'{{Short description|Mammalian protein found in Homo sapiens}} {{Infobox_gene}} '''Protein tyrosine phosphatase, receptor type, C''' also known as '''PTPRC''' is an [[enzyme]] that, in humans, is encoded by the ''PTPRC'' [[gene]].<ref name="pmid2169617">{{cite journal | vauthors = Kaplan R, Morse B, Huebner K, Croce C, Howk R, Ravera M, Ricca G, Jaye M, Schlessinger J | display-authors = 6 | title = Cloning of three human tyrosine phosphatases reveals a multigene family of receptor-linked protein-tyrosine-phosphatases expressed in brain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 18 | pages = 7000–4 | date = September 1990 | pmid = 2169617 | pmc = 54670 | doi = 10.1073/pnas.87.18.7000 | bibcode = 1990PNAS...87.7000K | doi-access = free }}</ref> PTPRC is also known as '''CD45''' [[antigen]] (CD stands for [[cluster of differentiation]]), which was originally called '''leukocyte common antigen''' ('''LCA''').<ref name="entrez">{{cite web | title = Entrez Gene: PTPRC protein tyrosine phosphatase, receptor type, C| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5788}}</ref> == Function == The protein product of this gene, best known as CD45, is a member of the [[protein tyrosine phosphatase]] (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, [[mitotic]] cycle, and oncogenic transformation. CD45 contains an extracellular domain, a single transmembrane segment, and two tandem intracytoplasmic [[catalytic domain]]s, and thus belongs to the [[receptor type PTP]] family.{{cn|date=November 2020}} CD45 is a [[type I transmembrane protein]] that is present in various isoforms on all differentiated [[hematopoietic]] cells (except [[erythrocytes]] and [[plasma cells]]).<ref name="pmid16423050">{{cite journal | vauthors = Holmes N | title = CD45: all is not yet crystal clear | journal = Immunology | volume = 117 | issue = 2 | pages = 145–55 | date = February 2006 | pmid = 16423050 | pmc = 1782222 | doi = 10.1111/j.1365-2567.2005.02265.x }}</ref> CD45 has been shown to be an essential regulator of [[T-cell antigen receptor|T-]] and [[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 kinase]]s required for the antigen receptor signaling via its cytoplasmic domain. CD45 also suppresses [[Janus kinase|JAK kinases]], and so functions as a negative regulator of [[cytokine]] receptor signaling.{{cn|date=November 2020}} Many alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported.<ref name="entrez" /> [[Antibodies]] against the different isoforms of CD45 are used in routine [[immunohistochemistry]] to differentiate between immune cell types, as well as to differentiate between [[histological section]]s from [[lymphoma]]s and [[carcinoma]]s.<ref name=Leong>{{cite book| last1 = Leong | first1 = Anthony S-Y | last2 = Cooper | first2 = Kumarason | last3 = Leong | first3 = F Joel W-M | name-list-style = vanc |year=2003 |title=Manual of Diagnostic Cytology |edition=2nd |publisher=Greenwich Medical Media, Ltd. |pages=121–124 |isbn=1-84110-100-1 }}</ref> == 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.<ref>{{cite web | title = Mini-review: CD45 characterization and Isoforms | url = https://www.bio-rad-antibodies.com/cd45-characterization-isoforms-structure-function-antibodies-minireview.html | publisher = Bio-Rad Laboratories, Inc. }}</ref> 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 [[N-terminal]] region, which extends linearly out from the cell and bears the [[O-linked glycan]] chains. {{cn|date=November 2020}} CD45 isoforms show cell-type and differentiation-stage specific expression, a pattern which is quite well conserved in mammals.<ref name="pmid12414720">{{cite journal | vauthors = Hermiston ML, Xu Z, Weiss A | title = CD45: a critical regulator of signaling thresholds in immune cells | journal = Annual Review of Immunology | volume = 21 | pages = 107–37 | date = 2003 | pmid = 12414720 | doi = 10.1146/annurev.immunol.21.120601.140946 }}</ref> 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.{{cn|date=November 2020}} 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 [[Protein-protein interaction|interact]] with: * [[GANAB]],<ref name = "pmid9148925">{{cite journal | vauthors = Arendt CW, Ostergaard HL | title = Identification of the CD45-associated 116-kDa and 80-kDa proteins as the alpha- and beta-subunits of alpha-glucosidase II | journal = The Journal of Biological Chemistry | volume = 272 | issue = 20 | pages = 13117–25 | date = May 1997 | pmid = 9148925 | doi = 10.1074/jbc.272.20.13117 | doi-access = free }}</ref><ref name = "pmid10921916">{{cite journal | vauthors = Baldwin TA, Gogela-Spehar M, Ostergaard HL | title = Specific isoforms of the resident endoplasmic reticulum protein glucosidase II associate with the CD45 protein-tyrosine phosphatase via a lectin-like interaction | journal = The Journal of Biological Chemistry | volume = 275 | issue = 41 | pages = 32071–6 | date = October 2000 | pmid = 10921916 | doi = 10.1074/jbc.M003088200 | doi-access = free }}</ref><ref name = "pmid11564800">{{cite journal | vauthors = Baldwin TA, Ostergaard HL | title = Developmentally regulated changes in glucosidase II association with, and carbohydrate content of, the protein tyrosine phosphatase CD45 | journal = Journal of Immunology | volume = 167 | issue = 7 | pages = 3829–35 | date = October 2001 | pmid = 11564800 | doi = 10.4049/jimmunol.167.7.3829 | doi-access = free }}</ref> * [[LYN]],<ref name = "pmid7516335">{{cite journal | vauthors = Brown VK, Ogle EW, Burkhardt AL, Rowley RB, Bolen JB, Justement LB | title = Multiple components of the B cell antigen receptor complex associate with the protein tyrosine phosphatase, CD45 | journal = The Journal of Biological Chemistry | volume = 269 | issue = 25 | pages = 17238–44 | date = June 1994 | doi = 10.1016/S0021-9258(17)32545-0 | pmid = 7516335 | doi-access = free }}</ref> * [[Lck]],<ref name = "pmid8473339">{{cite journal | vauthors = Koretzky GA, Kohmetscher M, Ross S | title = CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line | journal = The Journal of Biological Chemistry | volume = 268 | issue = 12 | pages = 8958–64 | date = April 1993 | doi = 10.1016/S0021-9258(18)52965-3 | pmid = 8473339 | doi-access = free }}</ref><ref name = "pmid8576115">{{cite journal | vauthors = Ng DH, Watts JD, Aebersold R, Johnson P | title = Demonstration of a direct interaction between p56lck and the cytoplasmic domain of CD45 in vitro | journal = The Journal of Biological Chemistry | volume = 271 | issue = 3 | pages = 1295–300 | date = January 1996 | pmid = 8576115 | doi = 10.1074/jbc.271.3.1295 | doi-access = free }}</ref> and * [[SKAP1]].<ref name = "pmid11909961">{{cite journal | vauthors = Wu L, Fu J, Shen SH | title = SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription | journal = Molecular and Cellular Biology | volume = 22 | issue = 8 | pages = 2673–86 | date = April 2002 | pmid = 11909961 | pmc = 133720 | doi = 10.1128/mcb.22.8.2673-2686.2002 }}</ref> CD45 has been recently shown to interact with the [[HCMV]] UL11 protein. This interaction results in functional paralysis of [[T cell]]s.<ref name="pmid22174689">{{cite journal | vauthors = Gabaev I, Steinbrück L, Pokoyski C, Pich A, Stanton RJ, Schwinzer R, Schulz TF, Jacobs R, Messerle M, Kay-Fedorov PC | display-authors = 6 | title = The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells | journal = PLOS Pathogens | volume = 7 | issue = 12 | pages = e1002432 | date = December 2011 | pmid = 22174689 | pmc = 3234252 | doi = 10.1371/journal.ppat.1002432 | doi-access = free }}</ref> 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.<ref>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.</ref> == 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 [[lipid raft]]s on murine and human non-transformed hematopoietic cells, but CD45 positioning within lipid rafts is modified during their oncogenic transformation to [[acute myeloid leukemia]]. CD45 colocalizes with lipid rafts on AML cells, which contributes to elevated [[GM-CSF]] signal intensity involved in proliferation of leukemic cells.{{cn|date=November 2020}} == Use as a congenic marker == There are two identifiable [[alleles]] of CD45 in mice: CD45.1 (Ly5.1 historically) and CD45.2 (Ly5.2 historically).<ref name="url_JAX_NOTES">{{cite web | author = Mobraaten LE | url = http://jaxmice.jax.org/jaxnotes/archive/458b.html | title = JAX NOTES: Ly5 Gene Nomenclature, C57BL/6J and SJL/J - A History of Change | publisher = The Jackson Laboratory | year = 1994 | access-date = 2015-01-08 | archive-url = https://web.archive.org/web/20150108142539/http://jaxmice.jax.org/jaxnotes/archive/458b.html | archive-date = 2015-01-08 | url-status = dead }}</ref> These two types of CD45 are believed to be functionally identical. As such, they are routinely used in scientific research to allow identification of cells. For instance, [[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 [[Chimera (genetics)|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.{{cn|date=November 2020}} In 2016 a new knock-in mouse was generated on the [[C57BL/6]] background to be a perfect congenic strain.<ref>{{Cite journal|last1=Mercier|first1=Francois E.|last2=Sykes|first2=David B.|last3=Scadden|first3=David T.|date=14 June 2016|title=Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1(STEM) Mouse|journal=Stem Cell Reports|volume=6|issue=6|pages=985–992|doi=10.1016/j.stemcr.2016.04.010|issn=2213-6711|pmc=4911492|pmid=27185283}}</ref> 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.<ref>{{Cite web|title=002014 - B6.SJL-Ptprc Pepc/BoyJ|url=https://www.jax.org/strain/002014|access-date=2020-10-11|website=www.jax.org}}</ref> {{Clear}} == References == {{reflist}} ==Bibliography== {{refbegin}} * {{cite journal | vauthors = Tchilian EZ, Beverley PC | title = CD45 in memory and disease | journal = Archivum Immunologiae et Therapiae Experimentalis | volume = 50 | issue = 2 | pages = 85–93 | year = 2002 | pmid = 12022705 }} * {{cite journal | vauthors = Ishikawa H, Tsuyama N, Abroun S, Liu S, Li FJ, Otsuyama K, Zheng X, Kawano MM | display-authors = 6 | title = Interleukin-6, CD45 and the src-kinases in myeloma cell proliferation | journal = Leukemia & Lymphoma | volume = 44 | issue = 9 | pages = 1477–81 | date = September 2003 | pmid = 14565647 | doi = 10.3109/10428190309178767 | s2cid = 19867177 }} * {{cite journal | vauthors = Stanton T, Boxall S, Bennett A, Kaleebu P, Watera C, Whitworth J, French N, Dawes R, Hill AV, Bodmer W, Beverley PC, Tchilian EZ | display-authors = 6 | title = CD45 variant alleles: possibly increased frequency of a novel exon 4 CD45 polymorphism in HIV seropositive Ugandans | journal = Immunogenetics | volume = 56 | issue = 2 | pages = 107–10 | date = May 2004 | pmid = 15057492 | doi = 10.1007/s00251-004-0668-z | s2cid = 10179258 }} * {{cite journal | vauthors = Huntington ND, Tarlinton DM | title = CD45: direct and indirect government of immune regulation | journal = Immunology Letters | volume = 94 | issue = 3 | pages = 167–74 | date = July 2004 | pmid = 15275963 | doi = 10.1016/j.imlet.2004.05.011 }} * {{cite web | url = http://www.bio.davidson.edu/courses/immunology/Students/spring2006/Jameson/CD45.html | title = CD45 | author = Jameson R | year = 2006 | work = Immunology course for undergraduates | publisher = Davidson College | access-date = 2011-10-24 }} {{refend}} == External links == * {{PDBe-KB2|P08575|Receptor-type tyrosine-protein phosphatase C}} {{PDB Gallery|geneid=5788}} {{Clusters of differentiation}} {{Protein tyrosine phosphatases}} [[Category:Clusters of differentiation]] :)'