) has a different exon 1 sequence and lacks exon 34 as compared to transcript variant 4. The resulting isoform (g) is shorter and has a different carboxyl terminus as compared to the isoform (d) encoded by transcript variant 4.

Source sequence(s)

AB002356, AF440100, DA759613, U77352

Consensus CDS

CCDS41642.1

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000378745, OTTHUMP00000197134, ENST00000395336, OTTHUMT00000317744

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 141

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 247

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 492

DENN; DENN (AEX-3) domain
NM_130476.2 → NP_569832.2 MAP kinase-activating death domain protein isoform h

Status: REVIEWED

Description

Transcript Variant: This variant (8) has a different exon 1 sequence, lacks exons 16, 21 and 26, and uses an alternate in-frame splice site in exon 23, as compared to transcript variant 4. The resulting isoform (h) is shorter than isoform d.

Source sequence(s)

AF440100, DA759613, U44953, U77352

Consensus CDS

CCDS44586.1

UniProtKB/Swiss-Prot

Q8WXG6

Related

ENSP00000384287, OTTHUMP00000238029, ENST00000402192, OTTHUMT00000398339

Conserved Domains (3) summary

cl04084
Location:486 – 554
Blast Score: 141

dDENN; dDENN domain

cl04085
Location:8 – 98
Blast Score: 245

uDENN; uDENN domain

cl11519
Location:173 – 402
Blast Score: 486

DENN; DENN (AEX-3) domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p5 Primary Assembly

Range

47290927..47351582

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

46989904..47050670

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC018410.24 (51676..93890)	None
genomic	AC090582.9	None
genomic	CH471064.2	EAW67930.1
		EAW67931.1
		EAW67932.1
		EAW67933.1
		EAW67934.1
		EAW67935.1
		EAW67936.1
		EAW67937.1
		EAW67938.1
		EAW67939.1
		EAW67940.1
genomic	U48254.1	AAB05595.1
mRNA	AB002356.1	BAA20814.2
mRNA	AF440100.1	AAL40265.1
mRNA	AF440101.1	AAL40266.1
mRNA	AF440102.1	AAL40267.1
mRNA	AF440103.1	AAL40268.1
mRNA	AF440434.1	AAL35261.1
mRNA	AK092919.1	None
mRNA	AK093619.1	None
mRNA	AK292442.1	BAF85131.1
mRNA	AK308780.1	None
mRNA	AU077339.1	None
mRNA	BC040484.1	AAH40484.1
mRNA	BE242736.1	None
mRNA	DA187733.1	None
mRNA	DA759613.1	None
mRNA	U44953.1	AAD12154.1
mRNA	U77352.1	AAB57735.1