PTPRC (CD45, leukocyte common antigen) is a type I transmembrane receptor-type protein tyrosine phosphatase expressed on all nucleated hematopoietic cells. A large, heavily O- and N-glycosylated extracellular region, whose length varies through alternative splicing of exons 4-6 (CD45RA, RB, RC and the short CD45RO isoform), is followed by a single transmembrane segment and a cytoplasmic region with two tandem PTP domains, of which the membrane-proximal D1 domain is catalytic and the D2 domain contributes to substrate recognition. CD45's best-defined substrates are Src-family kinases: by dephosphorylating the inhibitory C-terminal tyrosine (Tyr505 in LCK), it keeps LCK, FYN, LYN and HCK in an activatable state, which is required for T cell and B cell antigen receptor signaling and for Fc receptor signaling in myeloid cells. CD45 can also dephosphorylate activating sites, such as the LCK activation-loop Tyr394 and kinase-domain tyrosines of HCK and LYN, so it both enables and restrains immunoreceptor signaling depending on its level and membrane localization; its size-based exclusion from close contacts between T cells and antigen-presenting cells is part of models of TCR triggering. CD45 also acts as a JAK phosphatase that dampens cytokine and interferon receptor signaling. It associates with LCK, ankyrin, the integrin CD11a and the tetraspanin CD53, and has no established physiological ligand, although galectin-1 binds it and viral proteins (cytomegalovirus UL11, adenovirus E3/49K, which dimerizes the ectodomain) bind and inhibit it. CD45 deficiency in humans causes severe combined immunodeficiency with defective T and B lymphocyte function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IGI PMID:12574355 Human activation-induced cytidine deaminase is induced by IL... | MARK AS OVER ANNOTATED | Summary: Anti-CD45 antibody treatment inhibited IL-4-induced AID mRNA expression in human B cells. Reason: The effect on AICDA transcription is a distal consequence of CD45 dephosphorylating JAK1/JAK3 and reducing STAT6 activation. PTPRC has no role in transcriptional machinery; the informative terms are the JAK-STAT and IL-4 signaling regulation terms from the same paper. Supporting Evidence: PMID:12574355 IL-4-induced AID expression is mediated via the JAK/STAT signaling pathway, and can be negatively regulated by the JAK phosphatase activity of CD45 PMID:12574355 triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID expression, and this CD45-mediated AID inhibition correlated with the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and STAT6 phosphorylations |
| GO:0001779 natural killer cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: NK cell differentiation, propagated from mouse Ptprc. Reason: Mouse loss-of-function phenotype transferred by orthology. It records that PTPRC is necessary for the outcome, through its control of Src-family kinase activity in antigen receptor signaling, not that the phosphatase performs a step of this process. Kept as non-core. |
| GO:0001779 natural killer cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: NK cell differentiation, propagated from mouse Ptprc. Reason: Mouse loss-of-function phenotype transferred by orthology. It records that PTPRC is necessary for the outcome, through its control of Src-family kinase activity in antigen receptor signaling, not that the phosphatase performs a step of this process. Kept as non-core. |
| GO:0001915 negative regulation of T cell mediated cytotoxicity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of T cell mediated cytotoxicity, propagated from mouse Ptprc. Reason: Partial loss of CD45 activity causes T cell hyperactivation in mice, consistent with the negative arm of its dual regulation of LCK. This is a downstream consequence of the phosphatase activity and is kept as non-core. Supporting Evidence: PMID:17719247 Peripheral T cells with very low activity of CD45 phosphatase displayed reduced TCR signaling, whereas intermediate activity caused hyperactivation of CD4+ and CD8+ T cells. |
| GO:0001915 negative regulation of T cell mediated cytotoxicity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of T cell mediated cytotoxicity, propagated from mouse Ptprc. Reason: Partial loss of CD45 activity causes T cell hyperactivation in mice, consistent with the negative arm of its dual regulation of LCK. This is a downstream consequence of the phosphatase activity and is kept as non-core. Supporting Evidence: PMID:17719247 Peripheral T cells with very low activity of CD45 phosphatase displayed reduced TCR signaling, whereas intermediate activity caused hyperactivation of CD4+ and CD8+ T cells. |
| GO:0001960 negative regulation of cytokine-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of cytokine-mediated signaling, propagated from mouse Ptprc. Reason: CD45 directly dephosphorylates and binds JAKs and negatively regulates cytokine receptor signaling; human data (anti-CD45 suppressing IL-4-induced JAK1/JAK3/STAT6 phosphorylation) agree. This JAK phosphatase role is a direct activity of PTPRC in hematopoietic cells. Supporting Evidence: PMID:11201744 In vitro, CD45 directly dephosphorylates and binds to JAKs. PMID:11201744 Here we show that CD45 suppresses JAK (Janus kinase) kinases and negatively regulates cytokine receptor signalling. PMID:12574355 triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID expression, and this CD45-mediated AID inhibition correlated with the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and STAT6 phosphorylations |
| GO:0001960 negative regulation of cytokine-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Negative regulation of cytokine-mediated signaling, propagated from mouse Ptprc. Reason: CD45 directly dephosphorylates and binds JAKs and negatively regulates cytokine receptor signaling; human data (anti-CD45 suppressing IL-4-induced JAK1/JAK3/STAT6 phosphorylation) agree. This JAK phosphatase role is a direct activity of PTPRC in hematopoietic cells. Supporting Evidence: PMID:11201744 In vitro, CD45 directly dephosphorylates and binds to JAKs. PMID:11201744 Here we show that CD45 suppresses JAK (Janus kinase) kinases and negatively regulates cytokine receptor signalling. PMID:12574355 triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID expression, and this CD45-mediated AID inhibition correlated with the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and STAT6 phosphorylations |
| GO:0002244 hematopoietic progenitor cell differentiation | IMP PMID:21911094 CD45 regulates homing and engraftment of immature normal and... | KEEP AS NON CORE | Summary: Antibody or inhibitor blockade of CD45 reduced development of human hematopoietic progenitors. Reason: Blocking-antibody and inhibitor phenotype; it shows that CD45 activity is needed for progenitor development and engraftment, not that CD45 performs a differentiation step. Non-core. Supporting Evidence: PMID:21911094 In addition, CD45 inhibition negatively affected development of hematopoietic progenitors in vitro and their recovery in transplanted recipients in vivo |
| GO:0002639 positive regulation of immunoglobulin production | IMP PMID:1793833 The role of CD45 in the activation, proliferation and differ... | KEEP AS NON CORE | Summary: Anti-CD45 antibody suppressed immunoglobulin synthesis by human B cells. Reason: Antibody perturbation of CD45 in B cells; consistent with its requirement for B cell antigen receptor signaling but a distal outcome. Non-core. Supporting Evidence: PMID:1793833 T29/33 antibody also suppressed immunoglobulin synthesis in B cells, independently of its suppressive effect on proliferation. |
| GO:0004725 protein tyrosine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein tyrosine phosphatase activity, inferred by phylogeny (PAINT). Reason: PTPRC is a receptor-type PTP whose membrane-proximal D1 domain is catalytically active; the IBA is consistent with direct biochemical demonstration of CD45 PTPase activity. Supporting Evidence: PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. |
| GO:0004725 protein tyrosine phosphatase activity | IDA PMID:2853967 Demonstration that the leukocyte common antigen CD45 is a pr... | ACCEPT | Summary: Purified human CD45 co-purifies and co-sediments with protein tyrosine phosphatase activity. Reason: Direct biochemical evidence that CD45 is a protein tyrosine phosphatase. This is the core molecular function. Supporting Evidence: PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. |
| GO:0004725 protein tyrosine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein tyrosine phosphatase activity from automated pipelines (InterPro/EC). Reason: Correct; PTPRC carries two PTP domains, of which D1 is catalytic. Supporting Evidence: PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. |
| GO:0004725 protein tyrosine phosphatase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Protein tyrosine phosphatase activity transferred from an ortholog. Reason: Correct and supported by direct human evidence. Supporting Evidence: PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. |
| GO:0004725 protein tyrosine phosphatase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Protein tyrosine phosphatase activity transferred from an ortholog. Reason: Correct and supported by direct human evidence. Supporting Evidence: PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. |
| GO:0004725 protein tyrosine phosphatase activity | TAS PMID:15095367 Neuronal expression of CD22: novel mechanism for inhibiting ... | ACCEPT | Summary: Traceable author statement that CD45 is a transmembrane protein-tyrosine phosphatase. Reason: Correct; consistent with direct biochemical evidence. Supporting Evidence: PMID:15095367 We previously demonstrated that the transmembrane protein-tyrosine phosphatase CD45 plays an important role in negatively regulating microglial activation. PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. |
| GO:0004725 protein tyrosine phosphatase activity | TAS Reactome:R-HSA-202214 | ACCEPT | Summary: Reactome: CD45 dephosphorylates LCK pY505. Reason: Correct. Dephosphorylation of the LCK inhibitory C-terminal tyrosine is the best characterized substrate reaction. Supporting Evidence: Reactome:R-HSA-202214 The activatory role is to dephosphorylate an inhibitory site tyrosine 505 (Y505) at the C-terminal end of Lck |
| GO:0005001 transmembrane receptor protein tyrosine phosphatase activity | IGI PMID:12574355 Human activation-induced cytidine deaminase is induced by IL... | ACCEPT | Summary: Anti-CD45 ligation suppressed IL-4-induced JAK and STAT6 phosphorylation in human B cells. Reason: PTPRC is a single-pass transmembrane PTP whose catalytic activity can be modulated from outside the cell (antibody ligation here; galectin-1 and CMV UL11 binding elsewhere). The transmembrane receptor PTP term is the standard GO classification for receptor-type PTPs and is acceptable, although a physiological ligand that regulates CD45 activity is not established. CD45 has no known physiological ligand, but extracellular dimerizing ligands such as adenovirus E3/49K modulate its catalytic activity (PMID:39454026), which fits the receptor-PTP framing. Supporting Evidence: PMID:12574355 triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID expression, and this CD45-mediated AID inhibition correlated with the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and STAT6 phosphorylations PMID:10369126 Incubation of Jurkat cells with galectin-1 suppressed the immunoprecipitated PTPase activity of CD45. PMID:39454026 The adenovirus E3/49K protein has taught us that, despite a lack of a known ligand, CD45 activity can be modulated by extracellular dimerizing ligands that perturb its phosphatase activity and alter T cell responses. |
| GO:0005001 transmembrane receptor protein tyrosine phosphatase activity | TAS PMID:15557316 Phenotypical and functional alterations in the mucosal immun... | ACCEPT | Summary: Traceable author statement that CD45 is a transmembrane receptor PTP. Reason: Correct classification of a receptor-type PTP; the ligand question is noted in suggested_questions. CD45 has no known physiological ligand, but extracellular dimerizing ligands such as adenovirus E3/49K modulate its catalytic activity (PMID:39454026), which fits the receptor-PTP framing. Supporting Evidence: PMID:15557316 The protein tyrosine phosphatase CD45 has been shown to be an important regulator of antigen-receptor signaling in both T and B lymphocytes. PMID:39454026 The adenovirus E3/49K protein has taught us that, despite a lack of a known ligand, CD45 activity can be modulated by extracellular dimerizing ligands that perturb its phosphatase activity and alter T cell responses. |
| GO:0005001 transmembrane receptor protein tyrosine phosphatase activity | TAS PMID:2845400 The leukocyte common antigen (CD45): a putative receptor-lin... | ACCEPT | Summary: Sequence similarity of CD45 cytoplasmic domains to PTP1B led to the proposal that CD45 is a receptor-linked PTP. Reason: Historic sequence-based proposal later confirmed biochemically (PMID:2853967). Acceptable classification. CD45 has no known physiological ligand, but extracellular dimerizing ligands such as adenovirus E3/49K modulate its catalytic activity (PMID:39454026), which fits the receptor-PTP framing. Supporting Evidence: PMID:2845400 On this basis, it is proposed that the CD45 family has protein tyrosine phosphatase activity and may represent a set of cell-surface receptors involved in signal transduction. PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. PMID:39454026 The adenovirus E3/49K protein has taught us that, despite a lack of a known ligand, CD45 activity can be modulated by extracellular dimerizing ligands that perturb its phosphatase activity and alter T cell responses. |
| GO:0005102 signaling receptor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Signaling receptor binding, propagated from mouse Ptprc. Reason: CD45 associates laterally with several leukocyte surface receptors (CD2, LFA-1/ITGAL, DPP4) and is bound by ligands such as galectin-1, CD22 and CMV UL11, but none of these interactions is established as a function of PTPRC itself. The term is vague and kept as non-core. Supporting Evidence: PMID:1970422 Using chemical crosslinking techniques, we now show that CD45 is linked to CD2 on the surface of human T lymphocytes. PMID:15946252 CD45 Mp-D1 was found to be the main interacting region for the CD11a cytoplasmic tail. |
| GO:0005102 signaling receptor binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Signaling receptor binding, propagated from mouse Ptprc. Reason: CD45 associates laterally with several leukocyte surface receptors (CD2, LFA-1/ITGAL, DPP4) and is bound by ligands such as galectin-1, CD22 and CMV UL11, but none of these interactions is established as a function of PTPRC itself. The term is vague and kept as non-core. Supporting Evidence: PMID:1970422 Using chemical crosslinking techniques, we now show that CD45 is linked to CD2 on the surface of human T lymphocytes. PMID:15946252 CD45 Mp-D1 was found to be the main interacting region for the CD11a cytoplasmic tail. |
| GO:0005515 protein binding | IPI PMID:10369126 Galectin-1, a natural ligand for the receptor-type protein t... | REMOVE | Summary: IPI with LCK cited to the galectin-1 paper. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. The CD45-LCK interaction is captured as protein kinase binding (GO:0019901) on rows from PMID:14625311 and PMID:8576115. |
| GO:0005515 protein binding | IPI PMID:10369126 Galectin-1, a natural ligand for the receptor-type protein t... | REMOVE | Summary: Galectin-1 binds CD45 glycans. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. Here CD45 is the glycoprotein ligand recognized by the galectin lectin domain; the binding activity is galectin-1's, so no informative MF follows for PTPRC. Supporting Evidence: PMID:10369126 In the present work, placental galectin-1 has been identified to be a natural ligand for the receptor-type protein tyrosine phosphatase CD45. |
| GO:0005515 protein binding | IPI PMID:11909961 SKAP55 coupled with CD45 positively regulates T-cell recepto... | REMOVE | Summary: SKAP55 (SKAP1) identified as a CD45 substrate that associates with CD45 in T cells. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. This is an enzyme-substrate association, already captured by protein tyrosine phosphatase activity. Supporting Evidence: PMID:11909961 SKAP55, the Src kinase-associated phosphoprotein of unknown function, was found as a substrate which associated with CD45 in vivo. |
| GO:0005515 protein binding | IPI PMID:12370829 The transmembrane receptor protein tyrosine phosphatase DEP1... | REMOVE | Summary: Beta-catenin interaction cited to a DEP1 (PTPRJ) substrate-trapping study. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. The cached abstract states that the CD45 catalytic domain did not detectably bind catenins, so the interaction itself is doubtful for CD45; the generic term is removed in any case. Supporting Evidence: PMID:12370829 Catalytic domains of the tyrosine phosphatases PTP-PEST, CD45, and PTPbeta did not interact with proteins of the catenin family to detectable levels |
| GO:0005515 protein binding | IPI PMID:15946252 Integrin CD11a cytoplasmic tail interacts with the CD45 memb... | MODIFY | Summary: The CD45 membrane-proximal region and D1 domain bind the CD11a (ITGAL) cytoplasmic tail. Reason: Yeast two-hybrid and in vitro binding map the interaction to CD45 Mp-D1 and the integrin alpha-L tail. Integrin binding is the informative MF term; the functional significance remains open. Proposed replacements: integrin binding Supporting Evidence: PMID:15946252 CD45 Mp-D1 was found to be the main interacting region for the CD11a cytoplasmic tail. PMID:15946252 Our in vitro binding and enzymatic assays showed that the homodimeric CD45 cytoplasmic tail interacts with that of CD11a. |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: Phosphopeptide-substrate assay (EGFR-derived peptide) in a large-scale PTP profiling study. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. These rows reflect CD45 dephosphorylating phosphopeptides in vitro, i.e. enzyme-substrate contact already captured by protein tyrosine phosphatase activity. Supporting Evidence: PMID:19167335 CD45 and members of subgroups R3 and R5 were extremely promiscuous and dephosphorylated most phosphopeptides with reasonable activity |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: Phosphopeptide-substrate assay (ERBB2-derived peptide) in a large-scale PTP profiling study. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. These rows reflect CD45 dephosphorylating phosphopeptides in vitro, i.e. enzyme-substrate contact already captured by protein tyrosine phosphatase activity. Supporting Evidence: PMID:19167335 CD45 and members of subgroups R3 and R5 were extremely promiscuous and dephosphorylated most phosphopeptides with reasonable activity |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: Phosphopeptide-substrate assay (LCK-derived peptide) in a large-scale PTP profiling study. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. These rows reflect CD45 dephosphorylating phosphopeptides in vitro, i.e. enzyme-substrate contact already captured by protein tyrosine phosphatase activity. Supporting Evidence: PMID:19167335 CD45 and members of subgroups R3 and R5 were extremely promiscuous and dephosphorylated most phosphopeptides with reasonable activity |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: Phosphopeptide-substrate assay (CTNNB1-derived peptide) in a large-scale PTP profiling study. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. These rows reflect CD45 dephosphorylating phosphopeptides in vitro, i.e. enzyme-substrate contact already captured by protein tyrosine phosphatase activity. Supporting Evidence: PMID:19167335 CD45 and members of subgroups R3 and R5 were extremely promiscuous and dephosphorylated most phosphopeptides with reasonable activity |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: Phosphopeptide-substrate assay (CSK-derived peptide) in a large-scale PTP profiling study. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. These rows reflect CD45 dephosphorylating phosphopeptides in vitro, i.e. enzyme-substrate contact already captured by protein tyrosine phosphatase activity. Supporting Evidence: PMID:19167335 CD45 and members of subgroups R3 and R5 were extremely promiscuous and dephosphorylated most phosphopeptides with reasonable activity |
| GO:0005515 protein binding | IPI PMID:19167335 Large-scale structural analysis of the classical human prote... | REMOVE | Summary: Phosphopeptide-substrate assay (ERBB3-derived peptide) in a large-scale PTP profiling study. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. These rows reflect CD45 dephosphorylating phosphopeptides in vitro, i.e. enzyme-substrate contact already captured by protein tyrosine phosphatase activity. Supporting Evidence: PMID:19167335 CD45 and members of subgroups R3 and R5 were extremely promiscuous and dephosphorylated most phosphopeptides with reasonable activity |
| GO:0005515 protein binding | IPI PMID:1970422 Association of CD2 and CD45 on human T lymphocytes. | REMOVE | Summary: CD45 chemically crosslinked to CD2 on human T cells. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. Crosslinking shows proximity in the membrane, not a defined binding activity. Supporting Evidence: PMID:1970422 Using chemical crosslinking techniques, we now show that CD45 is linked to CD2 on the surface of human T lymphocytes. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: High-throughput EGFR interaction network study in colorectal cancer cells. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. The cached full text does not mention CD45 or PTPRC; no informative function can be derived. |
| GO:0005515 protein binding | IPI PMID:7507203 Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase... | MODIFY | Summary: CSK-phosphorylated CD45 binds the LCK SH2 domain. Reason: Generic protein binding; the informative term for PTPRC is protein kinase binding, reflecting its association with its principal substrate kinase LCK. Proposed replacements: protein kinase binding Supporting Evidence: PMID:7507203 Tyrosine-phosphorylated CD45 bound p56lck through the SH2 domain of the kinase. |
| GO:0005515 protein binding | IPI PMID:7507203 Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase... | REMOVE | Summary: CSK phosphorylates CD45 on Tyr-1193. Reason: Generic protein binding is uninformative about PTPRC function. Removal does not dispute the reported interaction. Here CD45 is the substrate of the CSK kinase; the activity belongs to CSK. Supporting Evidence: PMID:7507203 Here we report that CD45 was phosphorylated by p50csk on two tyrosine residues, one of them identified as Tyr-1193. |
| GO:0005515 protein binding | IPI PMID:8576115 Demonstration of a direct interaction between p56lck and the... | MODIFY | Summary: Recombinant LCK binds the CD45 cytoplasmic domain directly and stoichiometrically. Reason: Generic protein binding; protein kinase binding is the informative term for this direct association with LCK. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8576115 In this study, recombinant purified p56lck was found to specifically associate with recombinant CD45 cytoplasmic domain protein, but not to the cytoplasmic domain of another related tyrosine phosphatase, receptor protein-tyrosine phosphatase alpha. |
| GO:0005515 protein binding | IPI PMID:8576115 Demonstration of a direct interaction between p56lck and the... | MODIFY | Summary: Recombinant LCK binds the CD45 cytoplasmic domain directly and stoichiometrically. Reason: Generic protein binding; protein kinase binding is the informative term for this direct association with LCK. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8576115 In this study, recombinant purified p56lck was found to specifically associate with recombinant CD45 cytoplasmic domain protein, but not to the cytoplasmic domain of another related tyrosine phosphatase, receptor protein-tyrosine phosphatase alpha. |
| GO:0005886 plasma membrane | EXP PMID:22174689 The human cytomegalovirus UL11 protein interacts with the re... | ACCEPT | Summary: CD45 on the T cell surface, where it is bound by CMV UL11. Reason: Correct; CD45 is a type I plasma membrane protein. Supporting Evidence: PMID:22174689 CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. |
| GO:0005886 plasma membrane | IDA PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | ACCEPT | Summary: CD45 recruited to the T cell surface upon TCR stimulation. Reason: Correct. Supporting Evidence: PMID:12354383 With T cell receptor stimulation, intracellular pools of CD45 and spectrin move to the surface. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Plasma membrane from automated pipelines. Reason: Correct. Supporting Evidence: PMID:2956090 a single transmembrane-spanning region and a large cytoplasmic domain of 707 amino acids shared by all of the structural variants |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Plasma membrane transferred from an ortholog. Reason: Correct. Supporting Evidence: PMID:2956090 a single transmembrane-spanning region and a large cytoplasmic domain of 707 amino acids shared by all of the structural variants |
| GO:0005886 plasma membrane | TAS PMID:2956090 Structural variants of human T200 glycoprotein (leukocyte-co... | ACCEPT | Summary: Human T200 cDNA predicts an extracellular region, one transmembrane segment and a cytoplasmic domain. Reason: Correct. Supporting Evidence: PMID:2956090 a single transmembrane-spanning region and a large cytoplasmic domain of 707 amino acids shared by all of the structural variants |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202214 | ACCEPT | Summary: Reactome places CD45 at the plasma membrane in TCR signaling. Reason: Correct. Supporting Evidence: Reactome:R-HSA-202214 The activatory role is to dephosphorylate an inhibitory site tyrosine 505 (Y505) at the C-terminal end of Lck |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-373746 | ACCEPT | Summary: Reactome: SEMA4D associates with cell-surface CD45. Reason: Correct location. Supporting Evidence: Reactome:R-HSA-373746 SEMA4D also associates with CD45, a cell surface protein tyrosine phosphatase (PTP) |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798743 | ACCEPT | Summary: Reactome neutrophil degranulation: CD45 delivered to the plasma membrane from secretory vesicles. Reason: Correct location. Supporting Evidence: Reactome:R-HSA-6798743 Secretory vesicles provide a reservoir of membrane-associated receptors |
| GO:0005925 focal adhesion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Focal adhesion, propagated from mouse macrophage data. Reason: CD45 colocalizes with beta2 integrin and LYN at adhesion sites in mouse macrophages, where it restrains SFK activity. A context-specific location; non-core. Supporting Evidence: PMID:9197241 We found that CD45 colocalized with beta2 integrin and the Src family kinase p53/56(lyn) to adhesion sites in bone marrow-derived macrophages. |
| GO:0005925 focal adhesion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Focal adhesion, propagated from mouse macrophage data. Reason: CD45 colocalizes with beta2 integrin and LYN at adhesion sites in mouse macrophages, where it restrains SFK activity. A context-specific location; non-core. Supporting Evidence: PMID:9197241 We found that CD45 colocalized with beta2 integrin and the Src family kinase p53/56(lyn) to adhesion sites in bone marrow-derived macrophages. |
| GO:0006469 negative regulation of protein kinase activity | IDA PMID:9197241 CD45 regulates Src family member kinase activity associated ... | KEEP AS NON CORE | Summary: CD45 dephosphorylates the activation-loop tyrosine of HCK and LYN in macrophages, lowering their activity. Reason: Direct consequence of the phosphatase acting on the SFK activating tyrosine, the negative arm of CD45's dual regulation of Src kinases. Valid but secondary to the positive role on the C-terminal tyrosine; non-core. Supporting Evidence: PMID:9197241 CD45 decreases Src family kinase activity by dephosphorylating the tyrosine residue located within the kinase domain. |
| GO:0006469 negative regulation of protein kinase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of protein kinase activity transferred from an ortholog. Reason: As above; valid but non-core. Supporting Evidence: PMID:9197241 CD45 decreases Src family kinase activity by dephosphorylating the tyrosine residue located within the kinase domain. PMID:17719247 These results are explained by a rheostat mechanism whereby CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56(lck) tyrosine kinase phosphorylation sites. |
| GO:0006470 protein dephosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: Protein dephosphorylation transferred from an ortholog. Reason: Direct consequence of the PTP activity. Supporting Evidence: PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. PMID:14625311 The Src family kinase, Lck, is a major CD45 substrate in T cells and CD45 dephosphorylation of Lck is important for both T cell development and activation. |
| GO:0006933 negative regulation of cell adhesion involved in substrate-bound cell migration | IMP PMID:21911094 CD45 regulates homing and engraftment of immature normal and... | KEEP AS NON CORE | Summary: CD45 blockade produced a hyperadhesive phenotype in human progenitors and murine leukocytes. Reason: Consistent with CD45 restraining integrin-dependent adhesion (also seen in T cell lines), but a blocking-antibody phenotype; non-core. Supporting Evidence: PMID:21911094 Moreover, CD45 blockage induced a hyperadhesive phenotype in immature human progenitor cells as well as in murine leukocytes PMID:10358156 The absence of CD45 correlated with enhanced adhesion to fibronectin via integrin alpha5beta1 (VLA-5), but not alpha4beta1 (VLA-4) in both cell lines. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: Signal transduction, inferred by phylogeny. Reason: Correct, if general; CD45 regulates immunoreceptor and cytokine signaling. Supporting Evidence: PMID:9197241 CD45 is a leukocyte-specific transmembrane protein tyrosine phosphatase that activates Src family kinases associated with B-cell and T-cell antigen receptor signaling by constitutive dephosphorylation of the inhibitory carboxy-terminal tyrosine phosphorylation site. |
| GO:0007166 cell surface receptor signaling pathway | TAS PMID:2845400 The leukocyte common antigen (CD45): a putative receptor-lin... | ACCEPT | Summary: Proposal that CD45 is a receptor-linked PTP involved in signal transduction. Reason: General but correct parent of the antigen receptor signaling roles. Supporting Evidence: PMID:2845400 On this basis, it is proposed that the CD45 family has protein tyrosine phosphatase activity and may represent a set of cell-surface receptors involved in signal transduction. |
| GO:0008201 heparin binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Heparin binding, propagated electronically from a rodent ortholog. Reason: No human evidence and no source paper available in this review to evaluate glycosaminoglycan binding by the CD45 ectodomain. Left undecided. |
| GO:0009897 external side of plasma membrane | IDA PMID:17213291 FcRL6, a new ITIM-bearing receptor on cytolytic cells, is br... | ACCEPT | Summary: External side of plasma membrane (CD45 used as a surface marker; ortholog transfer). Reason: Correct for the heavily glycosylated CD45 ectodomain, which is the antigen recognized by surface anti-CD45 antibodies. Supporting Evidence: PMID:12100025 We found 99.5 +/- 3.2%, 42.3 +/- 5.8% and 96.7 +/- 2.6% PMN expressed CD45, CD45RA and CD45RO molecules on the cell surface, respectively. |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: External side of plasma membrane (CD45 used as a surface marker; ortholog transfer). Reason: Correct for the heavily glycosylated CD45 ectodomain, which is the antigen recognized by surface anti-CD45 antibodies. Supporting Evidence: PMID:12100025 We found 99.5 +/- 3.2%, 42.3 +/- 5.8% and 96.7 +/- 2.6% PMN expressed CD45, CD45RA and CD45RO molecules on the cell surface, respectively. |
| GO:0009898 cytoplasmic side of plasma membrane | NAS PMID:15661907 CD45 signals outside of lipid rafts to promote ERK activatio... | MARK AS OVER ANNOTATED | Summary: Cytoplasmic side of plasma membrane, author statement about CD45 membrane compartmentalization. Reason: CD45 is an integral single-pass protein; its cytoplasmic PTP domains face the cytosol, but plasma membrane already describes the location. The leaflet term is redundant for an integral membrane protein. Supporting Evidence: PMID:2956090 a single transmembrane-spanning region and a large cytoplasmic domain of 707 amino acids shared by all of the structural variants |
| GO:0009986 cell surface | IDA PMID:12100025 Anti-CD45 isoform antibodies enhance phagocytosis and gene e... | ACCEPT | Summary: Cell surface. Reason: Correct. Supporting Evidence: PMID:12100025 We found 99.5 +/- 3.2%, 42.3 +/- 5.8% and 96.7 +/- 2.6% PMN expressed CD45, CD45RA and CD45RO molecules on the cell surface, respectively. |
| GO:0009986 cell surface | IDA PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | ACCEPT | Summary: Cell surface. Reason: Correct. Supporting Evidence: PMID:12354383 With T cell receptor stimulation, intracellular pools of CD45 and spectrin move to the surface. |
| GO:0009986 cell surface | IDA PMID:24337748 Guanylate binding protein 1-mediated interaction of T cell a... | ACCEPT | Summary: Cell surface. Reason: Correct. Supporting Evidence: PMID:24337748 We found higher cell spreading and enhanced surface expression of TCR/CD3 and CD45 in GBP-1 silenced T cells |
| GO:0009986 cell surface | IEA GO_REF:0000120 | ACCEPT | Summary: Cell surface. Reason: Correct. Supporting Evidence: PMID:22174689 CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. |
| GO:0010332 response to gamma radiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Response to gamma radiation (IEA), transferred from rat Ptprc, from a study of CD45 catalytic properties in thymocytes of irradiated rats (PMID:17290791). Reason: The row is transferred from rat Ptprc, annotated by direct assay in a study that compared the catalytic properties of CD45 purified from thymocytes of control and irradiated rats (PMID:17290791), so an experimental observation lies behind it. A change in the measured activity of the phosphatase after irradiation shows that CD45 is affected by the treatment, not that it acts in a response to radiation. The term over-reads the observation and is marked as an over-annotation rather than removed. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Regulation of gene expression. Reason: Too vague; any effect of CD45 on gene expression is a distal consequence of its regulation of receptor-proximal kinases. The specific signaling terms are informative. Supporting Evidence: PMID:12574355 IL-4-induced AID expression is mediated via the JAK/STAT signaling pathway, and can be negatively regulated by the JAK phosphatase activity of CD45 |
| GO:0010468 regulation of gene expression | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Regulation of gene expression. Reason: Too vague; any effect of CD45 on gene expression is a distal consequence of its regulation of receptor-proximal kinases. The specific signaling terms are informative. Supporting Evidence: PMID:12574355 IL-4-induced AID expression is mediated via the JAK/STAT signaling pathway, and can be negatively regulated by the JAK phosphatase activity of CD45 |
| GO:0010468 regulation of gene expression | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Regulation of gene expression. Reason: Too vague; any effect of CD45 on gene expression is a distal consequence of its regulation of receptor-proximal kinases. The specific signaling terms are informative. Supporting Evidence: PMID:12574355 IL-4-induced AID expression is mediated via the JAK/STAT signaling pathway, and can be negatively regulated by the JAK phosphatase activity of CD45 |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | ACCEPT | Summary: Detected in NK cell membrane proteome. Reason: Correct. |
| GO:0016020 membrane | TAS PMID:15095367 Neuronal expression of CD22: novel mechanism for inhibiting ... | ACCEPT | Summary: Transmembrane protein-tyrosine phosphatase. Reason: Correct. Supporting Evidence: PMID:15095367 We previously demonstrated that the transmembrane protein-tyrosine phosphatase CD45 plays an important role in negatively regulating microglial activation. |
| GO:0016311 dephosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: Dephosphorylation transferred from an ortholog. Reason: Correct, general parent of protein dephosphorylation. Supporting Evidence: PMID:2853967 The present study confirms that CD45 possesses intrinsic protein tyrosine phosphatase (PTPase) activity. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Protein kinase binding, propagated from mouse. Reason: CD45 binds its kinase substrates LCK and JAKs. Supporting Evidence: PMID:14625311 Analysis of the interaction between the cytoplasmic domain of CD45 and its substrate, Lck, revealed that the active, membrane-proximal phosphatase domain of CD45 (CD45-D1) bound to the phosphorylated Lck kinase domain, the SH2 domain, and the unique N-terminal region of Lck. PMID:11201744 In vitro, CD45 directly dephosphorylates and binds to JAKs. |
| GO:0019901 protein kinase binding | IPI PMID:14625311 Subdomain X of the kinase domain of Lck binds CD45 and facil... | ACCEPT | Summary: CD45 D1 and D2 domains bind the LCK kinase domain, SH2 domain and unique region. Reason: Direct binding of CD45 to LCK, its principal substrate; D2 binding to kinase subdomain X contributes to substrate recognition. Informative and accepted. Supporting Evidence: PMID:14625311 Analysis of the interaction between the cytoplasmic domain of CD45 and its substrate, Lck, revealed that the active, membrane-proximal phosphatase domain of CD45 (CD45-D1) bound to the phosphorylated Lck kinase domain, the SH2 domain, and the unique N-terminal region of Lck. |
| GO:0030183 B cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: B cell differentiation, transferred from mouse. Reason: Mouse loss-of-function phenotype transferred by orthology. It records that PTPRC is necessary for the outcome, through its control of Src-family kinase activity in antigen receptor signaling, not that the phosphatase performs a step of this process. Kept as non-core. Supporting Evidence: PMID:18249142 Analysis of CD148 and CD45 doubly deficient B cells and macrophages revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SFKs accompanied by substantial alterations in B and myeloid lineage development and defective immunoreceptor signaling. |
| GO:0030217 T cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: T cell differentiation, propagated from mouse. Reason: Mouse loss-of-function phenotype transferred by orthology. It records that PTPRC is necessary for the outcome, through its control of Src-family kinase activity in antigen receptor signaling, not that the phosphatase performs a step of this process. Kept as non-core. CD45 phosphatase activity is required for thymic development. Supporting Evidence: PMID:17719247 Whereas CD45 PTPase activity was absolutely required for the reconstitution of thymic development |
| GO:0030217 T cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: T cell differentiation, propagated from mouse. Reason: Mouse loss-of-function phenotype transferred by orthology. It records that PTPRC is necessary for the outcome, through its control of Src-family kinase activity in antigen receptor signaling, not that the phosphatase performs a step of this process. Kept as non-core. CD45 phosphatase activity is required for thymic development. Supporting Evidence: PMID:17719247 Whereas CD45 PTPase activity was absolutely required for the reconstitution of thymic development |
| GO:0030292 protein tyrosine kinase inhibitor activity | IDA PMID:12100025 Anti-CD45 isoform antibodies enhance phagocytosis and gene e... | REMOVE | Summary: Anti-CD45RO crosslinking on neutrophils lowered LCK protein expression. Reason: The paper measured LCK expression and tyrosine phosphorylation after antibody crosslinking; it did not show CD45 binding to and inhibiting a kinase as an enzyme regulator. CD45 acts on kinases catalytically, and the same paper interprets its effect as dephosphorylation of the LCK inhibitory site, which activates the kinase. Kinase inhibitor activity misdescribes PTPRC. Supporting Evidence: PMID:12100025 However, only anti-CD45RO suppressed Src family protein tyrosine kinase p56lck expression in the cells. |
| GO:0030506 ankyrin binding | IPI PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | KEEP AS NON CORE | Summary: Ankyrin binds the CD45 cytoplasmic domain directly with nanomolar affinity. Reason: Direct binding supported; it links CD45 to the spectrin-ankyrin skeleton and controls its surface display. Real but not the core activity. Supporting Evidence: PMID:12354383 Spectrin's effects are mediated by ankyrin, which binds directly to the cytoplasmic domain of CD45 (K(d) = 4.3 +/- 3.0 nM). |
| GO:0030507 spectrin binding | IDA PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | KEEP AS NON CORE | Summary: Beta-I spectrin associates with CD45. Reason: The abstract indicates spectrin effects are mediated through ankyrin, so the spectrin contact may be indirect; the curator saw the full text, so the row is kept, as non-core. Supporting Evidence: PMID:12354383 In both peripheral lymphocytes and Jurkat T cells, betaI spectrin and ankyrin associate with CD45. PMID:12354383 Spectrin's effects are mediated by ankyrin, which binds directly to the cytoplasmic domain of CD45 (K(d) = 4.3 +/- 3.0 nM). |
| GO:0030667 secretory granule membrane | TAS Reactome:R-HSA-6798743 | KEEP AS NON CORE | Summary: Neutrophil secretory vesicle membrane (Reactome). Reason: Intracellular pool mobilized to the neutrophil surface; context-specific, non-core. Supporting Evidence: Reactome:R-HSA-6798743 Secretory vesicles provide a reservoir of membrane-associated receptors |
| GO:0030890 positive regulation of B cell proliferation | IMP PMID:1793833 The role of CD45 in the activation, proliferation and differ... | KEEP AS NON CORE | Summary: Anti-CD45 antibody inhibited proliferation of human B cells. Reason: Antibody perturbation; downstream of BCR signaling regulation. Non-core. Supporting Evidence: PMID:1793833 The addition of T29/33 to B cells inhibited the proliferative response induced by various polyclonal B cell activators in a dose-dependent manner |
| GO:0032059 bleb | IDA PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | KEEP AS NON CORE | Summary: CD45 detected in membrane blebs. Reason: Abstract-only paper; cannot verify the detail, but the location is plausible for a surface protein. Non-core. |
| GO:0032677 regulation of interleukin-8 production | IDA PMID:12100025 Anti-CD45 isoform antibodies enhance phagocytosis and gene e... | KEEP AS NON CORE | Summary: Anti-CD45 antibody ligation increased IL-8 production by neutrophils. Reason: Antibody crosslinking effect; downstream readout. Non-core. Supporting Evidence: PMID:12100025 The production of IL-8 by PMN was also increased significantly after binding with antibodies (anti-CD45 > anti-CD45RO > anti-CD45RA). |
| GO:0032703 negative regulation of interleukin-2 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of IL-2 production (ortholog). Reason: Raft-localized CD45 antagonizes IL-2 production; a downstream output of its dual control of TCR signaling. Non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0032703 negative regulation of interleukin-2 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of IL-2 production (ortholog). Reason: Raft-localized CD45 antagonizes IL-2 production; a downstream output of its dual control of TCR signaling. Non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0032743 positive regulation of interleukin-2 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of IL-2 production (ortholog). Reason: Raft-excluded CD45 promotes IL-2 production; downstream output of TCR signaling. Non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0032743 positive regulation of interleukin-2 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of IL-2 production (ortholog). Reason: Raft-excluded CD45 promotes IL-2 production; downstream output of TCR signaling. Non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0032760 positive regulation of tumor necrosis factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of TNF production (ortholog). Reason: Fc receptor-induced TNF production requires CD45/CD148 in macrophages; downstream output. Non-core. Supporting Evidence: PMID:18249142 Moreover, Fc receptor-induced TNFΞ± production was also severely impaired in DKO BMDMs |
| GO:0032760 positive regulation of tumor necrosis factor production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of TNF production (ortholog). Reason: Fc receptor-induced TNF production requires CD45/CD148 in macrophages; downstream output. Non-core. Supporting Evidence: PMID:18249142 Moreover, Fc receptor-induced TNFΞ± production was also severely impaired in DKO BMDMs |
| GO:0042100 B cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: B cell proliferation (ortholog). Reason: Mouse loss-of-function phenotype transferred by orthology. It records that PTPRC is necessary for the outcome, through its control of Src-family kinase activity in antigen receptor signaling, not that the phosphatase performs a step of this process. Kept as non-core. Supporting Evidence: PMID:1793833 The addition of T29/33 to B cells inhibited the proliferative response induced by various polyclonal B cell activators in a dose-dependent manner |
| GO:0042100 B cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: B cell proliferation (ortholog). Reason: Mouse loss-of-function phenotype transferred by orthology. It records that PTPRC is necessary for the outcome, through its control of Src-family kinase activity in antigen receptor signaling, not that the phosphatase performs a step of this process. Kept as non-core. Supporting Evidence: PMID:1793833 The addition of T29/33 to B cells inhibited the proliferative response induced by various polyclonal B cell activators in a dose-dependent manner |
| GO:0042102 positive regulation of T cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of T cell proliferation (ortholog). Reason: Downstream outcome of CD45-dependent TCR signaling; non-core. Supporting Evidence: PMID:10700239 The population of peripheral blood T lymphocytes was greatly diminished and unresponsive to mitogen stimulation. |
| GO:0042102 positive regulation of T cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of T cell proliferation (ortholog). Reason: Downstream outcome of CD45-dependent TCR signaling; non-core. Supporting Evidence: PMID:10700239 The population of peripheral blood T lymphocytes was greatly diminished and unresponsive to mitogen stimulation. |
| GO:0042110 T cell activation | TAS PMID:12354383 The spectrin-ankyrin skeleton controls CD45 surface display ... | KEEP AS NON CORE | Summary: T cell activation. Reason: CD45 is required for T cell activation, but the informative process is antigen receptor signaling. Non-core. Supporting Evidence: PMID:12354383 In Jurkat T cells, betaI spectrin peptides suppress surface recruitment of CD45 and CD3 and abrogate T cell activation. |
| GO:0043395 heparan sulfate proteoglycan binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Heparan sulfate proteoglycan binding, electronic propagation from a rodent ortholog. Reason: No human evidence available in this review; left undecided. |
| GO:0043410 positive regulation of MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of MAPK cascade (ortholog). Reason: Raft-excluded CD45 promotes ERK-dependent responses downstream of the TCR; non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0044770 cell cycle phase transition | IMP PMID:1793833 The role of CD45 in the activation, proliferation and differ... | MARK AS OVER ANNOTATED | Summary: Anti-CD45 antibody blocked the G0/G1 to S transition of activated B cells. Reason: Blocking B cell entry into S phase reflects inhibition of activation signals; CD45 has no role in cell cycle machinery. Supporting Evidence: PMID:1793833 Antibody to CD45 appeared to block the G0(G1) to S phase transition in the cell cycle analysis by propidium iodide staining. |
| GO:0044855 plasma membrane raft distribution | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Plasma membrane raft distribution (ortholog). Reason: Raft-excluded CD45 promotes polarized synaptic raft clustering in T cells. Non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0044855 plasma membrane raft distribution | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Plasma membrane raft distribution (ortholog). Reason: Raft-excluded CD45 promotes polarized synaptic raft clustering in T cells. Non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0045121 membrane raft | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Membrane raft. Reason: A pool of CD45 partitions into rafts, while much of it is excluded; location is context dependent. Non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. PMID:15661907 CD45 is dynamically repositioned within lipid rafts and the immune synapse during T cell activation |
| GO:0045121 membrane raft | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Membrane raft. Reason: A pool of CD45 partitions into rafts, while much of it is excluded; location is context dependent. Non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. PMID:15661907 CD45 is dynamically repositioned within lipid rafts and the immune synapse during T cell activation |
| GO:0045202 synapse | EXP PMID:35767951 Tetraspanin CD53 controls TΒ cell immunity through regulation... | MODIFY | Summary: CD45 localization at the T cell contact studied with CD53. Reason: GO:0045202 synapse denotes a neuronal synapse. The UniProt 'Synapse' location for CD45 refers to the immunological synapse, where CD45 is repositioned during T cell activation. Replace with immunological synapse. Proposed replacements: immunological synapse Supporting Evidence: PMID:15661907 CD45 is dynamically repositioned within lipid rafts and the immune synapse during T cell activation PMID:15946252 Leucocyte adhesion receptor integrin CD11aCD18 and the transmembrane receptor-like protein tyrosine phosphatase (RPTP) CD45 mediate immune synapse formation and signalling during antigen presentation. |
| GO:0045202 synapse | IEA GO_REF:0000044 | MODIFY | Summary: UniProt subcellular location 'Synapse' mapped to GO:0045202. Reason: Mapping artefact: the UniProt location refers to the T cell immunological synapse, not a neuronal synapse. Proposed replacements: immunological synapse Supporting Evidence: PMID:15661907 CD45 is dynamically repositioned within lipid rafts and the immune synapse during T cell activation |
| GO:0045860 positive regulation of protein kinase activity | NAS PMID:15275963 CD45: direct and indirect government of immune regulation. | ACCEPT | Summary: Review: CD45 positively regulates Src-family kinases. Reason: CD45 dephosphorylates the inhibitory C-terminal tyrosine of LCK and other SFKs, keeping them in an activatable state. This positive regulation of kinase activity is the main way CD45 controls antigen receptor signaling. Supporting Evidence: PMID:15275963 Despite its clear role in positive regulation of signalling through the activation of the Src family of tyrosine kinases, many reports have shown CD45 to also negatively regulate this process. PMID:9197241 CD45 is a leukocyte-specific transmembrane protein tyrosine phosphatase that activates Src family kinases associated with B-cell and T-cell antigen receptor signaling by constitutive dephosphorylation of the inhibitory carboxy-terminal tyrosine phosphorylation site. Reactome:R-HSA-202214 The activatory role is to dephosphorylate an inhibitory site tyrosine 505 (Y505) at the C-terminal end of Lck |
| GO:0046426 negative regulation of receptor signaling pathway via JAK-STAT | IGI PMID:12574355 Human activation-induced cytidine deaminase is induced by IL... | ACCEPT | Summary: Anti-CD45 suppressed IL-4-activated JAK1/JAK3/STAT6 phosphorylation in human B cells. Reason: Supported directly and by the mouse JAK phosphatase study. Supporting Evidence: PMID:12574355 triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID expression, and this CD45-mediated AID inhibition correlated with the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and STAT6 phosphorylations PMID:11201744 Here we show that CD45 suppresses JAK (Janus kinase) kinases and negatively regulates cytokine receptor signalling. |
| GO:0048539 bone marrow development | IMP PMID:21911094 CD45 regulates homing and engraftment of immature normal and... | MARK AS OVER ANNOTATED | Summary: CD45 blockade impaired repopulation of mouse bone marrow by human CD34+ cells. Reason: Engraftment of transplanted progenitors is not bone marrow (organ) development; over-annotation of a homing phenotype. Supporting Evidence: PMID:21911094 Blocking CD45 inhibited homing and repopulation by immature human CD34(+) cells as well as homing of primary patient leukemic cells. |
| GO:0048864 stem cell development | IMP PMID:21911094 CD45 regulates homing and engraftment of immature normal and... | MARK AS OVER ANNOTATED | Summary: CD45 inhibition reduced development of hematopoietic progenitors. Reason: Inhibitor/antibody phenotype; stem cell development overstates the evidence. Supporting Evidence: PMID:21911094 In addition, CD45 inhibition negatively affected development of hematopoietic progenitors in vitro and their recovery in transplanted recipients in vivo |
| GO:0050764 regulation of phagocytosis | IDA PMID:12100025 Anti-CD45 isoform antibodies enhance phagocytosis and gene e... | KEEP AS NON CORE | Summary: Anti-CD45 antibody ligation enhanced neutrophil phagocytosis via increased CR3. Reason: Antibody crosslinking effect in neutrophils; non-core. Supporting Evidence: PMID:12100025 The interaction of CD45, CD45RA or CD45RO with its specific antibody on PMN enhanced phagocytosis markedly (34-83% increase), mainly via increased expression of complement receptor type 3 (CR3, CD11b) on the cells. |
| GO:0050766 positive regulation of phagocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of phagocytosis (ortholog). Reason: Fc receptor-mediated phagocytosis requires CD45/CD148 to keep SFKs active in macrophages; downstream outcome. Non-core. Supporting Evidence: PMID:18249142 Fc receptor mediated phagocytosis was severely impaired in DKO BMDM (40% of WT) |
| GO:0050766 positive regulation of phagocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of phagocytosis (ortholog). Reason: Fc receptor-mediated phagocytosis requires CD45/CD148 to keep SFKs active in macrophages; downstream outcome. Non-core. Supporting Evidence: PMID:18249142 Fc receptor mediated phagocytosis was severely impaired in DKO BMDM (40% of WT) |
| GO:0050850 positive regulation of calcium-mediated signaling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of calcium-mediated signaling (ortholog). Reason: Downstream consequence of enabling antigen receptor signaling; non-core. Supporting Evidence: PMID:10358156 In contrast, only a catalytically active CD45 cytoplasmic domain was required for TCR signaling. |
| GO:0050850 positive regulation of calcium-mediated signaling | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of calcium-mediated signaling (ortholog). Reason: Downstream consequence of enabling antigen receptor signaling; non-core. Supporting Evidence: PMID:10358156 In contrast, only a catalytically active CD45 cytoplasmic domain was required for TCR signaling. |
| GO:0050852 T cell receptor signaling pathway | IDA PMID:10358156 Regulation of integrin-mediated T cell adhesion by the trans... | ACCEPT | Summary: Catalytically active CD45 cytoplasmic domain required for TCR signaling in T cell lines. Reason: CD45 acts at the start of TCR signaling by keeping LCK activatable. Accepted. Supporting Evidence: PMID:10358156 In contrast, only a catalytically active CD45 cytoplasmic domain was required for TCR signaling. PMID:14625311 The Src family kinase, Lck, is a major CD45 substrate in T cells and CD45 dephosphorylation of Lck is important for both T cell development and activation. |
| GO:0050852 T cell receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: TCR signaling pathway (automated). Reason: Correct. Supporting Evidence: PMID:10358156 In contrast, only a catalytically active CD45 cytoplasmic domain was required for TCR signaling. |
| GO:0050852 T cell receptor signaling pathway | TAS PMID:15557316 Phenotypical and functional alterations in the mucosal immun... | ACCEPT | Summary: CD45 regulates antigen receptor signaling in T and B cells. Reason: Correct. Supporting Evidence: PMID:15557316 The protein tyrosine phosphatase CD45 has been shown to be an important regulator of antigen-receptor signaling in both T and B lymphocytes. |
| GO:0050852 T cell receptor signaling pathway | TAS Reactome:R-HSA-202403 | ACCEPT | Summary: Reactome TCR signaling: CD45 dephosphorylates LCK pY505. Reason: Correct. Supporting Evidence: Reactome:R-HSA-202214 The activatory role is to dephosphorylate an inhibitory site tyrosine 505 (Y505) at the C-terminal end of Lck |
| GO:0050853 B cell receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: B cell receptor signaling pathway (ortholog). Reason: CD45 (redundantly with CD148) dephosphorylates the inhibitory tyrosine of SFKs in B cells, enabling BCR signaling. Supporting Evidence: PMID:18249142 Analysis of CD148 and CD45 doubly deficient B cells and macrophages revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SFKs accompanied by substantial alterations in B and myeloid lineage development and defective immunoreceptor signaling. PMID:9197241 CD45 is a leukocyte-specific transmembrane protein tyrosine phosphatase that activates Src family kinases associated with B-cell and T-cell antigen receptor signaling by constitutive dephosphorylation of the inhibitory carboxy-terminal tyrosine phosphorylation site. |
| GO:0050853 B cell receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: B cell receptor signaling pathway (ortholog). Reason: CD45 (redundantly with CD148) dephosphorylates the inhibitory tyrosine of SFKs in B cells, enabling BCR signaling. Supporting Evidence: PMID:18249142 Analysis of CD148 and CD45 doubly deficient B cells and macrophages revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SFKs accompanied by substantial alterations in B and myeloid lineage development and defective immunoreceptor signaling. PMID:9197241 CD45 is a leukocyte-specific transmembrane protein tyrosine phosphatase that activates Src family kinases associated with B-cell and T-cell antigen receptor signaling by constitutive dephosphorylation of the inhibitory carboxy-terminal tyrosine phosphorylation site. |
| GO:0050856 regulation of T cell receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Regulation of TCR signaling pathway (ortholog). Reason: CD45 both enables and restrains TCR signaling through differential dephosphorylation of LCK Y505 and Y394. Supporting Evidence: PMID:17719247 These results are explained by a rheostat mechanism whereby CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56(lck) tyrosine kinase phosphorylation sites. PMID:15275963 Despite its clear role in positive regulation of signalling through the activation of the Src family of tyrosine kinases, many reports have shown CD45 to also negatively regulate this process. PMID:31641081 Acute inhibition of Csk revealed that CD45 suppressed ΞΆ-chain phosphorylation and was necessary for a regulatable pool of active Lck, thereby interconnecting the activating and suppressive roles of CD45 that tune antigen discrimination. |
| GO:0050856 regulation of T cell receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Regulation of TCR signaling pathway (ortholog). Reason: CD45 both enables and restrains TCR signaling through differential dephosphorylation of LCK Y505 and Y394. Supporting Evidence: PMID:17719247 These results are explained by a rheostat mechanism whereby CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56(lck) tyrosine kinase phosphorylation sites. PMID:15275963 Despite its clear role in positive regulation of signalling through the activation of the Src family of tyrosine kinases, many reports have shown CD45 to also negatively regulate this process. PMID:31641081 Acute inhibition of Csk revealed that CD45 suppressed ΞΆ-chain phosphorylation and was necessary for a regulatable pool of active Lck, thereby interconnecting the activating and suppressive roles of CD45 that tune antigen discrimination. |
| GO:0050857 positive regulation of antigen receptor-mediated signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of antigen receptor-mediated signaling (ortholog). Reason: Describes the main positive role of CD45 in both T and B cells. Supporting Evidence: PMID:9197241 CD45 is a leukocyte-specific transmembrane protein tyrosine phosphatase that activates Src family kinases associated with B-cell and T-cell antigen receptor signaling by constitutive dephosphorylation of the inhibitory carboxy-terminal tyrosine phosphorylation site. |
| GO:0050857 positive regulation of antigen receptor-mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of antigen receptor-mediated signaling (ortholog). Reason: Describes the main positive role of CD45 in both T and B cells. Supporting Evidence: PMID:9197241 CD45 is a leukocyte-specific transmembrane protein tyrosine phosphatase that activates Src family kinases associated with B-cell and T-cell antigen receptor signaling by constitutive dephosphorylation of the inhibitory carboxy-terminal tyrosine phosphorylation site. |
| GO:0051209 release of sequestered calcium ion into cytosol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Release of sequestered calcium into cytosol (ortholog). Reason: Calcium release is performed by IP3 receptors downstream of PLCG; CD45 acts far upstream. Over-annotation. |
| GO:0051209 release of sequestered calcium ion into cytosol | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Release of sequestered calcium into cytosol (ortholog). Reason: Calcium release is performed by IP3 receptors downstream of PLCG; CD45 acts far upstream. Over-annotation. |
| GO:0051607 defense response to virus | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Defense response to virus (ortholog). Reason: In the source mouse study CD45 negatively regulates interferon/JAK-dependent antiviral responses; the term overstates any participation of CD45 in viral defense. Supporting Evidence: PMID:11201744 Functionally, CD45 negatively regulates interleukin-3-mediated cellular proliferation, erythropoietin-dependent haematopoieisis and antiviral responses in vitro and in vivo. |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of cell cycle (ortholog). Reason: Indirect consequence of lymphocyte activation signals; over-annotation. Supporting Evidence: PMID:1793833 Antibody to CD45 appeared to block the G0(G1) to S phase transition in the cell cycle analysis by propidium iodide staining. |
| GO:0051726 regulation of cell cycle | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Regulation of cell cycle (ortholog). Reason: Indirect consequence of lymphocyte activation signals; over-annotation. Supporting Evidence: PMID:1793833 Antibody to CD45 appeared to block the G0(G1) to S phase transition in the cell cycle analysis by propidium iodide staining. |
| GO:0060369 positive regulation of Fc receptor mediated stimulatory signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of Fc receptor mediated stimulatory signaling (electronic, from mouse). Reason: CD45 and CD148 are both required for Fc receptor signaling in macrophages via SFK activation. Part of the general immunoreceptor role of CD45 in leukocytes beyond T cells. Supporting Evidence: PMID:18249142 The selective defect in the Fc receptor-mediated signaling in DKO BMDM suggests a requisite role of for both CD148 and CD45 in this pathway, but not in Toll-like receptor 4 pathways. |
| GO:0060369 positive regulation of Fc receptor mediated stimulatory signaling pathway | ISS PMID:18249142 Structurally distinct phosphatases CD45 and CD148 both regul... | ACCEPT | Summary: Positive regulation of Fc receptor signaling by sequence similarity to mouse, from the CD45/CD148 study. Reason: As above. Supporting Evidence: PMID:18249142 The selective defect in the Fc receptor-mediated signaling in DKO BMDM suggests a requisite role of for both CD148 and CD45 in this pathway, but not in Toll-like receptor 4 pathways. |
| GO:0070062 extracellular exosome | HDA PMID:12519789 Proteomic and biochemical analyses of human B cell-derived e... | KEEP AS NON CORE | Summary: Detected in B cell-derived exosome proteomes. Reason: Membrane protein carried on exosomes; non-core. Supporting Evidence: PMID:12519789 Mass spectrometric analysis indicated the abundant presence of major histocompatibility complex (MHC) class I and class II, heat shock cognate 70, heat shock protein 90, integrin alpha 4, CD45, moesin |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Detected in B cell-derived exosome proteomes. Reason: Membrane protein carried on exosomes; non-core. |
| GO:0070373 negative regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of ERK1/2 cascade (ortholog). Reason: Raft-localized CD45 opposes TCR signals; downstream readout, non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0070373 negative regulation of ERK1 and ERK2 cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of ERK1/2 cascade (ortholog). Reason: Raft-localized CD45 opposes TCR signals; downstream readout, non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of ERK1/2 cascade (ortholog). Reason: Raft-excluded CD45 promotes ERK-dependent responses; downstream readout, non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of ERK1/2 cascade (ortholog). Reason: Raft-excluded CD45 promotes ERK-dependent responses; downstream readout, non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0071944 cell periphery | IEA GO_REF:0000107 | ACCEPT | Summary: Cell periphery. Reason: Correct, general. |
| GO:0098552 side of membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Side of membrane (ARBA). Reason: Vague but not wrong for a type I membrane protein; non-core. |
| GO:0098857 membrane microdomain | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Membrane microdomain (ortholog). Reason: CD45 partitions between raft and non-raft domains; non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:0098857 membrane microdomain | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Membrane microdomain (ortholog). Reason: CD45 partitions between raft and non-raft domains; non-core. Supporting Evidence: PMID:15661907 We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. |
| GO:1902215 negative regulation of interleukin-4-mediated signaling pathway | IGI PMID:12574355 Human activation-induced cytidine deaminase is induced by IL... | KEEP AS NON CORE | Summary: Anti-CD45 ligation suppressed IL-4 signaling in human B cells. Reason: Specific instance of the JAK phosphatase role; kept as non-core. Supporting Evidence: PMID:12574355 triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID expression, and this CD45-mediated AID inhibition correlated with the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and STAT6 phosphorylations |
| GO:1903979 negative regulation of microglial cell activation | TAS PMID:15095367 Neuronal expression of CD22: novel mechanism for inhibiting ... | KEEP AS NON CORE | Summary: CD45 negatively regulates microglial activation (author statement). Reason: Context-specific myeloid role; non-core. Supporting Evidence: PMID:15095367 We previously demonstrated that the transmembrane protein-tyrosine phosphatase CD45 plays an important role in negatively regulating microglial activation. |
| GO:1904044 response to aldosterone | IEA GO_REF:0000107 | REMOVE | Summary: Response to aldosterone (electronic, rodent). Reason: No evidence or mechanism connecting PTPRC to aldosterone responses; likely an expression-change annotation. |
| GO:1904155 DN2 thymocyte differentiation | TAS PMID:15557316 Phenotypical and functional alterations in the mucosal immun... | MARK AS OVER ANNOTATED | Summary: DN2 thymocyte differentiation, cited to a CD45-null gut mucosa study. Reason: The cited abstract describes gut T cell populations in CD45-null mice and does not address the DN2 stage; the CD45 thymic block is a requirement, not a step CD45 performs. Supporting Evidence: PMID:15557316 These data suggest that CD45 is required for the development of the specialized T cell populations within the gut environment as has been previously shown for thymic development. |
| GO:2000473 positive regulation of hematopoietic stem cell migration | IMP PMID:21911094 CD45 regulates homing and engraftment of immature normal and... | KEEP AS NON CORE | Summary: CD45 blockade impaired motility and homing of human CD34+ cells. Reason: Antibody/inhibitor phenotype indicating a role in progenitor trafficking; non-core. Supporting Evidence: PMID:21911094 Blocking CD45 inhibited homing and repopulation by immature human CD34(+) cells as well as homing of primary patient leukemic cells. |
| GO:2000648 positive regulation of stem cell proliferation | IMP PMID:21911094 CD45 regulates homing and engraftment of immature normal and... | MARK AS OVER ANNOTATED | Summary: CD45 blockade reduced progenitor recovery in transplanted mice. Reason: The study does not measure stem cell proliferation directly; over-annotation. Supporting Evidence: PMID:21911094 In addition, CD45 inhibition negatively affected development of hematopoietic progenitors in vitro and their recovery in transplanted recipients in vivo |
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Download this section (compressed HTML)Q: Does CD45 have a physiological ligand that regulates its phosphatase activity? Galectin-1, CD22 and CLEC10A bind it and viral proteins (CMV UL11, adenovirus E3/49K) inhibit it, the latter by dimerizing the ectodomain (PMID:39454026), yet no host ligand is established. The answer bears on whether 'transmembrane receptor protein tyrosine phosphatase activity' (which requires signal binding) describes CD45 or is only a structural classification.
Q: Do the CD45RA/RB/RC versus CD45RO isoforms differ in catalytic activity, substrate access or dimerization in human T cells, or only in their segregation from the TCR at contacts?
Q: Is the reported beta-catenin binding (IPI from PMID:12370829) a curation error, since the abstract states CD45 catalytic domains did not detectably bind catenins?
Experiment: Quantitative phosphoproteomics in primary human T, B and myeloid cells after acute, chemically induced inactivation of CD45 (e.g. an engineered inhibitor-sensitive allele) to distinguish direct substrates (LCK Y505/Y394, JAKs, ITAMs) from indirect effects.
Type: phosphoproteomics
Experiment: Reconstituted supported-bilayer assays with CD45 isoforms of different ectodomain length to measure how ectodomain size controls exclusion from TCR-pMHC close contacts and the resulting ITAM phosphorylation.
Type: in vitro reconstitution
Experiment: Screen for endogenous ligands that dimerize or cluster the CD45 ectodomain (as adenovirus E3/49K does), and test whether they change CD45 catalytic activity and TCR signaling thresholds in primary human T cells.
Type: ligand screening
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