Seroatlas · Human Serome Atlas

MADD

MAP kinase-activating death domain protein

Also known as: DENN, KIAA0358, MADD_HUMAN, RAB3GEP

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q8WXG6
Gene: MADD
Ensembl: ENSG00000110514
Chromosome: 11
Canonical length: 1647 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Plasma membrane,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1647 residues, UniProt reviewed canonical sequence.

>Q8WXG6|MADD
     1  MVQKKKFCPR LLDYLVIVGA RHPSSDSVAQ TPELLRRYPL EDHTEFPLPP DVVFFCQPEG
    61  CLSVRQRRMS LRDDTSFVFT LTDKDTGVTR YGICVNFYRS FQKRISKEKG EGGAGSRGKE
   121  GTHATCASEE GGTESSESGS SLQPLSADST PDVNQSPRGK RRAKAGSRSR NSTLTSLCVL
   181  SHYPFFSTFR ECLYTLKRLV DCCSERLLGK KLGIPRGVQR DTMWRIFTGS LLVEEKSSAL
   241  LHDLREIEAW IYRLLRSPVP VSGQKRVDIE VLPQELQPAL TFALPDPSRF TLVDFPLHLP
   301  LELLGVDACL QVLTCILLEH KVVLQSRDYN ALSMSVMAFV AMIYPLEYMF PVIPLLPTCM
   361  ASAEQLLLAP TPYIIGVPAS FFLYKLDFKM PDDVWLVDLD SNRVIAPTNA EVLPILPEPE
   421  SLELKKHLKQ ALASMSLNTQ PILNLEKFHE GQEIPLLLGR PSNDLQSTPS TEFNPLIYGN
   481  DVDSVDVATR VAMVRFFNSA NVLQGFQMHT RTLRLFPRPV VAFQAGSFLA SRPRQTPFAE
   541  KLARTQAVEY FGEWILNPTN YAFQRIHNNM FDPALIGDKP KWYAHQLQPI HYRVYDSNSQ
   601  LAEALSVPPE RDSDSEPTDD SGSDSMDYDD SSSSYSSLGD FVSEMMKCDI NGDTPNVDPL
   661  THAALGDASE VEIDELQNQK EAEEPGPDSE NSQENPPLRS SSSTTASSSP STVIHGANSE
   721  PADSTEMDDK AAVGVSKPLP SVPPSIGKSN VDRRQAEIGE GSVRRRIYDN PYFEPQYGFP
   781  PEEDEDEQGE SYTPRFSQHV SGNRAQKLLR PNSLRLASDS DAESDSRASS PNSTVSNTST
   841  EGFGGIMSFA SSLYRNHSTS FSLSNLTLPT KGAREKATPF PSLKVFGLNT LMEIVTEAGP
   901  GSGEGNRRAL VDQKSSVIKH SPTVKREPPS PQGRSSNSSE NQQFLKEVVH SVLDGQGVGW
   961  LNMKKVRRLL ESEQLRVFVL SKLNRMVQSE DDARQDIIPD VEISRKVYKG MLDLLKCTVL
  1021  SLEQSYAHAG LGGMASIFGL LEIAQTHYYS KEPDKRKRSP TESVNTPVGK DPGLAGRGDP
  1081  KAMAQLRVPQ LGPRAPSATG KGPKELDTRS LKEENFIASI ELWNKHQEVK KQKALEKQRP
  1141  EVIKPVFDLG ETEEKKSQIS ADSGVSLTSS SQRTDQDSVI GVSPAVMIRS SSQDSEVSTV
  1201  VSNSSGETLG ADSDLSSNAG DGPGGEGSVH LASSRGTLSD SEIETNSATS TIFGKAHSLK
  1261  PSIKEKLAGS PIRTSEDVSQ RVYLYEGLLG RDKGSMWDQL EDAAMETFSI SKERSTLWDQ
  1321  MQFWEDAFLD AVMLEREGMG MDQGPQEMID RYLSLGEHDR KRLEDDEDRL LATLLHNLIS
  1381  YMLLMKVNKN DIRKKVRRLM GKSHIGLVYS QQINEVLDQL ANLNGRDLSI WSSGSRHMKK
  1441  QTFVVHAGTD TNGDIFFMEV CDDCVVLRSN IGTVYERWWY EKLINMTYCP KTKVLCLWRR
  1501  NGSETQLNKF YTKKCRELYY CVKDSMERAA ARQQSIKPGP ELGGEFPVQD LKTGEGGLLQ
  1561  VTLEGINLKF MHNQVFIELN HIKKCNTVRG VFVLEEFVPE IKEVVSHKYK TPMAHEICYS
  1621  VLCLFSYVAA VHSSEEDLRT PPRPVSS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MADD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.42
Highest tissue expression: 101 nTPM

Expression across tissuesHPA

Tissue

cerebellum: 101 nTPM
retina: 64 nTPM
cerebral cortex: 59 nTPM
pituitary gland: 57 nTPM
hippocampal formation: 34 nTPM
hypothalamus: 31 nTPM

Single-cell type

platelets: 219 nCPM
cone photoreceptor cells: 180 nCPM
rod photoreceptor cells: 154 nCPM
retinal horizontal cells: 150 nCPM
thyrotrophs: 120 nCPM
lactotrophs: 119 nCPM

Immune cell

basophil: 23 nTPM
non-classical monocyte: 6.6 nTPM
total PBMC: 5.8 nTPM
eosinophil: 5.4 nTPM
T-reg: 5.4 nTPM
intermediate monocyte: 5.3 nTPM

Brain region

cerebral cortex: 106 nTPM
hippocampal formation: 104 nTPM
cerebellum: 94 nTPM
basal ganglia: 88 nTPM
white matter: 86 nTPM
amygdala: 72 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MADD.

Disease | AllUniProt

Conditions MADD is implicated in, by any mechanism.

DEEAH syndrome (DEEAH) MIM:619004
Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia (NEDDISH) MIM:619005

Disease | GeneticClinVar

39 pathogenic / likely-pathogenic of 418 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Deeah syndrome
Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia
MADD-related disorder
Inborn genetic diseases
Autosomal recessive MADD-related disorders

Disease | ImmuneIEDB

Conditions an epitope on MADD was assayed in.

narcolepsy B cell
multiple sclerosis B cell
peripheral nervous system disease B cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.58
gnomAD pLI: 0
gnomAD missense Z: 1.1
DepMap mean gene effect: 0.01
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

cDENN domain
dDENN domain
uDENN domain
Tripartite DENN domain
DENN domain, C-terminal lobe
DENN (AEX-3) domain
uDENN domain
MAP kinase-activating death domain protein
MAP kinase-activating death domain protein, death domain
MAP kinase-activating death domain protein, C-terminal PH-like domain
MAP kinase-activating death domain protein death domain
MADD C-terminal PH-like domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of MADD in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MADD as an antibody target. Whether an autoantibody or antibody against MADD could matter depends on whether native MADD is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MADD is annotated at the cell surface, where native MADD is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label MADD as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...