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Q06643

- TNFC_HUMAN

UniProt

Q06643 - TNFC_HUMAN

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Protein

Lymphotoxin-beta

Gene

LTB

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. receptor binding Source: ProtInc

GO - Biological processi

  1. cell-cell signaling Source: ProtInc
  2. gene expression Source: Ensembl
  3. immune response Source: InterPro
  4. lymph node development Source: Ensembl
  5. positive regulation of interleukin-12 biosynthetic process Source: UniProtKB
  6. signal transduction Source: ProtInc
  7. skin development Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Names & Taxonomyi

Protein namesi
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 namesi
Name:LTB
Synonyms:TNFC, TNFSF3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6, UP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:6711. LTB.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1818CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei19 – 4830Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini49 – 244196ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30475.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 244244Lymphotoxin-betaPRO_0000185486Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi222 – 2221N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ06643.
PRIDEiQ06643.

Expressioni

Tissue specificityi

Spleen and thymus.

Gene expression databases

BgeeiQ06643.
CleanExiHS_LTB.
ExpressionAtlasiQ06643. baseline and differential.
GenevestigatoriQ06643.

Organism-specific databases

HPAiHPA048884.

Interactioni

Subunit structurei

Heterotrimer of either two LTB and one LTA subunits or (less prevalent) one LTB and two LTA subunits.

Protein-protein interaction databases

BioGridi110228. 2 interactions.
DIPiDIP-2996N.
IntActiQ06643. 5 interactions.
STRINGi9606.ENSP00000393693.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4MXWX-ray3.60B/D/Y/Z86-244[»]
ProteinModelPortaliQ06643.
SMRiQ06643. Positions 87-243.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tumor necrosis factor family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG44178.
GeneTreeiENSGT00390000007066.
HOGENOMiHOG000273916.
HOVERGENiHBG000209.
InParanoidiQ06643.
KOiK03157.
OMAiREYGPLW.
OrthoDBiEOG7V4B0Q.
PhylomeDBiQ06643.
TreeFamiTF337780.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiIPR006053. TNF.
IPR002961. TNF_C.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamiPF00229. TNF. 1 hit.
[Graphical view]
PRINTSiPR01234. TNECROSISFCT.
PR01237. TNFC.
SMARTiSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiPS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q06643-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MGALGLEGRG GRLQGRGSLL LAVAGATSLV TLLLAVPITV LAVLALVPQD
60 70 80 90 100
QGGLVTETAD PGAQAQQGLG FQKLPEEEPE TDLSPGLPAA HLIGAPLKGQ
110 120 130 140 150
GLGWETTKEQ AFLTSGTQFS DAEGLALPQD GLYYLYCLVG YRGRAPPGGG
160 170 180 190 200
DPQGRSVTLR SSLYRAGGAY GPGTPELLLE GAETVTPVLD PARRQGYGPL
210 220 230 240
WYTSVGFGGL VQLRRGERVY VNISHPDMVD FARGKTFFGA VMVG
Length:244
Mass (Da):25,390
Last modified:June 1, 1994 - v1
Checksum:iF41569459830ED4C
GO
Isoform 2 (identifier: Q06643-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:77
Mass (Da):7,780
Checksum:i8F1256D793D85397
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti60 – 6910DPGAQAQQGL → GLSAPGSGRT in AAB37342. (PubMed:9299492)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti70 – 701G → E.1 Publication
Corresponds to variant rs3093554 [ dbSNP | Ensembl ].
VAR_013025
Natural varianti84 – 841S → R.1 Publication
Corresponds to variant rs4647186 [ dbSNP | Ensembl ].
VAR_016331
Natural varianti87 – 871L → F.1 Publication
Corresponds to variant rs4647187 [ dbSNP | Ensembl ].
VAR_016332
Natural varianti111 – 1111A → P.1 Publication
Corresponds to variant rs3093555 [ dbSNP | Ensembl ].
VAR_013026
Natural varianti122 – 1221A → D.
Corresponds to variant rs2229699 [ dbSNP | Ensembl ].
VAR_029145

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei53 – 7725GLVTE…KLPEE → GLGFRSCQRRSQKQISAPGS QLPTS in isoform 2. 3 PublicationsVSP_006441Add
BLAST
Alternative sequencei78 – 244167Missing in isoform 2. 3 PublicationsVSP_006442Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK312210 mRNA. Translation: BAG35143.1.
CH471081 Genomic DNA. Translation: EAX03425.1.
BC069330 mRNA. Translation: AAH69330.1.
BC093783 mRNA. Translation: AAH93783.1.
CCDSiCCDS4703.1. [Q06643-1]
CCDS4704.1. [Q06643-2]
PIRiA46066.
JC5645.
RefSeqiNP_002332.1. NM_002341.1. [Q06643-1]
NP_033666.1. NM_009588.1. [Q06643-2]
UniGeneiHs.376208.

Genome annotation databases

EnsembliENST00000376117; ENSP00000365285; ENSG00000204487. [Q06643-1]
ENST00000383493; ENSP00000372985; ENSG00000206437. [Q06643-1]
ENST00000420402; ENSP00000398741; ENSG00000223448. [Q06643-1]
ENST00000421268; ENSP00000393693; ENSG00000238114. [Q06643-1]
ENST00000429299; ENSP00000410481; ENSG00000227507. [Q06643-1]
ENST00000444479; ENSP00000395102; ENSG00000236925. [Q06643-1]
ENST00000446745; ENSP00000416113; ENSG00000227507. [Q06643-2]
ENST00000456113; ENSP00000404014; ENSG00000236237. [Q06643-1]
ENST00000457552; ENSP00000404450; ENSG00000231314. [Q06643-1]
GeneIDi4050.
KEGGihsa:4050.
UCSCiuc003nuk.3. human. [Q06643-1]
uc003nul.3. human. [Q06643-2]

Polymorphism databases

DMDMi549088.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
AK312210 mRNA. Translation: BAG35143.1 .
CH471081 Genomic DNA. Translation: EAX03425.1 .
BC069330 mRNA. Translation: AAH69330.1 .
BC093783 mRNA. Translation: AAH93783.1 .
CCDSi CCDS4703.1. [Q06643-1 ]
CCDS4704.1. [Q06643-2 ]
PIRi A46066.
JC5645.
RefSeqi NP_002332.1. NM_002341.1. [Q06643-1 ]
NP_033666.1. NM_009588.1. [Q06643-2 ]
UniGenei Hs.376208.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4MXW X-ray 3.60 B/D/Y/Z 86-244 [» ]
ProteinModelPortali Q06643.
SMRi Q06643. Positions 87-243.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110228. 2 interactions.
DIPi DIP-2996N.
IntActi Q06643. 5 interactions.
STRINGi 9606.ENSP00000393693.

Polymorphism databases

DMDMi 549088.

Proteomic databases

PaxDbi Q06643.
PRIDEi Q06643.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000376117 ; ENSP00000365285 ; ENSG00000204487 . [Q06643-1 ]
ENST00000383493 ; ENSP00000372985 ; ENSG00000206437 . [Q06643-1 ]
ENST00000420402 ; ENSP00000398741 ; ENSG00000223448 . [Q06643-1 ]
ENST00000421268 ; ENSP00000393693 ; ENSG00000238114 . [Q06643-1 ]
ENST00000429299 ; ENSP00000410481 ; ENSG00000227507 . [Q06643-1 ]
ENST00000444479 ; ENSP00000395102 ; ENSG00000236925 . [Q06643-1 ]
ENST00000446745 ; ENSP00000416113 ; ENSG00000227507 . [Q06643-2 ]
ENST00000456113 ; ENSP00000404014 ; ENSG00000236237 . [Q06643-1 ]
ENST00000457552 ; ENSP00000404450 ; ENSG00000231314 . [Q06643-1 ]
GeneIDi 4050.
KEGGi hsa:4050.
UCSCi uc003nuk.3. human. [Q06643-1 ]
uc003nul.3. human. [Q06643-2 ]

Organism-specific databases

CTDi 4050.
GeneCardsi GC06M031582.
GC06Mi31559.
GC06Mj31535.
GC06Mk31530.
GC06Ml31587.
GC06Mm31624.
GC06Mn31538.
GC06Mo31538.
HGNCi HGNC:6711. LTB.
HPAi HPA048884.
MIMi 600978. gene.
neXtProti NX_Q06643.
PharmGKBi PA30475.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG44178.
GeneTreei ENSGT00390000007066.
HOGENOMi HOG000273916.
HOVERGENi HBG000209.
InParanoidi Q06643.
KOi K03157.
OMAi REYGPLW.
OrthoDBi EOG7V4B0Q.
PhylomeDBi Q06643.
TreeFami TF337780.

Miscellaneous databases

ChiTaRSi LTB. human.
GeneWikii Lymphotoxin_beta.
GenomeRNAii 4050.
NextBioi 15864.
PROi Q06643.
SOURCEi Search...

Gene expression databases

Bgeei Q06643.
CleanExi HS_LTB.
ExpressionAtlasi Q06643. baseline and differential.
Genevestigatori Q06643.

Family and domain databases

Gene3Di 2.60.120.40. 1 hit.
InterProi IPR006053. TNF.
IPR002961. TNF_C.
IPR021184. TNF_CS.
IPR006052. TNF_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view ]
Pfami PF00229. TNF. 1 hit.
[Graphical view ]
PRINTSi PR01234. TNECROSISFCT.
PR01237. TNFC.
SMARTi SM00207. TNF. 1 hit.
[Graphical view ]
SUPFAMi SSF49842. SSF49842. 1 hit.
PROSITEi PS00251. TNF_1. 1 hit.
PS50049. TNF_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. "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] (ISOFORM 2).
    Tissue: Spleen.
  9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. "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] (ISOFORMS 1 AND 2).
    Tissue: Colon.

Entry informationi

Entry nameiTNFC_HUMAN
AccessioniPrimary (citable) accession number: Q06643
Secondary accession number(s): P78370, Q52LU8, Q99761
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: October 29, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3