Mouse SWAM1 and SWAM2 are antibacterial proteins composed of a single whey acidic protein motif.
Antibacterial proteins are important participants in the innate immunity system. Elafin and SLPI are the whey acidic protein (WAP) motif proteins with both antibacterial activity and antiprotease activity, and their role in innate immunity is under intense investigation. We cloned two novel antibacterial WAP motif proteins from mice, SWAM1 and SWAM2. SWAM1 and SWAM2 are composed of a signal sequence and a single WAP motif that has high homologies with the WAP motifs of elafin and SLPI. SWAM1 is constitutively expressed in kidney and epididymis, and is induced in the pneumonic lung. SWAM2 is constitutively expressed in tongue. SWAM1 and SWAM2 inhibit the growth of both Escherichia coli and Staphylococcus aureus at a IC(90) (concentration that achieves 90% inhibition) of 10 microM. Human genes LOC149709 and huWAP2 are considered to be human SWAM1 and SWAM2, respectively. These and several WAP motif proteins (WAP1, elafin, SLPI, HE4, eppin, C20orf170, LOC164237, and WFDC3) form a gene cluster on human chromosome 20, suggesting that they may be derived from the same ancestral gene by gene duplication. Our results underscore the role of the WAP motif as a skeletal motif to form antibacterial proteins, and warrant the study of antibacterial activity in other WAP motif proteins.
Hagiwara
Koichi
K
Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. hagiwark@idac.tohoku.ac.jp
Kikuchi
Tohru
T
Endo
Yoshiyuki
Y
Huqun
Usui
Kazuhiro
K
Takahashi
Mitsu
M
Shibata
Naoko
N
Kusakabe
Takashi
T
Xin
Hong
H
Hoshi
Sachiko
S
Miki
Makoto
M
Inooka
Nozomu
N
Tokue
Yutaka
Y
Nukiwa
Toshihiro
T
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001483:Base Sequence; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000187:drug effects; D005786:Gene Expression Regulation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D008894:Milk Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D008894:Milk Proteins; D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C473257:SWAM1 protein, mouse; C473258:SWAM2 protein, mouse; C024471:whey acidic proteins