Reviewed, UniProtKB/Swiss-Prot P43489 (TNR4_HUMAN)

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor receptor superfamily member 4
Alternative name(s):
    OX40L receptor
    ACT35 antigen
    TAX transcriptionally-activated glycoprotein 1 receptor
    CD_antigen=CD134

Gene names

Name:	TNFRSF4
Synonyms:	TXGP1L

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	277 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for TNFSF4/OX40L/GP34.
Subunit structure	Interacts with TRAF2, TRAF3 and TRAF5. Ref.7 Ref.8
Subcellular location	Membrane; Single-pass type I membrane protein.
Sequence similarities	Contains 4 TNFR-Cys repeats.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	T cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB immune response Ref.1 Traceable author statement. Source: ProtInc negative regulation of gene-specific transcription Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of B cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of immunoglobulin secretion Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cell surface Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	tumor necrosis factor receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Potential

Chain

29 – 277

249

Tumor necrosis factor receptor superfamily member 4

PRO_0000034554

Regions

Topological domain

29 – 214

186

Extracellular Potential

Transmembrane

215 – 235

21

Potential

Topological domain

236 – 277

42

Cytoplasmic Potential

Repeat

30 – 65

36

TNFR-Cys 1

Repeat

66 – 107

42

TNFR-Cys 2

Repeat

108 – 126

19

TNFR-Cys 3; truncated

Repeat

127 – 167

41

TNFR-Cys 4

Amino acid modifications

Glycosylation

146

1

N-linked (GlcNAc...) Potential

Glycosylation

160

1

N-linked (GlcNAc...) Potential

Disulfide bond

31 ↔ 42

Ref.9

Disulfide bond

43 ↔ 56

Ref.9

Disulfide bond

46 ↔ 64

Ref.9

Disulfide bond

67 ↔ 81

Ref.9

Disulfide bond

84 ↔ 99

Ref.9

Disulfide bond

87 ↔ 107

Ref.9

Disulfide bond

109 ↔ 125

Ref.9

Disulfide bond

128 ↔ 141

Ref.9

Disulfide bond

147 ↔ 166

By similarity

Natural variations

Natural variant

10

1

R → C Ref.4

VAR_025164

Secondary structure

1

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277

Helix Strand Turn

Details...

Beta strand

33 – 38

6

Beta strand

41 – 44

4

Beta strand

50 – 54

5

Beta strand

58 – 60

3

Beta strand

63 – 66

4

Beta strand

77 – 79

3

Helix

89 – 91

3

Beta strand

93 – 97

5

Beta strand

106 – 109

4

Beta strand

113 – 115

3

Turn

121 – 123

3

Beta strand

124 – 127

4

Turn

147 – 151

5

Beta strand

153 – 156

4

Beta strand

160 – 162

3

Beta strand

165 – 167

3

Sequences

	Sequence		Length	Mass (Da)
	P43489-1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 49F15525941550BF	FASTA	277	29,341
	10 20 30 40 50 60 MCVGARRLGR GPCAALLLLG LGLSTVTGLH CVGDTYPSND RCCHECRPGN GMVSRCSRSQ 70 80 90 100 110 120 NTVCRPCGPG FYNDVVSSKP CKPCTWCNLR SGSERKQLCT ATQDTVCRCR AGTQPLDSYK 130 140 150 160 170 180 PGVDCAPCPP GHFSPGDNQA CKPWTNCTLA GKHTLQPASN SSDAICEDRD PPATQPQETQ 190 200 210 220 230 240 GPPARPITVQ PTEAWPRTSQ GPSTRPVEVP GGRAVAAILG LGLVLGLLGP LAILLALYLL 250 260 270 RRDQRLPPDA HKPPGGGSFR TPIQEEQADA HSTLAKI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen." Latza U., Duerkop H., Schnittger S., Ringeling J., Eitelbach F., Hummel M., Fonatsch C., Stein H. Eur. J. Immunol. 24:677-683(1994) [PubMed: 7510240] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification of OX40 ligand and preliminary characterization of its activities on OX40 receptor." Baum P.R., Gayle R.B. III, Ramsdell F., Srinivasan S., Sorensen R.A., Watson M.L., Seldin M.F., Clifford K.N., Grabstein K., Alderson M.R. Circ. Shock 44:30-34(1994) [PubMed: 7704935] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The HTLV-I protein transcriptionally modulates OX40 antigen expression." Pankow R., Duerkop H., Latza U., Krause H., Kunzendorf U., Pohl T., Bulfone-Paus S. J. Immunol. 165:263-270(2000) [PubMed: 10861060] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	NIEHS SNPs program Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CYS-10.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Brain.
[7]	"4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB." Arch R.H., Thompson C.B. Mol. Cell. Biol. 18:558-565(1998) [PubMed: 9418902] [Abstract] Cited for: INTERACTION WITH TRAF1; TRAF2 AND TRAF3.
[8]	"Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB activation." Kawamata S., Hori T., Imura A., Takaori-Kondo A., Uchiyama T. J. Biol. Chem. 273:5808-5814(1998) [PubMed: 9488716] [Abstract] Cited for: INTERACTION WITH TRAF2 AND TRAF5.
[9]	"The crystal structure of the costimulatory OX40-OX40L complex." Compaan D.M., Hymowitz S.G. Structure 14:1321-1330(2006) [PubMed: 16905106] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 29-170 IN COMPLEX WITH TNFSF4, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X75962 mRNA. Translation: CAA53576.1.
S76792 mRNA. Translation: AAB33944.1. Different initiation.
AJ277151 Genomic DNA. Translation: CAB96543.1.
DQ118974 Genomic DNA. Translation: AAZ15374.1.
AL162741 Genomic DNA. Translation: CAI23250.1.
BC105070 mRNA. Translation: AAI05071.1.
BC105072 mRNA. Translation: AAI05073.1.

IPI

IPI00018859.

PIR

I37552.

RefSeq

NP_003318.1.

UniGene

Hs.129780

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D0A	X-ray	2.00	G/H/I/J/K/L	262-266	[»]
2HEV	X-ray	2.41	R	29-170	[»]
2HEY	X-ray	2.00	R/T	29-170	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:3024N.

Genome annotation databases

Ensembl

ENSG00000186827. Homo sapiens. [Contig view]

GeneID

7293.

KEGG

hsa:7293.

Organism-specific databases

GeneCards

GC01M001136.

H-InvDB

HIX0028755.
HIX0074191.

HGNC

HGNC:11918. TNFRSF4.

HPA

CAB016128.

MIM

600315. gene.

PharmGKB

PA36611.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P43489.

HOVERGEN

P43489.

OMA

P43489. YNEAVNY.

Enzyme and pathway databases

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.

Gene expression databases

ArrayExpress

P43489.

Bgee

P43489.

CleanEx

HS_TNFRSF4.

GermOnline

ENSG00000186827. Homo sapiens.

Family and domain databases

InterPro

IPR001368. TNFR_Cys_rich_reg.
[Graphical view]

Pfam

PF00020. TNFR_c6. 2 hits.
[Graphical view]

SMART

SM00208. TNFR. 3 hits.
[Graphical view]

PROSITE

PS00652. TNFR_NGFR_1. 2 hits.
PS50050. TNFR_NGFR_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

28515.

SOURCE

Search...

Entry information

Entry name

TNR4_HUMAN

Accession

Primary (citable) accession number: P43489
Secondary accession number(s): Q13663, Q2M312, Q5T7M0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	June 16, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)