The Adhesion Molecule Facts: Book

301 Pages·2000·40.99 MB·English

by  Clare M. Isacke and Michael A. Horton (Auth.)

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THE
A D H E S I O N
MOLECULE
FactsBook
Second Edition
Clare M. Isacke
Imperial College of Science, Technology and Medicine,
London, UK
Michael A. Horton
University College London, London, UK
ACADEMIC PRESS
A Harcourt Science and Technology Company
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This book is printed on acid-free paper.
Copyright (cid:0)9 2000 by ACADEMIC PRESS
All Rights Reserved.
No part of this publication may be reproduced or transmitted in any form or by
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ISBN 0-12-356505-7
Library of Congress Catalog Card Number: 00-104879
A catalogue for this book is available from the British Library
Typeset by Mackreth Media Services, Hemel Hempstead, UK
Printed in Great Britain by Redwood Books, Trowbridge, Wiltshire
00 01 02 03 04 05 RB 9 8 7 6 5 4 3 2 1
The authors acknowledge all those who have helped in the completion of this
book. In particular we would like to thank Chau Chong for excellent secretarial
help, our laboratories for their patience while the book was being written and
members of the UK Adhesion Group who filled in questionnaires suggesting
molecules that should be included. Many colleagues were invaluable in checking
entries and providing unpublished information. We would particularly like to
thank Ann Ager, Chris Buckley, Paul Crocker, Pat Doherty, Kurt Drickamer,
Nancy Hog, Gudrun Ihrke, David Jackson, Sirpa Jalltanen, Clive Landis, Tony
Magee, Fiona Watt, Sue Watt and Lisa Williams. Writing this book was greatly
helped by the recent publication of The Leucocyte Antigen FactsBook, and we
would like to acknowledge Neil Barclay, Marion Brown, Alex Law, Andrew
McKnight, Michael Tomlinson and Anton van der Merwe whose hard work made
our task much easier.
With the published literature on adhesion molecules increasing by several
thousand papers per annum and the various mammalian genome projects
sequencing apace, a book will inevitably contain omissions and inaccuracies, and
the references have a danger of being superseded. For this we apologize. However,
with access to electronic databases on the World Wide Web (see Chapter3 ),t his is
relatively easy to remedy and the reader is asked to bear with us and make their
own updates relating to a favourite molecule.
AIDS Acquired immunodeficiency syndrome
B B lymphocyte
BCR B cell antigen receptor
CCP Complement control protein
CD Cluster of differentiation
CNR Cadherin-related neuronal receptor
cs Chondroitin sulphate
ECM Extracellular matrix
EGF Epidermal growth factor
ERM Ezrin/radixin/moesin
ES Embryonic stem
EST Expressed sequence tag
FAK Focal adhesion kinase
FGF Fibroblast growth factor
GAG Gl y cosaminoglycan
GalNAc N-A cetylgalactosamine
GlcNAc N-A cetylglucosamine
GPI Gly cosyl-phosphatidylinositol
GSK Glycogen synthase kinase
HEV High endothelial venule
IFN Interferon
Ig Immunoglobulin
IgSF Immunoglobulin superfamily
IL Interleukin
ITIM Immunoreceptor tyrosine-based inhibitory motif
kb Kilobase pairs
kDa Kilodalton
LAD Leucocyte adhesion deficiency
LPS Lipopoly saccharide
LRR Leucine-rich repeat
MAPK Mitogen-activated protein kinase
MGI Mouse Genome Informatics
MHC Major histocompatibility complex
NK Natural killer
NMR Nuclear magnetic resonance
OMIM Online Mendelian Inheritance in Man
PI Phosphatidylinositol
SDS-PAGE Polyacrylamide gel electrophoresis in sodium dodecyl sulphate
SH2 Src homology domain 2
SH3 Src homology domain 3
sLeA Sialyl-Lewis*
sLeX Sialyl-LewisX
T T lymphocyte
TM Transmembrane
TM4SF Tetraspan supcrfamily
TNF Tumour nccrosis factor
WFl Wingless
www Wnrld Widc Wch
Size Type Size
(approximate (approximate
amino acids) 8 amino acids)
D
Cadherin T 10 Lectin C-type 120
repeat
h Galccrin or 140
Collagennus Vatisblc Lectin S-type
domain length
a
0 LRR repeats
24
Complement "r'
control protein 60
(CCPF Link 90
p+
Drsrnoglein @ 30 70-90
repeat
Scavenger 110
Epidermal p receptor
growth 40
factor (EGF)
OTHER SYMBOLS USED
N-g Iy cory lation si teP h
Fihronectin
type 111 /FnN Q-linked glymwlation /
Glrcmoam inoglvcan -SJ
-
GPI anchor in
lipid hilayer
Jrn munoglohulin Site of propeptide cleavage
(Ig) C2 set [c.R.i n cad herins!
Unknown nr unclear molecular
7
cnnfnrrnation nr membrane
attnchrnent/linkajy
Figure 1 Icons used for the protein domains and repeats that are present in
adhesion molecules.
AIMS OF THE BOOK
The primary aim of this book is to provide a compendium of the major cell surface
adhesion molecules. The entries have been designed to allow the reader to
establish the main structural and functional features of a molecule quickly and to
provide sufficient information for accessing further information. A detailed
explanation of the organization of the entries is included in this chapter. In
addition there are two further chapters preceding the individual entries. Chapter 2
provides a background to the main adhesion molecule families and Chapter 3
provides information as to how to access information on adhesion molecules on
the World Wide Web.
CRITERIA FOR SELECTION
Deciding on which molecules should be included in this book was a difficult task
and many researchers may be offended to find the subject of their work missing.
The difficulties arise in several areas. First, the majority of adhesion receptors
belong to a family group based on recognizable structural features. With the rapid
advances in cloning and proteomics, new molecules which contain these
structural features are frequently appearing in the literature and databases.
However, for many of these new molecules there is no information as to whether
they function as adhesion molecules. Unless such information has been obtained,
these molecules have not been given individual entries but they are discussed in
the relevant sections in Chapter 2.
Second, some molecules have been shown to be bona fide adhesion molecules
but have been omitted unless a mammalian orthologue has been established. In
the majority of cases these molecules have been identified in Drosophila
melanogaster or in Caenorhabditis elegans. Both these organisms have extensive
databases associated with them that can be accessed for further information
(see Chapter 3 and C. elegans: http://www.sanger.ac.uk/Projects/C-elegansl;
http://www.wormbase.org/; D. melanogaster: http://flybase.bio.indiana.edu/).
Third, molecules which function in cell recognition rather than cell adhesion
have been omitted. These include components of the immune recognition
complexes such as the T and B cell receptors, receptor:ligand pairs such as Notch
and Jagged/Serrate. Although not easy to assess, recognition molecules are
judged as those that play a crucial role in mediating cel1:cell interactions but do
not alone mediate adhesion. Similarly, in the past few years, the distinction
between adhesion molecules and signalling receptors has become increasingly
blurred, and indeed many adhesion and signalling receptors act in concert to
mediate their biological effects. Again, unless such receptors have been
demonstrated themselves to have adhesive properties, they have been omitted.
Finally, there is an increasing number of transmembrane molecules that
associate with adhesion molecules and in many cases modulate their function.
However, these association molecules, such as members of the tetraspan
superfamily (TM4SF) do not alone mediate adhesion. Similarly, intracellular
components which associate with adhesion molecules have not been included.
ORGANIZATION OF THE DATA
Name
The most commonly used name for each molecule has been used and other names
that are currently still in use are given also. Many of the adhesion molecules
originally were given different names but gradually a consensus of nomenclature
has arisen. As will be discussed in Chapter 2, cadherins, integrins, selectins and
syndecans have family names. An equivalent situation does not exist for the
immunoglobulin superfamily (IgSF),w hich reflects the diversity of function within
this family. However, within the IgSFs, nomenclature for subfamilies, such as the
siglecs and ICAMs, is becoming more common. Many of the adhesion molecules
are expressed by leucocytes and consequently they have a CD (cluster of
differentiation) nomenclature (see Leucocyte Antigen FactsBook'). In some cases
this is the most commonly used name, especially for those molecules that were
originally characterized in different laboratories and hence given different names.
In other cases, molecules have a CD nomenclature but an earlier consensus for
another name means that the CD number is not commonly used.
Family
The family to which the adhesion molecule belongs is given. Some families are
further divided and, in these cases, the subfamily is also provided. Further
information into the organization of families and subfamilies is given in Chapter
2. The 'other molecule' section contains those proteins that we decided to include
on the basis of functional information but which again do not fit into the major
adhesion molecule families.
Molecular diagram
Many of the adhesion molecules are expressed by leucocytes and are therefore
listed in the Leucocyte Antigen FactsBook'. To aid cross-referencing, we have used
the same icons for the protein domains and repeats. In addition, new icons have
been used to represent domains not found in leucocyte antigens. The aim of the
diagram is to provide a visual representation of the molecule indicating the
subunit composition, how it is attached to the membrane, its orientation, the
number and type of protein domains, the degree and type of glycosylation and the
position of any proteolytic cleavage sites. The icons and symbols are shown in Fig.
1. The cytoplasmic domains of the majority of adhesion molecules do not contain
recognizable protein domains and therefore these are represented by squiggly lines,
the length of which is proportional to the sequence length. Nuclear magnetic
resonance (NMR)a nd crystallographic data are increasingly available for domains
present within some of the families of adhesion molecules (e.g. IgSF, cadherins,
integrins). We have not attempted to discuss or illustrate detailed atomic
structural data for any of the molecules; we do though discuss and reference this in
general terms in Chapter 2 and the individual molecule entries.
Size of the receptor
The number of amino acids and calculated relative molecular weight (M,) of the
entire polypeptide backbone (including thes ignal sequence) is given. The M,o f the
fully processed molecule obtained from sodium dodecyl sulphate-polyacrylamide
gel electrophoresis (SDS-PAGE)u nder reducing conditions is given in kilodaltons
(kDa).W here relevant, sizes under non-reducing conditions are also listed. As all
the adhesion molecules are processed through the rough endoplasmic reticulum
and Golgi apparatus, this value reflects the size of the glycosylated protein. In the
case of the type I proteins this reflects the loss of the N-terminal signal sequence
and for the classical cadherins, desmocollins and desmogleins, the additional loss
of the propeptide sequence.
Glycos ylation
All of the adhesion molecules are glycosylated, but in the majority of cases the
extent and nature of the carbohydrate modification isn ot known.
N-linked carbohydrates are attached to Asn residues within the consensus motif
Asn-X-Ser or Asn-X-Thr, where X is any amino acid except Pro. The number of
these motifs present in the polypeptide backbone is given and the approximate
positions shown in the diagram. It should be noted that not all potential N-linked
sites are necessarily occupied.
0-linked sugars are attached to Ser or Thr residues but there is no consensus
sequence for this modification. In most molecules, 0-linked glycosylation is
found in stretches of sequence with a preponderance of Ser, Thr and Pro amino
acids, where specificity depends on a combination of sequence context, secondary
structure and accessibility. It should be noted that the acceptor sequence context
for 0-glycosylation of serine is different from that of threonine. A programme
for the prediction of 0-glycosylation sites is available at the web site:
http://www.cbs.dtu.dk/services/.
The approximate predicted positions of the 0-linked sugars are indicated in the
diagrams and the following terms are used to describe the extent of 0-
glycosylation:
No entry There are no data from sequence or biochemical studies to indicate
the level of 0-glycosylation.
0 The absence of 0-glycosylation is indicated by biochemical analysis.
+ to + + + Biochemical data indicate that 0-glycosylation occurs a low (+),
moderate (++ )o r high (++ + ) level.
Glycosaminoglycans (GAG) have been identified on syndecans 1-4, CD44 and
dystroglycan. With the exception of keratan sulphate, which is not found on any of
the adhesion molecules listed here, GAGS are attached via a xylose residue linkage
to specific serine residues in the protein core. Attachment requires the presence of
a C-terminal Gly; however, not all Ser-Gly sites are GAG modified.
Gene location and size
The chromosome location of the human gene is given together with the gene size
and number of exons, where known. As indicated in the text, where the genomic
structure has been established in non-human species, the gene size and number of
exons for that species is given. Due to the rapidly changing information on the
‘human genome’ we have not attempted to provide a gene structure diagram which
inevitably is likely to be superceded.
Alternative forms
Many of the adhesion molecules are subject to alternative splicing and other
modifications and this section summarizes what is known
about the different
isoforms. Where relevant, the position of sequences encoded by alternatively spliced
exons or the position of exon insertion is indicated in the amino acid sequence.
Structure
Biochemical and structural data are summarized in this section.
Ligands
This section describes the ligands characterized for each adhesion molecule. In many
cases the ‘ligand’ is another membrane-bound molecule and therefore may be more
properly described as a ’counter receptor’. In some cases a physiological ligand has
not been identified but molecules have still been included in the book where their
structure or function strongly suggests that they are adhesion molecules.
Function
Functional data are summarized in this section. In some cases a physiological
function can only be predicted.
Distribution
The tissue and cellular distribution of the adhesion molecule is described in this
section. It should be noted that in many cases a full analysis of tissue distribution
has not been undertaken and therefore may be wider than described. Where
relevant the subcellular distribution of the molecule is also discussed.
Disease association
The OMIM (Online Mendelian Inheritance in Man) accession number for each
molecule is given (information as to how to access information from the OMIM
databases is given in Chapter 3).W here relevant the association of a molecule with
a particular disease is described. In addition, the use of reagents directed against
these molecules for disease prediction or in therapy is also indicated.
Knockout
The MGI (Mouse GenomeI nformatics) accession number is given. As described in
Chapter 3, accessing knockout mouse databases provides a large amount of
information about the function of the murine homologue of the adhesion
molecule. Where a knockout has been generated, the phenotype is described.