CD33

CD33 (CD33 Molecule) is a Protein Coding gene. Diseases associated with CD33 include Gallbladder Lymphoma and Extracutaneous Mastocytoma. Among its related pathways are Hematopoietic Stem Cell Differentiation Pathways and Lineage-specific Markers and Innate Immune System. Gene Ontology (GO) annotations related to this gene include receptor activity and carbohydrate binding. An important paralog of this gene is SIGLEC6.

CD33 Molecule

Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state (PubMed:10611343, PubMed:15597323, PubMed:11320212).
Preferentially recognizes and binds alpha-2,3- and more avidly alpha-2,6-linked sialic acid-bearing glycans (PubMed:7718872).
Upon engagement of ligands such as C1q or syalylated glycoproteins, two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) located in CD33 cytoplasmic tail are phosphorylated by Src-like kinases such as LCK (PubMed:28325905, PubMed:10887109).
These phosphorylations provide docking sites for the recruitment and activation of protein-tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:10556798, PubMed:10206955, PubMed:10887109).
In turn, these phosphatases regulate downstream pathways through dephosphorylation of signaling molecules (PubMed:10206955, PubMed:10887109).
One of the repressive effect of CD33 on monocyte activation requires phosphoinositide 3-kinase/PI3K (PubMed:15597323).

Cell adhesion Source: GO_Central
Cell-cell adhesion Source: ARUK-UCL
Cell-cell signaling Source: ProtInc
Immune response-inhibiting signal transduction Source: UniProtKB
Negative regulation of calcium ion transport Source: ARUK-UCL
Negative regulation of cell population proliferation Source: ProtInc
Negative regulation of interleukin-1 beta production Source: ARUK-UCL
Negative regulation of interleukin-8 production Source: ARUK-UCL
Negative regulation of monocyte activation Source: ARUK-UCL
Negative regulation of tumor necrosis factor production Source: ARUK-UCL
Neutrophil degranulation Source: Reactome
Positive regulation of protein secretion Source: UniProtKB
Positive regulation of protein tyrosine phosphatase activity Source: ARUK-UCL
Regulation of immune response Source: Reactome
Signal transduction Source: ProtInc

Isoform CD33M: Cell membrane
Isoform CD33m: Peroxisome. CD33m isoform does not localize to cell surfaces but instead accumulates in peroxisomes.

Extracellular: 18-259
Helical: 260-282
Cytoplasmic: 283-364

Glycosylated. Glycosylation at Asn-100 is critical for regulating ligand recognition.
Phosphorylation of Tyr-340 is involved in binding to PTPN6 and PTPN11. Phosphorylation of Tyr-358 is involved in binding to PTPN6. LCK phosphorylates Tyr-340 efficiently and Tyr-358 to a lesser extent.