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CD33; myeloid cell surface antigen CD33; sialic acid-binding Ig-like lectin 3; siglec-3; gp67 (SIGLEC3)

Function: - putative adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells - preferentially binds to alpha-2,6-linked sialic acid - the sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface - in the immune response, 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 - induces apoptosis in acute myeloid leukemia (in vitro) - interacts with PTPN6/SHP-1 & PTPN11/SHP-2 upon phosphorylation - phosphorylation of Tyr-340 is involved in binding to PTPN6 & PTPN11 - phosphorylation of Tyr-358 is involved in binding to PTPN6 Structure: - contains 2 ITIM motifs - phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases - belongs to the immunoglobulin superfamily, SIGLEC (sialic acid binding Ig-like lectin) family - contains 1 Ig-like C2-type domain (immunoglobulin-like) - contains 1 Ig-like V-type domain (immunoglobulin-like) Compartment: cell membrane Expression: - precursor myeloid cells, myeloid stem cells - most monocytic cells, mature monocytes - epidermal Langerhans cells (variable) - granulocytes, mature bone marrow cells & non-myeloid cells stain negatively with antibody. - microglia [6] Pathology: - expressed in a) AML-M1, AML-M2, AML-M3, AML-M4, AML-M5: ~75-85% b) AML-M7 variable c) CML ~90% d) blasts (all) e) ALL (some) - CD33 may be a microglial on-off switch, activating microglia as part of an inflammatory pathway sensing brain injury as an infection [6] - microglia may mistake early Alzheimer's disease as an infection [6]

Related

CD33 Ag in tissue CD33 cells in specimen

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen phosphoprotein sialic acid-binding immunoglobulin-like lectin

Properties

SIZE: entity length = 364 aa MW = 40 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-17} immunoglobulin superfamily domain {19-135} MOTIF: cysteine residue {C36} MODIFICATION: cysteine residue {C169} cysteine residue {C41} MODIFICATION: cysteine residue {C101} N-glycosylation site {N100} cysteine residue {C101} MODIFICATION: cysteine residue {C41} N-glycosylation site {N113} binding site SITE: 119-119 FOR-BINDING-OF: sialic acid immunoglobulin superfamily domain {145-228} MOTIF: N-glycosylation site {N160} cysteine residue {C163} MODIFICATION: cysteine residue {C212} cysteine residue {C169} MODIFICATION: cysteine residue {C36} N-glycosylation site {N209} cysteine residue {C212} MODIFICATION: cysteine residue {C163} N-glycosylation site {N230} transmembrane domain {260-282} immunoreceptor tyrosine-based inhibitory motif (ITIM) {338-343} MOTIF: Tyr phosphorylation site {Y340} immunoreceptor tyrosine-based inhibitory motif (ITIM) {356-361} MOTIF: Tyr phosphorylation site {Y358}

Database Correlations

OMIM 159590 UniProt P20138 PFAM correlations Entrez Gene 945

References

  1. Cotran et al Robbins Pathologic Basis of Disease, W.B. Saunders Co, Philadelphia, PA 1989 pg 165
  2. http://www.pathologyoutlines.com/cdmarkers.html 15 October 2002
  3. Entrez Gene :accession 945
  4. Functional glycomics gateway - glycan binding - siglec-3 http://www.functionalglycomics.org/glycomics/GBPServlet?&operationtype=view&cbpId=cbp_hum_Itlect_270
  5. UniProt :accession P20138
  6. Stetka B The Cell That Might Trigger Alzheimer's Disease. Medscape. Jan 31, 2022 https://www.medscape.com/viewarticle/967592