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Identification
HMDB Protein ID HMDBP14336
Secondary Accession Numbers None
Name Myeloid cell surface antigen CD33
Synonyms
  1. Sialic acid-binding Ig-like lectin 3
  2. gp67
  3. Siglec-3
Gene Name CD33
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function 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).
Pathways
  • Hematopoietic cell lineage
Reactions Not Available
GO Classification
Biological Process
signal transduction
cell-cell signaling
cell-cell adhesion
neutrophil degranulation
cell adhesion
negative regulation of interleukin-1 beta production
positive regulation of protein secretion
negative regulation of tumor necrosis factor production
immune response-inhibiting signal transduction
negative regulation of monocyte activation
positive regulation of protein tyrosine phosphatase activity
negative regulation of calcium ion transport
negative regulation of cell proliferation
negative regulation of interleukin-8 production
regulation of immune response
Cellular Component
cell surface
specific granule membrane
plasma membrane
Golgi apparatus
tertiary granule membrane
nucleoplasm
peroxisome
external side of plasma membrane
integral to plasma membrane
Molecular Function
carbohydrate binding
signaling receptor activity
sialic acid binding
protein phosphatase binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 237
Molecular Weight 39824.885
Theoretical pI 8.678
Pfam Domain Function
Signals
  • 1-17;
Transmembrane Regions
  • 260-282;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P20138
UniProtKB/Swiss-Prot Entry Name CD33_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  3. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [PubMed:15057824 ]
  4. Vitale C, Romagnani C, Falco M, Ponte M, Vitale M, Moretta A, Bacigalupo A, Moretta L, Mingari MC: Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or leukemic myeloid cells. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15091-6. [PubMed:10611343 ]
  5. Simmons D, Seed B: Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells. J Immunol. 1988 Oct 15;141(8):2797-800. [PubMed:3139766 ]
  6. Yousef GM, Ordon MH, Foussias G, Diamandis EP: Genomic organization of the siglec gene locus on chromosome 19q13.4 and cloning of two new siglec pseudogenes. Gene. 2002 Mar 20;286(2):259-70. [PubMed:11943481 ]
  7. Freeman SD, Kelm S, Barber EK, Crocker PR: Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules. Blood. 1995 Apr 15;85(8):2005-12. [PubMed:7718872 ]
  8. Ulyanova T, Blasioli J, Woodford-Thomas TA, Thomas ML: The sialoadhesin CD33 is a myeloid-specific inhibitory receptor. Eur J Immunol. 1999 Nov;29(11):3440-9. [PubMed:10556798 ]
  9. Taylor VC, Buckley CD, Douglas M, Cody AJ, Simmons DL, Freeman SD: The myeloid-specific sialic acid-binding receptor, CD33, associates with the protein-tyrosine phosphatases, SHP-1 and SHP-2. J Biol Chem. 1999 Apr 23;274(17):11505-12. [PubMed:10206955 ]
  10. Vitale C, Romagnani C, Puccetti A, Olive D, Costello R, Chiossone L, Pitto A, Bacigalupo A, Moretta L, Mingari MC: Surface expression and function of p75/AIRM-1 or CD33 in acute myeloid leukemias: engagement of CD33 induces apoptosis of leukemic cells. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5764-9. Epub 2001 Apr 24. [PubMed:11320212 ]
  11. Hernandez-Caselles T, Martinez-Esparza M, Perez-Oliva AB, Quintanilla-Cecconi AM, Garcia-Alonso A, Alvarez-Lopez DM, Garcia-Penarrubia P: A study of CD33 (SIGLEC-3) antigen expression and function on activated human T and NK cells: two isoforms of CD33 are generated by alternative splicing. J Leukoc Biol. 2006 Jan;79(1):46-58. doi: 10.1189/jlb.0205096. [PubMed:16380601 ]
  12. Sgroi D, Nocks A, Stamenkovic I: A single N-linked glycosylation site is implicated in the regulation of ligand recognition by the I-type lectins CD22 and CD33. J Biol Chem. 1996 Aug 2;271(31):18803-9. doi: 10.1074/jbc.271.31.18803. [PubMed:8702538 ]
  13. Paul SP, Taylor LS, Stansbury EK, McVicar DW: Myeloid specific human CD33 is an inhibitory receptor with differential ITIM function in recruiting the phosphatases SHP-1 and SHP-2. Blood. 2000 Jul 15;96(2):483-90. [PubMed:10887109 ]
  14. Lajaunias F, Dayer JM, Chizzolini C: Constitutive repressor activity of CD33 on human monocytes requires sialic acid recognition and phosphoinositide 3-kinase-mediated intracellular signaling. Eur J Immunol. 2005 Jan;35(1):243-51. doi: 10.1002/eji.200425273. [PubMed:15597323 ]
  15. Son M, Diamond B, Volpe BT, Aranow CB, Mackay MC, Santiago-Schwarz F: Evidence for C1q-mediated crosslinking of CD33/LAIR-1 inhibitory immunoreceptors and biological control of CD33/LAIR-1 expression. Sci Rep. 2017 Mar 21;7(1):270. doi: 10.1038/s41598-017-00290-w. [PubMed:28325905 ]
  16. Siddiqui SS, Springer SA, Verhagen A, Sundaramurthy V, Alisson-Silva F, Jiang W, Ghosh P, Varki A: The Alzheimer's disease-protective CD33 splice variant mediates adaptive loss of function via diversion to an intracellular pool. J Biol Chem. 2017 Sep 15;292(37):15312-15320. doi: 10.1074/jbc.M117.799346. Epub 2017 Jul 26. [PubMed:28747436 ]