Q15628 (TRADD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor type 1-associated DEATH domain protein
Short name=TNFR1-associated DEATH domain protein

Alternative name(s):
TNFRSF1A-associated via death domain

Gene names

Name:

TRADD

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	312 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The nuclear form acts as a tumor suppressor by preventing ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12, leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of CDKN2A By similarity. Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa-B.
Subunit structure	Interacts with TRIP12 By similarity. Heterodimer with TNFRSF1A/TNFR1. Interacts with DAB2IP, FADD, HIPK2, KRT14, KRT16, KRT17, KRT18, RIPK1, SQSTM1, TRAF1, TRAF2 and TRPC4AP. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Cytoplasm › cytoskeleton. Note: Shuttles between the cytoplasm and the nucleus By similarity. Ref.12
Tissue specificity	Found in all examined tissues.
Domain	Requires the intact death domain to associate with TNFRSF1A/TNFR1.
Sequence similarities	Contains 1 death domain.
Sequence caution	The sequence AAA98482.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Cytoskeleton Nucleus
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Traceable author statement. Source: Reactome extrinsic apoptotic signaling pathway Inferred from mutant phenotype PubMed 16611992. Source: UniProtKB induction of apoptosis Inferred from direct assay Ref.9. Source: BHF-UCL positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern PubMed 12761501. Source: UniProtKB positive regulation of hair follicle development Inferred from electronic annotation. Source: Compara tumor necrosis factor-mediated signaling pathway Traceable author statement Ref.9. Source: BHF-UCL
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell receptor complex Inferred from direct assay Ref.9. Source: BHF-UCL
Molecular_function	binding, bridging Inferred from physical interaction Ref.9. Source: BHF-UCL signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-359215,EBI-359215
KRT18	P05783	11	EBI-359215,EBI-297888
TNFRSF1A	P19438	10	EBI-359215,EBI-299451

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 312

312

Tumor necrosis factor receptor type 1-associated DEATH domain protein

PRO_0000065602

Regions

Domain

179 – 289

111

Death

Region

222 – 289

68

Interaction with KRT14 and KRT18

Motif

147 – 163

17

Nuclear export signal By similarity

Motif

231 – 244

14

Nuclear localization signal By similarity

Compositional bias

192 – 198

7

Poly-Pro

Secondary structure

1

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312

Helix Strand Turn

Details...

Beta strand

12 – 25

14

Helix

28 – 33

6

Turn

35 – 37

3

Helix

38 – 52

15

Turn

56 – 58

3

Beta strand

59 – 66

8

Beta strand

68 – 79

12

Helix

80 – 91

12

Helix

94 – 106

13

Beta strand

114 – 120

7

Helix

125 – 128

4

Helix

132 – 141

10

Helix

150 – 162

13

Sequences

	Sequence		Length	Mass (Da)
	Q15628 [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 5645D7E63E5FF05A	FASTA	312	34,247
	10 20 30 40 50 60 MAAGQNGHEE WVGSAYLFVE SSLDKVVLSD AYAHPQQKVA VYRALQAALA ESGGSPDVLQ 70 80 90 100 110 120 MLKIHRSDPQ LIVQLRFCGR QPCGRFLRAY REGALRAALQ RSLAAALAQH SVPLQLELRA 130 140 150 160 170 180 GAERLDALLA DEERCLSCIL AQQPDRLRDE ELAELEDALR NLKCGSGARG GDGEVASAPL 190 200 210 220 230 240 QPPVPSLSEV KPPPPPPPAQ TFLFQGQPVV NRPLSLKDQQ TFARSVGLKW RKVGRSLQRG 250 260 270 280 290 300 CRALRDPALD SLAYEYEREG LYEQAFQLLR RFVQAEGRRA TLQRLVEALE ENELTSLAED 310 LLGLTDPNGG LA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation." Hsu H., Xiong J., Goeddel D.V. Cell 81:495-504(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Sequence, genomic organisation, and mutation analysis of the human TRADD gene in childhood B- and T-lineage acute lymphoblastic leukemia and ALPS." Scheuerpflug C.G., Dechant M., Fellenberg J., Ewerbeck V., Debatin K.M. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning of the human TRADD gene locus." Kaiser C., Kohstall B., Kieser A. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	SeattleSNPs variation discovery resource Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Mammary gland.
[7]	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].
[8]	"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]. Tissue: Pancreas.
[9]	"TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex." Hsu H., Huang J., Shu H.-B., Baichwal V.R., Goeddel D.V. Immunity 4:387-396(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RIPK1.
[10]	"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation." Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J. EMBO J. 18:3044-3053(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SQSTM1.
[11]	"The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells." Li X., Wang Y., Debatin K.-M., Hug H. Biochem. Biophys. Res. Commun. 277:513-517(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIPK2.
[12]	"Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD." Inada H., Izawa I., Nishizawa M., Fujita E., Kiyono T., Takahashi T., Momoi T., Inagaki M. J. Cell Biol. 155:415-426(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH KRT14 AND KRT18.
[13]	"AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation." Zhang H., Zhang R., Luo Y., D'Alessio A., Pober J.S., Min W. J. Biol. Chem. 279:44955-44965(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DAB2IP.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway." Tsao D.H., McDonagh T., Telliez J.-B., Hsu S., Malakian K., Xu G.Y., Lin L.L. Mol. Cell 5:1051-1057(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-179.
[16]	"A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction." Park Y.C., Ye H., Hsia C., Segal D., Rich R.L., Liou H.C., Myszka D.G., Wu H. Cell 101:777-787(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-179 IN COMPLEX WITH TRAF2.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L41690 mRNA. Translation: AAA98482.1. Different initiation.
AJ311614, AJ311615, AJ311616 Genomic DNA. Translation: CAC38018.2.
AY995114 Genomic DNA. Translation: AAX89407.1.
BT006934 mRNA. Translation: AAP35580.1.
AY575851 Genomic DNA. Translation: AAS68637.1.
AK315654 mRNA. Translation: BAG38020.1.
CH471092 Genomic DNA. Translation: EAW83081.1.
BC004491 mRNA. Translation: AAH04491.1.

IPI

IPI00018744.

PIR

A56911.

RefSeq

NP_003780.1. NM_003789.3.

UniGene

Hs.460996.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F2H	NMR	-	A	1-169	[»]
1F3V	X-ray	2.00	A	1-179	[»]

ProteinModelPortal

Q15628.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-285N.

IntAct

Q15628. 9 interactions.

MINT

MINT-99115.

STRING

9606.ENSP00000341268.

PTM databases

PhosphoSite

Q15628.

Polymorphism databases

DMDM

6094511.

Proteomic databases

PaxDb

Q15628.

PRIDE

Q15628.

Protocols and materials databases

DNASU

8717.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000345057; ENSP00000341268; ENSG00000102871.

GeneID

8717.

KEGG

hsa:8717.

UCSC

uc002erh.1. human.

Organism-specific databases

CTD

8717.

GeneCards

GC16M067188.

HGNC

HGNC:12030. TRADD.

HPA

CAB004602.

MIM

603500. gene.

neXtProt

NX_Q15628.

PharmGKB

PA36707.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47236.

HOGENOM

HOG000059664.

HOVERGEN

HBG054083.

InParanoid

Q15628.

KO

K03171.

OMA

LRFCGRQ.

OrthoDB

EOG40VVQD.

PhylomeDB

Q15628.

Enzyme and pathway databases

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.
ceramidepathway. Ceramide signaling pathway.
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

Q15628.

Bgee

Q15628.

CleanEx

HS_TRADD.

Genevestigator

Q15628.

GermOnline

ENSG00000102871. Homo sapiens.

Family and domain databases

Gene3D

1.10.533.10. 1 hit.
3.30.70.680. 1 hit.

InterPro

IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR009095. TRADD_N.
[Graphical view]

Pfam

PF00531. Death. 1 hit.
PF09034. TRADD_N. 1 hit.
[Graphical view]

ProDom

PD182470. TRADD_N. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00005. DEATH. 1 hit.
[Graphical view]

SUPFAM

SSF47986. DEATH_like. 1 hit.
SSF55044. TRADD_N. 1 hit.

PROSITE

PS50017. DEATH_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q15628.

GenomeRNAi

8717.

NextBio

32687.

SOURCE

Search...

Entry information

Entry name

TRADD_HUMAN

Accession

Primary (citable) accession number: Q15628
Secondary accession number(s): B2RDS3, Q52NZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 128 of the entry and version 2 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.