CD22

CD22
Identifiers
AliasesCD22, SIGLEC-2, SIGLEC2, CD22 molecule
External IDsOMIM: 107266 MGI: 88322 HomoloGene: 31052 GeneCards: CD22
Orthologs
SpeciesHumanMouse
Entrez

933

12483

Ensembl

ENSG00000012124

ENSMUSG00000030577

UniProt

P20273

P35329

RefSeq (mRNA)

NM_001043317
NM_009845

RefSeq (protein)

NP_001172028
NP_001172029
NP_001172030
NP_001265346
NP_001762

NP_001036782
NP_033975

Location (UCSC)Chr 19: 35.32 – 35.35 MbChr 7: 30.87 – 30.88 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins.[5] It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases.[6]

CD22 is a sugar binding transmembrane protein, which specifically binds sialic acid with an immunoglobulin (Ig) domain located at its N-terminus. The presence of Ig domains makes CD22 a member of the immunoglobulin superfamily. CD22 functions as an inhibitory receptor for B cell receptor (BCR) signaling. It is also involved in the B cell trafficking to Peyer's patches in mice.[7] In mice, it has been shown that CD22 blockade restores homeostatic microglial phagocytosis in aging brains.[8]

image of microglia

As a drug target

An immunotoxin, BL22 (CAT-3888), that targets this receptor was developed at the NIH.[9] BL22 was superseded by moxetumomab pasudotox (HA22, CAT-8015).[10] Moxetumomab pasudotox is approved in the EU and USA for treatment of relapsed or refractory hairy cell leukemia.[11][12]

As a treatment for acute lymphoblastic leukemia (ALL), Inotuzumab ozogamicin is an antibody-drug conjugate that targets this molecule.

Interactions

CD22 has been shown to interact with Grb2,[13][14] PTPN6,[14][15][16][17][18] LYN,[13][16] SHC1[13] and INPP5D.[13]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000012124 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030577 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Crocker PR, Clark EA, Filbin M, Gordon S, Jones Y, Kehrl JH, et al. (February 1998). "Siglecs: a family of sialic-acid binding lectins". Glycobiology. 8 (2): v. doi:10.1093/glycob/8.2.0. PMID 9498912.
  6. ↑ Hatta Y, Tsuchiya N, Matsushita M, Shiota M, Hagiwara K, Tokunaga K (April 1999). "Identification of the gene variations in human CD22". Immunogenetics. 49 (4): 280–6. doi:10.1007/s002510050494. PMID 10079291. S2CID 22947237.
  7. ↑ Lee M, Kiefel H, LaJevic MD, Macauley MS, Kawashima H, O'Hara E, et al. (October 2014). "Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing". Nature Immunology. 15 (10): 982–95. doi:10.1038/ni.2983. PMC 4222088. PMID 25173345.
  8. ↑ Pluvinage JV, Wyss-Coray T, et al. (April 11, 2019). "CD22 blockade restores homeostatic microglial phagocytosis in aging brains". Nature. 568 (7751): 187–192. Bibcode:2019Natur.568..187P. doi:10.1038/s41586-019-1088-4. PMC 6574119. PMID 30944478.
  9. ↑ Clinical trial number NCT00074048 for "BL22 Immunotoxin in Treating Patients Previously Treated With Cladribine for Hairy Cell Leukemia" at ClinicalTrials.gov
  10. ↑ http://www.cambridgeantibody.com/__data/assets/pdf_file/10857/CAT-3888,_CAT-8015_and_CAT-5001_Nov06.pdf Archived 2007-02-27 at the Wayback Machine CAT URL Redirects to Medimmune home page
  11. ↑ "Lumoxiti EPAR". European Medicines Agency (EMA). 9 December 2020. Retrieved 16 July 2021..
  12. ↑ "Moxetumomab pasudotox-tdfk FDA Approval". U.S. Food and Drug Administration (FDA). Retrieved 20 April 2020.
  13. 1 2 3 4 Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF (June 2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". The Journal of Biological Chemistry. 275 (23): 17420–7. doi:10.1074/jbc.M001892200. PMID 10748054.
  14. 1 2 Otipoby KL, Draves KE, Clark EA (November 2001). "CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1". The Journal of Biological Chemistry. 276 (47): 44315–22. doi:10.1074/jbc.M105446200. PMID 11551923.
  15. ↑ Blasioli J, Paust S, Thomas ML (January 1999). "Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22". The Journal of Biological Chemistry. 274 (4): 2303–7. doi:10.1074/jbc.274.4.2303. PMID 9890995.
  16. 1 2 Greer SF, Justement LB (May 1999). "CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1". Journal of Immunology. 162 (9): 5278–86. PMID 10228003.
  17. ↑ Law CL, Sidorenko SP, Chandran KA, Zhao Z, Shen SH, Fischer EH, Clark EA (February 1996). "CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-gamma(1) upon B cell activation". The Journal of Experimental Medicine. 183 (2): 547–60. doi:10.1084/jem.183.2.547. PMC 2192439. PMID 8627166.
  18. ↑ Adachi T, Wienands J, Wakabayashi C, Yakura H, Reth M, Tsubata T (July 2001). "SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates". The Journal of Biological Chemistry. 276 (28): 26648–55. doi:10.1074/jbc.M100997200. PMID 11356834.
  • CD22+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
  • Human CD22 genome location and CD22 gene details page in the UCSC Genome Browser.
  • Overview of all the structural information available in the PDB for UniProt: P20273 (B-cell receptor CD22) at the PDBe-KB.
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