Search:
  • GENE_NAME : CD10

    CD_NAME : CD10

    DESC: membrane metallo-endopeptidase; neutral endopeptidase; enkephalinase; CALLA; CD10
    OTH_NAMES: CALLA; CD10; NEP
    CLONE_NAME ISO_TYPE SUBMITTER AVAILABLE_FROM
    HI10a IgG1  Chen  BD Biosciences
    MEM-78 IgG1 Horejsi BioLegend
    SN5c IgG1  Seon  AbD Serotec
    W8E7 IgG2a  Commercial  BD Biosciences
    HI10a IgG1  Chen  BioLegend
    SN5c IgG1  Seon  eBioscience
  • CLONE_NAME ISO_TYPE SUBMITTER AVAILABLE_FROM
    24.1 IgG3 Braun M
    79 unknown Bai
    97C5 IgG1  Bühring 
    AL2 IgG2b  LeBacq-Verheyden 
    AL3 IgM  LeBacq-Verheyden 
    ALB2 unknown  Boucheix 
    B-E3 IgG2a  Vermot-Desroches
    BA-3 IgG2  LeBien 
    BL-A11 IgG1  Fiebig 
    CLB-CALLA1 unknown  von den Borne 
    F2B1.10 IgG1  Poncelet 
    F103.11 IgG1  Plesner 
    HI10a IgG1  Chen  BD Biosciences
    HI10b IgG1  Chen 
    IF-6 IgG1  Fujimoto 
    IF-6 IgG1  Fujimoto 
    J5 IgG2a  Ritz J 
    J13 IgM  Ritz 
    K14 IgG2b  Bernard 
    K50 IgG3  Bernard 
    M-L57 unknown  Rieber 
    MEM-78 IgG1 Horejsi BioLegend
    NL-1 IgG2a  Ueda R 
    NU-N1 unknown  Yokoyama 
    NU-N2 unknown  Yokoyama 
    PHM6 unknown  Kraft 
    RPH-12 IgG3  Erber 
    S-8 unknown  Pesando 
    SJ5-1B4 IgG1  Johnson 
    SN5c IgG1  Seon  AbD Serotec
    SS-2/36 unknown  Mason 
    SYB4 unknown  Breard 
    UL-93 IgM  Raghavachar 
    UL-96 IgM  Raghavachar 
    VILA1 IgM  Knapp 
    W8E7 IgG2a  Commercial  BD Biosciences
    WCMH15.14 IgG1  Cassano 
    Wu174 IgG1  Wang 
    HI10a IgG1  Chen  BioLegend
    SN5c IgG1  Seon  eBioscience
  • STRUCTURE


    CD10 is a type 2 transmembrane glycoprotein of M13 family.1-2 It displays a short cytoplasmatic N-terminal domain involved in signaling.1 The long extracellular C-terminal domain has catalytic activity and contains a zincin motif.1, 3-4

    1. Shipp MA, Richardson NE, Sayre PH, Brown NR, Masteller EL, Clayton LK, Ritz J, Reinherz EL. Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Proc Natl Acad Sci U S A. 1988;85:4819-23.
    2. Erdös EG, Skidgel RA. Neutral endopeptidase 24.11 (enkephalinase) and related regulators of peptide hormones. FASEB J. 1989;3:145-51.
    3. Shipp MA, Look AT. Hematopoietic differentiation antigens that are membrane-associated enzymes: cutting is the key! Blood. 1993:15;82:1052-70.
    4. Tam LT, Engelbrecht S, Talent JM, Gracy RW, Erdös EG. The importance of disulfide bridges in human endopeptidase (enkephalinase) after proteolytic cleavage. Biochem Biophys Res Commun. 1985;133:1187-92
  • LIGANDS


    Extracellular
    Biologically active peptides including enkephalins1-2, fMLP3, neurotensin4, substance P4-5, amyloid β-peptide6, bradykinin1,3, angiotensin I and II1, oxytocin7, endothelins8, calcitonin gene-related peptide5, FGF-29, IL1 beta10, atrial natriuretic factor11 and bombesin-like peptides. 12

    Intracellular associate molecules

    Lyn13, PTEN14 and ERM proteins.15

    1. Gafford JT, Skidgel RA, Erdös EG, Hersh LB. Human kidney "enkephalinase", a neutral metalloendopeptidase that cleaves active peptides. Biochemistry. 1983;22:3265-71.
    2. Malfroy B, Swerts JP, Guyon A, Roques BP, Schwartz JC. High-affinity enkephalin-degrading peptidase in brain is increased after morphine. Nature. 1978;276:523-6.
    3. Connelly JC, Skidgel RA, Schulz WW, Johnson AR, Erdös EG. Neutral endopeptidase 24.11 in human neutrophils: cleavage of chemotactic peptide. ProcNatl Acad Sci U S A. 1985;82:8737-41.
    4. Skidgel RA, Engelbrecht S, Johnson AR, Erdös EG. Hydrolysis of substance p and neurotensin by converting enzyme and neutral endopeptidase. Peptides. 1984;5:769-76.
    5. Katayama M, Nadel JA, Bunnett NW, Di Maria GU, Haxhiu M, Borson DB. Catabolism of calcitonin gene-related peptide and substance P by neutral endopeptidase. Peptides. 1991;12:563-7.
    6. Shirotani K, Tsubuki S, Iwata N, Takaki Y, Harigaya W, Maruyama K, Kiryu-Seo S, Kiyama H, Iwata H, Tomita T, Iwatsubo T, Saido TC. Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases. J Biol Chem. 2001;276:21895-901.
    7. Johnson AR, Skidgel RA, Gafford JT, Erdös EG. Enzymes in placental microvilli: angiotensin I converting enzyme, angiotensinase A, carboxypeptidase, and neutral endopeptidase ("enkephalinase"). Peptides. 1984;5:789-96.
    8. Vijayaraghavan J, Scicli AG, Carretero OA, Slaughter C, Moomaw C, Hersh LB. The hydrolysis of endothelins by neutral endopeptidase 24.11 enkephalinase. J Biol Chem. 1990;265:14150-5.
    9. Horiguchi A, Chen DY, Goodman OB Jr, Zheng R, Shen R, Guan H, Hersh LB, Nanus DM. Neutral endopeptidase inhibits prostate cancer tumorigenesis by reducing FGF-2-mediated angiogenesis. Prostate Cancer Prostatic Dis. 2008;11:79-87.
    10. Delikat SE, Galvani DW, Zuzel M. A function of CD10 on bone marrow stroma. Br J Haematol. 1994;87:655-7.
    11. Kenny AJ, Stephenson SL. Role of endopeptidase-24.11 in the inactivation of atrial natriuretic peptide. FEBS Lett. 1988;9;232:1-8.
    12. Shipp MA, Tarr GE, Chen CY, Switzer SN, Hersh LB, Stein H, Sunday ME, Reinherz EL. CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung. Proc Natl Acad Sci U S A. 1991;88:10662-6.
    13. Ganju RK, Shpektor RG, Brenner DG, Shipp MA. CD10/neutral endopeptidase 24.11 is phosphorylated by casein kinase II and coassociates with other phosphoproteins including the lyn src-related kinase. Blood. 1996;88:4159-65.
    14. Sumitomo M, Iwase A, Zheng R, Navarro D, Kaminetzky D, Shen R, Georgescu MM,Nanus DM. Synergy in tumor suppression by direct interaction of neutralendopeptidase with PTEN. Cancer Cell. 2004;5:67-78.
    15. Iwase A, Shen R, Navarro D, Nanus DM. Direct binding of neutral endopeptidase 24.11 to ezrin/radixin/moesin (ERM) proteins competes with the interaction ofCD44 with ERM proteins. J Biol Chem. 2004;279:11898-905.

  • GENE_NAME : CD10

    CD_NAME : CD10

    CD10 is expressed transiently on different stages of B-cell maturation. CD10 is displayed on common lymphoid progenitors, pro-B cells, pre-B cells I and II, immature B cells and transitional B cells but not in mature B cells.1-3 Expression of CD10 is recovered on follicular center B cells.4

    It is also expressed on neutrophils5, fibroblasts6, endometrial stromal cells7, renal tubular and glomerular cells8, myoepithelial cells of adult breast8, epithelial cells of prostate9, colon10, stomach10 and fetal small intestine8, immature lymphoid cells11, fetal thymocytes11, canaliculi surface of hepatocytes12, astrocytes13, neuronal cells14, bone marrow-derived mesenchymal stem cells15, adipose-derived stem cell16, mammary stem cells17, granulocytes18, apoptotic T cells19 and follicular helper T cells. 20

    It is lowly present on endothelial cells6 and prostate stromal cells. 9

    1. Blom B, Spits H. Development of human lymphoid cells. Annu Rev Immunol. 2006;24:287-320.
    2. Sims GP, Ettinger R, Shirota Y, Yarboro CH, Illei GG, Lipsky PE. Identification and characterization of circulating human transitional B cells. Blood. 2005;105:4390-8.
    3. Hystad ME, Myklebust JH, Bø TH, Sivertsen EA, Rian E, Forfang L, Munthe E, Rosenwald A, Chiorazzi M, Jonassen I, Staudt LM, Smeland EB. Characterization of early stages of human B cell development by gene expression profiling. J Immunol. 2007;179:3662-71.
    4. Dogan A, Bagdi E, Munson P, Isaacson PG. CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue addddnd B-cell lymphomas. Am J Surg Pathol. 2000;24:846-52.
    5. Painter RG, Dukes R, Sullivan J, Carter R, Erdös EG, Johnson AR. Function of neutral endopeptidase on the cell membrane of human neutrophils. J Biol Chem. 1988;263:9456-61.
    6. Johnson AR, Ashton J, Schulz WW, Erdös EG. Neutral metalloendopeptidase in human lung tissue and cultured cells. Am Rev Respir Dis. 1985;132:564-8.
    7. Imai K, Kanzaki H, Fujiwara H, Kariya M, Okamoto N, Takakura K, Maeda M, Mori T. Expression of aminopeptidase N and neutral endopeptidase on the endometrial stromal cells in endometriosis and adenomyosis. Hum Reprod. 1992;7:1326-8.
    8. Metzgar RS, Borowitz MJ, Jones NH, Dowell BL. Distribution of common acute lymphoblastic leukemia antigen in nonhematopoietic tissues. J Exp Med. 1981;154:1249-54.
    9. Song J, Aumüller G, Xiao F, Wilhelm B, Albrecht M. Cell specific expression of CD10/neutral endopeptidase 24.11 gene in human prostatic tissue and cells. Prostate. 2004;58:394-405.
    10. Sato Y, Itoh F, Hinoda Y, Ohe Y, Nakagawa N, Ueda R, Yachi A, Imai K. Expression of CD10/neutral endopeptidase in normal and malignant tissues of the human stomach and colon. J Gastroenterol. 1996;31:12-7.
    11. Greaves MF, Hariri G, Newman RA, Sutherland DR, Ritter MA, Ritz J. Selective expression of the common acute lymphoblastic leukemia (gp 100) antigen on immature lymphoid cells and their malignant counterparts. Blood. 1983;61:628-39.
    12. Loke SL, Leung CY, Chiu KY, Yau WL, Cheung KN, Ma L. Localisation of CD10 to biliary canaliculi by immunoelectron microscopical examination. J Clin Pathol. 1990;43:654-6.
    13. Mulder SD, Veerhuis R, Blankenstein MA, Nielsen HM. The effect of amyloid associated proteins on the expression of genes involved in amyloid-β clearance by adult human astrocytes. Exp Neurol. 2012;233:373-9.
    14. Wang R, Wang S, Malter JS, Wang DS. Effects of HNE-modification induced by Abeta on neprilysin expression and activity in SH-SY5Y cells. J Neurochem. 2009;108:1072-82.
    15. Siegel G, Kluba T, Hermanutz-Klein U, Bieback K, Northoff H, Schäfer R. Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells. BMC Med. 2013;11:146.
    16. Raposio E, Bonomini S, Calderazzi F. Isolation of autologous adipose tissue-derived mesenchymal stem cells for bone repair. Orthop Traumatol Surg Res. 2016;102:909-912.
    17. Bachelard-Cascales E, Chapellier M, Delay E, Pochon G, Voeltzel T, Puisieux A,Caron de Fromentel C, Maguer-Satta V. The CD10 enzyme is a key player to identify and regulate human mammary stem cells. Stem Cells. 2010;28:1081-8.
    18. Braun MP, Martin PJ, Ledbetter JA, Hansen JA. Granulocytes and cultured human fibroblasts express common acute lymphoblastic leukemia-associated antigens. Blood. 1983;61:718-25.
    19. Cutrona G, Leanza N, Ulivi M, Melioli G, Burgio VL, Mazzarello G, Gabutti ,Roncella S, Ferrarini M. Expression of CD10 by human T cells that undergo apoptosis both in vitro and in vivo. Blood. 1999;94:3067-76.
    20. Amé-Thomas P, Hoeller S, Artchounin C, Misiak J, Braza MS, Jean R, Le Priol J, Monvoisin C, Martin N, Gaulard P, Tarte K. CD10 delineates a subset of human IL-4 producing follicular helper T cells involved in the survival of follicular lymphoma B cells. Blood. 2015;125:2381-5.

     


  • GENE_NAME : CD10

    CD_NAME : CD10

    CD10 is a zinc-dependent metalloendoprotease which cleaves several biologically active peptides.1 It regulates inflammation through degradation of proinflammatory molecules.2 CD10 is also involved in metabolizing amyloid B-peptides in the brain and regulates the maturation of B cells in mice.3-4 CD10 processes several neuropeptides including enkephalins and substance P.5-6 Last, CD10 modulates both lung and breast morphogenesis.7-8

    1. Maguer-Satta V, Besançon R, Bachelard-Cascales E. Concise review: neutral endopeptidase (CD10): a multifaceted environment actor in stem cells, physiological mechanisms, and cancer. Stem Cells. 2011;29:389-96.
    2. Shipp MA, Stefano GB, Switzer SN, Griffin JD, Reinherz EL. CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation. Blood. 1991;78:1834-41.
    3. Shirotani K, Tsubuki S, Iwata N, Takaki Y, Harigaya W, Maruyama K, Kiryu-Seo S, Kiyama H, Iwata H, Tomita T, Iwatsubo T, Saido TC. Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases. J Biol Chem. 2001;276:21895-901.
    4. Salles G, Rodewald HR, Chin BS, Reinherz EL, Shipp MA. Inhibition ofCD10/neutral endopeptidase 24.11 promotes B-cell reconstitution and maturation in vivo. Proc Natl Acad Sci U S A. 1993;90:7618-22.
    5. Vijayaraghavan J, Scicli AG, Carretero OA, Slaughter C, Moomaw C, Hersh LB. The hydrolysis of endothelins by neutral endopeptidase 24.11 enkephalinase). J Biol Chem. 1990;265:14150-5.
    6. Skidgel RA, Engelbrecht S, Johnson AR, Erdös EG. Hydrolysis of substance p and neurotensin by converting enzyme and neutral endopeptidase. Peptides. 1984;5:769-76.
    7. Sunday ME, Hua J, Torday JS, Reyes B, Shipp MA. CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation. J Clin Invest. 1992;90:2517-25.
    8. Atherton AJ, Anbazhagan R, Monaghan P, Bartek J, Gusterson BA. Immunolocalisation of cell surface peptidases in the developing human breast. Differentiation. 1994;56:101-6.

  • GENE_NAME : CD10

    CD_NAME : CD10

    Cell marker

    Can be used for the identification of the stage of B cells1 and for classification of B cell leukemias and lymphomas.2 CD10 is also a marker of renal and hepatic neoplasias3-4, endometrial and thyroid neoplasms.5-6

    Useful as a prognostic marker in cancer including breast carcinoma7, ovarian cancer8, head and neck squamous carcinoma9, prostate cancer10,acute lymphoblastic leukemia11 and renal malignancies.4

    1. Vale AM, Schroeder HW Jr. Clinical consequences of defects in B-cell development. J Allergy Clin Immunol. 2010;125:778-87.
    2. Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood. 2008;111:3941-67.
    3. Borscheri N, Roessner A, Röcken C. Canalicular immunostaining of neprilysin (CD10) as a diagnostic marker for hepatocellular carcinomas. Am J Surg Pathol. 2001;25:1297-303.
    4. Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R. CD10 is a diagnostic and prognostic marker in renal malignancies. Histopathology. 2004;45:460-7.
    5. Tomoda C, Kushima R, Takeuti E, Mukaisho K, Hattori T, Kitano H. CD10 expression is useful in the diagnosis of follicular carcinoma and follicular variant of papillary thyroid carcinoma. Thyroid. 2003;13:291-5.
    6. McCluggage WG, Sumathi VP, Maxwell P. CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms. Histopathology. 2001;39:273-8.
    7. Makretsov NA, Hayes M, Carter BA, Dabiri S, Gilks CB, Huntsman DG. Stromal CD10 expression in invasive breast carcinoma correlates with poor prognosis, estrogen receptor negativity, and high grade. Mod Pathol. 2007;20:84-9.
    8. Kajiyama H, Shibata K, Terauchi M, Morita T, Ino K, Mizutani S, Kikkawa F. Neutral endopeptidase 24.11/CD10 suppresses progressive potential in ovarian carcinoma in vitro and in vivo. Clin Cancer Res. 2005;11:1798-808.
    9. Fukusumi T, Ishii H, Konno M, Yasui T, Nakahara S, Takenaka Y, Yamamoto Y, Nishikawa S, Kano Y, Ogawa H, Hasegawa S, Hamabe A, Haraguchi N, Doki Y, Mori M, Inohara H. CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma. Br J Cancer. 2014;111:506-14.
    10. Dall'Era MA, True LD, Siegel AF, Porter MP, Sherertz TM, Liu AY. Differential expression of CD10 in prostate cancer and its clinical implication. BMC Urol. 2007;7:3.
    11. Dakka N, Bellaoui H, Bouzid N, Khattab M, Bakri Y, Benjouad A. CD10 AND CD34 expression in childhood acute lymphoblastic leukemia in Morocco: clinical relevance and outcome. Pediatr Hematol Oncol. 2009;26:216-31.

     

    Therapeutic

    As an enzyme, inhibitors of CD10 are currently being used for therapy. Acertophan is used for treatment of acute diarrhea.1 Sacubitril/valsartan, a dual agent that consists of the angiotensin II type 1 receptor blocker and a CD10 inhibitor, is administered in patients with chronic heart failure and reduced ejection fraction.2-3 Furthermore, clinicals trials support the use of sacubitril/valsartan for treating hypertension.4

    1. Baumer P, Danquechin Dorval E, Bertrand J, Vetel JM, Schwartz JC, Lecomte JM. Effects of acetorphan, an enkephalinase inhibitor, on experimental and acute diarrhoea. Gut. 1992;33:753-8.
    2. Packer M, McMurray JJ, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL ,Shi VC, Solomon SD, Swedberg K, Zile M, Andersen K, Arango JL, Arnold JM, Bělohlávek J, Böhm M, Boytsov S, Burgess LJ, Cabrera W, Calvo C, Chen CH, Dukat A, Duarte YC, Erglis A, Fu M, Gomez E, Gonzàlez-Medina A, Hagège AA, Huang J, Katova T, Kiatchoosakun S, Kim KS, Kozan Ö, Llamas EB, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires FJ, Refsgaard J, Rosenthal A, Senni M, Sibulo AS Jr, Silva-Cardoso J, Squire IB, Starling RC, Teerlink JR, Vanhaecke J, Vinereanu D, Wong RC; PARADIGM-HF Investigators and Coordinators. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.Circulation. 2015;131:54-61.
    3. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure.  N Engl J Med. 2014;371:993-1004.
    4. Chrysant SG. Pharmacokinetic, pharmacodynamic, and antihypertensive effects of the neprilysin inhibitor LCZ-696: sacubitril/valsartan. J Am Soc Hypertens. 2017;11:461-468.

  • GENE_NAME : CD10

    CD_NAME : CD10

    GENERAL_INFORMATION

    NCBI_NAME MME
    NCBI_OTHER_NAME CALLA; CD10; NEP
    SWISS_NAMES NEP_HUMAN
    DESC membrane metallo-endopeptidase; neutral endopeptidase; enkephalinase; CALLA; CD10

    LOCUS_INFO_LINKS

    HGNC_LOCUS_TAG: 7154
    ONLINE_MENDELIAN_INHERITANCE: 120520
    NCBI_HOMOLOGENE: 5275
    NCBI_MAP: 3q25.1-q25.2
    NCBI_ENTRE_GENE_ENTRY: 4311
    GENE_SIZE: 104034
    EN_GE_EN:
    MRNA_SEQ_LENGTH: 5595
    PRCORENC: 99 to 2351
    ENTREN: ENST00000360490
    PROTEIN_LENGTH_NCBI_REFSEQ: 751
    NCBI_REF_SEF_ENTRY: NP_000893 , 4505203
    PROTEIN_LENGTH_SWISPROT: 749
    ENSEMBLE_PROT_ENTRY: ENSP00000353679
    PR_MO_WEIGHT: 85382
    SWPROT_PROTEIN_ENTRY: NEP_HUMAN , P09473
    PR_SW_PR: 5.54
    IPI_NUMBER: IPI00247063
    NCBI_CONSV_DOMAINS: 4505203
    ENSM_NUMBER: P09473

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