Regulator of complement activation (RCA) locus in chicken: identification of chicken RCA gene cluster and functional RCA proteins.
A 150-kb DNA fragment, which contains the gene of the chicken complement regulatory protein CREM (formerly named Cremp), was isolated from a microchromosome by screening bacterial artificial chromosome library. Within 100 kb of the cloned region, three complete genes encoding short consensus repeats (SCRs, motifs with tandemly arranged 60 aa) were identified by exon-trap method and 3'- or 5'-RACE. A chicken orthologue of the human gene 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2, which exists in close proximity to the regulator of complement activation genes in humans and mice, was located near this chicken SCR gene cluster. Moreover, additional genes encoding SCR proteins appeared to be present in this region. Three distinct transcripts were detected in RNA samples from a variety of chicken organs and cell lines. Two novel genes named complement regulatory secretory protein of chicken (CRES) and complement regulatory GPI-anchored protein of chicken (CREG) besides CREM were identified by cloning corresponding cDNA. Based on the predicted primary structures and properties of the expressed molecules, CRES is a secretory protein, whereas CREG is a GPI-anchored membrane protein. CREG and CREM were protected host cells from chicken complement-mediated cytolysis. Likewise, a membrane-bound form of CRES, which was artificially generated, also protected host cells from chicken complement. Taken together, the chicken possesses an regulator of complement activation locus similar to those of the mammals, and the gene products function as complement regulators.
Oshiumi
Hiroyuki
H
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Shida
Kyoko
K
Goitsuka
Ryo
R
Kimura
Yuko
Y
Katoh
Jun
J
Ohba
Shinya
S
Tamaki
Yuichiroh
Y
Hattori
Takashi
T
Yamada
Nozomi
N
Inoue
Norimitsu
N
Matsumoto
Misako
M
Mizuno
Shigeki
S
Seya
Tsukasa
T
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000302:isolation & purification* / Q000502:physiology; D001483:Base Sequence; D016466:CHO Cells; D002645:Chickens; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003167:Complement Activation / Q000235:genetics*; D015941:Complement Hemolytic Activity Assay; D016384:Consensus Sequence; D006224:Cricetinae; D051786:Cyclic AMP Response Element Modulator; D015891:Cystatins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D005819:Genetic Markers; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000302:isolation & purification* / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D020449:Repetitive Sequences, Amino Acid; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D014162:Transfection
D030161:Avian Proteins; C114068:CREG1 protein, human; C489714:CST8 protein, human; C419395:Cremp protein, chicken; D015891:Cystatins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D008565:Membrane Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator