O08859 · TSG6_MOUSE

  • Protein
    Tumor necrosis factor-inducible gene 6 protein
  • Gene
    Tnfaip6
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Major regulator of extracellular matrix organization during tissue remodeling (By similarity).
Catalyzes the transfer of a heavy chain (HC) from inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. Cleaves the ester bond between the C-terminus of the HC and GalNAc residue of the chondroitin sulfate chain in I-alpha-I complex followed by transesterification of the HC to hyaluronan. In the process, potentiates the antiprotease function of I-alpha-I complex through release of free bikunin (By similarity).
Acts as a catalyst in the formation of hyaluronan-HC oligomers and hyaluronan-rich matrix surrounding the cumulus cell-oocyte complex, a necessary step for oocyte fertilization (PubMed:12668637).
Assembles hyaluronan in pericellular matrices that serve as platforms for receptor clustering and signaling. Enables binding of hyaluronan deposited on the surface of macrophages to LYVE1 on lymphatic endothelium and facilitates macrophage extravasation. Alters hyaluronan binding to functionally latent CD44 on vascular endothelium, switching CD44 into an active state that supports leukocyte rolling (By similarity).
Modulates the interaction of chemokines with extracellular matrix components and proteoglycans on endothelial cell surface, likely preventing chemokine gradient formation. In a negative feedback mechanism, may limit excessive neutrophil recruitment at inflammatory sites by antagonizing the association of CXCL8 with glycosaminoglycans on vascular endothelium (By similarity).
Has a role in osteogenesis and bone remodeling. Inhibits BMP2-dependent differentiation of mesenchymal stem cell to osteoblasts. Protects against bone erosion during inflammation by inhibiting TNFSF11/RANKL-dependent osteoclast activation (By similarity) (PubMed:18586671).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site183Ca2+ (UniProtKB | ChEBI)
Binding site191Ca2+ (UniProtKB | ChEBI)
Binding site232Ca2+ (UniProtKB | ChEBI)
Binding site234Ca2+ (UniProtKB | ChEBI)
Binding site235Ca2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentextracellular region
Cellular Componentextracellular space
Molecular Functioncalcium ion binding
Molecular Functioncarboxylesterase activity
Molecular Functionfibronectin binding
Molecular Functionhyaluronic acid binding
Biological Processcell adhesion
Biological Processfibronectin fibril organization
Biological Processhyaluronan metabolic process
Biological Processnegative regulation of BMP signaling pathway
Biological Processnegative regulation of inflammatory response
Biological Processnegative regulation of neutrophil chemotaxis
Biological Processnegative regulation of osteoblast differentiation
Biological Processnegative regulation of osteoclast differentiation
Biological Processovarian cumulus expansion
Biological Processpositive regulation of cell migration
Biological Processpositive regulation of receptor clustering

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Tumor necrosis factor-inducible gene 6 protein
  • Alternative names
    • TNF-stimulated gene 6 protein (TSG-6)
    • Tumor necrosis factor alpha-induced protein 6 (TNF alpha-induced protein 6)

Gene names

    • Name
      Tnfaip6
    • Synonyms
      Tnfip6, Tsg6

Organism names

  • Taxonomic identifier
  • Strains
    • CD-1
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    O08859

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

Mutant female mice are infertile due to impaired cumulus oophorus expansion upon gonadotropin surge (PubMed:12668637).
Mutant mice have twice the bone mass of wild-type littermates. They show increased trabecular number and trabecular thickness (PubMed:18586671).

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 7 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation.

TypeIDPosition(s)Description
Signal1-17
ChainPRO_000002669318-275Tumor necrosis factor-inducible gene 6 protein
Disulfide bond58↔127
Disulfide bond82↔103
Glycosylation118N-linked (GlcNAc...) asparagine
Disulfide bond135↔161
Disulfide bond188↔210
Glycosylation258N-linked (GlcNAc...) asparagine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in epiphyseal and metaphyseal bone marrow of both the femur and tibia (at protein level).

Developmental stage

Expressed in cumulus cell-oocyte complexes during expansion.

Gene expression databases

Interaction

Subunit

Interacts (via Link domain) with inter-alpha-inhibitor (I-alpha-I) component bikunin. Interacts with ITIH2/HC2; this interaction is required for transesterification of the HC to hyaluronan. Interacts (via Link and CUB domains) with ITIH1. Chondroitin sulfate may be required for the stability of the complex. Interacts (via Link domain) with various C-X-C and C-C chemokines including PF4, CXCL8, CXCL11, CXCL12, CCL2, CCL7, CCL19, CCL21, and CCL27; this interaction interferes with chemokine binding to glycosaminoglycans. Interacts (primarily via Link domain) with BMP2; this interaction is inhibited by hyaluronan. Interacts (via both Link and CUB domains) with TNFSF11. Interacts (via CUB domain) with FN1 (via type III repeats 9-14); this interaction enhances fibronectin fibril assembly. TNFAIP6 may act as a bridging molecule between FN1 and THBS1.

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for domain, compositional bias, region.

TypeIDPosition(s)Description
Domain36-129Link
Domain135-247CUB
Compositional bias253-267Polar residues
Region253-275Disordered

Domain

The Link domain interacts with various extracellular matrix components, including heparin, heparan sulfates, hyaluronan and I-alpha-I complex. It is required for binding to various chemokines.
The CUB domain is necessary for calcium ion binding and transesterification reaction. It is required for binding to FN1.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    275
  • Mass (Da)
    30,924
  • Last updated
    1997-07-01 v1
  • Checksum
    1CD247228260B8F9
MVVLLCLCVLLWEEAHGWGFKNGIFHNSIWLEQAAGVYHREARAGRYKLTYAEAKAVCEFEGGRLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYGIRLNRSERWDAYCYNPHAKECGGVFTDPKRIFKSPGFPNEYDDNQVCYWHIRLKYGQRIHLSFLDFDLEHDPGCLADYVEIYDSYDDVHGFVGRYCGDELPEDIISTGNVMTLKFLSDASVTAGGFQIKYVTVDPASKSSQAKNTSTTGNKKFLPGRFSHL

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias253-267Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U83903
EMBL· GenBank· DDBJ
AAC53527.1
EMBL· GenBank· DDBJ
mRNA
BC021155
EMBL· GenBank· DDBJ
AAH21155.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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