CD13 ANPEP (alanyl aminopeptidase), APN (aminopeptidase N), EC 3.4.11.2, gp150,
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
Monocyte
Granulocyte
Myeloid Cell
Leukemia cell
Lymphoid Cell
Lymphocyte
Epithelial Cell
Endothelial Cell
Fibroblast
Bone Marrow
Stromal Cell
Osteoclast
Brain Cell
Bile duct
150 / 150

Expression
CD13 is expressed on the suface of early committed progenitors of granulocytes and monocytes CFU-GM and on all cells of these lineages as they mature.  It is also expressed on endothelial cells, epithelial cells from renal proximal tubules and intestinal brush border, bone marrow, stromal cells, fibroblasts, brain cells, osteoclasts, and cells lining bile duct canaliculi and is expressed on a small proportion of large granular lymphocytes but not other lymphocytes.  CD13 is a marker for the most acute myeloid leukemias and a smaller proportion of acute lymphoid leukemias.  

Structure
MOLECULAR FAMILY NAME FOR CD13: Belongs to the metalloendopeptidase M1 family.

CD13 is a single-pass type-2 967 aa glycoprotein.  It contains a large extracellular C terminal domain which contains 10 N-glycosylated sites and numerous O-glycosylation sites, a transmembrane that acts as a signal peptide and a short cytoplasmic domain.  CD13 is a member of a group of type 2 integral membrane metalloproteases that includes the leukocyte antigens CD10, CD26, CD73 and BP-1.  The mature form of CD13 is expressed on the cell surface as a homodimer.  CD13 is identical in structure to aminopeptidase N, a membrane bound zinc-binding metalloprotease which degrades regulatory peptides produced by diverse cell types.  In common with CD10, the expression of CD13 appears to be controlled by distinct promoters in different cell types, and several CD13 transcripts have been identified that differ only in their 5' untranslated region.  The extracellular domain contains the characteristic pentapeptide motif, His-Glu-Ile/Leu/Met-Xaa-His, associated with zinc binding and catalytic activity in a number of zinc-dependent metalloproteases.  CD13 is expressed as a noncovalently linked homodimer.

MOLECULAR MASS OF CD13
Cell Type Unreduced Reduced
Unspecified 150 kDa 

POST-TRANSCRIPTIONAL MODIFICATION OF CD13: No information.

POST-TRANSLATIONAL MODIFICATION OF CD13

CD13 is highly glycosylated. Variations in O-linked glycosylation produces different epitopes effecting mAb recognition.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD13

CD13 is a receptor for coronaviruses and RNA viruses that cause respiratory disease in humans and several species of animals.  The binding site on CD13 for the swine coronavirus transmissible gastroenteritis virus (TGEV) is distinct from the enzymatic site.



Function
CD13 processes signaling peptides.  CD13 is a zinc-binding metalloprotease which plays a role in cell surface antigen presentation by trimming the N-terminal aa from MHC Class II-bound peptides.  CD13 ectopeptidase activity is also thought to downregulate cellular responses to peptide hormones by reducing the local concentration of peptide available for receptor binding.  Neutral amino acid are preferentially cleaved by CD13, although basic and acidic residues can also be removed.  Peptide substrates for CD13 include opioid peptides and enkephalins in the brain, the phagocytosis-stimulating tetrapeptide tuftsin, and the neutrophil chemoattractant fMLP.  CD13 appears to act in concert with another metalloprotease, CD10, in the hydrolysis of these peptides.  Unlike CD10, CD13 activity is inhibited by the peptide hormones substance P and bradykinin.  CD13 is upregulated by the anti-inflammatory cytokine IL-4, which suggests a possible indirect mechanism of IL-4 action through the modulation of cell surface antigen processing and/or bioactive peptides.  CD13 also appears to play a role, by a mechanism that is unclear, in the infection of cells by human cytomegalovirus (CMV), a herpesvirus.

BIOCHEMICAL ACTIVITY

Functional studies show that CD13/APN catalyzes the removal of 1 aa from the amino terminus of small peptides and probably plays a role in their final digestion.  CD13 participates in trimming peptides bound to MHC class II molecules.  CD13 cleaves MIP-1 chemokine, which alters target cell specificity from basophils to eosinophils.

DISEASE RELEVANCE AND FUNCTION OF CD13 IN INTACT ANIMAL

CD13 plays a role in the final digestion of peptides in the small intestine generated from hydrolysis of proteins by gastric and pancreatic proteases.  The function in proximal tubular epithelial cells and other cell types is less clear.  CD13 is a receptor for one strain of human coronavirus that is an important cause of  upper respiratory tract infections.  CD13 is a marker for acute myeloid and some acute lymphoid leukemias.  Defects in this gene appear to be a cause of  these various types of leukemia or lymphoma.  CD13 serves an important function for the early events in the interaction between CMV and the target cells.  CMV incorporates the cellular CD13 protein in its envelope.  In certain immunocompromised patients a CMV infection induces a CD13-specific antibody response.  The presence of CD13-autoantibodies is strongly associated with the development of chronic graft versus host disease (GVHD) following bone marrow transplantation.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD13: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD13: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 290P15144
MouseU77083
RatA32852P15684M25073
Antibodies
25-2B   View Reactivity
CVS19   View Reactivity
WM15   View Reactivity

Revised June 25, 2008


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