DEDD2_HUMAN
ID DEDD2_HUMAN Reviewed; 326 AA.
AC Q8WXF8; Q8NBR2; Q8NES1; Q8TAA8; Q96D35;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=DNA-binding death effector domain-containing protein 2;
DE AltName: Full=DED-containing protein FLAME-3;
DE AltName: Full=FADD-like anti-apoptotic molecule 3;
GN Name=DEDD2; Synonyms=FLAME3; ORFNames=PSEC0004;
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), TISSUE SPECIFICITY, AND INTERACTION
RP WITH CASP8.
RX PubMed=11741985; DOI=10.1074/jbc.m110749200;
RA Roth W., Stenner-Liewen F., Pawlowski K., Godzik A., Reed J.C.;
RT "Identification and characterization of DEDD2, a death effector domain-
RT containing protein.";
RL J. Biol. Chem. 277:7501-7508(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH CASP8 AND 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
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 [6]
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: May play a critical role in death receptor-induced apoptosis
CC and may target CASP8 and CASP10 to the nucleus. May regulate
CC degradation of intermediate filaments during apoptosis. May play a role
CC in the general transcription machinery in the nucleus and might be an
CC important regulator of the activity of GTF3C3.
CC -!- SUBUNIT: Interacts with CASP8, CASP10 and GTF3C3. Homodimerizes and
CC heterodimerizes with DEDD. {ECO:0000269|PubMed:11741985,
CC ECO:0000269|PubMed:11965497, ECO:0000269|PubMed:12527898}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:11965497}.
CC Note=Nuclear, accumulated in subnuclear structures resembling nucleoli.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WXF8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WXF8-2; Sequence=VSP_010312;
CC -!- TISSUE SPECIFICITY: Expressed in most tissues. High levels were found
CC in liver, kidney, heart, ovary, spleen, testes, skeletal muscle and
CC peripheral blood leukocytes. Expression was absent or low in colon and
CC small intestine. Expression is relatively high in the tumor cell lines
CC chronic myologenous leukemia K-562 and the colorectal adenocarcinoma
CC SW480. Expression is moderate in the cervical carcinoma HeLa, the
CC Burkitt's lymphoma Raji, the lung carcinoma A-549, and the melanoma G-
CC 361. In contrast, two leukemia cell lines, HL-60 (promyelocytic
CC leukemia) and MOLT-4 (lymphoblastic leukemia), show relatively low
CC levels. {ECO:0000269|PubMed:11741985, ECO:0000269|PubMed:11965497}.
CC -!- DOMAIN: Interactions with CASP8 and CASP10 are mediated by the DED
CC domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH13372.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF443591; AAL48220.1; -; mRNA.
DR EMBL; AF457575; AAM10835.1; -; mRNA.
DR EMBL; AY125488; AAM95240.1; -; mRNA.
DR EMBL; AK075328; BAC11551.1; -; mRNA.
DR EMBL; BC013372; AAH13372.2; ALT_FRAME; mRNA.
DR EMBL; BC027930; AAH27930.1; -; mRNA.
DR CCDS; CCDS12597.1; -. [Q8WXF8-1]
DR CCDS; CCDS59391.1; -. [Q8WXF8-2]
DR RefSeq; NP_001257543.1; NM_001270614.1. [Q8WXF8-1]
DR RefSeq; NP_001257544.1; NM_001270615.1. [Q8WXF8-2]
DR RefSeq; NP_579874.1; NM_133328.3. [Q8WXF8-1]
DR AlphaFoldDB; Q8WXF8; -.
DR SMR; Q8WXF8; -.
DR BioGRID; 127838; 17.
DR IntAct; Q8WXF8; 8.
DR MINT; Q8WXF8; -.
DR STRING; 9606.ENSP00000470082; -.
DR iPTMnet; Q8WXF8; -.
DR PhosphoSitePlus; Q8WXF8; -.
DR BioMuta; DEDD2; -.
DR DMDM; 47116024; -.
DR MassIVE; Q8WXF8; -.
DR PaxDb; Q8WXF8; -.
DR PeptideAtlas; Q8WXF8; -.
DR PRIDE; Q8WXF8; -.
DR ProteomicsDB; 75029; -. [Q8WXF8-1]
DR ProteomicsDB; 75030; -. [Q8WXF8-2]
DR Antibodypedia; 17411; 210 antibodies from 30 providers.
DR DNASU; 162989; -.
DR Ensembl; ENST00000336034.8; ENSP00000336972.4; ENSG00000160570.14. [Q8WXF8-2]
DR Ensembl; ENST00000595337.5; ENSP00000470082.1; ENSG00000160570.14. [Q8WXF8-1]
DR Ensembl; ENST00000596251.6; ENSP00000471512.1; ENSG00000160570.14. [Q8WXF8-1]
DR GeneID; 162989; -.
DR KEGG; hsa:162989; -.
DR MANE-Select; ENST00000596251.6; ENSP00000471512.1; NM_133328.4; NP_579874.1.
DR UCSC; uc002osu.3; human. [Q8WXF8-1]
DR CTD; 162989; -.
DR GeneCards; DEDD2; -.
DR HGNC; HGNC:24450; DEDD2.
DR HPA; ENSG00000160570; Low tissue specificity.
DR neXtProt; NX_Q8WXF8; -.
DR OpenTargets; ENSG00000160570; -.
DR PharmGKB; PA134912744; -.
DR VEuPathDB; HostDB:ENSG00000160570; -.
DR eggNOG; ENOG502QQKR; Eukaryota.
DR GeneTree; ENSGT00390000008714; -.
DR HOGENOM; CLU_053869_0_0_1; -.
DR InParanoid; Q8WXF8; -.
DR OMA; WSDYMNG; -.
DR OrthoDB; 653785at2759; -.
DR PhylomeDB; Q8WXF8; -.
DR TreeFam; TF331807; -.
DR PathwayCommons; Q8WXF8; -.
DR SignaLink; Q8WXF8; -.
DR BioGRID-ORCS; 162989; 13 hits in 1082 CRISPR screens.
DR ChiTaRS; DEDD2; human.
DR GenomeRNAi; 162989; -.
DR Pharos; Q8WXF8; Tbio.
DR PRO; PR:Q8WXF8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8WXF8; protein.
DR Bgee; ENSG00000160570; Expressed in granulocyte and 182 other tissues.
DR ExpressionAtlas; Q8WXF8; baseline and differential.
DR Genevisible; Q8WXF8; HS.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; NAS:UniProtKB.
DR GO; GO:0030262; P:apoptotic nuclear changes; IDA:UniProtKB.
DR GO; GO:0019725; P:cellular homeostasis; NAS:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0006396; P:RNA processing; NAS:UniProtKB.
DR GO; GO:0016075; P:rRNA catabolic process; NAS:UniProtKB.
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; DNA-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..326
FT /note="DNA-binding death effector domain-containing protein
FT 2"
FT /id="PRO_0000191277"
FT DOMAIN 25..104
FT /note="DED"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT REGION 104..194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 104..109
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 155..173
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 133..153
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..170
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 145..149
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12235123,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010312"
FT CONFLICT 27
FT /note="H -> N (in Ref. 2; AAM10835)"
FT /evidence="ECO:0000305"
FT CONFLICT 56
FT /note="A -> G (in Ref. 2; AAM10835)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="D -> G (in Ref. 4; BAC11551)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="C -> R (in Ref. 2; AAM10835)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="Missing (in Ref. 5; AAH13372)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 326 AA; 36179 MW; 3F7B0B307CC870CD CRC64;
MALSGSTPAP CWEEDECLDY YGMLSLHRMF EVVGGQLTEC ELELLAFLLD EAPGAAGGLA
RARSGLELLL ELERRGQCDE SNLRLLGQLL RVLARHDLLP HLARKRRRPV SPERYSYGTS
SSSKRTEGSC RRRRQSSSSA NSQQGQWETG SPPTKRQRRS RGRPSGGARR RRRGAPAAPQ
QQSEPARPSS EGKVTCDIRL RVRAEYCEHG PALEQGVASR RPQALARQLD VFGQATAVLR
SRDLGSVVCD IKFSELSYLD AFWGDYLSGA LLQALRGVFL TEALREAVGR EAVRLLVSVD
EADYEAGRRR LLLMEEEGGR RPTEAS
