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PR01701

Identifier
CD164ANTIGEN  [View Relations]  [View Alignment]  
Accession
PR01701
No. of Motifs
4
Creation Date
19-DEC-2001
Title
CD164 antigen signature
Database References
Literature References
1. ZANNETTINO, A.C.W., BUHRING, H.J., NIUTTA, S., WATT, S.M., BENTON, M.A. 
AND SIMMONS, P.J.
The sialomucin CD164 (MGC-24v) is an adhesive glycoprotein expressed by 
human hematopoietic progenitor and bone marrow stromal cells that serves as 
a potent negative regulator of hematopoiesis.
BLOOD 92 2613-2628 (1998).
 
2. KUROSAWA, N., KANEMISTU, Y., MATSUI, T., SHIMADA, K., ISHIHAMA, H. AND 
MURAMATSU, T.
Genomic analysis of a murine cell-surface sialomucin, MGC-24/CD164.
EUR.J.BIOCHEM. 265 466-472 (1999).
 
3. CHAN, J., PRODHOE, J.E., JORGENSEN, B., IHRKE, G., DOYONNAS, R., 
ZANNETTINO, A.C.W., BUCKLE, V.J., WARD, C.J., SIMMONS, P.J. AND WATT, S.M.
Relationship between novel isoforms, functionally important domains and 
subcellular distribution of CD164/endolyn. 
J.BIOL.CHEM. 276 2139-2152 (2001).

Documentation
The interaction of haematopoietic cells with stromal/endothelial cells in 
their immediate microenvironment is thought to be of major importance in the 
regulation of haematopoietic stem self-renewal, quiescence, commitment and 
migration. These interactions involve cooperation between adhesion receptors,
their cognate ligands and cytokines. A wide variety of adhesion and cell
surface molecules participate in these processes. Based on domain structure
and function, these cell adhesion molecules (CAMs) can be classified into 5
main groups, including the Ig, integrin, cadherin, selectin and mucin-like
families [1].
 
The mucin-like molecules represent an emerging family of glycoproteins 
expressed by tissues of the haematopoietic system. Although exhibiting 
limited similarity at the cDNA level, the expressed proteins share the
common characteristic of being highly glycosylated, with predominantly
O-linked carbohydrate side chains linked to serine and threonine residues.
Their nonglobular, thread-like structure resembles that of classical mucins
of epithelial cells. Carbohydrate chains in mucins are largely attached by
an alpha 1,3 linkage between N-acetylgalactosamine and the oxygen atom of
serine or threonine (O-glycosidic bond), although some oligosaccharides are
attached via the nitrogen of asparagine and N-acetylgalactosamine (N-
glycosidic bond). The dense array of O-linked side chains in mucin-like
molecules carries at least two important structural implications: first is
the extended structure that makes many of the mucin-like molecules long
enough to protrude beyond the polysaccharide glycocalyx that surrounds the
cell; second is the optimal exposure and high multiplicity of the terminal
sugars. By virtue of their negative charge and extended configuration, 
mucin-like glycoproteins may act as a repulsive barrier around the cell; 
nevertheless, when an opposing cell has specific receptors for mucin,
adhesion surmounts repulsion. Although mucin receptors may be widely
expressed, their functions may differ on different cell types, or on the
same type under different states of activation. This functional diversity
is dependent on the core mucin peptide and on the cell-specific expression
of glycosyl transferases. These in turn regulate the structure and
presentation of the O-linked oligosaccharide sidechains, membrane anchorage,
signal transduction abilities and/or the trafficking of the mucin to the
correct cellular domain [1-3]. 
 
CD164 is a mucin-like receptor, or sialomucin, with specificity in receptor/
ligand interactions that depends on the structural characteristics of the
mucin-like receptor. Its functions include mediating, or regulating, 
haematopoietic progenitor cell adhesion and the negative regulation of their 
growth and/or-differentiation. It exists in the native state as a disulphide-
linked homodimer of two 80-85kDa subunits. It is usually expressed by CD34+ 
and CD341o/- haematopoietic stem cells and associated microenvironmental 
cells. It contains, in its extracellular region, two mucin domains (I and II)
linked by a non-mucin domain, which has been predicted to contain intra-
disulphide bridges. This receptor may play a key role in haematopoiesis 
by facilitating the adhesion of human CD34+ cells to bone marrow stroma and 
by negatively regulating CD34+ CD341o/- haematopoietic progenitor cell 
proliferation. These effects involve the CD164 class I and/or II epitopes 
recognised by the monoclonal antibodies (mAbs) 105A5 and 103B2/9E10. These 
epitopes are carbohydrate-dependent and are located on the N-terminal 
mucin domain I [2,3].
 
It has been found that murine MGC-24v and rat endolyn share significant 
sequence similarities with human CD164. However, CD164 lacks the consensus 
glycosaminoglycan (GAG)-attachment site found in MGC-24; it is possible 
that GAG-association is responsible for the high molecular weight of the
epithelial-derived MGC-24 glycoprotein [1].
 
Genomic structure studies have placed CD164 within the mucin-subgroup that
comprises multiple exons, and demonstrate the diverse chromosomal
distribution of this family of molecules. Molecules with such multiple
exons may have sophisticated regulatory mechanisms that involve not only
post-translational modifications of the oligosaccharide side chains, but
also differential exon usage. Although differences in the intron and exon
sizes are seen between the mouse and human genes, the predicted proteins
are similar in size and structure, maintaining functionally important
motifs that regulate cell proliferation or subcellular distribution [3]. 
 
CD164 is a gene whose expression depends on differential usage of poly-
adenylation sites within the 3'-UTR. The conserved distribution of the 
3.2- and 1.2-kb CD164 transcripts between mouse and human suggests that 
(i) a mechanism may exist to regulate tissue-specific polyadenylation, and 
(ii) differences in polyadenylation are important for the expression and
function of CD164 in different tissues. Two other aspects of the structure
of CD164 are of particular interest. First, it shares one of several
conserved features of a cytokine-binding pocket - in this respect, it is
notable that evidence exists for a class of cell-surface sialomucin
modulators that directly interact with growth factor receptors to regulate 
their response to physiological ligands. Second, its cytoplasmic tail  
contains a C-terminal YHTL motif found in many endocytic membrane proteins
or receptors. These Tyr-based motifs bind to adaptor proteins, which mediate
the sorting of membrane proteins into transport vesicles from the plasma
membrane to the endosomes, and between intracellular compartments [2,3].
 
CD164ANTIGEN is a 4-element fingerprint that provides a signature for the
CD164 cell-surface sialomucin MGC-24 family of proteins. The fingerprint was
derived from an initial alignment of 4 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length - motif 1
lies in the putative signal sequence. Two iterations on SPTR39_17f were
required to reach convergence, at which point a true set comprising 7 
sequences was identified. 
Summary Information
7 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
47777
30000
20000
1234
True Positives
MG24_HUMAN    O95413        Q9BPV0        Q9NR26        
Q9QX82 Q9R0L9 Q9Z317
Sequence Titles
MG24_HUMAN  PUTATIVE MUCIN CORE PROTEIN 24 PRECURSOR (MULTI-GLYCOSYLATED CORE PROTEIN 24) (MGC-24) (MUC-24) (CD164 ANTIGEN) - Homo sapiens (Human). 
O95413 SIALOMUCIN CD164 (CD164 ISOFORM DELTA 5) - Homo sapiens (Human).
Q9BPV0 CD164 ISOFORM DELTA 4 - Homo sapiens (Human).
Q9NR26 CD164 - Homo sapiens (Human).
Q9QX82 ENDOLYN PRECURSOR - Rattus norvegicus (Rat).
Q9R0L9 CELL-SURFACE SIALOMUCIN MGC-24 (CD164 ANTIGEN) - Mus musculus (Mouse).
Q9Z317 MGC-24V - Mus musculus (Mouse).
Scan History
SPTR39_17f 2  250  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
SRSLLWAATC MG24_HUMAN 5 5 -
SRSLLWAATC Q9NR26 5 5 -
SRSLLWAATC O95413 5 5 -
SRRLLWAATC Q9R0L9 5 5 -

Motif 2 width=17
Element Seqn Id St Int Rpt
PETCEGRNSCVSCFNVS MG24_HUMAN 58 43 -
PETCEGRNSCVSCFNVS Q9NR26 58 43 -
PETCEGRNSCVSCFNVS O95413 58 43 -
PETCASFNSCVSCVNAT Q9R0L9 55 40 -

Motif 3 width=13
Element Seqn Id St Int Rpt
GTTNNTVTPTSQP MG24_HUMAN 143 68 -
GTTNNTVTPTSQP Q9NR26 143 68 -
GTTNNTVTPTSQP O95413 124 49 -
GTTNTTLTPTSQP Q9R0L9 143 71 -

Motif 4 width=13
Element Seqn Id St Int Rpt
RKSTFDAASFIGG MG24_HUMAN 157 1 -
RKSTFDAASFIGG Q9NR26 157 1 -
RKSTFDAASFIGG O95413 138 1 -
RKSTFDAASFIGG Q9R0L9 157 1 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
SRSLLWAATC MG24_HUMAN 5 5 -
SRSLLWAATC Q9NR26 5 5 -
SRSLLWAATC Q9BPV0 5 5 -
SRSLLWAATC O95413 5 5 -
SRRLLWAATC Q9R0L9 5 5 -
SRRLLWAATC Q9Z317 5 5 -
SRGLFWAATC Q9QX82 5 5 -

Motif 2 width=17
Element Seqn Id St Int Rpt
PETCEGRNSCVSCFNVS MG24_HUMAN 58 43 -
PETCEGRNSCVSCFNVS Q9NR26 58 43 -
PETCEGRNSCVSCFNVS Q9BPV0 58 43 -
PETCEGRNSCVSCFNVS O95413 58 43 -
PETCASFNSCVSCVNAT Q9R0L9 55 40 -
PETCASFNSCVSCVNAT Q9Z317 55 40 -
PETCESFNSCVSCVNAT Q9QX82 54 39 -

Motif 3 width=13
Element Seqn Id St Int Rpt
GTTNNTVTPTSQP MG24_HUMAN 143 68 -
GTTNNTVTPTSQP Q9NR26 143 68 -
GTTNNTVTPTSQP Q9BPV0 130 55 -
GTTNNTVTPTSQP O95413 124 49 -
GTTNTTLTPTSQP Q9R0L9 143 71 -
GTTNTTLTPTSQP Q9Z317 143 71 -
GATNTTVTPTSQP Q9QX82 141 70 -

Motif 4 width=13
Element Seqn Id St Int Rpt
RKSTFDAASFIGG MG24_HUMAN 157 1 -
RKSTFDAASFIGG Q9NR26 157 1 -
RKSTFDAASFIGG Q9BPV0 144 1 -
RKSTFDAASFIGG O95413 138 1 -
RKSTFDAASFIGG Q9R0L9 157 1 -
RKSTFDAASFIGG Q9Z317 157 1 -
RKSTFDAASFIGG Q9QX82 155 1 -