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Protein

MAP kinase-activating death domain protein

Gene

Madd

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a significant role in regulating cell proliferation, survival and death through alternative mRNA splicing. Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms. Component of the TNFRSF1A signaling complex: MADD links TNFRSF1A with MAP kinase activation. Plays an important regulatory role in physiological cell death (TNF-alpha-induced, caspase-mediated apoptosis).2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-RNO-5357905. Regulation of TNFR1 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
MAP kinase-activating death domain protein
Alternative name(s):
Rab3 GDP/GTP exchange factor
Gene namesi
Name:MaddImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi619922. Madd.

Subcellular locationi

  • Membrane By similarity
  • Cytoplasm By similarity

GO - Cellular componenti

  • cytosol Source: RGD
  • integral component of membrane Source: UniProtKB
  • nucleus Source: RGD
  • synapse Source: RGD
  • synaptic vesicle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 16021601MAP kinase-activating death domain protein1 PublicationPRO_0000278140Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei688 – 6881PhosphoserineCombined sources
Modified residuei691 – 6911PhosphoserineCombined sources
Modified residuei778 – 7781PhosphoserineCombined sources
Modified residuei812 – 8121PhosphoserineCombined sources
Modified residuei817 – 8171PhosphoserineBy similarity
Modified residuei819 – 8191PhosphoserineBy similarity
Modified residuei900 – 9001PhosphoserineBy similarity
Modified residuei909 – 9091PhosphoserineCombined sources
Modified residuei1038 – 10381PhosphoserineCombined sources
Modified residuei1040 – 10401PhosphothreonineCombined sources
Modified residuei1045 – 10451PhosphothreonineCombined sources
Modified residuei1089 – 10891PhosphoserineBy similarity
Modified residuei1194 – 11941PhosphothreonineBy similarity
Modified residuei1196 – 11961PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO08873.
PRIDEiO08873.

PTM databases

iPTMnetiO08873.
PhosphoSiteiO08873.

Expressioni

Tissue specificityi

Expressed in all tissues examined with the highest expression in brain.1 Publication

Gene expression databases

ExpressionAtlasiO08873. baseline and differential.
GenevisibleiO08873. RN.

Interactioni

Subunit structurei

Interacts with the death domain of TNFRSF1A through its own death domain. Interacts with PIDD1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi250173. 2 interactions.
STRINGi10116.ENSRNOP00000017360.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 9774UDENNAdd
BLAST
Domaini171 – 401231DENNPROSITE-ProRule annotationAdd
BLAST
Domaini484 – 55774dDENNPROSITE-ProRule annotationAdd
BLAST
Domaini1295 – 137076DeathSequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1118 – 120790Ser-richSequence analysisAdd
BLAST

Sequence similaritiesi

Belongs to the MADD family.Curated
Contains 1 dDENN domain.PROSITE-ProRule annotation
Contains 1 death domain.Sequence analysis
Contains 1 DENN domain.PROSITE-ProRule annotation
Contains 1 uDENN domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3570. Eukaryota.
ENOG410XP23. LUCA.
GeneTreeiENSGT00760000118819.
HOGENOMiHOG000231438.
HOVERGENiHBG079455.
InParanoidiO08873.
OMAiMHSQVFI.
OrthoDBiEOG708VXV.
PhylomeDBiO08873.

Family and domain databases

InterProiIPR005112. dDENN_dom.
IPR001194. DENN_dom.
IPR005113. uDENN_dom.
[Graphical view]
PfamiPF02141. DENN. 1 hit.
PF03456. uDENN. 1 hit.
[Graphical view]
SMARTiSM00801. dDENN. 1 hit.
SM00799. DENN. 1 hit.
SM00800. uDENN. 1 hit.
[Graphical view]
PROSITEiPS50947. DDENN. 1 hit.
PS50211. DENN. 1 hit.
PS50946. UDENN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O08873-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVQKKFCPRL LDYLVIVGAR HPSSDSVAQT PELLRRYPLE DHPEFPLPPD
60 70 80 90 100
VVFFCQPEGC LSVRQRRMSL RDDTSFVFTL TDKDTGVTRY GICVNFYRSF
110 120 130 140 150
QKRMPKEKAE GGAGPRGKEG AHAPCASEEA ATESSESGST LQPPSADSTP
160 170 180 190 200
DVNQSPRGKR RAKAGNRSRN STLTSLCVLS HYPFFSTFRE CLYTLKRLVD
210 220 230 240 250
CCSERLLGKK PGIPRGVQRD TMWRIFTGSL LVEEKSSALL HDLREIEAWI
260 270 280 290 300
YRLLRSPVPV SGQKRVDIEV LPQEVQQALT FALPDPSRFT LVDFPLHLPL
310 320 330 340 350
ELLGVDACLQ VLTCILLEHK VVLQSRDYNA LSMSVMAFVA MIYPLEYMFP
360 370 380 390 400
VIPLLPTCMA SAEQLLLAPT PYIIGVPASF FLYKLDFKMP DDVWLVDLDS
410 420 430 440 450
NRVIAPTNAE VLPILPEPES LELKKHLKQA LASMSLNTQP ILNLEKFHEG
460 470 480 490 500
QETPLLLGRF SNDLQSTPST EFNPLIYGND VDSVDVATRV AMVRFFNSAN
510 520 530 540 550
VLQGFQMHTR TLRLFPRPVV AFQAGSFLAS RPRQTPFAEK LARTQAVEYF
560 570 580 590 600
GEWILNPSNY AFQRIHNNTF DPALIGDKPK WYAHQLQPIH YRVYDSNSQL
610 620 630 640 650
AEALSVPPER DSESDPTDDS GSDSMDYDDS SSSYSSLGDF VSEMMKCDIN
660 670 680 690 700
GDTPNVDPLT HAALGDASEV EIDELQPQKE GEEPGPDSEN SQENLPLRSS
710 720 730 740 750
SSTTASSSPS TIVHGAHSEP ADSTEVGDKA ATGISKPLPP VPPSICKSTV
760 770 780 790 800
DRRQTETGEG SVCQRTYDHP YFEPQYGSPA EEDDDEQGES YTPRFSQHAS
810 820 830 840 850
GSRAQKLLRP NSLKLASDSD AESDSRASSP NSTVSNNSTE GFGGIMSFAS
860 870 880 890 900
SLYRNHSTSF SLSNLTLPTK GAREKTTPFP SLKGNRRALV DQKSSVIKHS
910 920 930 940 950
PTVKREPPSP QGRSSNSSEN QQFLKEVVHS VLDGQGVGWL NMKKVRRLLE
960 970 980 990 1000
SEQLRVFVLS KLSRAVQSED DARQDVIQDV EISRKVYKGM LDLLKCTVLS
1010 1020 1030 1040 1050
LEQSYAHAGL GGMASIFGLL EIAQTHYYSK EPDKRKRSPT ENVNTPVGKD
1060 1070 1080 1090 1100
PGLAGRGDPK AMAQLRVPQL GPRAPSATGR GPKELDTRSL KEENFVASVG
1110 1120 1130 1140 1150
PEVIKPVFDL GETEEKKSQI SADSGVSLAS ASQRTDQDSV IGVSPAVMIR
1160 1170 1180 1190 1200
SSSQDSEVSN SSGETLGADS DLSSNAGDGP GGEGSAHLAS SRATLSDSEI
1210 1220 1230 1240 1250
ETNSATSTIF GKAHSLKPKE KPASSPVRSS EDVSQRVYLY EGLLGRDKGS
1260 1270 1280 1290 1300
MWDQLEDAAM ETFSISKERS TLWDQMQFWE DAFLDAVMLE REGMGMDQGP
1310 1320 1330 1340 1350
QEMIDRYLSL GEHDRKRLED DEDRLLATLL HNLISYMLLM KVNKNDIRKK
1360 1370 1380 1390 1400
VRRLMGKSHV GLVYSQQINE VLDQLTNLNG RDLSIRSSGS RHMKKQTFVV
1410 1420 1430 1440 1450
HAGTDTNGDI FFMEVCDDCV VLRSNIGTVY ERWWYEKLIN MTYCPKTKVL
1460 1470 1480 1490 1500
CLWRRNGSET QLNKFYTKKC RELYYCVKDS MERAAARQQS IKPGPELGGE
1510 1520 1530 1540 1550
FPVQDMKTGE GGLLQVTLEG INLKFMHNQV FIELNHIKKC NTVRGVFVLE
1560 1570 1580 1590 1600
EFVPEIKEVV SHKYKTPMAH EICYSVLCLF SYVAAVRSSE EDLRTPPRPV

SS
Length:1,602
Mass (Da):177,992
Last modified:July 1, 1997 - v1
Checksum:i3A5071DE637B2A56
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U72995 mRNA. Translation: AAC53149.1.
PIRiT31671.
RefSeqiNP_446037.1. NM_053585.1.
UniGeneiRn.90117.

Genome annotation databases

EnsembliENSRNOT00000017360; ENSRNOP00000017360; ENSRNOG00000012568.
GeneIDi94193.
KEGGirno:94193.
UCSCiRGD:619922. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U72995 mRNA. Translation: AAC53149.1.
PIRiT31671.
RefSeqiNP_446037.1. NM_053585.1.
UniGeneiRn.90117.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250173. 2 interactions.
STRINGi10116.ENSRNOP00000017360.

PTM databases

iPTMnetiO08873.
PhosphoSiteiO08873.

Proteomic databases

PaxDbiO08873.
PRIDEiO08873.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000017360; ENSRNOP00000017360; ENSRNOG00000012568.
GeneIDi94193.
KEGGirno:94193.
UCSCiRGD:619922. rat.

Organism-specific databases

CTDi8567.
RGDi619922. Madd.

Phylogenomic databases

eggNOGiKOG3570. Eukaryota.
ENOG410XP23. LUCA.
GeneTreeiENSGT00760000118819.
HOGENOMiHOG000231438.
HOVERGENiHBG079455.
InParanoidiO08873.
OMAiMHSQVFI.
OrthoDBiEOG708VXV.
PhylomeDBiO08873.

Enzyme and pathway databases

ReactomeiR-RNO-5357905. Regulation of TNFR1 signaling.

Miscellaneous databases

NextBioi617842.
PROiO08873.

Gene expression databases

ExpressionAtlasiO08873. baseline and differential.
GenevisibleiO08873. RN.

Family and domain databases

InterProiIPR005112. dDENN_dom.
IPR001194. DENN_dom.
IPR005113. uDENN_dom.
[Graphical view]
PfamiPF02141. DENN. 1 hit.
PF03456. uDENN. 1 hit.
[Graphical view]
SMARTiSM00801. dDENN. 1 hit.
SM00799. DENN. 1 hit.
SM00800. uDENN. 1 hit.
[Graphical view]
PROSITEiPS50947. DDENN. 1 hit.
PS50211. DENN. 1 hit.
PS50946. UDENN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of a GDP/GTP exchange protein specific for the Rab3 subfamily small G proteins."
    Wada M., Nakanishi H., Satoh A., Hirano H., Obaishi H., Matsuura Y., Takai Y.
    J. Biol. Chem. 272:3875-3878(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-23; 119-138; 680-699; 748-766; 905-920; 962-985; 1061-1083; 1106-1116; 1222-1248 AND 1493-1507, FUNCTION, TISSUE SPECIFICITY.
    Tissue: Brain1 Publication.
  2. "Down-regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer's disease brain and hippocampal neurons."
    Del Villar K., Miller C.A.
    Proc. Natl. Acad. Sci. U.S.A. 101:4210-4215(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  3. "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
    Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
    Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-812, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688; SER-691; SER-778; SER-812; SER-909; SER-1038; THR-1040; THR-1045 AND SER-1196, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiMADD_RAT
AccessioniPrimary (citable) accession number: O08873
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: July 1, 1997
Last modified: May 11, 2016
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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 one 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.