{PDOC00955}
{PS01241; LINK_1}
{PS50963; LINK_2}
{BEGIN}
*************************************
* Link domain signature and profile *
*************************************

The Link  domain [1] is a hyaluronan(HA)-binding  region  found in proteins of
vertebrates that  are  involved  in the assembly of extracellular matrix, cell
adhesion, and  migration. It is about 100 amino acids in length. The structure
has been  shown [2]  to consist of two alpha helices and two antiparallel beta
sheets  arranged  around  a large  hydrophobic  core similar to that of C-type
lectin <See  PDOC00537>.  As shown in the schematic representation this domain
contains four conserved cysteines involved in two disulfide bonds.

                              +----------+
                              |          |
                  ************|***********
              xxxxCxxxxxxxxxxxCxxxxxxxxxxCxxxxxxxxxxxxxxxCxxxxx
                  |                                      |
                  +--------------------------------------+

'C': conserved cysteine involved in a disulfide bond.
'*': position of the pattern.

The Link  domain has also been termed HABM [1] (HA binding module) and PTR [3]
(proteoglycan tandem repeat). Proteins with such a domain are listed below:

 - The cartilage link protein (LP), a proteoglycan that togethers with HA  and
   aggrecan forms  multimolecular aggregates. It consists of an Ig-like V-type
   domain and two copies of the Link domain.
 - The  proteoglycans  aggrecan,  brevican,  neurocan  and versican, which are
   expressed in  the  CNS.  These  proteins  are composed of an Ig-like V-type
   region, two  or  four  (only  in aggrecan) Link domains, up to two EGF-like
   repeats, a variable length domain containing the site of attachments of the
   sugars, followed, in the C-terminal by a C-type lectin and a Sushi domain.
 - CD44  antigen. The main cell surface receptor for HA. CD44 is known by many
   different names  and  also  exists in many different forms due to extensive
   alternative splicing  of its 19 exons. It contains a single N-terminal Link
   domain, which has been shown to be involved in HA-binding [4].
 - Tumor  necrosis  factor-inducible protein TSG-6. It is possibly involved in
   cell-cell and    cell-matrix    interactions    during   inflammation   and
   tumorgenesis. It contains a Link domain and a CUB domain.

We developed  a  signature  pattern  for  this domain, which is located in the
middle of the sequence and covers the first three conserved cysteines. We also
developed a profile, which covers the entire Link domain.

-Consensus pattern: C-x(15)-A-x(3,4)-[GK]-x(3)-C-x(2)-G-x(8,9)-P-x(7)-C
                    [The 3 C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 the 4th  link domain of human aggrecan, which lacks a leucine between the 1st
 cysteine and the conserved alanine in comparision with other link domains.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: December 2004 / Pattern and text revised.

[ 1] Barta E., Deak F., Kiss I.
     "Evolution of the hyaluronan-binding module of link protein."
     Biochem. J. 292:947-949(1993).
     PubMed=8318021
[ 2] Kohda D., Morton C.J., Parkar A.A., Hatanaka H., Inagaki F.M.,
     Campbell I.D., Day A.J.
     "Solution structure of the link module: a hyaluronan-binding domain
     involved in extracellular matrix stability and cell migration."
     Cell 86:767-775(1996).
     PubMed=8797823
[ 3] Brisset N.C., Perkins S.J.
     FEBS Lett. 388:211-216(1996).
[ 4] Peach R.J., Hollenbaugh D., Stamenkovic I., Aruffo A.
     "Identification of hyaluronic acid binding sites in the extracellular
     domain of CD44."
     J. Cell Biol. 122:257-264(1993).
     PubMed=8314845

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{END}