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Q06643

- TNFC_HUMAN

UniProt

Q06643 - TNFC_HUMAN

Protein

Lymphotoxin-beta

Gene

LTB

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      Previous versions | rss
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    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

    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

    Organism-specific databases

    HGNCiHGNC:6711. LTB.

    Subcellular locationi

    GO - Cellular componenti

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

    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

    ArrayExpressiQ06643.
    BgeeiQ06643.
    CleanExiHS_LTB.
    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:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4MXWX-ray3.60B/D/Y/Z86-244[»]
    ProteinModelPortaliQ06643.
    SMRiQ06643. Positions 87-243.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1818CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini49 – 244196ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei19 – 4830Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the tumor necrosis factor family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG44178.
    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

    MGALGLEGRG GRLQGRGSLL LAVAGATSLV TLLLAVPITV LAVLALVPQD    50
    QGGLVTETAD PGAQAQQGLG FQKLPEEEPE TDLSPGLPAA HLIGAPLKGQ 100
    GLGWETTKEQ AFLTSGTQFS DAEGLALPQD GLYYLYCLVG YRGRAPPGGG 150
    DPQGRSVTLR SSLYRAGGAY GPGTPELLLE GAETVTPVLD PARRQGYGPL 200
    WYTSVGFGGL VQLRRGERVY VNISHPDMVD FARGKTFFGA VMVG 244
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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.

    Chemistry

    DrugBanki DB00065. Infliximab.
    DB00641. Simvastatin.

    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 GC06M031549.
    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.
    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

    ArrayExpressi Q06643.
    Bgeei Q06643.
    CleanExi HS_LTB.
    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

    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 1, 2014
    This is version 142 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