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PR01473

Identifier
ICAM  [View Relations]  [View Alignment]  
Accession
PR01473
No. of Motifs
3
Creation Date
14-FEB-2001
Title
Intercellular adhesion molecule (ICAM) family signature
Database References
PRINTS; PR01472 ICAMVCAM1
PDB; 1IAM
SCOP; 1IAM
CATH; 1IAM
Literature References
1. GAHMBERG, C,G., TOLVANEN, M. AND  KOTOVUORI, P.
Leukocyte adhesion. Structure and function of human leukocyte
beta2-integrins and their cellular ligands.
EUR.J.BIOCHEMISTRY 245 215-232 (1997).
 
2. LEE, Y. W., KUHN, H., HENNIG, B., NEISH, A.S. AND TOBOREK, M.
IL-4 induced oxidative stress upregulates VCAM-1 gene expression in human
endothelial cells.
J.MOL.CELL.CARDIO. 33 83-94 (2001).
 
3. STANLEY, P., MCDOWALL, A. BATES, P.A., BRASHAW, J. AND  HOGG, N.
The second domain of intercellular adhesion molecule-1 (ICAM-1) maintains
the structural integrity of the leukocyte function-associated antigen-1
BIOCHEM.J. 351 79-86 (2000).
 
4. BELLA, J., KOLATKAR, P.R., MARLOR, C.W., GREVE, J.M. AND ROSSMANN, M.G.
The structure of the two amino-terminal domains of human ICAM-1 suggests 
how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand.
PROC.NATL.ACAD.SCI.U.S.A. 95 4140-4145(1998). 
 
5. KOTOVUORI, A., PESSA-MORIKAWA, T., KOTOVUORI, P., NORTAMO, P. AND 
GAHMBERG, C.G.
ICAM-2 and a peptide from its binding domain are efficient activators
of leukocyte adhesion and integrin  affinity.
PROC.NATL.ACAD.SCI.U.S.A. 96 3017-3022 (1999).
 
6. NEELAMEGHAM, S., TAYLOR, A.D., SHANKARAN, H., SMITH, W.C. AND SIMON, S.I.
Shear and time-depeneant changes in Mac-1, LFA, and ICAM-3 binding
regulate neutrophil homotypic adhesion.
J.IMMUNOL. 164 3798-3805 (2000).
 
7. HERMAND, P., HUET, M., CALLEBAUT, I., GANE, P., IHANUS, E.,
GAHMBERG, C.G., CARTRON, J.P. AND BAILLY, P.
Binding sites of leukocyte beta 2-integrins (LFA-1, MAC-1) on the human
ICAM-4/LW blood group protein.
J.BIOL.CHEM. 275 26002-26010 (2000).
 
8. TIAN, L., KILGANNON, P., YOSHIHARA, Y., MORI, K., GALLATIN, W.M., 
CARPEN, O. AND GAHMBERG, C.G.
Binding of T lymphocytes to hippocampal neurons through ICAM-5 
integrin CD11a/CD18.
EUR.J.IMMUNOL. 30 810-818 (2000).

Documentation
Intercellular adhesion molecules (ICAMs) are part of the immunoglobulin
superfamily. They are important in inflammation, immune responses and in 
intracellular signalling events [1]. 
 
The ICAM family consists of five members, designated ICAM-1 to ICAM-5. They
are known to bind to leucocyte integrins CD11/CD18 during inflammation and
in immune responses. In addition, ICAMs may exist in soluble forms in human
plasma, due to activation and proteolysis mechanisms at cell surfaces [1]. 
 
ICAM-1 (CD54) contains five Ig-like domains. It is expressed on leucocytes, 
endothelial and epithelial cells, and is upregulated in response to 
bacterial invasion. The protein is a receptor for CD11a,b/CD18 (also termed
leukocyte-function associated (LFA) anitgen), fibrinogen, human rhinoviruses
and plasmodium falciparum-infected erythrocytes. ICAM-1binding sites for 
CD11a/CD18 and its other binding partners are located in the first domain
and are overlapping. ICAM-1 domain 2 seems to play an important role in
maintaining the conformation of domain 1 and particularly the structural 
integrity of the LFA-1 ligand-binding site [3].  
 
The 3-dimensional atomic structure of the tandem N-terminal Ig-like domains 
(D1 and D2) of ICAM-1 has been determined to 2.2A resolution and fitted into
a cryoelectron microscopy reconstruction of a rhinovirus-ICAM-1 complex [4].
Extensive charge interactions between ICAM-1 and human rhinoviruses are
largely conserved in  major and minor receptor groups of rhinoviruses [4].
The interaction of ICAMs with LFA-1 is mediated by a divalent cation bound
to the insertion (I)-domain on the alpha chain of LFA-1 and the carboxyl 
group of a conserved glutamic acid residue on ICAMs [4]. 
 
ICAM-2 (CD102) has two Ig-like domains. It is expressed on endothelial
cells, leucocytes and platelets, and binds to CD11a,b/CD18. The protein is
refractory to proinflammatory cytokines, and plays an important role in the
adhesion of leucocytes to the uninduced endothelium [5].
 
ICAM-3 (CD50) contains five Ig-like domains and binds to leucocyte integrins
CD11a,d/CD18. The protein plays an important role in the immune response and
perhaps in signal transduction [6].
 
ICAM-4 (LW blood group Ag) is red blood cell (RBC) specific and binds to 
CD11a,b/CD18. It is associated with the RBC Rh antigens and could be 
important in retaining immature red cells in the bone marrow, or in the 
uptake of senescent cells into the spleen [7].
 
ICAM-5 (telencephalin) has nine Ig-like domains and is confined to the 
telencephalon of the brain. The role of this CD11a/CD18 binding molecule 
is not yet known [8].
 
ICAM is a 3-element fingerprint that provides a signature for the ICAM
family of adhesion molecules. The fingerprint was derived from an initial
alignment of 6 sequences: the motifs were drawn from conserved regions 
towards the N-terminal portion of the alignment - motif 1 lies within the 
N-terminal region of domain 2; and motifs 2 and 3 lie in the N-terminal
region of the extracellular domain. Two iterations on SPTR39_14f were
required to reach convergence, at which point a true set comprising 14 
sequences was identified. A single partial match was also found, Q9Z133, a
testicular cell adhesion molecule 1 (TCAM1) from Rattus norvegicus that
matches motifs 2 and 3.
Summary Information
  14 codes involving  3 elements
1 codes involving 2 elements
Composite Feature Index
3141414
2011
123
True Positives
ICA1_BOVIN    ICA1_HUMAN    ICA1_MOUSE    ICA1_RAT      
ICA2_HUMAN ICA2_MOUSE ICA3_BOVIN ICA3_HUMAN
O97692 Q14600 Q28730 Q60625
Q9UMF0 Q9Y6F3
True Positive Partials
Codes involving 2 elements
Q9Z133
Sequence Titles
ICA1_BOVIN  INTERCELLULAR ADHESION MOLECULE-1 PRECURSOR (ICAM-1) - Bos taurus (Bovine). 
ICA1_HUMAN INTERCELLULAR ADHESION MOLECULE-1 PRECURSOR (ICAM-1) (MAJOR GROUP RHINOVIRUS RECEPTOR) (CD54) - Homo sapiens (Human).
ICA1_MOUSE INTERCELLULAR ADHESION MOLECULE-1 PRECURSOR (MALA-2) - Mus musculus (Mouse).
ICA1_RAT INTERCELLULAR ADHESION MOLECULE-1 PRECURSOR - Rattus norvegicus (Rat).
ICA2_HUMAN INTERCELLULAR ADHESION MOLECULE-2 PRECURSOR (ICAM-2) (CD102) - Homo sapiens (Human).
ICA2_MOUSE INTERCELLULAR ADHESION MOLECULE-2 PRECURSOR (ICAM-2) (CD102) (LYMPHOCYTE FUNCTION-ASSOCIATED AG-1 COUNTER-RECEPTOR) - Mus musculus (Mouse).
ICA3_BOVIN INTERCELLULAR ADHESION MOLECULE-3 PRECURSOR (ICAM-3) - Bos taurus (Bovine).
ICA3_HUMAN INTERCELLULAR ADHESION MOLECULE-3 PRECURSOR (ICAM-3) (CDW50) (CD50 ANTIGEN) (ICAM-R) - Homo sapiens (Human).
O97692 INTERCELLULAR ADHESION MOLECULE-1 PRECURSOR - Ovis aries (Sheep).
Q14600 INTERCELLULAR ADHESION MOLECULE 2 (ICAM-2) - Homo sapiens (Human).
Q28730 TELECEPHALIN PRECURSOR - Oryctolagus cuniculus (Rabbit).
Q60625 TELENCEPHALIN PRECURSOR - Mus musculus (Mouse).
Q9UMF0 TELENCEPHALIN PRECURSOR - Homo sapiens (Human).
Q9Y6F3 TELENCEPHALIN - Homo sapiens (Human).

Q9Z133 TESTICULAR CELL ADHESION MOLECULE 1 (TCAM1) - Rattus norvegicus (Rat).
Scan History
SPTR39_14f 2  15   NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
PSWQPVGKNLTLRC ICA1_HUMAN 122 122 -
PLWQPVGEELNLSC ICA1_BOVIN 121 121 -
PLWQPVGEELNLSC ICA3_BOVIN 128 128 -
PPWQPVGQNFTLRC ICA3_HUMAN 126 126 -
PTLVAVGKSFTIEC ICA2_HUMAN 121 121 -
PPRVFVGEDFTIEC ICA2_MOUSE 121 121 -

Motif 2 width=12
Element Seqn Id St Int Rpt
CRTELDLRPQGL ICA1_HUMAN 186 50 -
CRWELDLRSQGL ICA1_BOVIN 186 51 -
CRSELDLRSQGL ICA3_BOVIN 193 51 -
CRTELDMQPQGL ICA3_HUMAN 190 50 -
CLAVLDLMSRGG ICA2_HUMAN 190 55 -
CQAELDLRPHGG ICA2_MOUSE 189 54 -

Motif 3 width=17
Element Seqn Id St Int Rpt
GLELFENTSAPYQLQTF ICA1_HUMAN 196 -2 -
GLELFQNTSAPRKLQTY ICA1_BOVIN 196 -2 -
GLELFQNTSAPRKLQTY ICA3_BOVIN 203 -2 -
GLGLFVNTSAPRQLRTF ICA3_HUMAN 200 -2 -
GGNIFHKHSAPKMLEIY ICA2_HUMAN 200 -2 -
GGYIIRSISEYQILEVY ICA2_MOUSE 199 -2 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
PPWQPVGENFTLSC Q28730 126 126 -
PPWQPVGENFTLSC Q9UMF0 129 129 -
PPWQPVGENFTLSC Q9Y6F3 129 129 -
PSWQPVGENFTLSC Q60625 129 129 -
PSWQPVGKNLTLRC ICA1_HUMAN 122 122 -
PLWQPVGEELNLSC ICA1_BOVIN 121 121 -
PLWQPVGEELNLSC O97692 121 121 -
PLWQPVGEELNLSC ICA3_BOVIN 128 128 -
PPWQPVGQNFTLRC ICA3_HUMAN 126 126 -
PAWQQVGKDLTLRC ICA1_MOUSE 121 121 -
PAWQQVGKNLILRC ICA1_RAT 122 122 -
PTLVAVGKSFTIEC ICA2_HUMAN 121 121 -
PTLVAVGKSFTIEC Q14600 121 121 -
PPRVFVGEDFTIEC ICA2_MOUSE 121 121 -

Motif 2 width=12
Element Seqn Id St Int Rpt
CRAELDLRPQGL Q28730 195 55 -
CRAELDLRPHGL Q9UMF0 198 55 -
CRAELDLRPHGL Q9Y6F3 198 55 -
CLAELDLRPHGL Q60625 198 55 -
CRTELDLRPQGL ICA1_HUMAN 186 50 -
CRWELDLRSQGL ICA1_BOVIN 186 51 -
CRWELDLRSQGL O97692 186 51 -
CRSELDLRSQGL ICA3_BOVIN 193 51 -
CRTELDMQPQGL ICA3_HUMAN 190 50 -
CRTELDLRPQGL ICA1_MOUSE 188 53 -
CFTELDLRPQGL ICA1_RAT 186 50 -
CLAVLDLMSRGG ICA2_HUMAN 190 55 -
CLAVLDLMSRGG Q14600 190 55 -
CQAELDLRPHGG ICA2_MOUSE 189 54 -

Motif 3 width=17
Element Seqn Id St Int Rpt
GLALFENSSAPRQLWTY Q28730 205 -2 -
GLGLFENSSAPRELRTF Q9UMF0 208 -2 -
GLGLFENSSAPRELRTF Q9Y6F3 208 -2 -
GLGLFANSSAPRQLRTF Q60625 208 -2 -
GLELFENTSAPYQLQTF ICA1_HUMAN 196 -2 -
GLELFQNTSAPRKLQTY ICA1_BOVIN 196 -2 -
GLELFQNTSAPRKLQTY O97692 196 -2 -
GLELFQNTSAPRKLQTY ICA3_BOVIN 203 -2 -
GLGLFVNTSAPRQLRTF ICA3_HUMAN 200 -2 -
GLALFSNVSEARSLRTF ICA1_MOUSE 198 -2 -
GLSLFKNVSEVRQLRTF ICA1_RAT 196 -2 -
GGNIFHKHSAPKMLEIY ICA2_HUMAN 200 -2 -
GGNIFHKHSAPKMLEIY Q14600 200 -2 -
GGYIIRSISEYQILEVY ICA2_MOUSE 199 -2 -