DEDD_HUMAN
ID DEDD_HUMAN Reviewed; 318 AA.
AC O75618; D3DVF5; O60737;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Death effector domain-containing protein;
DE AltName: Full=DEDPro1;
DE AltName: Full=Death effector domain-containing testicular molecule;
DE AltName: Full=FLDED-1;
GN Name=DEDD; Synonyms=DEDPRO1, DEFT; ORFNames=KE05;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9774341; DOI=10.1093/emboj/17.20.5974;
RA Stegh A.H., Schickling O., Ehret A., Scaffidi C., Peterhaensel C.,
RA Hofmann T.G., Grummt I., Krammer P.H., Peter M.E.;
RT "DEDD, a novel death effector domain-containing protein, targeted to the
RT nucleolus.";
RL EMBO J. 17:5974-5986(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9832420; DOI=10.1210/endo.139.12.6335;
RA Leo C.P., Hsu S.Y., McGee E.A., Salanova M., Hsueh A.J.W.;
RT "DEFT, a novel death effector domain-containing molecule predominantly
RT expressed in testicular germ cells.";
RL Endocrinology 139:4839-4848(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Pan G.;
RT "FLDED-1, a novel molecule with a DED-like domain.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Thome M., Tschopp J.;
RT "DEDPRO1, a novel DED-containing protein.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Dendritic cell;
RA Zhao Z., Huang X., Li N., Zhu X., Cao X.;
RT "A novel gene from human dendritic cell.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP FUNCTION, AND INTERACTION WITH KRT8; KRT18 AND CASP3.
RX PubMed=12235123; DOI=10.1083/jcb.200112124;
RA Lee J.C., Schickling O., Stegh A.H., Oshima R.G., Dinsdale D., Cohen G.M.,
RA Peter M.E.;
RT "DEDD regulates degradation of intermediate filaments during apoptosis.";
RL J. Cell Biol. 158:1051-1066(2002).
RN [11]
RP INTERACTION WITH GTF3C3.
RX PubMed=11965497; DOI=10.1038/sj/cdd/4401038;
RA Zhan Y., Hegde R., Srinivasula S.M., Fernandes-Alnemri T., Alnemri E.S.;
RT "Death effector domain-containing proteins DEDD and FLAME-3 form nuclear
RT complexes with the TFIIIC102 subunit of human transcription factor IIIC.";
RL Cell Death Differ. 9:439-447(2002).
RN [12]
RP INTERACTION WITH CASP8 AND CASP10.
RX PubMed=12527898; DOI=10.1038/sj.onc.1206099;
RA Alcivar A., Hu S., Tang J., Yang X.;
RT "DEDD and DEDD2 associate with caspase-8/10 and signal cell death.";
RL Oncogene 22:291-297(2003).
CC -!- FUNCTION: A scaffold protein that directs CASP3 to certain substrates
CC and facilitates their ordered degradation during apoptosis. May also
CC play a role in mediating CASP3 cleavage of KRT18. Regulates degradation
CC of intermediate filaments during apoptosis. May play a role in the
CC general transcription machinery in the nucleus and might be an
CC important regulator of the activity of GTF3C3. Inhibits DNA
CC transcription in vitro (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:12235123}.
CC -!- SUBUNIT: Interacts with CASP8, CASP10, KRT8, KRT18, CASP3 and FADD.
CC Homodimerizes and heterodimerizes with DEDD2.
CC {ECO:0000269|PubMed:11965497, ECO:0000269|PubMed:12235123,
CC ECO:0000269|PubMed:12527898}.
CC -!- INTERACTION:
CC O75618; Q06481: APLP2; NbExp=3; IntAct=EBI-1043164, EBI-79306;
CC O75618-1; P14635: CCNB1; NbExp=3; IntAct=EBI-15621191, EBI-495332;
CC O75618-1; P06493: CDK1; NbExp=2; IntAct=EBI-15621191, EBI-444308;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus {ECO:0000250}.
CC Note=Translocated to the nucleus during CD95-mediated apoptosis where
CC it is localized in the nucleoli (By similarity). Following apoptosis
CC induction, the mono and/or diubiquitination form increases and forms
CC filamentous structures that colocalize with KRT8 and KRT18 intermediate
CC filament network in simple epithelial cells. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75618-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75618-2; Sequence=VSP_003846;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in testis.
CC {ECO:0000269|PubMed:9832420}.
CC -!- PTM: Exists predominantly in a mono- or diubiquitinated form.
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DR EMBL; AF083236; AAC33105.1; -; mRNA.
DR EMBL; AF100341; AAD16414.1; -; mRNA.
DR EMBL; AF043733; AAC80280.1; -; mRNA.
DR EMBL; AJ010973; CAA09445.1; -; mRNA.
DR EMBL; AF064605; AAC17110.3; -; mRNA.
DR EMBL; CR536556; CAG38793.1; -; mRNA.
DR EMBL; AL591806; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52648.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52650.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52651.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52652.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52653.1; -; Genomic_DNA.
DR EMBL; BC016724; AAH16724.1; -; mRNA.
DR EMBL; BC013910; AAH13910.1; -; mRNA.
DR CCDS; CCDS1219.1; -. [O75618-1]
DR CCDS; CCDS81391.1; -. [O75618-2]
DR RefSeq; NP_001034800.1; NM_001039711.1. [O75618-1]
DR RefSeq; NP_001034801.1; NM_001039712.1. [O75618-1]
DR RefSeq; NP_127491.1; NM_032998.2. [O75618-1]
DR RefSeq; XP_016858291.1; XM_017002802.1. [O75618-1]
DR AlphaFoldDB; O75618; -.
DR BioGRID; 114627; 28.
DR DIP; DIP-41944N; -.
DR IntAct; O75618; 18.
DR MINT; O75618; -.
DR STRING; 9606.ENSP00000356985; -.
DR iPTMnet; O75618; -.
DR PhosphoSitePlus; O75618; -.
DR BioMuta; DEDD; -.
DR EPD; O75618; -.
DR MassIVE; O75618; -.
DR MaxQB; O75618; -.
DR PaxDb; O75618; -.
DR PeptideAtlas; O75618; -.
DR PRIDE; O75618; -.
DR ProteomicsDB; 50122; -. [O75618-1]
DR ProteomicsDB; 50123; -. [O75618-2]
DR Antibodypedia; 34292; 236 antibodies from 33 providers.
DR DNASU; 9191; -.
DR Ensembl; ENST00000368006.8; ENSP00000356985.3; ENSG00000158796.17. [O75618-1]
DR Ensembl; ENST00000458050.6; ENSP00000414821.2; ENSG00000158796.17. [O75618-1]
DR Ensembl; ENST00000490843.6; ENSP00000476946.1; ENSG00000158796.17. [O75618-1]
DR Ensembl; ENST00000545495.5; ENSP00000445835.1; ENSG00000158796.17. [O75618-1]
DR GeneID; 9191; -.
DR KEGG; hsa:9191; -.
DR MANE-Select; ENST00000368006.8; ENSP00000356985.3; NM_032998.3; NP_127491.1.
DR UCSC; uc001fxz.5; human. [O75618-1]
DR CTD; 9191; -.
DR DisGeNET; 9191; -.
DR GeneCards; DEDD; -.
DR HGNC; HGNC:2755; DEDD.
DR HPA; ENSG00000158796; Low tissue specificity.
DR MIM; 606841; gene.
DR neXtProt; NX_O75618; -.
DR OpenTargets; ENSG00000158796; -.
DR PharmGKB; PA27236; -.
DR VEuPathDB; HostDB:ENSG00000158796; -.
DR eggNOG; ENOG502QRWB; Eukaryota.
DR GeneTree; ENSGT00390000008714; -.
DR HOGENOM; CLU_053869_0_0_1; -.
DR InParanoid; O75618; -.
DR OMA; KTXIRLR; -.
DR PhylomeDB; O75618; -.
DR TreeFam; TF331807; -.
DR PathwayCommons; O75618; -.
DR SignaLink; O75618; -.
DR BioGRID-ORCS; 9191; 11 hits in 1083 CRISPR screens.
DR ChiTaRS; DEDD; human.
DR GeneWiki; DEDD; -.
DR GenomeRNAi; 9191; -.
DR Pharos; O75618; Tbio.
DR PRO; PR:O75618; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75618; protein.
DR Bgee; ENSG00000158796; Expressed in oocyte and 208 other tissues.
DR ExpressionAtlas; O75618; baseline and differential.
DR Genevisible; O75618; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IBA:GO_Central.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:1901837; P:negative regulation of transcription of nucleolar large rRNA by RNA polymerase I; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0007283; P:spermatogenesis; TAS:ProtInc.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001875; DED_dom.
DR InterPro; IPR038856; DEDD/DEDD2.
DR PANTHER; PTHR15205; PTHR15205; 1.
DR Pfam; PF01335; DED; 1.
DR SMART; SM00031; DED; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50168; DED; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cytoplasm; DNA-binding; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..318
FT /note="Death effector domain-containing protein"
FT /id="PRO_0000191274"
FT DOMAIN 25..103
FT /note="DED"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT REGION 128..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 160..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 132..147
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 194
FT /note="D -> GEEIQGFQRWSRLEGEYKELLGHWAVYAIQY (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_003846"
SQ SEQUENCE 318 AA; 36794 MW; FF9D5FF9B61F6BB6 CRC64;
MAGLKRRASQ VWPEEHGEQE HGLYSLHRMF DIVGTHLTHR DVRVLSFLFV DVIDDHERGL
IRNGRDFLLA LERQGRCDES NFRQVLQLLR IITRHDLLPY VTLKRRRAVC PDLVDKYLEE
TSIRYVTPRA LSDPEPRPPQ PSKTVPPHYP VVCCPTSGPQ MCSKRPARGR ATLGSQRKRR
KSVTPDPKEK QTCDIRLRVR AEYCQHETAL QGNVFSNKQD PLERQFERFN QANTILKSRD
LGSIICDIKF SELTYLDAFW RDYINGSLLE ALKGVFITDS LKQAVGHEAI KLLVNVDEED
YELGRQKLLR NLMLQALP
