Affinage

Showing ANPEP — LAP1 is a alias.

ANPEP

Aminopeptidase N · UniProt P15144

Length
967 aa
Mass
109.5 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANPEP/CD13 is a cell-surface, zinc-dependent aminopeptidase N that doubles as a multifunctional signaling and adhesion receptor governing vascular morphogenesis, myeloid trafficking, endocytic regulation, and epithelial polarity (PMID:2564851, PMID:11157481, PMID:23997214). It is a type II integral membrane protein anchored by a single N-terminal hydrophobic signal-anchor segment, with a large extracellular C-terminal domain carrying the zinc-binding metalloprotease consensus that sequentially hydrolyzes neutral N-terminal residues from peptides such as Leu- and Met-enkephalin, while substance P and bradykinin act as natural inhibitors (PMID:2564851, PMID:7535053). Its enzymatic activity drives a defined subset of functions—chemoattraction of CD4+ T cells, degradation of type-IV collagen to enable tumor invasion, and bradykinin B2 receptor internalization with downstream Cdc42 activation and filopodia formation during endothelial invasion and angiogenic tube formation (PMID:10806168, PMID:8097496, PMID:17363739, PMID:11157481). Many of its roles, however, are peptidase-independent: a conserved cytoplasmic tyrosine is Src-phosphorylated upon CD13 cross-linking to activate FAK/ERK and recruit IQGAP1 and α-actinin, linking CD13 to the cytoskeleton to drive monocyte adhesion, homotypic aggregation, and inflammatory trafficking through its C-terminal domain, as well as FAK-dependent adhesion of mesenchymal and muscle satellite stem cells (PMID:23997214, PMID:18495788, PMID:16415167, PMID:24627994, PMID:24409152, PMID:24307555). CD13 also serves as a primary phagocytic receptor sufficient to confer particle uptake on non-phagocytic cells via actin, PI3K, and Syk, and as a negative regulator of TLR4 endocytic (IRF-3) signaling and receptor-mediated antigen uptake in dendritic cells through co-internalization into Rab5 endosomes (PMID:25934926, PMID:25801433, PMID:22544935). Its short intracellular domain partners with Par6 to couple apical cargo to Rab11-endosomes during epithelial lumen formation (PMID:34349123). CD13 is the cellular receptor for human coronavirus 229E and porcine coronaviruses (PEDV, PDCoV), with receptor activity governed by an N-glycosylation determinant and largely independent of peptidase activity (PMID:9658094, PMID:11559807, PMID:20074871, PMID:32056711). In cancer, CD13 stabilizes HDAC5 to drive an LSD1–NF-κB axis and activates P38/Hsp27/CREB–ATG7-dependent autophagy, promoting proliferation, invasion, and chemoresistance (PMID:33377659, PMID:32571958).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1989 High

    Establishing that the myeloid antigen CD13/gp150 is identical to aminopeptidase N defined the protein as a single-pass type II membrane metallopeptidase, unifying an immunological marker with an enzymatic activity.

    Evidence cDNA cloning, retroviral expression in fibroblasts, and N-terminal protein sequencing identifying the signal-anchor and zinc-binding consensus

    PMID:2428842 PMID:2564851

    Open questions at the time
    • Catalytic mechanism and substrate spectrum not yet defined
    • Physiological functions beyond peptidase activity unaddressed
  2. 1995 High

    Defining the natural substrates and inhibitors demonstrated that CD13 sequentially degrades enkephalins and is blocked by proline-bearing peptides, grounding its role in regulatory-peptide turnover.

    Evidence In vitro enzymatic assays with purified pig APN and live HL60 cells, with Km/Ki determination for natural peptides

    PMID:7535053

    Open questions at the time
    • Physiological consequence of enkephalin/peptide cleavage in vivo not established
    • Full endogenous substrate repertoire incomplete
  3. 1998 High

    Transcriptional control of CD13 was mapped to DMP1, c-Myb/Ets-1 cooperation and growth/hypoxia signals, explaining its inducible expression in angiogenesis and myeloid contexts.

    Evidence Promoter reporter assays, EMSA, dominant-negative/deletion constructs; hypoxia and growth-factor promoter responsiveness in angiogenesis models

    PMID:11157481 PMID:9786929

    Open questions at the time
    • Relative contribution of each transcription factor in vivo unclear
    • Link between promoter regulation and specific physiological outputs not fully resolved
  4. 1998 High

    Identification of human APN as the HCoV-229E receptor, refined by an N-glycosylation determinant, revealed a peptidase-independent role of CD13 as a coronavirus entry factor and explained species specificity.

    Evidence Antibody-blocking virus attachment/infection assays and site-directed mutagenesis of the 288–295 glycosylation site

    PMID:11559807 PMID:9658094

    Open questions at the time
    • Structural basis of virus–APN binding not resolved
    • Whether enzymatic activity contributes at all to entry not addressed here
  5. 2001 High

    CD13 was shown to be functionally essential for capillary tube formation and to act through B2R internalization and Cdc42 activation, establishing an angiogenic signaling role requiring its catalytic activity.

    Evidence In vitro/in vivo angiogenesis assays with CD13 antagonists; B2R internalization, Cdc42 activation, and wild-type vs. catalytically inactive CD13 rescue

    PMID:11157481 PMID:17363739

    Open questions at the time
    • Direct enzymatic substrate driving B2R internalization not identified
    • Mechanism linking peptidase activity to membrane organization unresolved
  6. 2010 High

    A CD13-null mouse separated essential from dispensable functions, showing CD13 is required for antibody-dependent monocyte adhesion but not for hematopoietic development, phagocytosis, or antigen presentation in vivo.

    Evidence Genetic knockout with hematopoietic profiling, adhesion, phagocytosis, antigen presentation, and inflammatory disease models

    PMID:20430777

    Open questions at the time
    • Redundancy with other aminopeptidases may mask phenotypes
    • Discrepancy with later phagocytic-receptor findings not reconciled
  7. 2014 High

    CD13 was established as a peptidase-independent adhesion/signaling receptor: its cytoplasmic tyrosine and C-terminal domain drive Src/FAK/ERK signaling, IQGAP1/α-actinin cytoskeletal coupling, and myeloid and stem-cell adhesion and trafficking in vivo.

    Evidence Y→F mutagenesis, reciprocal Co-IP, kinase inhibition, chimeric domain mapping, KO MSC/satellite cells, and adoptive-transfer/ischemia models

    PMID:23997214 PMID:24307555 PMID:24409152 PMID:24627994

    Open questions at the time
    • Upstream trigger for physiological CD13 clustering in vivo unclear
    • Identity of the homotypic or heterotypic adhesion ligand incomplete
  8. 2015 High

    CD13 was defined as a negative regulator of endocytic innate signaling and as a sufficient primary phagocytic receptor, revealing dual roles in controlling uptake and downstream IRF-3/p38/Akt signaling.

    Evidence CD13 KO dendritic cells/mice, co-internalization imaging into Rab5 endosomes, reconstitution in HEK293, and PI3K/Syk inhibitor controls

    PMID:22544935 PMID:25801433 PMID:25934926

    Open questions at the time
    • Molecular mechanism by which CD13 restrains TLR4/antigen-receptor endocytosis not defined
    • How phagocytic-receptor function reconciles with earlier KO phagocytosis data unresolved
  9. 2020 Medium

    In hepatocellular carcinoma CD13 was placed at the head of signaling cascades—HDAC5–LSD1–NF-κB stabilization and P38/Hsp27/CREB–ATG7 autophagy—driving proliferation, invasion, and chemoresistance.

    Evidence Co-IP/LC-MS/MS, promoter-binding and autophagy assays, and xenograft/PDX models with CD13 inhibition

    PMID:32571958 PMID:33377659

    Open questions at the time
    • Whether CD13 acts as scaffold or signal initiator mechanistically unclear
    • Single-lab findings without independent replication
  10. 2021 High

    CD13 was identified as an apical polarity determinant that couples cargo to Rab11-endosomes via its short intracellular domain and Par6 association, a peptidase-independent role in epithelial lumen formation.

    Evidence CD13 KO cells, live imaging, Par6 Co-IP, Rab11-endosome colocalization, domain mutagenesis, and 3D lumen assays

    PMID:34349123

    Open questions at the time
    • Direct intracellular-domain interaction partner mediating Rab11 coupling not defined
    • Relationship between apical polarity role and tube/lumen angiogenesis role unintegrated
  11. 2023 Medium

    In stroke, CD13 was shown to bidirectionally regulate injury, promoting acute myeloid transmigration while supporting chronic recovery angiogenesis through CXCL12/CXCR4.

    Evidence CD13 KO mice in MCAO model with flow cytometry, vascular quantification, and behavioral testing

    PMID:37817190

    Open questions at the time
    • CXCL12/CXCR4 link partially inferred rather than mechanistically proven
    • Cell-type contribution (endothelial vs. myeloid CD13) not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CD13's distinct functional modes—enzymatic peptide processing, virus receptor activity, cytoplasmic signaling, endocytic regulation, and apical polarity—are coordinated within a single molecule and which are dominant in specific physiological tissues.
  • No structural model integrating catalytic, receptor, and scaffolding functions
  • No unified accounting of when peptidase activity is required versus dispensable
  • Cell-type-specific division of CD13 functions in vivo not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 4 GO:0060089 molecular transducer activity 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0060090 molecular adaptor activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0005576 extracellular region 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-5653656 Vesicle-mediated transport 4
Partners
ACTNFCGR1AHDAC5IQGAP1PAR6TLR4TM4SF1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 CD13 (gp150) is identical to aminopeptidase N: it is an integral membrane protein with a single 24 amino acid N-terminal hydrophobic segment that serves as both signal for membrane insertion and stable membrane-spanning anchor, with the remainder forming a large extracellular C-terminal domain containing the zinc-binding metalloprotease pentapeptide consensus sequence. cDNA cloning, retroviral expression in mouse fibroblasts, amino-terminal protein sequence analysis The Journal of clinical investigation High 2564851
1986 The human myeloid membrane antigen gp150 gene was molecularly cloned, shown to encode a 4.0-kb polyadenylated transcript, mapped to chromosome 15q25-26, and shown to be biologically active when transfected into NIH 3T3 cells; gp130 was identified as a carbohydrate-differing precursor to the mature cell-surface gp150. Bacteriophage lambda library cloning, DNA transfection, in situ hybridization, pulse-chase metabolic labeling, biochemical analysis The Journal of clinical investigation High 2428842
2001 CD13/APN is functionally essential for capillary tube (lumen) formation during angiogenesis; functional antagonists of CD13/APN block tube formation but not proliferation of primary vascular endothelial cells, and CD13/APN expression is transcriptionally upregulated by hypoxia and angiogenic growth factors via elements in the proximal promoter. In vitro tube formation assay with CD13 antagonists, reporter assays with CD13 proximal promoter, in vivo models (retinal neovascularization, chorioallantoic membrane angiogenesis, xenograft tumor growth) Blood High 11157481
2007 CD13 controls endothelial cell invasion and filopodia formation by facilitating bradykinin B2 receptor (B2R) internalization and downstream Cdc42 activation at the plasma membrane; CD13 inhibition blocks B2R internalization, abrogating invasion and filopodia; wild-type but not catalytically inactive mutant CD13 restores membrane protein organization, indicating peptidase activity is required for CD13's regulatory function. B2R internalization assay, Cdc42 activation assay, filopodia imaging, cholesterol depletion/repletion experiments, expression of wild-type vs. enzymatic mutant CD13 Blood High 17363739
1998 The CD13/APN promoter is transcriptionally activated by the DMP1 transcription factor binding to a specific consensus site; DMP1 activation of CD13 requires intact DNA-binding and transactivation domains of DMP1 and is antagonized by D-type cyclins in a CDK-independent manner; CD13 expression is additionally co-regulated by cooperative interaction between c-Myb and Ets-1. Promoter reporter assays, electrophoretic mobility shift assay (EMSA), dominant-negative and deletion mutant analyses of DMP1 and cyclin constructs The Journal of biological chemistry High 9786929
2001 An N-glycosylation site at amino acids 288–295 of human APN is a critical molecular determinant of species-specific coronavirus receptor activity: introduction of an N-glycosylation sequon at position 291–293 abolished HCoV-229E receptor activity of hAPN, while single-amino-acid revertants removing this sequon fully restored binding and receptor activity. Site-directed mutagenesis of hAPN, virus binding and infection assays in transfected cells Journal of virology High 11559807
1998 Human APN (CD13) serves as the functional cellular receptor for human coronavirus 229E (HCoV-229E) in neural cells: hAPN is expressed on neuronal and glial cell line surfaces, anti-hAPN monoclonal antibody WM15 inhibits radiolabeled HCoV-229E attachment and infection, and attachment level correlates with hAPN surface amount. Flow cytometry for receptor expression, radiolabeled virus attachment assay, antibody blocking, indirect immunofluorescence infection assay Journal of virology High 9658094
2013 CD13 cross-linking induces phosphorylation of Src, FAK, and ERK, and CD13 itself is phosphorylated on its cytoplasmic tyrosine in a Src-dependent manner; CD13 is constitutively associated with the scaffolding protein IQGAP1, and cross-linking induces complex formation with α-actinin, linking CD13 to the cytoskeleton; mutation of the conserved cytoplasmic tyrosine to phenylalanine abolishes adhesion, downstream signaling, and cytoskeletal changes; phospho-CD13 is present in vivo in peritoneal exudate cells, and monocytes expressing the mutant CD13 show severely impaired migration into the inflamed peritoneum. Phosphoprotein analysis, Src/FAK/ERK inhibition assays, site-directed mutagenesis (Y→F), co-immunoprecipitation with IQGAP1 and α-actinin, adoptive transfer in murine peritonitis model Journal of immunology High 23997214
2008 CD13 ligation and clustering by mAb or viral ligands induces myeloid/endothelial cell adhesion via signal transduction-dependent monocytic cytoskeletal rearrangement and filopodia formation; soluble recombinant CD13 blocks this adhesion; CD13 molecules from monocytic and endothelial cells co-immunoprecipitate, indicating direct homotypic CD13–CD13 interaction; anti-CD13 antibodies reduce leukocyte infiltration in murine peritonitis. Antibody-mediated cross-linking adhesion assays, recombinant CD13 blocking, co-immunoprecipitation, adhesion to immobilized recombinant CD13, murine peritonitis model Journal of leukocyte biology High 18495788
2015 CD13 negatively regulates TLR4 endocytic signaling: CD13 is co-internalized with TLR4, CD14, and dynamin into Rab5+ early endosomes upon LPS stimulation; CD13 KO dendritic cells show enhanced p-IRF-3 activation and transcription of IRF-3 target genes in response to TLR4 ligands while TLR4 surface signaling is unaffected; CD13 KO mice show enhanced IFNβ-mediated JAK-STAT signaling, elevated iNOS, and increased oxidative stress and tissue injury upon ischemia; CD13 and TLR4 co-immunoprecipitate in activated macrophages. CD13 KO mice, co-immunoprecipitation, IRF-3 phosphorylation assays, endosomal co-localization imaging, in vivo ischemia model, flow cytometry Journal of immunology High 25801433
2012 CD13 negatively regulates receptor-mediated, dynamin-dependent endocytosis of antigens (OVA, transferrin) in dendritic cells but not fluid-phase or phagocytic uptake; CD13 is co-internalized with antigen but does not co-immunoprecipitate with antigen receptors; CD13 KO DCs show dysregulated phosphorylation of p38MAPK and Akt; lack of CD13 significantly enhances T cell responses to soluble OVA antigen in vivo. CD13 KO mice, in vitro antigen uptake assays, co-immunoprecipitation (negative), kinase inhibition, in vivo T cell response assays Journal of immunology High 22544935
2006 CD13 antibody-mediated ligation induces apoptosis in AML cells independently of its APN enzymatic activity: anti-CD13 mAbs (MY7, SJ1D1, WM15) cause sub-G1 accumulation, DNA fragmentation, phosphatidylserine externalization, mitochondrial depolarization, Bcl-2/Mcl-1 downregulation, Bax upregulation, and activation of caspase-9, caspase-8, and caspase-3; enzymatic inhibitors of APN alone are ineffective; internalization of CD13–mAb complex precedes mitochondrial events. Flow cytometry (cell cycle, apoptosis markers), Western blotting (Bcl-2, Bax, caspases), caspase inhibitor experiments, comparison of enzyme-blocking vs. non-blocking antibodies FASEB journal High 21566207
2005 CD13 associates with tumor-associated antigen L6 (TAL6) in a co-immunoprecipitable complex on lung cancer cells; CD13 enhances cancer cell migration and invasion; expression of enzymatically inactive CD13 mutant also significantly enhances cell migration, indicating that CD13's effect on motility does not strictly depend on its peptidase activity. Co-immunoprecipitation, antibody-mediated co-patching immunofluorescence, Transwell migration/invasion assays, enzymatic inhibitors, catalytically inactive CD13 mutant expression International journal of cancer High 15812828
2006 CD13 mediates homotypic aggregation (HA) of monocytic cells via antibody cross-linking in a tyrosine kinase- and MAP kinase-dependent manner, independently of integrin signaling and independently of CD13 enzymatic activity; during HA, CD13 actively redistributes to cell–cell contact zones as observed by live cell imaging. Homotypic aggregation assays, enzyme inhibitor controls vs. kinase inhibitors, live cell imaging, colchicine/cytoskeletal perturbation Journal of leukocyte biology Medium 16415167
2005 CD13/APN functionally interacts with FcγRI on monocytes: during FcγR-mediated phagocytosis, CD13 redistributes to the phagocytic cup and is co-internalized into phagosomes; co-cross-linking of CD13 with FcγRI increases the level and duration of Syk phosphorylation; FcγRI and CD13 co-localize in zones of cellular polarization. Confocal microscopy of phagocytosis, Syk phosphorylation assays, co-cross-linking with specific mAbs, co-localization imaging Journal of leukocyte biology Medium 15758076
1995 Purified and native membrane-bound CD13/APN sequentially and completely hydrolyzes Leu-enkephalin and Met-enkephalin from the amino terminus; substance P and bradykinin are natural inhibitors of CD13/APN (Ki = 0.44 µM and 9.4 µM, respectively) due to their N-terminal proline at the second residue, which prevents hydrolysis. In vitro enzymatic assay with purified pig APN and live HL60 cells, Km and Ki measurements with natural peptide substrates and inhibitors Biochemical and biophysical research communications High 7535053
1993 Cell-surface aminopeptidase N/CD13 is involved in tumor cell invasion through degradation of type-IV collagen: anti-CD13 mAb WM15 inhibits both aminopeptidase activity and type-IV collagen degradation by tumor cells, and reduces invasion through Matrigel in a concentration-dependent manner without affecting adhesion or migration. Matrigel invasion assay, type-IV collagen degradation assay, aminopeptidase activity assay with specific mAb inhibition International journal of cancer Medium 8097496
2009 Porcine APN receptor density directly determines PEDV infection efficiency: overexpression of recombinant pAPN in ST cells rescues productive PEDV infection; the enzymatic active motif-null mutant pAPN retains receptor activity and supports viral production; APN inhibitor blocking the protease active site has no effect on viral infection, showing enzymatic activity is dispensable for PEDV receptor function. Stable cell line overexpression, enzymatic active-site mutant APN expression, aminopeptidase inhibitor treatment, viral infection/replication assays Veterinary microbiology High 20074871
2019 APN (ANPEP) is a receptor for porcine deltacoronavirus (PDCoV) in porcine alveolar macrophages (PAMs): ANPEP knockout pigs generated by CRISPR/Cas9 show PAM resistance to PDCoV infection, but lung-derived fibroblast-like cells from the same KO pigs remain fully permissive, indicating APN is necessary in macrophages but dispensable in fibroblast cells for PDCoV infection. CRISPR/Cas9 ANPEP knockout pigs, viral infection of primary cell types, ex vivo and in vivo PDCoV challenge Virology High 32056711
2020 CD13 interacts with HDAC5 to promote its protein stability; stabilized HDAC5 deacetylates LSD1 to stabilize it; LSD1 then decreases NF-κB p65 methylation, leading to p65 protein stability and NF-κB pathway activation; this CD13–HDAC5–LSD1–NF-κB axis promotes HCC proliferation, invasion, and sorafenib resistance. Co-immunoprecipitation, LC-MS/MS, Western blotting, xenograft models, patient-derived xenograft models Clinical and translational medicine Medium 33377659
2020 CD13 overexpression activates the P38/Hsp27/CREB signaling pathway; CREB binds the ATG7 promoter to induce autophagy; this CD13-driven autophagy promotes HCC chemoresistance; CD13 inhibition downregulates ATG7, autophagy, and tumor growth in vivo. Western blotting, CREB-ATG7 promoter binding assay, autophagy assays, in vivo xenograft models with CD13 inhibitor The Journal of pharmacology and experimental therapeutics Medium 32571958
2014 CD13 regulates mesenchymal stem cell (MSC) adhesion and migration via FAK activation: CD13 KO MSCs show impaired adhesion and migration on extracellular matrices, decreased phospho-FAK levels, and cytoskeletal alterations; CD13 antibody cross-linking of human MSCs increases adhesion to endothelial monolayers and induces FAK activation; CD13 KO MSCs show significantly poorer tissue repair in ischemic limb injury with reduced vascularization. CD13 KO mice, cell adhesion/migration assays, FAK phosphorylation assay, antibody cross-linking, in vivo ischemic limb model with cell injection Frontiers in physiology High 24409152
2014 CD13 is required for muscle satellite stem cell anchorage and differentiation timing: CD13 KO muscle shows markedly reduced satellite cell numbers, impaired satellite cell adhesion, and accelerated differentiation; CD13 co-localizes with Pax7 on satellite cells; phospho-FAK and ERK levels are reduced in injured CD13 KO muscle. CD13 KO mice, satellite cell isolation and characterization, adhesion assays, differentiation assays, immunofluorescence co-localization, Western blotting for FAK/ERK Stem cells Medium 24307555
2015 CD13 is a primary phagocytic receptor in human macrophages and monocytic cells: hCD13 expression alone in non-phagocytic HEK293 cells is sufficient to enable internalization of large particles bound through CD13; CD13-mediated phagocytosis is independent of FcγRs, CR3, and most phagocytic receptors, independent of CD13 enzymatic activity, but requires actin rearrangement, PI3K activation, and partial Syk activation; CD13 cross-linking induces pSyk and ROS production. Phagocytosis assays with receptor-specific opsonization, CD13 expression in non-phagocytic HEK293 cells, pharmacological inhibitors of PI3K and Syk, actin disruption, ROS measurement Journal of leukocyte biology High 25934926
2014 CD13-dependent monocyte/endothelial adhesion is mediated by the C-terminal domain of CD13; lack of either monocytic or endothelial CD13 reduces myeloid cell trafficking into sites of inflammation in vivo; CD13 expression is enriched on pro-inflammatory monocyte subsets. Adoptive transfer of WT and CD13 KO myeloid cells into thioglycollate-challenged mice, chimeric CD13 (mouse/human) constructs identifying C-terminal domain requirement, flow cytometry of monocyte subsets Immunology Medium 24627994
2000 CD13/APN enzymatic activity is responsible for its chemoattractant function for CD4+ T lymphocytes: soluble CD13/APN induces chemotactic migration of lymphocytes (more so for CD4+ than CD8+ T cells), and the aminopeptidase inhibitor bestatin abolishes this chemotactic activity. In vitro chemotaxis assay, bestatin inhibition of APN activity, BALF chemotaxis assay from sarcoidosis patients American journal of respiratory and critical care medicine Medium 10806168
2006 Cell-surface CD13/APN regulates TNFα-induced neutrophil apoptosis by controlling shedding of TNFRI: APN inhibition (actinonin, bestatin) augments TNFα-induced killing and prevents TNFRI shedding, resulting in enhanced TNFα signaling; an inverse correlation exists between neutrophil APN activity and sensitivity to TNFα-induced apoptosis. Neutrophil apoptosis assays, TNFRI shedding measurement, APN activity measurement, pharmacological APN inhibitors The Journal of biological chemistry Medium 16533817
2002 High cell-surface CD13/aminopeptidase N activity enables leukemic cells to resist endothelial IL-8-induced apoptosis; K562 cells transfected with CD13 acquire resistance to IL-8-induced apoptosis; aminopeptidase inhibitor bestatin restores IL-8-induced apoptosis in CD13-overexpressing cells and increases endothelial IL-8 secretion. CD13 transfection into K562 cells, apoptosis assays, aminopeptidase inhibitor bestatin treatment, co-culture with endothelial cells, IL-8 ELISA Journal of the National Cancer Institute Medium 12096087
2021 CD13 localizes to the apical membrane and associates with Par6 as part of an apical polarity complex; CD13 is required to couple apical protein cargo to Rab11-endosomes and for capture of endosomes at the apical initiation site during epithelial lumen formation; this polarity function utilizes the short intracellular domain of CD13 but is independent of peptidase activity. CD13 KO cell lines, live imaging, co-immunoprecipitation with Par6, Rab11-endosome colocalization assay, domain deletion/mutation constructs, 3D lumen formation assay Nature communications High 34349123
1993 CD13/aminopeptidase N activity is present in soluble form in cell-free plasma and represents the predominant quantitative aminopeptidase N activity in flowing blood; immunoaffinity-isolated plasma CD13 has similar electrophoretic characteristics to cell-derived material; lymphocyte-associated aminopeptidase N-like activity is not inhibitable by anti-CD13 antibodies, suggesting a distinct non-CD13 enzyme. Aminopeptidase N functional assay with chromogenic substrates, anti-CD13 mAb inhibition, immunoaffinity purification from plasma, SDS-PAGE, cell fractionation Experimental hematology Medium 7902291
2010 In a CD13 null mouse, lack of CD13 completely ablates anti-CD13-dependent monocyte adhesion to wild-type endothelial cells, but CD13 is dispensable for normal hematopoietic development, proliferation, phagocytosis, and antigen presentation; a slight decrease in actin-independent erythrocyte uptake was observed in CD13 KO cells. CD13 null mouse generation, hematopoietic profiling, monocyte adhesion assay, in vitro phagocytosis and antigen presentation assays, inflammatory disease models Journal of leukocyte biology High 20430777
2023 CD13 facilitates acute post-stroke monocyte and neutrophil transmigration into the brain; CD13 KO mice show reduced acute infarct volume; however, loss of CD13 impairs chronic post-stroke angiogenesis and recovery, associated with reduced CXCL12/CXCR4 signaling and reduced CD13+/lectin+ blood vessels at day 15 post-stroke. CD13 KO mice, MCAO stroke model, flow cytometry of infiltrating myeloid cells, CXCL12/CXCR4 quantification, angiogenesis assessment, behavioral testing Journal of neuroinflammation Medium 37817190

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N. The Journal of clinical investigation 467 2564851
2008 The moonlighting enzyme CD13: old and new functions to target. Trends in molecular medicine 337 18603472
1993 Role of aminopeptidase N (CD13) in tumor-cell invasion and extracellular matrix degradation. International journal of cancer 321 8097496
2001 CD13/APN is activated by angiogenic signals and is essential for capillary tube formation. Blood 275 11157481
2011 Aminopeptidase N (CD13) as a target for cancer chemotherapy. Cancer science 273 21205077
1994 Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid. Blood 230 7949141
2006 Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects. Medicinal research reviews 206 16216010
1999 CD13--not just a marker in leukemia typing. Immunology today 202 10098327
1992 Generation of signals activating neutrophil functions by leukocyte integrins: LFA-1 and gp150/95, but not CR3, are able to stimulate the respiratory burst of human neutrophils. The Journal of cell biology 177 1346398
1998 Diadenosine oligophosphates (Ap(n)A), a novel class of signalling molecules? FEBS letters 175 9607303
2020 Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia. Blood 171 31951650
2003 Clinical significance of aminopeptidase N/CD13 expression in human pancreatic carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 109 12684426
2007 CD13/APN regulates endothelial invasion and filopodia formation. Blood 95 17363739
2001 Molecular determinants of species specificity in the coronavirus receptor aminopeptidase N (CD13): influence of N-linked glycosylation. Journal of virology 92 11559807
2004 Murine gammaherpesvirus 68 lacking gp150 shows defective virion release but establishes normal latency in vivo. Journal of virology 88 15113892
2009 Contribution of the porcine aminopeptidase N (CD13) receptor density to porcine epidemic diarrhea virus infection. Veterinary microbiology 86 20074871
2020 CD13 promotes hepatocellular carcinogenesis and sorafenib resistance by activating HDAC5-LSD1-NF-κB oncogenic signaling. Clinical and translational medicine 81 33377659
2010 Critical role of flanking residues in NGR-to-isoDGR transition and CD13/integrin receptor switching. The Journal of biological chemistry 74 20064928
2008 CD13 is a novel mediator of monocytic/endothelial cell adhesion. Journal of leukocyte biology 73 18495788
2005 CD13 (aminopeptidase N) can associate with tumor-associated antigen L6 and enhance the motility of human lung cancer cells. International journal of cancer 67 15812828
2020 CD13/Aminopeptidase N Is a Potential Therapeutic Target for Inflammatory Disorders. Journal of immunology (Baltimore, Md. : 1950) 62 31848300
2005 Tumor-specific gene delivery mediated by a novel peptide-polyethylenimine-DNA polyplex targeting aminopeptidase N/CD13. Human gene therapy 61 15703489
2003 PepN is the major aminopeptidase in Escherichia coli: insights on substrate specificity and role during sodium-salicylate-induced stress. Microbiology (Reading, England) 61 14663077
1991 Characterization and overexpression of the Lactococcus lactis pepN gene and localization of its product, aminopeptidase N. Applied and environmental microbiology 59 1685079
1996 Identification and characterization of murine gammaherpesvirus 68 gp150: a virion membrane glycoprotein. Journal of virology 55 8648686
1985 Transfer and expression of the gene encoding a human myeloid membrane antigen (gp150). The Journal of clinical investigation 54 3973018
2004 The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer. International journal of oncology 53 15492809
2015 CD13 restricts TLR4 endocytic signal transduction in inflammation. Journal of immunology (Baltimore, Md. : 1950) 51 25801433
2011 Enhanced expression of CD13 in vessels of inflammatory and neoplastic tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 51 21339174
1986 Nucleotide sequence of the pepN gene encoding aminopeptidase N of Escherichia coli. Gene 51 2436977
2000 The membrane glycoprotein gp150 is encoded by the lagC gene and mediates cell-cell adhesion by heterophilic binding during Dictyostelium development. Developmental biology 49 11071787
1992 Characterization of the Lactococcus lactis pepN gene encoding an aminopeptidase homologous to mammalian aminopeptidase N. FEBS letters 49 1352755
2019 The use of cells from ANPEP knockout pigs to evaluate the role of aminopeptidase N (APN) as a receptor for porcine deltacoronavirus (PDCoV). Virology 48 32056711
2011 Aminopeptidase-N/CD13 is a potential proapoptotic target in human myeloid tumor cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 48 21566207
2006 CD13 in cell adhesion: aminopeptidase N (CD13) mediates homotypic aggregation of monocytic cells. Journal of leukocyte biology 48 16415167
1996 CD13-specific autoimmunity in cytomegalovirus-infected immunocompromised patients. Transplantation 48 8610387
1986 Molecular cloning, expression, and chromosomal localization of the gene encoding a human myeloid membrane antigen (gp150). The Journal of clinical investigation 48 2428842
2001 Inhibition of aminopeptidase N (AP-N) and urokinase-type plasminogen activator (uPA) by zinc suppresses the invasion activity in human urological cancer cells. Biological & pharmaceutical bulletin 47 11256475
2013 Tyrosine phosphorylation of CD13 regulates inflammatory cell-cell adhesion and monocyte trafficking. Journal of immunology (Baltimore, Md. : 1950) 46 23997214
2008 DP IV/CD26, APN/CD13 and related enzymes as regulators of T cell immunity: implications for experimental encephalomyelitis and multiple sclerosis. Frontiers in bioscience : a journal and virtual library 46 17981717
1995 Substance P and bradykinin are natural inhibitors of CD13/aminopeptidase N. Biochemical and biophysical research communications 45 7535053
2021 Is tumour-expressed aminopeptidase N (APN/CD13) structurally and functionally unique? Biochimica et biophysica acta. Reviews on cancer 43 34695533
2002 Leukemic cell-surface CD13/aminopeptidase N and resistance to apoptosis mediated by endothelial cells. Journal of the National Cancer Institute 43 12096087
2006 Expression of aminopeptidase N/CD13 in human ovarian cancers. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 42 17009972
1998 Regulation of the CD13/aminopeptidase N gene by DMP1, a transcription factor antagonized by D-type cyclins. The Journal of biological chemistry 42 9786929
1993 CD13 (GP150; aminopeptidase-N): predominant functional activity in blood is localized to plasma and is not cell-surface associated. Experimental hematology 42 7902291
2007 The murine gammaherpesvirus-68 gp150 acts as an immunogenic decoy to limit virion neutralization. PloS one 40 17684552
2002 PepN, the major Suc-LLVY-AMC-hydrolyzing enzyme in Escherichia coli, displays functional similarity with downstream processing enzymes in Archaea and eukarya. Implications in cytosolic protein degradation. The Journal of biological chemistry 40 12482750
1998 Involvement of aminopeptidase N (CD13) in infection of human neural cells by human coronavirus 229E. Journal of virology 40 9658094
2015 Expression and clinical significance of aminopeptidase N/CD13 in non-small cell lung cancer. Journal of cancer research and therapeutics 39 25879366
2005 Aminopeptidase N (CD13) functionally interacts with FcgammaRs in human monocytes. Journal of leukocyte biology 39 15758076
2000 CD13/N-aminopeptidase is involved in the development of dendritic cells and macrophages from cord blood CD34(+) cells. Blood 38 10627449
2000 CD13/aminopeptidase N, a novel chemoattractant for T lymphocytes in pulmonary sarcoidosis. American journal of respiratory and critical care medicine 38 10806168
2012 CD13 regulates dendritic cell cross-presentation and T cell responses by inhibiting receptor-mediated antigen uptake. Journal of immunology (Baltimore, Md. : 1950) 37 22544935
2005 Progress in the development of aminopeptidase N (APN/CD13) inhibitors. Current medicinal chemistry. Anti-cancer agents 37 15992355
1993 Cloning, DNA sequence analysis and partial characterization of pepN, a lysyl aminopeptidase from Lactobacillus delbrückii ssp. lactis DSM7290. European journal of biochemistry 37 8223547
2010 CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse. Journal of leukocyte biology 36 20430777
1992 Purification and partial characterization of a cell adhesion molecule (gp150) involved in postaggregation stage cell-cell binding in Dictyostelium discoideum. The Journal of biological chemistry 36 1577768
2014 CD13 promotes mesenchymal stem cell-mediated regeneration of ischemic muscle. Frontiers in physiology 35 24409152
1991 CD-13 ('gp150'; aminopeptidase-N): co-expression on endothelial and haemopoietic cells with conservation of functional activity. Immunology and cell biology 35 1723966
2013 Characterization of the recombinant exopeptidases PepX and PepN from Lactobacillus helveticus ATCC 12046 important for food protein hydrolysis. PloS one 34 23894590
2015 CD13 mediates phagocytosis in human monocytic cells. Journal of leukocyte biology 33 25934926
2005 Cells of human aminopeptidase N (CD13) transgenic mice are infected by human coronavirus-229E in vitro, but not in vivo. Virology 33 15840518
2006 Aminopeptidase N (CD13) regulates tumor necrosis factor-alpha-induced apoptosis in human neutrophils. The Journal of biological chemistry 32 16533817
2006 Detection of cytotoxic CD13-specific autoantibodies in sera from patients with ulcerative colitis and Crohn's disease. Journal of autoimmunity 32 16584867
2017 Silencing FLI or targeting CD13/ANPEP lead to dephosphorylation of EPHA2, a mediator of BRAF inhibitor resistance, and induce growth arrest or apoptosis in melanoma cells. Cell death & disease 31 29048432
2009 Increased APN/CD13 and acid aminopeptidase activities in head and neck squamous cell carcinoma. Head & neck 31 19373777
1994 Expression of aminopeptidase N/CD13 in tumour-infiltrating lymphocytes from human renal cell carcinoma. Immunology letters 31 7829125
1990 Expression of aminopeptidase N (CD13) in mesenchymal tumors. The American journal of pathology 31 1978569
2009 Cell-based evidence for aminopeptidase N/CD13 inhibitor actinonin targeting of MT1-MMP-mediated proMMP-2 activation. Cancer letters 30 19264392
1996 Myeloid antigen, CD13, CD14, and/or CD33 expression is restricted to certain lymphoid neoplasms. American journal of clinical pathology 30 8659452
2014 Molecular mechanisms regulating CD13-mediated adhesion. Immunology 29 24627994
2023 The Role of the Ectopeptidase APN/CD13 in Cancer. Biomedicines 28 36979703
2016 The Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells. PLoS pathogens 28 27077376
2003 Scabrous and Gp150 are endosomal proteins that regulate Notch activity. Development (Cambridge, England) 28 12756167
1986 The nucleotide sequence of the pepN gene and its over-expression in Escherichia coli. Gene 28 3549459
2016 CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells. Stem cell reports 27 26771355
2003 Putative hAPN receptor binding sites in SARS_CoV spike protein. Acta pharmacologica Sinica 27 12791172
2017 Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells. Oncotarget 26 29069816
2013 Aminopeptidase N (CD13) is involved in phagocytic processes in human dendritic cells and macrophages. BioMed research international 26 24063007
1994 Characterization and expression of the pepN gene encoding a general aminopeptidase from Lactobacillus helveticus. FEMS microbiology letters 26 7851738
2020 CD13 Induces Autophagy to Promote Hepatocellular Carcinoma Cell Chemoresistance Through the P38/Hsp27/CREB/ATG7 Pathway. The Journal of pharmacology and experimental therapeutics 25 32571958
2014 CD13 regulates anchorage and differentiation of the skeletal muscle satellite stem cell population in ischemic injury. Stem cells (Dayton, Ohio) 25 24307555
2014 Possible contribution of aminopeptidase N (APN/CD13) to migration and invasion of human osteosarcoma cell lines. International journal of oncology 25 25340499
2004 Expression of CD13/aminopeptidase N and CD10/neutral endopeptidase on cultured human keratinocytes. Immunology letters 25 14757368
2017 Potential therapeutic impact of CD13 expression in non-small cell lung cancer. PloS one 24 28604784
1994 Purification and characterization of a general aminopeptidase (St-PepN) from Streptococcus salivarius ssp. thermophilus CNRZ 302. Journal of dairy science 24 7836577
2023 CD13 facilitates immune cell migration and aggravates acute injury but promotes chronic post-stroke recovery. Journal of neuroinflammation 23 37817190
2014 Near-infrared fluorescence imaging of CD13 receptor expression using a novel Cy5.5-labeled dimeric NGR peptide. Amino acids 23 24652439
1998 Human cytomegalovirus infection downregulates expression of the cellular aminopeptidases CD10 and CD13. Virology 23 9792845
1993 Expression of monocyte/macrophage markers (CD13, CD14, CD68) on human keratinocytes in healthy and diseased skin. The Journal of dermatology 23 7688777
2007 Clinicopathological significance of aminopeptidase N/CD13 expression in human gastric carcinoma. Hepato-gastroenterology 22 17419227
2020 CD13 as a new tumor target for antibody-drug conjugates: validation with the conjugate MI130110. Journal of hematology & oncology 21 32264921
2003 Changes in monocytic expression of aminopeptidase N/CD13 after major trauma. Clinical and experimental immunology 21 14632756
1993 Abundant (A)n.(T)n mononucleotide repeats in the pig genome: linkage mapping of the porcine APOB, FSA, ALOX12, PEPN and RLN loci. Animal genetics 21 7904801
2003 CD13/aminopeptidase N in collagen vascular diseases. Rheumatology international 20 13680152
1997 Transmembrane glycoprotein gp150 is a substrate for receptor tyrosine phosphatase DPTP10D in Drosophila cells. Molecular and cellular biology 20 9372917
2021 CD13 orients the apical-basal polarity axis necessary for lumen formation. Nature communications 19 34349123
2016 Aminopeptidase N (APN/CD13) as a target molecule for scirrhous gastric cancer. Clinics and research in hepatology and gastroenterology 19 26774363
2000 CD30+ anaplastic large-cell lymphoma with aberrant expression of CD13: case report and review of the literature. Journal of clinical laboratory analysis 19 11138613

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