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CD13
CD13
Aminopeptidase N (EC 3.4.11.2), gpl50, p161 (mouse)
Molecular weights Polypeptide
109 512
SDS-PAGE reduced unreduced
150-170 kDa 150-170 kDa
Carbohydrate N-linked sites O-linked
11 + abundant
Human gene location and size 15q25-q26; 20 kb 1 NH2
NH2
Tissue distribution CD 13 is expressed by granulocytes and monocytes and their precursors. CD 13 is a marker for most acute myeloid leukaemias and a smaller proportion of acute lymphoid leukaemias. Various non-haematopoietic cells express CD13, including epithelial cells from renal proximal tubules and intestinal brush border, endothelial cells, fibroblasts, brain cells, bone marrow stromal cells, osteoclasts and cells lining the biliary caniculae a.
Structure CD13 is a member of a group of type II integral membrane metalloproteases that includes the leucocyte antigens CD10, CD26, CD73 and BP-12. 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 a. The CD13 glycoprotein has a short N-terminal cytoplasmic tail, a transmembrane region that functions as a signal peptide, and a large C-terminal extracellular region that contains 11 N-linked glycosylation sites and also O-linked glycosylation. 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 non-covalently linked homodimer 2.
i
Ligands and associated molecules CD13 is a receptor for coronaviruses, RNA viruses that cause respiratory disease in humans and several species of animals 2. The binding site on CD 13 for the swine coronavirus TGEV (transmissible gastroenteritis virus)is distinct from the enzymatic site 3.
Function CD13 is a zinc-binding metalloprotease which plays a role in cell surface antigen presentation by trimming the N-terminal amino acids from MHC
16~
CD13
Class II-bound peptides 4. CD 13 ectopeptidase activity is also thought to downregulate cellular responses to peptide hormones by reducing the local concentration of peptide available for receptor binding 2. Neutral amino acids 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 2. Unlike CD 10, CD 13 activity is inhibited by the peptide hormones substance P and bradykinin s. 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 6. CD13 also appears to play a role, by a mechanism that is unclear, in the infection of cells by human cytomegalovirus (CMV), a herpesvirus 7.
Database accession numbers Human Rat Mouse
PIR
SWISSPR OT
EMBL/GENBANK
REFERENCE
S01658 A32852
P15144 P15684
X13276 M25073 U77083
8,9 lo 11
A m i n o acid s e q u e n c e of h u m a n C D 13 MAKGFYISKS PSASATTNPA YVFKGSSTVR DKTELVEPTE GNVRKVVATT PKGPSTPLPE RIWARPSAIA AGAMENWGLV IEWWNDLWLN SSHPLSTPAS ASYLHTFAYQ VITVDTSTGT WLIDVRAQND SAIPVINRAQ SLSYFKLMFD YSEVNAISTA IAQGGEEEWD PDLIRKQDAT LIQAVTRRFS VKENKEVVLQ
LGILGILLGV SATTLDQSKA FTCKEATDVI YLVVHLKGSL QMQAADARKS DPNWNVTEFH AGHGDYALNV TYRENSLLFD EGFASYVEYL EINTPAQISE NTIYLNLWDH LSQEHFLLDP LFSTSGNEWV IINDAFNLAS RSEVYGPMKN CSNGVPECEE FAWEQFRNAT STIISITNNV TEYELQQLEQ WFTENSK
AAVCTIIALS WNRYRLPNTL IIHSKKLNYT VKDSQYEMDS FPCFDEPAMK TTPKMSTYLL TGPILNFFAG PLSSSSSNKE GADYAEPTWN LFDAISYSKG LQEAVNNRSI DSNVTRPSEF LLNLNVTGYY AHKVPVTLAL YLKKQVTPLF MVSGLFKQWM LVNEADKLRA IGQGLVWDFV FKKDNEETGF
VVYSQEKNKN KPDSYQVTLR LSQGHRVVLR EFEGELADDL AEFNITLIHP AFIVSEFDYV HYDTPYPLPK RVVTVIAHEL LKDLMVLNDV ASVLRMLSSF QLPTTVRDIM NYVWIVPITS RVNYDEENWR NNTLFLIEER IHFRNNTNNW ENPNNNPIHP ALACSKELWI QSNWKKLFND GSGTRALEQA
ANSSPVASTT PYLTPNDRGL GVGGSQPPDI AGFYRSEYME KDLTALSNML EKQASNGVLI SDQIGLPDFN AHQWFGNLVT YRVMAVDALA LSEDVFKQGL NRWTLQMGFP IRDGRQQQDY KIQTQLQRDH QYMPWEAALS REIPENLMDQ NLRSTVYCNA LNRYLSYTLN YGGGSFSFSN LEKTKANIKW
5O i00 150 200 250 300 350 400 450 5O0 55O 600 650 7OO 75O 800 850 900 950 967
References 1 2 3 4 s 6 z
Look, A.T. et al. (1986) J. Clin. Invest. 78, 914-921. Shipp, M.A. and Look, A.T. (1993) Blood 82, 1052-1070. Delmas, B. et al. (1994) J. Virol. 68, 5216-5224. Larsen, S.L. et al. (1996) J. Exp. Med. 184, 183-189. Xu, Y. et al. (1995) Biochem. Biophys. Res. Commun. 208, 664-674. van Hal, P.T.W. et al. (1994) J. Immunol. 153, 2718-2728. Giugni, T.D. et al. (1996) J. Infect. Dis. 173, 1062-1071.
L67
CD13
s Look, A.T. et al. (1989) J. Clin. Invest. 83, 1299-1307. 9 0 l s e n , J. et al. (1988) FEBS Lett. 238, 307-314. lo Watt, V.M. and Yip, C.C. (1989)J. Biol. Chem. 264, 5480-5487. 11 Chen, H. et al. (1996) J. Immunol. 157, 2593-2600.
L6~
Aminopeptidase N (EC 3.4.11.2), gpl50, p161 (mouse)
Molecular weights Polypeptide
109 512
SDS-PAGE reduced unreduced
150-170 kDa 150-170 kDa
Carbohydrate N-linked sites O-linked
11 + abundant
Human gene location and size 15q25-q26; 20 kb 1 NH2
NH2
Tissue distribution CD 13 is expressed by granulocytes and monocytes and their precursors. CD 13 is a marker for most acute myeloid leukaemias and a smaller proportion of acute lymphoid leukaemias. Various non-haematopoietic cells express CD13, including epithelial cells from renal proximal tubules and intestinal brush border, endothelial cells, fibroblasts, brain cells, bone marrow stromal cells, osteoclasts and cells lining the biliary caniculae a.
Structure CD13 is a member of a group of type II integral membrane metalloproteases that includes the leucocyte antigens CD10, CD26, CD73 and BP-12. 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 a. The CD13 glycoprotein has a short N-terminal cytoplasmic tail, a transmembrane region that functions as a signal peptide, and a large C-terminal extracellular region that contains 11 N-linked glycosylation sites and also O-linked glycosylation. 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 non-covalently linked homodimer 2.
i
Ligands and associated molecules CD13 is a receptor for coronaviruses, RNA viruses that cause respiratory disease in humans and several species of animals 2. The binding site on CD 13 for the swine coronavirus TGEV (transmissible gastroenteritis virus)is distinct from the enzymatic site 3.
Function CD13 is a zinc-binding metalloprotease which plays a role in cell surface antigen presentation by trimming the N-terminal amino acids from MHC
16~
CD13
Class II-bound peptides 4. CD 13 ectopeptidase activity is also thought to downregulate cellular responses to peptide hormones by reducing the local concentration of peptide available for receptor binding 2. Neutral amino acids 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 2. Unlike CD 10, CD 13 activity is inhibited by the peptide hormones substance P and bradykinin s. 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 6. CD13 also appears to play a role, by a mechanism that is unclear, in the infection of cells by human cytomegalovirus (CMV), a herpesvirus 7.
Database accession numbers Human Rat Mouse
PIR
SWISSPR OT
EMBL/GENBANK
REFERENCE
S01658 A32852
P15144 P15684
X13276 M25073 U77083
8,9 lo 11
A m i n o acid s e q u e n c e of h u m a n C D 13 MAKGFYISKS PSASATTNPA YVFKGSSTVR DKTELVEPTE GNVRKVVATT PKGPSTPLPE RIWARPSAIA AGAMENWGLV IEWWNDLWLN SSHPLSTPAS ASYLHTFAYQ VITVDTSTGT WLIDVRAQND SAIPVINRAQ SLSYFKLMFD YSEVNAISTA IAQGGEEEWD PDLIRKQDAT LIQAVTRRFS VKENKEVVLQ
LGILGILLGV SATTLDQSKA FTCKEATDVI YLVVHLKGSL QMQAADARKS DPNWNVTEFH AGHGDYALNV TYRENSLLFD EGFASYVEYL EINTPAQISE NTIYLNLWDH LSQEHFLLDP LFSTSGNEWV IINDAFNLAS RSEVYGPMKN CSNGVPECEE FAWEQFRNAT STIISITNNV TEYELQQLEQ WFTENSK
AAVCTIIALS WNRYRLPNTL IIHSKKLNYT VKDSQYEMDS FPCFDEPAMK TTPKMSTYLL TGPILNFFAG PLSSSSSNKE GADYAEPTWN LFDAISYSKG LQEAVNNRSI DSNVTRPSEF LLNLNVTGYY AHKVPVTLAL YLKKQVTPLF MVSGLFKQWM LVNEADKLRA IGQGLVWDFV FKKDNEETGF
VVYSQEKNKN KPDSYQVTLR LSQGHRVVLR EFEGELADDL AEFNITLIHP AFIVSEFDYV HYDTPYPLPK RVVTVIAHEL LKDLMVLNDV ASVLRMLSSF QLPTTVRDIM NYVWIVPITS RVNYDEENWR NNTLFLIEER IHFRNNTNNW ENPNNNPIHP ALACSKELWI QSNWKKLFND GSGTRALEQA
ANSSPVASTT PYLTPNDRGL GVGGSQPPDI AGFYRSEYME KDLTALSNML EKQASNGVLI SDQIGLPDFN AHQWFGNLVT YRVMAVDALA LSEDVFKQGL NRWTLQMGFP IRDGRQQQDY KIQTQLQRDH QYMPWEAALS REIPENLMDQ NLRSTVYCNA LNRYLSYTLN YGGGSFSFSN LEKTKANIKW
5O i00 150 200 250 300 350 400 450 5O0 55O 600 650 7OO 75O 800 850 900 950 967
References 1 2 3 4 s 6 z
Look, A.T. et al. (1986) J. Clin. Invest. 78, 914-921. Shipp, M.A. and Look, A.T. (1993) Blood 82, 1052-1070. Delmas, B. et al. (1994) J. Virol. 68, 5216-5224. Larsen, S.L. et al. (1996) J. Exp. Med. 184, 183-189. Xu, Y. et al. (1995) Biochem. Biophys. Res. Commun. 208, 664-674. van Hal, P.T.W. et al. (1994) J. Immunol. 153, 2718-2728. Giugni, T.D. et al. (1996) J. Infect. Dis. 173, 1062-1071.
L67
CD13
s Look, A.T. et al. (1989) J. Clin. Invest. 83, 1299-1307. 9 0 l s e n , J. et al. (1988) FEBS Lett. 238, 307-314. lo Watt, V.M. and Yip, C.C. (1989)J. Biol. Chem. 264, 5480-5487. 11 Chen, H. et al. (1996) J. Immunol. 157, 2593-2600.
L6~