CD249 ENPEP (glutamyl aminopeptidase[APA]), APA (aminopeptidase A), gp160
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
Stromal Cell
Bone Marrow
Thymic Epithelial Cell
Endothelium
B Cell
Endothelial Cell
Epithelial Cell
Small intestine
Kidney
160 / 160

Expression
CD249 is expressed in mice on early B lineage cells and on a population of thymic cortical epithelial cells, but not on mature lymphocytes.  IL-7 has been shown to selectively induce  expression on pre-B cells coincident with their growth.  Expression on bone marrow stromal cell lines correlates with their ability to support growth of B lineage cells.  The molecule is widely expressed on other tissues including the vascular endothelium, kidney glomeruli and renal proximately tubule cells, glomerulus of nephrons and the brush border of the small intestine.  Northern blot analysis indicates a similar expression pattern in humans.  CD249 is expressed on endothelial and epithelial cells.

Structure
MOLECULAR FAMILY NAME: Belongs to the M1 peptidase family.

CD249 is a single-pass type-2 957 aa glycoprotein.  It contains a large 918 aa extracellular C-terminal domain which contains a zinc-binding motif typical of zinc-dependent metallohydrolases and 13 N-linked glycosylation sites, a 21 aa type-2 signal anchor transmembrane domain and an 18 aa N-terminal cytoplasmic domain.  CD249 forms disulphide-linked homodimers and each subunit binds one zinc ion.  Human CD249 shows a sequence similarity to human CD13 (aminopeptidase N or APN). 

MOLECULAR MASS
Cell Type Unreduced Reduced
160 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD249 can be phosphorylated.  The catalytic activity releases N-terminal glutamate (and to a lesser extent aspartate) from a peptide.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD249

CD249 binds to a wide range of oligopeptides.  CD249 associates with angiotensin II and cholecystokinin-8.

Function
CD249 is a zinc-dependent metallopeptidase that catalyses the release of N-terminal glutamate (and to a lesser extent aspartate) from peptides such as cholecystokinin-8 and angiotensin II.  It  plays a role in the renin-angiotensin catabolic pathway and is involved in the formation of brain angiotensin III which has a stimulatory effect on the central nervous system control of blood pressure.  It also plays a regulatory role in angiotensin.  For example, in the kidney, CD249 removes the N-terminal Asp-residues of angiotensins 1 and 2, rendering them less potent as vasoconstrictors.  A possible role for CD249 in regulating B-cell growth and development has been suggested.  However, CD249 knockout mice are phenotypically normal and show no abnormality in T- and B-cell development and response to antigen.  Deficient mice do fail to produce the expected angiogenic reaction ro hypoxia or growth factors.  In mice the BP-1 mAb blocks CD249 enzymatic activity and inhibits IL-7-driven proliferation of pre-B cells in the context of the bone marrow microenvironment, but does not inhibit the growth of purified pre-B cells in response to IL-7.  This suggests that CD249 cleaves, and inactivates, a peptide which serves as a natural inhibitor of B cell precursor proliferation. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD249 IN INTACT ANMIAL

CD249 is a potential therapeutic target in the treatment of hypertension and prevention of tumor angiogenesis.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD249: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD249: No information.

ADDITIONAL INSIGHTS

For further information see Rozenfeld, R. et al (2004) J. Biol. Chem. 279: 43285-43295. 



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2028Q07075
MouseS30398P16406M29961
RatP50123S73583
Antibodies

Revised June 25, 2008


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