Isolation of cDNA clones specifying the fourth component of mouse complement and its isotype, sex-limited protein.

Takahashi, Masayoshi; Natsuume‐Sakai, Shunnosuke; Nonaka, Manabu; Tanaka, Satoshi; Shimizu, Akira; Honjo, Tasuku

doi:10.1073/pnas.81.21.6822

Cited by 34 publications

(35 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations led to the proposal that the C3, C4, and a2M genes are derived from a common ancestral gene (16). The sequences of murine and human C3 and human C4 and partial cDNA sequences of murine C4 have recently been determined (17)(18)(19)(20)(21). Comparison of human a2M with murine C3 revealed a 25% overall sequence homology (17,18,22), supporting the proposal of their common evolutionary origin.…”

mentioning

confidence: 78%

“…The C3 sequence is from ref. 17. tein and of human C3 and C4 (17)(18)(19)(20)(21)46). At the 3' end of the cDNA sequence (nucleotide positions 4558-4563) an A-A-T-A-A-A poly(A) addition signal was observed, 89 nucleotides downstream from the translational stop codon and 14 nucdeotides upstream from a stretch of 9 adenines, which appears to be the beginning portion of the poly(A) tail.…”

Section: E a S P A F L A V P V E K E A P H C I C A N G R 0 T V S W mentioning

confidence: 99%

See 1 more Smart Citation

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Kan¹,

Solomon²,

Belt³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Six a2-macroglobulin (a2M) cDNA clones were isolated from a human liver cDNA library by using synthetic oligonucleotides as hybridization probes. One of these, pa2M1, carries a 4.6-kilobase-pair insert, which was sequenced. The insert contains the coding sequences for the mature a2M polypeptide (1451 amino acids) and for a 23-amino acid signal peptide at the NH2 terminus of the precursor proa2M. At the 3' end of the insert a poly(A) addition signal A-A-T-A-A-A and part of the poly(A) tail of the messenger RNA were found. The protein sequence deduced from the nucleotide sequence agrees with the published a2M amino acid sequence for all except three residues. The a2M locus was assigned to human chromosome 12 by Southern blot analysis with DNA from a panel of mouse/human somatic cell hybrids, using a2M cDNA as a hybridization probe.a2-Macroglobulin (a2M) is a serum glycoprotein and a major plasma proteinase inhibitor with a wide specificity. a2M-related proteins are present in all vertebrate species (1-4). Human a2M is a tetramer of four identical 185-kDa subunits, arranged as a pair of dimers each consisting of two disulfidelinked monomers (5, 6). The a2M polypeptide has a so-called bait region and an internal thiol ester bond, which account for its properties as a proteinase inhibitor. The bait region, composed of a series of target peptide bonds for plasma proteinases (7, 8) (13,14).This suggests that the conformational change, which accompanies the complex formation between a2M and proteinases and the hydrolysis of the thiol ester bond, exposes regions of the a2M molecule that are recognized by these receptors. Receptor-mediated endocytosis of proteinase-a2M complexes by macrophages and liver cells leads to clearance of the complexes from the circulation.Internal thiol ester bonds are also found in the complement proteins C3 and C4 (15), which are derived from precursor polypeptides of size similar to a2M (180-200 kDa). Their thiol ester sites are found in positions comparable to those in a2M, and the amino acid sequences of all three thiol ester sites are conserved. These observations led to the proposal that the C3, C4, and a2M genes are derived from a common ancestral gene (16). The sequences of murine and human C3 and human C4 and partial cDNA sequences of murine C4 have recently been determined (17-21). Comparison of human a2M with murine C3 revealed a 25% overall sequence homology (17,18,22

show abstract

mentioning

confidence: 78%

Section: E a S P A F L A V P V E K E A P H C I C A N G R 0 T V S W mentioning

confidence: 99%

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Kan¹,

Solomon²,

Belt³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…This C4 isotype is therefore called sex-limited protein, or Slp. C4 and Slp express predominantly in the liver, and despite the marked differences in their function and regulation, their coding regions show about 96% sequence identity (9,20,21,26).…”

mentioning

confidence: 99%

“…Differences between C4 and Slp cDNA sequences have already identified regions of C4 critical for hemolytic efficiency (9,20,21,26). Further comparison should reveal cis-acting DNA sequences involved in the hormonal and developmental regulation of Slp as well as the tissue-specific expression of both genes.…”

mentioning

confidence: 99%

Molecular genetics of androgen-dependent and -independent expression of mouse sex-limited protein.

Stavenhagen¹,

Loreni²,

Hemenway³

et al. 1987

Mol. Cell. Biol.

View full text Add to dashboard Cite

Genes of the mouse S locus encoding C4 (the fourth component complement) and Slp (sex-limited protein) show extensive homology but are distinct in their function and regulation. In some mouse strains, such as B10.D2, Slp is androgen regulated, whereas in others, such as B10.W7R, expression of Slp is constitutive. We have previously shown that the B10.W7R strain has multiple Slp genes. In this report, we present the structure of the single C4 and four Slp genes of the B10.W7R S locus and compare the upstream flanking regions by partial sequence analysis and function in transfection assays. Of the four Slp genes, three (Slpw7.A, Slpw7.B, and Slpw7.C) have upstream and promoter regions very similar to those of C4. The fourth Slp gene (Slpw7.D) is instead virtually identical to the androgen-regulated allele (Slpd from the B10.D2 mouse) in upstream regions. In particular, far-upstream sequences from both Slpd and Slpw7.D render the bacterial chloramphenicol acetyltransferase gene hormonally responsive upon transfection into mammary carcinoma cell lines. The upstream sequences between 2 to 3 kilobases of the Slp promoter initiate transcription from multiple sites when fused proximal to the chloramphenicol acetyltransferase gene, and these transcripts are threefold more abundant in the presence of androgen. This behavior is similar for Slpd and Slpw7.D, which suggests that Slpw7.D may be androgen regulated but that this is masked in vivo by constitutive expression of the other Slp genes. Nonhomologous recombination is implicated not only in expanding the copy number of C4 and Slp genes in the B10.W7R mouse but also in creating hybrid genes with regulatory features of C4 and structural features of Slp.

show abstract

“…C4 and Slp DNA clones from several mouse strains have been characterized (14,24,26). In strains with H-2-linked * Corresponding author.…”

mentioning

confidence: 99%

A complex androgen-responsive enhancer resides 2 kilobases upstream of the mouse Slp gene.

Loreni¹,

Stavenhagen²,

Kalff³

et al. 1988

Mol. Cell. Biol.

View full text Add to dashboard Cite

show abstract

Isolation of cDNA clones specifying the fourth component of mouse complement and its isotype, sex-limited protein.

Cited by 34 publications

References 46 publications

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Nucleotide sequence of cDNA encoding human alpha 2-macroglobulin and assignment of the chromosomal locus.

Molecular genetics of androgen-dependent and -independent expression of mouse sex-limited protein.

A complex androgen-responsive enhancer resides 2 kilobases upstream of the mouse Slp gene.

Contact Info

Product

Resources

About