Reviewed, UniProtKB/Swiss-Prot P28908 (TNR8_HUMAN)

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor receptor superfamily member 8
Alternative name(s):
    CD30L receptor
    Lymphocyte activation antigen CD30
    Ki-1 antigen
    CD_antigen=CD30

Gene names

Name:	TNFRSF8
Synonyms:	CD30, D1S166E

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	595 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 TNFSF8/CD30L. May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-B.
Subunit structure	Interacts with TRAF1, TRAF2, TRAF3 and TRAF5. Ref.8 Ref.9 Ref.10 Ref.11
Subcellular location	Isoform Long: Cell membrane; Single-pass type I membrane protein. Isoform Short: Cytoplasm.
Post-translational modification	Phosphorylated on serine and tyrosine residues.
Involvement in disease	Most specific Hodgkin disease associated antigen.
Sequence similarities	Contains 6 TNFR-Cys repeats.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative initiation Polymorphism
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Traceable author statement. Source: ProtInc positive regulation of TRAIL biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of apoptosis Inferred from direct assay. Source: UniProtKB positive regulation of tumor necrosis factor biosynthetic process Inferred from direct assay. Source: UniProtKB signal transduction Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: IntAct transmembrane receptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Traf1	P39428	1	EBI-529023,EBI-520123	From a different organism.
Traf2	P39429	1	EBI-529023,EBI-520016	From a different organism.

Alternative products

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

Isoform Long (identifier: P28908-1)

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 Short (identifier: P28908-2)

Also known as: Cytoplasmic; C30V;

The sequence of this isoform differs from the canonical sequence as follows:
     1-463: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18
	Chain	19 – 595	577	Tumor necrosis factor receptor superfamily member 8		PRO_0000034573
Regions
	Topological domain	19 – 379	361	Extracellular Potential
	Transmembrane	380 – 407	28	Potential
	Topological domain	408 – 595	188	Cytoplasmic Potential
	Repeat	28 – 66	39	TNFR-Cys 1
	Repeat	68 – 106	39	TNFR-Cys 2
	Repeat	107 – 150	44	TNFR-Cys 3
	Repeat	205 – 241	37	TNFR-Cys 4
	Repeat	243 – 281	39	TNFR-Cys 5
	Repeat	282 – 325	44	TNFR-Cys 6
	Compositional bias	347 – 377	31	Pro/Ser/Thr-rich
Amino acid modifications
	Modified residue	452	1	Phosphoserine
	Glycosylation	101	1	N-linked (GlcNAc...) Potential
	Glycosylation	276	1	N-linked (GlcNAc...) Potential
	Disulfide bond	29 ↔ 44		By similarity
	Disulfide bond	45 ↔ 58		By similarity
	Disulfide bond	48 ↔ 65		By similarity
	Disulfide bond	69 ↔ 81		By similarity
	Disulfide bond	84 ↔ 98		By similarity
	Disulfide bond	87 ↔ 106		By similarity
	Disulfide bond	108 ↔ 122		By similarity
	Disulfide bond	131 ↔ 149		By similarity
	Disulfide bond	233 ↔ 240		By similarity
	Disulfide bond	244 ↔ 256		By similarity
	Disulfide bond	259 ↔ 273		By similarity
	Disulfide bond	262 ↔ 281		By similarity
	Disulfide bond	283 ↔ 297		By similarity
	Disulfide bond	289 ↔ 300		By similarity
Natural variations
	Alternative sequence	1 – 463	463	Missing in isoform Short.		VSP_018900
	Natural variant	273	1	C → F: dbSNP rs2230624.		VAR_054213
	Natural variant	273	1	C → Y		VAR_018753
	Natural variant	297	1	C → R: dbSNP rs1763642. Ref.6		VAR_055257
	Natural variant	314	1	P → S: dbSNP rs2275170.		VAR_055258
	Natural variant	402	1	S → G: dbSNP rs2230625. Ref.5		VAR_018754
	Natural variant	466	1	Q → R: dbSNP rs35511003.		VAR_055259

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified December 1, 1992. Version 1. Checksum: 7A407CC78A6E0BC8	FASTA	595	63,747
	10 20 30 40 50 60 MRVLLAALGL LFLGALRAFP QDRPFEDTCH GNPSHYYDKA VRRCCYRCPM GLFPTQQCPQ 70 80 90 100 110 120 RPTDCRKQCE PDYYLDEADR CTACVTCSRD DLVEKTPCAW NSSRVCECRP GMFCSTSAVN 130 140 150 160 170 180 SCARCFFHSV CPAGMIVKFP GTAQKNTVCE PASPGVSPAC ASPENCKEPS SGTIPQAKPT 190 200 210 220 230 240 PVSPATSSAS TMPVRGGTRL AQEAASKLTR APDSPSSVGR PSSDPGLSPT QPCPEGSGDC 250 260 270 280 290 300 RKQCEPDYYL DEAGRCTACV SCSRDDLVEK TPCAWNSSRT CECRPGMICA TSATNSCARC 310 320 330 340 350 360 VPYPICAAET VTKPQDMAEK DTTFEAPPLG TQPDCNPTPE NGEAPASTSP TQSLLVDSQA 370 380 390 400 410 420 SKTLPIPTSA PVALSSTGKP VLDAGPVLFW VILVLVVVVG SSAFLLCHRR ACRKRIRQKL 430 440 450 460 470 480 HLCYPVQTSQ PKLELVDSRP RRSSTQLRSG ASVTEPVAEE RGLMSQPLME TCHSVGAAYL 490 500 510 520 530 540 ESLPLQDASP AGGPSSPRDL PEPRVSTEHT NNKIEKIYIM KADTVIVGTV KAELPEGRGL 550 560 570 580 590 AGPAEPELEE ELEADHTPHY PEQETEPPLG SCSDVMLSVE EEGKEDPLPT AASGK
	Isoform Short (Cytoplasmic) (C30V). Checksum: 211648B504B6313F	FASTA	132	14,088
	10 20 30 40 50 60 MSQPLMETCH SVGAAYLESL PLQDASPAGG PSSPRDLPEP RVSTEHTNNK IEKIYIMKAD 70 80 90 100 110 120 TVIVGTVKAE LPEGRGLAGP AEPELEEELE ADHTPHYPEQ ETEPPLGSCS DVMLSVEEEG 130 KEDPLPTAAS GK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease." Duerkop H., Latza U., Hummel M., Eitelbach F., Seed B., Stein H. Cell 68:421-427(1992) [PubMed: 1310894] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Lymphoid tissue.
[2]	"Opposite effects of the CD30 ligand are not due to CD30 mutations: results from cDNA cloning and sequence comparison of the CD30 antigen from different sources." Jung W., Krueger S., Renner C., Gause A., Sahin U., Trumper L., Pfreundschuh M. Mol. Immunol. 31:1329-1334(1994) [PubMed: 7527901] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
[3]	"A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and is expressed in alveolar macrophages." Horie R., Ito K., Tatewaki M., Nagai M., Aizawa S., Higashihara M., Ishida T., Inoue J., Takizawa H., Watanabe T. Blood 88:2422-2432(1996) [PubMed: 8839832] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[4]	"Structure of the Hodgkin's disease associated human CD30 gene and the influence of a microsatellite region on its expression in CD30+ cell lines." Durkop H., Oberbarnscheidt M., Latza U., Bulfone-Paus S. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM LONG). Tissue: Placenta.
[5]	NIEHS SNPs program Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-273 AND GLY-402.
[6]	"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], VARIANT ARG-297.
[7]	"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] (ISOFORM SHORT). Tissue: Blood.
[8]	"T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors." Lee S.Y., Park C.G., Choi Y. J. Exp. Med. 183:669-674(1996) [PubMed: 8627180] [Abstract] Cited for: INTERACTION WITH TRAF1 AND TRAF2.
[9]	"Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily." Boucher L.-M., Marengere L.E., Lu Y., Thukral S., Mak T.W. Biochem. Biophys. Res. Commun. 233:592-600(1997) [PubMed: 9168896] [Abstract] Cited for: INTERACTION WITH TRAF3.
[10]	"Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5)." Mizushima S., Fujita M., Ishida T., Azuma S., Kato K., Hirai M., Otsuka M., Yamamoto T., Inoue J. Gene 207:135-140(1998) [PubMed: 9511754] [Abstract] Cited for: INTERACTION WITH TRAF5.
[11]	"Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation." Aizawa S., Nakano H., Ishida T., Horie R., Nagai M., Ito K., Yagita H., Okumura K., Inoue J., Watanabe T. J. Biol. Chem. 272:2042-2045(1997) [PubMed: 8999898] [Abstract] Cited for: INTERACTION WITH TRAF5.
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-452, MASS SPECTROMETRY. Tissue: T-cell.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

M83554 mRNA. Translation: AAA51947.1.
S75768 mRNA. Translation: AAD14188.1.
D86042 mRNA. Translation: BAA12973.1.
AJ289159 Genomic DNA. Translation: CAC16652.1.
AY498860 Genomic DNA. Translation: AAR32099.1.
AL357835 Genomic DNA. Translation: CAH73719.1.
BC063482 mRNA. Translation: AAH63482.2.

IPI

IPI00006073.
IPI00759738.

PIR

A42086.

RefSeq

NP_001234.2.
NP_694421.1.

UniGene

Hs.1314

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1D01	X-ray	2.00	G/H/I	576-583	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:2930N.

IntAct

P28908. 3 interactions.

STRING

P28908.

PTM databases

PhosphoSite

P28908.

Proteomic databases

PRIDE

P28908.

Genome annotation databases

Ensembl

ENST00000263932; ENSP00000263932; ENSG00000120949; Homo sapiens. [Genome view]

GeneID

943.

KEGG

hsa:943.

Organism-specific databases

CTD

943.

GeneCards

GC01P012057.

H-InvDB

HIX0028774.

HGNC

HGNC:11923. TNFRSF8.

HPA

CAB000016.

MIM

153243. gene.

PharmGKB

PA36616.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P28908.

HOVERGEN

P28908.

Gene expression databases

ArrayExpress

P28908.

Bgee

P28908.

CleanEx

HS_TNFRSF8.

Genevestigator

P28908.

GermOnline

ENSG00000120949. Homo sapiens.

Family and domain databases

InterPro

IPR001368. TNFR_Cys_rich_reg.
IPR020416. Tumour_necrosis_fac_receptor-8.
[Graphical view]

Pfam

PF00020. TNFR_c6. 3 hits.
[Graphical view]

PRINTS

PR01923. TNFACTORR8.

SMART

SM00208. TNFR. 4 hits.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

NextBio

3908.

SOURCE

Search...

Entry information

Entry name

TNR8_HUMAN

Accession

Primary (citable) accession number: P28908
Secondary accession number(s): B1AN79, Q6P4D9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	December 1, 1992
Last modified:	November 24, 2009
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.