Link domain

Link domain
Structure of the hyaluronan-binding domain of human CD44
Identifiers
Symbol	LINK
Pfam	PF00193
Pfam clan	CL0056
InterPro	IPR000538
SMART	SM00445
PROSITE	PDOC00955
SCOP2	1o7b / SCOPe / SUPFAM
CDD	cd01102
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

A Link domain or Link module, also known as Xlink domain (X for extracellular), is a protein domain that binds to hyaluronic acid. ^[1] It is important in blood cell migration and apoptosis. ^[2] The link domain is found in some extracellular proteins in vertebrates such as the hyalectans. ^[3] It appears to be involved in extracellular matrix assembly and stability, cell adhesion, and migration. ^{[3] [4]}

Structure

The structure has been shown to consist of two alpha helices and two antiparallel beta sheets arranged around a large hydrophobic core similar to that of C-type lectin. ^[5] This domain contains four conserved cysteines involved in two disulphide bonds. The link domain has also been termed HABM (hyaluronic acid binding module) ^[4] and PTR (proteoglycan tandem repeat). ^[6]

Link domain proteins

Proteins which contain the link domain include:

• the hyalectans (a family of 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 6 (TSG-6), which may be involved in cell-cell and cell-matrix interactions during inflammation and tumourigenesis;
• CD44 antigen, the main cell surface receptor for HA.

See also

• Hyaladherin

References

1. "Link domain signature and profile". PROSITE. December 2004. Retrieved 30 September 2016.
2. Yoneda M, Nakamura T, Murai M, Wada H (2010). "Evidence for the heparin-binding ability of the ascidian Xlink domain and insight into the evolution of the Xlink domain in chordates". J Mol Evol. 71 (1): 51–9. Bibcode:2010JMolE..71...51Y. doi:10.1007/s00239-010-9363-x. PMID   20582409. S2CID   10614265.
3. Hynes, RO; Naba, A (21 September 2011). "Overview of the Matrisome--An Inventory of Extracellular Matrix Constituents and Functions". Cold Spring Harbor Perspectives in Biology. 4 (1) a004903. doi:10.1101/cshperspect.a004903. PMC   3249625 . PMID   21937732.
4. Barta E, Deák F, Kiss I (June 1993). "Evolution of the hyaluronan-binding module of link protein". Biochem. J. 292 (3): 947–9. doi:10.1042/bj2920947. PMC   1134205 . PMID   8318021.
5. Kohda D, Morton CJ, Parkar AA, Hatanaka H, Inagaki FM, Campbell ID, Day AJ (September 1996). "Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration". Cell. 86 (5): 767–75. doi: 10.1016/S0092-8674(00)80151-8 . PMID   8797823. S2CID   16347386.
6. Brissett NC, Perkins SJ (June 1996). "The protein fold of the hyaluronate-binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C-type lectin superfamily". FEBS Lett. 388 (2–3): 211–6. doi: 10.1016/0014-5793(96)00576-5 . PMID   8690089. S2CID   24295651.

This article incorporates text from the public domain Pfam and InterPro: IPR000538