Q06643 (TNFC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lymphotoxin-beta
Short name=LT-beta

Alternative name(s):
Tumor necrosis factor C
Short name=TNF-C
Tumor necrosis factor ligand superfamily member 3

Gene names

Name:	LTB
Synonyms:	TNFC, TNFSF3

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

General annotation (Comments)

Function	Cytokine that binds to LTBR/TNFRSF3. May play a specific role in immune response regulation. Provides the membrane anchor for the attachment of the heterotrimeric complex to the cell surface. Isoform 2 is probably non-functional.
Subunit structure	Heterotrimer of either two LTB and one LTA subunits or (less prevalent) one LTB and two LTA subunits.
Subcellular location	Membrane; Single-pass type II membrane protein Potential.
Tissue specificity	Spleen and thymus.
Sequence similarities	Belongs to the tumor necrosis factor family.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Cytokine
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell-cell signaling Traceable author statement. Source: ProtInc immune response Inferred from electronic annotation. Source: InterPro positive regulation of interleukin-12 biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q06643-1)

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: Q06643-2)

The sequence of this isoform differs from the canonical sequence as follows:
     53-77: GLVTETADPGAQAQQGLGFQKLPEE → GLGFRSCQRRSQKQISAPGSQLPTS
     78-244: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 244	244	Lymphotoxin-beta		PRO_0000185486
Regions
	Topological domain	1 – 18	18	Cytoplasmic Potential
	Transmembrane	19 – 48	30	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	49 – 244	196	Extracellular Potential
Amino acid modifications
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	53 – 77	25	GLVTE…KLPEE → GLGFRSCQRRSQKQISAPGS QLPTS in isoform 2.		VSP_006441
	Alternative sequence	78 – 244	167	Missing in isoform 2.		VSP_006442
	Natural variant	70	1	G → E. Ref.6 Corresponds to variant rs3093554 [ dbSNP | Ensembl ].		VAR_013025
	Natural variant	84	1	S → R. Ref.7 Corresponds to variant rs4647186 [ dbSNP | Ensembl ].		VAR_016331
	Natural variant	87	1	L → F. Ref.7 Corresponds to variant rs4647187 [ dbSNP | Ensembl ].		VAR_016332
	Natural variant	111	1	A → P. Ref.6 Corresponds to variant rs3093555 [ dbSNP | Ensembl ].		VAR_013026
	Natural variant	122	1	A → D. Corresponds to variant rs2229699 [ dbSNP | Ensembl ].		VAR_029145
Experimental info
	Sequence conflict	60 – 69	10	DPGAQAQQGL → GLSAPGSGRT in AAB37342. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: F41569459830ED4C	FASTA	244	25,390
	10 20 30 40 50 60 MGALGLEGRG GRLQGRGSLL LAVAGATSLV TLLLAVPITV LAVLALVPQD QGGLVTETAD 70 80 90 100 110 120 PGAQAQQGLG FQKLPEEEPE TDLSPGLPAA HLIGAPLKGQ GLGWETTKEQ AFLTSGTQFS 130 140 150 160 170 180 DAEGLALPQD GLYYLYCLVG YRGRAPPGGG DPQGRSVTLR SSLYRAGGAY GPGTPELLLE 190 200 210 220 230 240 GAETVTPVLD PARRQGYGPL WYTSVGFGGL VQLRRGERVY VNISHPDMVD FARGKTFFGA VMVG
	Isoform 2 [UniParc]. Checksum: 8F1256D793D85397	FASTA	77	7,780
	10 20 30 40 50 60 MGALGLEGRG GRLQGRGSLL LAVAGATSLV TLLLAVPITV LAVLALVPQD QGGLGFRSCQ 70 RRSQKQISAP GSQLPTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface." Browning J.L., Ngam-Ek A., Lawton P., Demarinis J., Tizard R., Chow E.P., Hession C., O'Brine-Greco B., Foley S.F., Ware C.F. Cell 72:847-856(1993) [PubMed: 7916655] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: T-cell.
[2]	"Identification of two lymphotoxin beta isoforms expressed in human lymphoid cell lines and non-Hodgkin's lymphomas." Warzocha K., Renard N., Charlot C., Bienvenu J., Coiffier B., Salles G. Biochem. Biophys. Res. Commun. 238:273-276(1997) [PubMed: 9299492] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]	"A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC." Neville M.J., Campbell R.D. J. Immunol. 162:4745-4754(1999) [PubMed: 10202016] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[4]	"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse." Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L. Genome Res. 13:2621-2636(2003) [PubMed: 14656967] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region." Shiina S., Tamiya G., Oka A., Inoko H. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	SeattleSNPs variation discovery resource Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLU-70 AND PRO-111.
[7]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-84 AND PHE-87.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	L11016 Genomic DNA. Translation: AAA99888.1. U89922 mRNA. Translation: AAC51769.1. U79029 mRNA. Translation: AAB37342.1. L11015 mRNA. Translation: AAA36191.1. Y14768 Genomic DNA. Translation: CAA75069.1. AF129756 Genomic DNA. Translation: AAD18089.1. BA000025 Genomic DNA. Translation: BAB63395.1. AY070219 Genomic DNA. Translation: AAL49954.1. AY070219 Genomic DNA. Translation: AAL49955.1. AY216497 Genomic DNA. Translation: AAO21134.1. BC069330 mRNA. Translation: AAH69330.1.
IPI	IPI00032334. IPI00215776.
PIR	A46066. JC5645.
RefSeq	NP_002332.1. NM_002341.1. NP_033666.1. NM_009588.1.
UniGene	Hs.376208.
3D structure databases
ProteinModelPortal	Q06643.
SMR	Q06643. Positions 84-243.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2996N.
IntAct	Q06643. 5 interactions.
Polymorphism databases
DMDM	549088.
Proteomic databases
PRIDE	Q06643.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000376117; ENSP00000365285; ENSG00000204487. ENST00000383493; ENSP00000372985; ENSG00000206437. ENST00000420402; ENSP00000398741; ENSG00000223448. ENST00000421268; ENSP00000393693; ENSG00000238114. ENST00000429299; ENSP00000410481; ENSG00000227507. ENST00000444479; ENSP00000395102; ENSG00000236925. ENST00000456113; ENSP00000404014; ENSG00000236237. ENST00000457552; ENSP00000404450; ENSG00000231314.
GeneID	4050.
KEGG	hsa:4050.
UCSC	uc003nuk.1. human.
Organism-specific databases
CTD	4050.
GeneCards	GC06M031549.
HGNC	HGNC:6711. LTB.
MIM	600978. gene.
neXtProt	NX_Q06643.
PharmGKB	PA30475.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG125616.
HOVERGEN	HBG000209.
InParanoid	Q06643.
OMA	YGPGTPE.
OrthoDB	EOG4FFD2N.
PhylomeDB	Q06643.
Gene expression databases
CleanEx	HS_LTB.
Genevestigator	Q06643.
GermOnline	ENSG00000204487. Homo sapiens.
Family and domain databases
InterPro	IPR006052. TNF. IPR006053. TNF_a/b/c. IPR002961. TNF_C. IPR021184. TNF_CS. IPR008983. Tumour_necrosis_fac-like. [Graphical view]
Gene3D	G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
KO	K03157.
Pfam	PF00229. TNF. 1 hit. [Graphical view]
PRINTS	PR01234. TNECROSISFCT. PR01237. TNFC.
SMART	SM00207. TNF. 1 hit. [Graphical view]
SUPFAM	SSF49842. TNF_like. 1 hit.
PROSITE	PS00251. TNF_1. 1 hit. PS50049. TNF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00065. Infliximab. DB00641. Simvastatin.
NextBio	15864.
SOURCE	Search...

Entry information

Entry name

TNFC_HUMAN

Accession

Primary (citable) accession number: Q06643
Secondary accession number(s): P78370, Q99761

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	January 25, 2012
This is version 118 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.