CD330 Siglec10 (sialic acid binding Ig-like lectin 10), SLG2 (siglec-like protein 2)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Monocyte
Leukocyte
Eosinophil
Brain
Tonsil
Colon
Liver
Spleen
Stomach
Thymus
Small intestine
Pancreas
NK Cell
Neutrophil
Bone Marrow
Lung
Spinal cord
Lymph Node
Ovary
Appendix
T Cell
B Cell
Placenta
Tongue
Blood
Mouth
Larynx
Peripheral blood
90 / 90
120 / 120

Expression

The CD330 isoform is expressed strongly by peripheral blood leukocytes, eosinophils,  natural NK cell populations, neutrophils, monocytes in bone marrow, spleen and spinal cord.  The isoform 5 is most abundantly expressed isoform and is strongly expressed in lymph node, lung, ovary and appendix.  Isoform 1 is found at high levels and isoform 2 is at lower levels in bone marrow, spleen and spinal cord.  Isoform 2 is also found in the brain and isoform 4 is specifically found in  CD56-CD16+ NK cells.  The isoform 3 is expressed in T and B cells.  There is expression in  blood, uncharacterized tissues, mouth, and tonsil.  Expression is also in thymus, colon, embryronic tissue, liver, small intestine, mammary gland, placenta, stomach, larynx and pancreas.



Structure
MOLECULAR FAMILY NAME:  Belongs to the immunoglobulin gen family.

CD330 is a single-pass type-1 681 aa lectin glycoprotein.  It contains a 16 aa signal sequence, a 534 aa extracellular domain which contains 3 Ig-like C2-type domains, 1 N-terminal Ig-like V-like domain and 5 potential N-linked glycosylation sites, a 21 aa transmembrane region and a 126 aa cytoplasmic domain with 3 putative tyrosine ITIMs.  The V-type domain bears a critical arginine carboxyl group of sialic acid as well as two conserved aromatic residues (Phe26 and Tyr124) required for interaction with N-acetyl and glycerol side chains of sialic acid.  The unique pattern of cysteines in the V-type domain and the N-terminal C-2-type domain of CD33-related Siglecs from intra-sheet and interdomain disulphide bonds.  The 3 ITIMs contain 2 immunoreceptor tyrosine-based inhibitory motifs.  The ITIM associated with Tyr667 is phosphorylated by Src family kinases Lck, Jak3 and Emt and recruits SHP-1 and to a lesser extent SHP-2.  The motif associated with Tyr691 resembles a signaling lymphocyte activating molecule (SLAM)-like motif that acts as a docking for SLAM-associated protein (SAP), although SAP binding hasw yet to de demonstrated.  One copy of the cytoplasmic motif is referred to an ITIM is involved in modulation of cellular responses.  CD330 is most closely related to CD170 (Siglec 5) and has a 69% homology at the amino acid level.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 6 different isoforms by RNA splicing.  Isoforms 1-4 and 6 are long type-1 glycoproteins.  Isoforms 1-4 retain the V-type domain but vary in the number and arrangement of the C2-type domains.  Isoform 2 is a soluble form and isoform 5 is a secreted protein.

POST-TRANSLATIONAL MODIFICATION

CD330 has 5 potential N-linked glycosylation sites.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD330

CD330 binds α2,6 and α2,3 sialylated glycoconjugates but can also bind α2,3 sialylated glycoconjugates including GT1b ganglioside.

Function
The role of CD330 remains unclear but it is based on the structure of the cytoplasmic domain which is predicted to act as an inhibitory receptor.  CD330 is a putatuve adhesion molecule that mediates sialic-acid dependent binding to cells.  It preferentially binds to α2, or 2,6-linked sialic acid.  The sialic acid recognition site may be masked by cis interactions with the acids on the same surface.  In the immune response, it may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules.  Binding assays have demonstrated that the extracellular domain binds peripheral blood leukocytes.  CD330 expression has been found to be upregulated on some transformed blood cell lines.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD330 IN INTACT ANIMAL

The expression of CD330 by eosinophils and its upregulation of CD330 on eosinophils from asthmatics had led to the suggestion that CD330 may modulate eosinophil activity during an allergic reaction.
 


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD330: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD330: No information.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene89790Q96LC7
Antibodies

Revised June 25, 2008


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