Link domain explained

Symbol:	LINK
Link domain
Pfam:	PF00193
Pfam Clan:	CL0056
Interpro:	IPR000538
Smart:	SM00445
Prosite:	PDOC00955
Scop:	1o7b
Cdd:	cd01102

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.^[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

Notes and References

1. Web site: Link domain signature and profile. PROSITE. 30 September 2016. December 2004.
2. Yoneda M, Nakamura T, Murai M, Wada H . 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 . 2010 . 71 . 1 . 51–9 . 20582409 . 10.1007/s00239-010-9363-x . 2010JMolE..71...51Y . 10614265 .
3. Hynes. RO. Naba. A. Overview of the Matrisome--An Inventory of Extracellular Matrix Constituents and Functions. Cold Spring Harbor Perspectives in Biology. 21 September 2011. 4. 1. a004903. 10.1101/cshperspect.a004903. 3249625. 21937732.
4. Barta E, Deák F, Kiss I . Evolution of the hyaluronan-binding module of link protein . Biochem. J. . 292 . 3. 947–9 . June 1993 . 8318021 . 1134205 . 10.1042/bj2920947.
5. Kohda D, Morton CJ, Parkar AA, Hatanaka H, Inagaki FM, Campbell ID, Day AJ . Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration . Cell . 86 . 5 . 767–75 . September 1996 . 8797823 . 10.1016/S0092-8674(00)80151-8. 16347386 . free .
6. Brissett NC, Perkins SJ . 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 . June 1996 . 8690089 . 10.1016/0014-5793(96)00576-5. 24295651 . free .