Identification of a mammalian angiopoietin-related protein expressed specifically in liver.
Based on searches of EST databases for signal sequences and amphipathic helices, we have identified and cloned an angiopoietin-like gene, ANGPTL3. Multiple tissue Northern blots show that ANGPTL3 is expressed principally in the liver. ANGPTL3 is expressed early during liver development, and expression is maintained in adult liver. Human ANGPTL3 is a 460-amino-acid polypeptide with the characteristic structure of angiopoietins: a signal peptide, an extended helical domain predicted to form dimeric or trimeric coiled-coils, a short linker peptide, and a globular fibrinogen homology domain (FHD). Murine ANGPTL3 is a 455-acid polypeptide encoded by seven exons on mouse chromosome 4, spanning about 11 kb of DNA. ANGPTL3 contains the four conserved cysteines implicated in the intramolecular disulfide bonds within the FHD, but it does not contain two other cysteines that are found within the FHD of angiopoietins 1, 2, and 4. ANGPTL3 also does not contain the characteristic calcium binding motif found in the other angiopoietins. By radiation hybrid mapping and the use of surrounding genes, human ANGPTL3 maps to the 1p31 region.
Conklin
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D
ZymoGenetics, Inc., 1201 Eastlake Avenue East, Seattle, Washington 98012, USA. conklin@zgi.com
Gilbertson
D
D
Taft
D W
DW
Maurer
M F
MF
Whitmore
T E
TE
Smith
D L
DL
Walker
K M
KM
Chen
L H
LH
Wattler
S
S
Nehls
M
M
Lewis
K B
KB
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015152:Blotting, Northern; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D006031:Glycosylation; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D020161:Physical Chromosome Mapping; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C467628:Angpt1 protein, mouse; C404495:Angptl3 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; C118117:angiopoietin 4