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CD10 (neprilysin, neutral endopeptidase, enkephalinase, common acute lymphoblastic leukemia antigen, CALLA, atriopeptidase, MME, EPN)

Function: - thermolysin-like specificity - preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1 - substrates are polypeptides < 5 kD a) endorphins, enkephalins, cleavage of a Gly-Phe bond b) substance P, kinins c) somatostatin d) atrial natriuretic factor (ANF) e) amyloid A4 peptide - degrades amyloid beta-peptide (A4 amyloid peptide) [7,8,9] of senile plaques in Alzheimer's disease; [5] - it is thought that neprilysin & insulin-degrading enzyme may be major enzymes degrading the amyloid beta-peptide [6] Cofactor: binds 1 Zn+2 per subunit Structure: belongs to the peptidase M13 family Compartment: - plasma membrane - internal membranes - axonally transported; present in presynaptic membrane [7] Expression: - widely distributed - follicular center cells, pre-B cells, granulocytes cortical thymocytes, lympho-hematopoietic precursors - endometrial stroma, male GU epithelium, mesonephric remnants, liver, brush border in small bowel mucosa, placenta choroid plexus, brain, ovary, adrenal cortex Pathology: - expressed in many tumors including: follicular center cell lymphomas pre-B ALL ~75% CML in blast crisis ~90% hepatocellular carcinoma (canalicular pattern) ~68% sensitive, >95% specific with canalicular pattern mesonephric tumors renal cell carcinoma urothelial carcinoma prostate carcinoma pancreatic carcinoma uterine carcinoma endometrial stromal tumors smooth muscle tumors sarcomas melanomas microvillous inclusion disease - myeloid & erythroid precursors & female genital tract tumors stain negatively with antibody

Interactions

molecular events

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen zinc metalloprotease

Properties

SIZE: entity length = 750 aa MW = 86 kD COMPARTMENT: plasma membrane MOTIF: Stop-transfer sequence {16-23} transmembrane domain {29-51} cysteine residue {C57} MODIFICATION: cysteine residue {C62} cysteine residue {C62} MODIFICATION: cysteine residue {C57} cysteine residue {C80} MODIFICATION: cysteine residue {C735} cysteine residue {C88} MODIFICATION: cysteine residue {C695} binding site SITE: 103-103 FOR-BINDING-OF: Substrate carboxyl cysteine residue {C143} MODIFICATION: cysteine residue {C411} N-glycosylation site {N145} cysteine residue {C234} MODIFICATION: cysteine residue {C242} cysteine residue {C242} MODIFICATION: cysteine residue {C234} N-glycosylation site {N285} N-glycosylation site {N325} cysteine residue {C411} MODIFICATION: cysteine residue {C143} Zn+2-binding site SITE: 584-584 Zn+2-binding site SITE: 588-588 aspartate residue {D591} cysteine residue {C621} MODIFICATION: cysteine residue {C747} N-glycosylation site {N628} Zn+2-binding site SITE: 647-647 aspartate residue {D651} cysteine residue {C695} MODIFICATION: cysteine residue {C88} cysteine residue {C735} MODIFICATION: cysteine residue {C80} cysteine residue {C747} MODIFICATION: cysteine residue {C621} STATE: active state

Database Correlations

OMIM 120520 UniProt P08473 PFAM correlations Entrez Gene 4311 Kegg hsa:4311 ENZYME 3.4.24.11

References

  1. Cotran et al Robbins Pathologic Basis of Disease, W.B. Saunders Co, Philadelphia, PA 1989 pg 165
  2. UniProt :accession Q00973
  3. Journal Watch 20(5):38, 2000 Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, Kawashima-Morishima M, Lee HJ, Hama E, Sekine-Aizawa Y, Saido TC. Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat Med. 2000 Feb;6(2):143-50. PMID: 10655101
  4. Selkoe DJ. Clearing the brain's amyloid cobwebs. Neuron. 2001 Oct 25;32(2):177-80. Review. PMID: 11683988
  5. http://www.pathologyoutlines.com/cdmarkers.html 15 October 2002
  6. Greg Gole, UCLA Sepulveda VA, 02/12/2004, personal communication
  7. Iwata N, Mizukami H, Shirotani K, Takaki Y, Muramatsu S, Lu B, Gerard NP, Gerard C, Ozawa K, Saido TC. Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-beta peptide in mouse brain. J Neurosci. 2004 Jan 28;24(4):991-8. PMID: 14749444
  8. Marr RA, Guan H, Rockenstein E, Kindy M, Gage FH, Verma I, Masliah E, Hersh LB. Neprilysin regulates amyloid Beta peptide levels. J Mol Neurosci. 2004;22(1-2):5-11. PMID: 14742905
  9. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/MMEID41386ch3q25.html