Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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LINK Link (Hyaluronan-binding)

SMART accession number:	SM00445
Description:
Interpro abstract (IPR000538):	The link domain [(PUBMED:8318021)] is a hyaluronan(HA)-binding region found in proteins of vertebrates that are involved in the assembly of extracellular matrix, cell adhesion, and migration. The structure has been shown [(PUBMED:8797823)] to consist of two alpha helices and two antiparallel beta sheets arranged around a large hydrophobic core similar to that of C-type lectin. This domain contains four conserved cysteines involved in two disulphide bonds. The link domain has also been termed HABM [(PUBMED:8318021)] (HA binding module) and PTR [(PUBMED:8690089)] (proteoglycan tandem repeat). Proteins with such a domain include the proteoglycans aggrecan, brevican, neurocan and versican, which are expressed in the CNS; the cartilage link protein (LP), a proteoglycan that together with HA and aggrecan forms multimolecular aggregates; Tumour necrosis factor-inducible protein TSG-6, which may be involved in cell-cell and cell-matrix interactions during inflammation and tumourgenesis; and CD44 antigen, the main cell surface receptor for HA.
GO process:	cell adhesion (GO:0007155)
GO function:	hyaluronic acid binding (GO:0005540)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 1016 LINK domains in 595 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a LINK domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with LINK domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 50.00 map04640 Hematopoietic cell lineage 50.00 map04512 ECM-receptor interaction This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with LINK domain which could be assigned to a KEGG orthologous group, and not all proteins containing LINK domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of LINK domains in PDB

  PDB code	Main view	Title
  1o7b		Refined solution structure of the human tsg-6 link module
  1o7c		Solution structure of the human tsg-6 link module in the presence of a hyaluronan octasaccharide
  1poz		Solution structure of the hyaluronan binding domain of human cd44
  1uuh		Hyaluronan binding domain of human cd44
  2i83		Hyaluronan-binding domain of cd44 in its ligand-bound form
  2jcp		The hyaluronan binding domain of murine cd44
  2jcq		The hyaluronan binding domain of murine cd44 in a type a complex with an ha 8-mer
  2jcr		The hyaluronan binding domain of murine cd44 in a type b complex with an ha 8-mer
  2pf5		Crystal structure of the human tsg-6 link module

• Links (links to other resources describing this domain)

• BLOCKS	LINK
  PFAM	Xlink
  INTERPRO	IPR000538
  PROSITE	LINK

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