Reviewed, UniProtKB/Swiss-Prot Q13158 (FADD_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein FADD
Alternative name(s):
    FAS-associated death domain protein
    FAS-associating death domain-containing protein
    Mediator of receptor induced toxicity
    Growth-inhibiting gene 3 protein

Gene names

Name:	FADD
Synonyms:	MORT1
ORF Names:	GIG3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	208 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis.
Subunit structure	Interacts with CFLAR, PEA15 and MBD4. When phosphorylated, part of a complex containing HIPK3 and FAS. May interact with MAVS/IPS1. Interacts with MOCV v-CFLAR protein and LRDD. Ref.10 Ref.11 Ref.13 Ref.14
Tissue specificity	Expressed in a wide variety of tissues, except for peripheral blood mononuclear leukocytes.
Domain	Contains a death domain involved in the binding of the corresponding domain within Fas receptor.
Post-translational modification	Phosphorylated. Ref.12
Sequence similarities	Contains 1 death domain. Contains 1 DED (death effector) domain.

Ontologies

Keywords
Biological process	Apoptosis Host-virus interaction
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	activation of pro-apoptotic gene products Inferred from Experiment. Source: Reactome induction of apoptosis via death domain receptors Ref.1 Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW necrotic cell death Inferred from mutant phenotype. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA cytosol Ref.2 Inferred from Experiment. Source: Reactome death-inducing signaling complex Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular function	death receptor binding Ref.1 Traceable author statement. Source: ProtInc identical protein binding Ref.2 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-494804,EBI-494804
CASP10	Q92851	1	EBI-494804,EBI-495095
CASP8	Q14790	3	EBI-494804,EBI-78060
CASP8	Q14790-5	1	EBI-494804,EBI-288326
EDA2R	Q9HAV5	1	EBI-494804,EBI-526033
FAS	P25445	9	EBI-494804,EBI-494743
Fas	P25446	1	EBI-494804,EBI-296206	From a different organism.
MBD4	O95243	5	EBI-494804,EBI-348011
MYD88	Q99836	1	EBI-494804,EBI-447677
XPO5	Q9HAV4	1	EBI-494804,EBI-517949

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 208

208

Protein FADD

PRO_0000191279

Regions

Domain

3 – 81

79

DED

Domain

97 – 181

85

Death

Amino acid modifications

Modified residue

194

1

Phosphoserine Probable

Experimental info

Mutagenesis

121

1

V → N: No interaction with Fas receptor.

Sequence conflict

32

1

G → V in CAA59197. Ref.2

Secondary structure

1

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208

Helix Strand Turn

Details...

Helix

3 – 13

11

Helix

16 – 30

15

Helix

34 – 38

5

Beta strand

40 – 42

3

Helix

43 – 51

9

Helix

61 – 70

10

Helix

74 – 82

9

Beta strand

88 – 91

4

Helix

97 – 106

10

Helix

112 – 120

9

Helix

123 – 132

10

Helix

137 – 152

16

Turn

153 – 155

3

Helix

158 – 167

10

Helix

171 – 187

17

Sequences

	Sequence		Length	Mass (Da)
	Q13158-1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 0E65E2F852E83507	FASTA	208	23,279
	10 20 30 40 50 60 MDPFLVLLHS VSSSLSSSEL TELKFLCLGR VGKRKLERVQ SGLDLFSMLL EQNDLEPGHT 70 80 90 100 110 120 ELLRELLASL RRHDLLRRVD DFEAGAAAGA APGEEDLCAA FNVICDNVGK DWRRLARQLK 130 140 150 160 170 180 VSDTKIDSIE DRYPRNLTER VRESLRIWKN TEKENATVAH LVGALRSCQM NLVADLVQEV 190 200 QQARDLQNRS GAMSPMSWNS DASTSEAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis." Chinnaiyan A.M., O'Rourke K., Tewari M., Dixit V.M. Cell 81:505-512(1995) [PubMed: 7538907] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS. Tissue: Umbilical vein endothelial cell.
[2]	"A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain." Boldin M.P., Varfolomeev E.E., Pancer Z., Mett I.L., Camonis J.H., Wallach D. J. Biol. Chem. 270:7795-7798(1995) [PubMed: 7536190] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Identification of a human growth inhibition gene 3 (GIG3)." Kim J.W. Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	NIEHS SNPs program Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[10]	"PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis." Condorelli G., Vigliotta G., Cafieri A., Trencia A., Andalo P., Oriente F., Miele C., Caruso M., Formisano P., Beguinot F. Oncogene 18:4409-4415(1999) [PubMed: 10442631] [Abstract] Cited for: INTERACTION WITH PEA15.
[11]	"LRDD, a novel leucine rich repeat and death domain containing protein." Telliez J.-B., Bean K.M., Lin L.-L. Biochim. Biophys. Acta 1478:280-288(2000) [PubMed: 10825539] [Abstract] Cited for: INTERACTION WITH LRDD.
[12]	"FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits Fas-mediated Jun NH2-terminal kinase activation." Rochat-Steiner V., Becker K., Micheau O., Schneider P., Burns K., Tschopp J. J. Exp. Med. 192:1165-1174(2000) [PubMed: 11034606] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH HIPK3 AND FAS, PHOSPHORYLATION AT SER-194.
[13]	"Fas-associated death domain protein interacts with methyl-CpG binding domain protein 4: a potential link between genome surveillance and apoptosis." Screaton R.A., Kiessling S., Sansom O.J., Millar C.B., Maddison K., Bird A., Clarke A.R., Frisch S.M. Proc. Natl. Acad. Sci. U.S.A. 100:5211-5216(2003) [PubMed: 12702765] [Abstract] Cited for: INTERACTION WITH MBD4.
[14]	"IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction." Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., Takeuchi O., Akira S. Nat. Immunol. 6:981-988(2005) [PubMed: 16127453] [Abstract] Cited for: INTERACTION WITH MAVS.
[15]	"NMR structure and mutagenesis of the FADD (Mort1) death-effector domain." Eberstadt M., Huang B., Chen Z., Meadows R.P., Ng S.C., Zheng L., Lenardo M.J., Fesik S.W. Nature 392:941-945(1998) [PubMed: 9582077] [Abstract] Cited for: STRUCTURE BY NMR OF 1-83.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

U24231 mRNA. Translation: AAA86517.1.
X84709 mRNA. Translation: CAA59197.1.
AY423721 mRNA. Translation: AAS00484.1.
AK291005 mRNA. Translation: BAF83694.1.
BT006927 mRNA. Translation: AAP35573.1.
CR456738 mRNA. Translation: CAG33019.1.
DQ449938 Genomic DNA. Translation: ABD96828.1.
CH471076 Genomic DNA. Translation: EAW74761.1.
BC000334 mRNA. Translation: AAH00334.1.

IPI

IPI00011919.

PIR

A56912.

RefSeq

NP_003815.1.

UniGene

Hs.86131

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A1W	NMR	-	A	1-83	[»]
1A1Z	NMR	-	A	1-83	[»]
1E3Y	NMR	-	A	93-192	[»]
1E41	NMR	-	A	93-192	[»]
2GF5	NMR	-	A	2-191	[»]
3EZQ	X-ray	2.73	B/D/F/H/J/L/N/P	93-208	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:286N.

IntAct

Q13158. 17 interactions.

PTM databases

PhosphoSite

Q13158.

Proteomic databases

PeptideAtlas

Q13158.

PRIDE

Q13158.

Genome annotation databases

Ensembl

ENSG00000168040. Homo sapiens. [Contig view]

GeneID

8772.

KEGG

hsa:8772.

Organism-specific databases

GeneCards

GC11P069726.

H-InvDB

HIX0009893.

HGNC

HGNC:3573. FADD.

HPA

CAB010209.
HPA001464.

MIM

602457. gene.

PharmGKB

PA27972.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q13158.

HOVERGEN

Q13158.

OMA

Q13158. LEQNDLE.

Enzyme and pathway databases

Pathway_Interaction_DB

ceramidepathway. Ceramide signaling pathway.
faspathway. FAS signaling pathway (CD95).
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
tnfpathway. TNF receptor signaling pathway.
trail_pathway. TRAIL signaling pathway.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

Q13158.

Bgee

Q13158.

CleanEx

HS_FADD.

GermOnline

ENSG00000168040. Homo sapiens.

Family and domain databases

InterPro

IPR000488. Death.
IPR011029. DEATH-like.
IPR001875. DED.
IPR016729. FADD.
[Graphical view]

Gene3D

G3DSA:1.10.533.10. DEATH_like. 1 hit.

Pfam

PF00531. Death. 1 hit.
PF01335. DED. 1 hit.
[Graphical view]

PIRSF

PIRSF018586. FADD. 1 hit.

SMART

SM00005. DEATH. 1 hit.
SM00031. DED. 1 hit.
[Graphical view]

PROSITE

PS50017. DEATH_DOMAIN. 1 hit.
PS50168. DED. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

32890.

SOURCE

Search...

Entry information

Entry name

FADD_HUMAN

Accession

Primary (citable) accession number: Q13158
Secondary accession number(s): Q14866, Q6IBR4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	June 16, 2009
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)