PTPRC

Source: Wikipedia, the free encyclopedia.
(Redirected from
CD45
)
PTPRC
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_001267798
NM_002838
NM_080921
NM_080922

NM_001111316
NM_001268286
NM_011210

RefSeq (protein)

NP_001254727
NP_002829
NP_563578
NP_563578.2
NP_002829.3

NP_001104786
NP_001255215
NP_035340

Location (UCSC)Chr 1: 198.64 – 198.76 MbChr 1: 137.99 – 138.1 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene.[5] PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leukocyte common antigen (LCA).[6]

Function

The protein product of this gene, best known as CD45, is a member of the

receptor type PTP family.[citation needed
]

CD45 is a

B-cell antigen receptor signalling. It functions through either direct interaction with components of the antigen receptor complexes via its extracellular domain (a form of co-stimulation), or by activating various Src family kinases required for the antigen receptor signaling via its cytoplasmic domain. CD45 also suppresses JAK kinases, and so functions as a negative regulator of cytokine receptor signaling.[citation needed
]

Many alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported.

Isoforms

The CD45 protein family consists of multiple members that are all products of a single complex gene. This gene contains 34

exons, producing a massive protein with extracellular and cytoplasmic domains that are both unusually large. Exons 4, 5, and 6 (corresponding to protein regions A, B, and C) are alternatively spliced to generate up to eight different protein products featuring combinations of zero, one, two, or all three exons.[9]

CD45's large extracellular domain is highly glycosylated, and these eight isoforms allow wide variation in the structure of its side chains. The isoforms affect the protein's

]

CD45 isoforms show cell-type and differentiation-stage specific expression, a pattern which is quite well conserved in mammals.[10] These isoforms are often used as markers that identify and distinguish between different types of immune cells.

Naive T lymphocytes are typically positive for CD45RA, which includes only the A protein region. Activated and memory T lymphocytes express CD45RO, the shortest CD45 isoform, which lacks all three of the A, B, and C regions. This shortest isoform facilitates T cell activation.[citation needed]

CD45R (also known as CD45RABC) contains all three possible exons. It is the longest protein and migrates at 200 kDa when isolated from T cells. B cells also express CD45R with heavier glycosylation, bringing the molecular weight to 220 kDa, hence the name B220 (B cell isoform of 220 kDa).

Interactions

PTPRC has been shown to

interact
with:

CD45 has been recently shown to interact with the

HCMV UL11 protein. This interaction results in functional paralysis of T cells.[18] In addition, CD45 was shown to be the target of the species D adenovirus 19a E3/49K protein to inhibit the activation of NK and T cells.[19]

Clinical importance

CD45 is a pan-leukocyte protein with tyrosine phosphatase activity involved in the regulation of signal transduction in hematopoiesis. CD45 does not colocalize with

GM-CSF signal intensity involved in proliferation of leukemic cells.[citation needed
]

Use as a congenic marker

There are two identifiable

leukocytes can be transferred from a CD45.1 donor mouse, into a CD45.2 host mouse, and can be subsequently identified due to their expression of CD45.1. This technique is also routinely used when generating chimeras. An alternative system is the use of CD90 (Thy1) alleles, which CD90.1/CD90.2 system is used in the same manner as the CD45.1/CD45.2 system.[citation needed
]

In 2016 a new knock-in mouse was generated on the C57BL/6 background to be a perfect congenic strain.[21] This mouse, dubbed the CD45.1STEM mouse, differs from the C57BL/6 strain by a single base pair resulting in a single amino acid change that confers the difference in reactivity by the anti-CD45.1 and anti-CD45.2 antibodies. This strain was designed for competitive bone marrow transplantation assays and demonstrated perfect equivalence, unlike the previous standard, the "SJL" mouse, more formally known as Pep Boy.[22]

References

  1. ^ a b c ENSG00000262418 GRCh38: Ensembl release 89: ENSG00000081237, ENSG00000262418 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026395 - 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. PMID 2169617
    .
  6. ^ a b "Entrez Gene: PTPRC protein tyrosine phosphatase, receptor type, C".
  7. PMID 16423050
    .
  8. .
  9. ^ "Mini-review: CD45 characterization and Isoforms". Bio-Rad Laboratories, Inc.
  10. PMID 12414720
    .
  11. .
  12. .
  13. .
  14. .
  15. .
  16. .
  17. .
  18. .
  19. ^ Windheim M, Southcombe JH, Kremmer E, Chaplin L, Urlaub D, Falk CS, Claus M, Mihm J, Braithwaite M, Dennehy K, Renz H, Sester M, Watzl C, Burgert HG. A unique secreted adenovirus E3 protein binds to the leukocyte common antigen CD45 and modulates leukocyte functions. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):E4884-93.
  20. ^ Mobraaten LE (1994). "JAX NOTES: Ly5 Gene Nomenclature, C57BL/6J and SJL/J - A History of Change". The Jackson Laboratory. Archived from the original on 2015-01-08. Retrieved 2015-01-08.
  21. PMID 27185283
    .
  22. ^ "002014 - B6.SJL-Ptprc Pepc/BoyJ". www.jax.org. Retrieved 2020-10-11.

Bibliography

External links

  • Overview of all the structural information available in the PDB for UniProt: P08575 (Receptor-type tyrosine-protein phosphatase C) at the PDBe-KB.
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