{{Short description|Protein domain}} {{Infobox protein family | Symbol = LINK | Name = Link domain | image = PDB 1poz EBI.jpg | width = | caption = Structure of the hyaluronan-binding domain of human CD44 | Pfam = PF00193 | Pfam_clan = CL0056 | InterPro = IPR000538 | SMART = SM00445 | PROSITE = PDOC00955 | MEROPS = | SCOP = 1o7b | TCDB = | OPM family = | OPM protein = | CAZy = | 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.<ref>{{cite web|title=Link domain signature and profile|url=http://prosite.expasy.org/cgi-bin/prosite/prosite-search-ac?PDOC00955|website=PROSITE|access-date=30 September 2016|date=December 2004}}</ref> It is important in blood cell migration and apoptosis.<ref name="pmid20582409">{{cite journal|vauthors=Yoneda M, Nakamura T, Murai M, Wada H | title=Evidence for the heparin-binding ability of the ascidian Xlink domain and insight into the evolution of the Xlink domain in chordates. | journal=J Mol Evol | year= 2010 | volume= 71 | issue= 1 | pages= 51–9 | pmid=20582409 | doi=10.1007/s00239-010-9363-x | bibcode=2010JMolE..71...51Y | s2cid=10614265 }}</ref> The link domain is found in some extracellular proteins in vertebrates such as the hyalectans.<ref name="RH">{{cite journal|last1=Hynes|first1=RO|last2=Naba|first2=A|title=Overview of the Matrisome--An Inventory of Extracellular Matrix Constituents and Functions|journal=Cold Spring Harbor Perspectives in Biology|date=21 September 2011|volume=4|issue=1|article-number=a004903|doi=10.1101/cshperspect.a004903|pmc=3249625|pmid=21937732}}</ref> It appears to be involved in extracellular matrix assembly and stability, cell adhesion, and migration.<ref name="RH" /><ref name="pmid8318021">{{cite journal |vauthors=Barta E, Deák F, Kiss I | title = Evolution of the hyaluronan-binding module of link protein | journal = Biochem. J. | volume = 292 | issue = 3| pages = 947–9 |date=June 1993 | pmid = 8318021 | pmc = 1134205 | doi = 10.1042/bj2920947}}</ref>
==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.<ref name="pmid8797823">{{cite journal |vauthors=Kohda D, Morton CJ, Parkar AA, Hatanaka H, Inagaki FM, Campbell ID, Day AJ | title = Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration | journal = Cell | volume = 86 | issue = 5 | pages = 767–75 |date=September 1996 | pmid = 8797823 | doi = 10.1016/S0092-8674(00)80151-8| s2cid = 16347386 | doi-access = free }}</ref> This domain contains four conserved cysteines involved in two disulphide bonds. The link domain has also been termed HABM (hyaluronic acid binding module)<ref name="pmid8318021"/> and PTR (proteoglycan tandem repeat).<ref name="pmid8690089">{{cite journal |vauthors=Brissett NC, Perkins SJ | title = 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 | journal = FEBS Lett. | volume = 388 | issue = 2–3 | pages = 211–6 |date=June 1996 | pmid = 8690089 | doi = 10.1016/0014-5793(96)00576-5| s2cid = 24295651 | doi-access = free }}</ref>
==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== {{reflist|2}} {{InterPro content|IPR000538}}
Category:Protein domains Category:Extracellular matrix