Q8WXF8 (DEDD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA-binding death effector domain-containing protein 2

Alternative name(s):
DED-containing protein FLAME-3
FADD-like anti-apoptotic molecule 3

Gene names

Name:	DEDD2
Synonyms:	FLAME3
ORF Names:	PSEC0004

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	326 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a critical role in death receptor-induced apoptosis and may target CASP8 and CASP10 to the nucleus. May regulate degradation of intermediate filaments during apoptosis. May play a role in the general transcription machinery in the nucleus and might be an important regulator of the activity of GTF3C3.
Subunit structure	Interacts with CASP8, CASP10 and GTF3C3. Homodimerizes and heterodimerizes with DEDD. Ref.1 Ref.2 Ref.6
Subcellular location	Nucleus › nucleolus. Note: Nuclear, accumulated in subnuclear structures resembling nucleoli. Ref.2
Tissue specificity	Expressed in most tissues. High levels were found in liver, kidney, heart, ovary, spleen, testes, skeletal muscle and peripheral blood leukocytes. Expression was absent or low in colon and small intestine. Expression is relatively high in the tumor cell lines chronic myologenous leukemia K-562 and the colorectal adenocarcinoma SW480. Expression is moderate in the cervical carcinoma HeLa, the Burkitt's lymphoma Raji, the lung carcinoma A-549, and the melanoma G-361. In contrast, two leukemia cell lines, HL-60 (promyelocytic leukemia) and MOLT-4 (lymphoblastic leukemia), show relatively low levels. Ref.1 Ref.2
Domain	Interactions with CASP8 and CASP10 are mediated by the DED domain.
Sequence similarities	Contains 1 DED (death effector) domain.
Sequence caution	The sequence AAH13372.2 differs from that shown. Reason: Frameshift at position 186.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA processing Non-traceable author statement Ref.1. Source: UniProtKB apoptotic nuclear changes Inferred from direct assay Ref.1. Source: UniProtKB cellular homeostasis Non-traceable author statement Ref.1. Source: UniProtKB extrinsic apoptotic signaling pathway via death domain receptors Inferred from mutant phenotype Ref.1. Source: UniProtKB intracellular signal transduction Non-traceable author statement Ref.1. Source: UniProtKB negative regulation of transcription, DNA-dependent Non-traceable author statement Ref.1. Source: UniProtKB positive regulation of extrinsic apoptotic signaling pathway Inferred from mutant phenotype Ref.1. Source: UniProtKB rRNA catabolic process Non-traceable author statement Ref.1. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleolus Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling complex scaffold activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WXF8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8WXF8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     145-149: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 326	326	DNA-binding death effector domain-containing protein 2		PRO_0000191277
Regions
	Domain	25 – 104	80	DED
	Motif	104 – 109	6	Nuclear localization signal Potential
	Motif	155 – 173	19	Bipartite nuclear localization signal Potential
Natural variations
	Alternative sequence	145 – 149	5	Missing in isoform 2.		VSP_010312
Experimental info
	Sequence conflict	27	1	H → N in AAM10835. Ref.2
	Sequence conflict	56	1	A → G in AAM10835. Ref.2
	Sequence conflict	79	1	D → G in BAC11551. Ref.4
	Sequence conflict	207	1	C → R in AAM10835. Ref.2
	Sequence conflict	230	1	Missing in AAH13372. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 3F7B0B307CC870CD	FASTA	326	36,179
	10 20 30 40 50 60 MALSGSTPAP CWEEDECLDY YGMLSLHRMF EVVGGQLTEC ELELLAFLLD EAPGAAGGLA 70 80 90 100 110 120 RARSGLELLL ELERRGQCDE SNLRLLGQLL RVLARHDLLP HLARKRRRPV SPERYSYGTS 130 140 150 160 170 180 SSSKRTEGSC RRRRQSSSSA NSQQGQWETG SPPTKRQRRS RGRPSGGARR RRRGAPAAPQ 190 200 210 220 230 240 QQSEPARPSS EGKVTCDIRL RVRAEYCEHG PALEQGVASR RPQALARQLD VFGQATAVLR 250 260 270 280 290 300 SRDLGSVVCD IKFSELSYLD AFWGDYLSGA LLQALRGVFL TEALREAVGR EAVRLLVSVD 310 320 EADYEAGRRR LLLMEEEGGR RPTEAS
	Isoform 2 [UniParc]. Checksum: 2F0ABF19EF229FEE	FASTA	321	35,577
	10 20 30 40 50 60 MALSGSTPAP CWEEDECLDY YGMLSLHRMF EVVGGQLTEC ELELLAFLLD EAPGAAGGLA 70 80 90 100 110 120 RARSGLELLL ELERRGQCDE SNLRLLGQLL RVLARHDLLP HLARKRRRPV SPERYSYGTS 130 140 150 160 170 180 SSSKRTEGSC RRRRQSSSSA NSQQGSPPTK RQRRSRGRPS GGARRRRRGA PAAPQQQSEP 190 200 210 220 230 240 ARPSSEGKVT CDIRLRVRAE YCEHGPALEQ GVASRRPQAL ARQLDVFGQA TAVLRSRDLG 250 260 270 280 290 300 SVVCDIKFSE LSYLDAFWGD YLSGALLQAL RGVFLTEALR EAVGREAVRL LVSVDEADYE 310 320 AGRRRLLLME EEGGRRPTEA S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of DEDD2, a death effector domain-containing protein." Roth W., Stenner-Liewen F., Pawlowski K., Godzik A., Reed J.C. J. Biol. Chem. 277:7501-7508(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH CASP8.
[2]	"Death effector domain-containing proteins DEDD and FLAME-3 form nuclear complexes with the TFIIIC102 subunit of human transcription factor IIIC." Zhan Y., Hegde R., Srinivasula S.M., Fernandes-Alnemri T., Alnemri E.S. Cell Death Differ. 9:439-447(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH CASP8 AND GTF3C3.
[3]	"DEDD regulates degradation of intermediate filaments during apoptosis." Lee J.C., Schickling O., Stegh A.H., Oshima R.G., Dinsdale D., Cohen G.M., Peter M.E. J. Cell Biol. 158:1051-1066(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Teratocarcinoma.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Lung.
[6]	"DEDD and DEDD2 associate with caspase-8/10 and signal cell death." Alcivar A., Hu S., Tang J., Yang X. Oncogene 22:291-297(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CASP8 AND CASP10.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF443591 mRNA. Translation: AAL48220.1. AF457575 mRNA. Translation: AAM10835.1. AY125488 mRNA. Translation: AAM95240.1. AK075328 mRNA. Translation: BAC11551.1. BC013372 mRNA. Translation: AAH13372.2. Frameshift. BC027930 mRNA. Translation: AAH27930.1.
IPI	IPI00103531. IPI00410190.
RefSeq	NP_001257543.1. NM_001270614.1. NP_001257544.1. NM_001270615.1. NP_579874.1. NM_133328.3.
UniGene	Hs.515432. Hs.741580.
3D structure databases
ProteinModelPortal	Q8WXF8.
SMR	Q8WXF8. Positions 29-103.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WXF8. 1 interaction.
STRING	9606.ENSP00000336972.
PTM databases
PhosphoSite	Q8WXF8.
Polymorphism databases
DMDM	47116024.
Proteomic databases
PaxDb	Q8WXF8.
PRIDE	Q8WXF8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336034; ENSP00000336972; ENSG00000160570. ENST00000595337; ENSP00000470082; ENSG00000160570. ENST00000596251; ENSP00000471512; ENSG00000160570.
GeneID	162989.
KEGG	hsa:162989.
UCSC	uc002osu.1. human. uc002osw.1. human.
Organism-specific databases
CTD	162989.
GeneCards	GC19M042702.
HGNC	HGNC:24450. DEDD2.
HPA	HPA043419. HPA043554.
neXtProt	NX_Q8WXF8.
PharmGKB	PA134912744.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG42334.
HOGENOM	HOG000049120.
HOVERGEN	HBG007220.
InParanoid	Q8WXF8.
OMA	APCWEED.
OrthoDB	EOG4MPHR5.
PhylomeDB	Q8WXF8.
Gene expression databases
Bgee	Q8WXF8.
CleanEx	HS_DEDD2.
Genevestigator	Q8WXF8.
GermOnline	ENSG00000160570. Homo sapiens.
Family and domain databases
Gene3D	1.10.533.10. 1 hit.
InterPro	IPR011029. DEATH-like_dom. IPR001875. DED. [Graphical view]
Pfam	PF01335. DED. 1 hit. [Graphical view]
SMART	SM00031. DED. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50168. DED. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	162989.
NextBio	88251.

Entry information

Entry name

DEDD2_HUMAN

Accession

Primary (citable) accession number: Q8WXF8
Secondary accession number(s): Q8NBR2 , Q8NES1, Q8TAA8, Q96D35

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.