Gene Symbol: Slp
Description: complement component 4A (Rodgers blood group)
Alias: Slp, SlpA, sex-limited protein
Species: mouse
Products:     Slp

Top Publications

  1. Stavenhagen J, Loreni F, Hemenway C, Kalff M, Robins D. Molecular genetics of androgen-dependent and -independent expression of mouse sex-limited protein. Mol Cell Biol. 1987;7:1716-24 pubmed
    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...
  2. Stavenhagen J, Robins D. An ancient provirus has imposed androgen regulation on the adjacent mouse sex-limited protein gene. Cell. 1988;55:247-54 pubmed
    The mouse sex-limited protein (Slp) gene is dependent on androgen for expression, unlike its homologous neighbor, which encodes the fourth component of complement (C4)...
  3. White P, Chaplin D, Weis J, Dupont B, New M, Seidman J. Two steroid 21-hydroxylase genes are located in the murine S region. Nature. 1984;312:465-7 pubmed
    ..We found that there are two 21-OH genes in this region, located immediately 3' to the C4 and Slp genes.
  4. van den Berg C, Van Dijk H. Rapid, activity-guided isolation of sex-limited protein (Slp) from mouse serum by fractionated precipitation and high-performance liquid chromatography. J Immunol Methods. 1994;169:251-6 pubmed
    We have recently demonstrated that sex-limited protein (Slp) plays a key role in an EDTA-resistant mouse complement activation pathway...
  5. Steinmetz M, Malissen M, Hood L, Orn A, Maki R, Dastoornikoo G, et al. Tracts of high or low sequence divergence in the mouse major histocompatibility complex. EMBO J. 1984;3:2995-3003 pubmed
    ..Variable tracts appear to be the result of mechanisms which mutate certain coding and non-coding sequences to the same extent and selective pressures operating on the genes. ..
  6. Ogata R, Sepich D. Genes for murine fourth complement component (C4) and sex-limited protein (Slp) identified by hybridization to C4- and Slp-specific cDNA. Proc Natl Acad Sci U S A. 1984;81:4908-11 pubmed
    Murine fourth component of complement (C4) and sex-limited protein (Slp) are two closely related serum proteins whose structural genes lie in the S region of the murine H-2 complex...
  7. Sepich D, Noonan D, Ogata R. Complete cDNA sequence of the fourth component of murine complement. Proc Natl Acad Sci U S A. 1985;82:5895-9 pubmed
    ..A comparison of the B10.WR C4 sequence with those of C4 and sex-limited protein (Slp) from mouse strain FM (i) suggests that the difference in hemolytic activity between the C4 proteins from B10...
  8. Miyagoe Y, Georgatsou E, Varin Blank N, Meo T. The androgen-dependent C4-Slp gene is driven by a constitutively competent promoter. Proc Natl Acad Sci U S A. 1993;90:5786-90 pubmed
    The androgen-dependent liver protein Slp, together with its constitutively expressed closely related isoform C4, provides a model to address the question of which minimal alteration in DNA can shut off the expression of a gene in a ..
  9. Levi Strauss M, Carroll M, Steinmetz M, Meo T. A previously undetected MHC gene with an unusual periodic structure. Science. 1988;240:201-4 pubmed

More Information


  1. Georgatsou E, Bourgarel P, Meo T. Male-specific expression of mouse sex-limited protein requires growth hormone, not testosterone. Proc Natl Acad Sci U S A. 1993;90:3626-30 pubmed
    Sex-limited protein (Slp), an isoform of mouse complement component C4, is expressed predominantly in liver and nearly exclusively in sexually mature males or testosterone-treated females...
  2. Jiang P, Frederick K, Hansen T, Miller R. Localization of the mouse gene releasing sex-limited expression of Slp. Proc Natl Acad Sci U S A. 1996;93:913-7 pubmed
    To probe genetic variation in the regulation of sexual dimorphism, we have characterized the mouse protein Slp, coded by the gene sex-limited protein (Slp). Slp expression in many strains is limited to males and is androgen-dependent...
  3. van den Berg C, Demant P, Aerts P, Van Dijk H. Slp is an essential component of an EDTA-resistant activation pathway of mouse complement. Proc Natl Acad Sci U S A. 1992;89:10711-5 pubmed
    b>Slp (sex-limited protein) is a mouse serum protein encoded by a major histocompatibility complex class III gene. It is considered to be a product of a duplicated complement component C4 gene, but without functional activity...
  4. Huang Z, Takahashi M, Nonaka M. Differential expression of the five C4-related genes of H-2w7 mice. Immunogenetics. 1991;33:361-6 pubmed
    Mice bearing the H-2w7 haplotype have five C4-related genes, one C4, one Slp, and three C4/Slp hybrid genes. The expression of these five genes in the liver of H-2w7 mice was estimated at the steady state level of their respective mRNA...
  5. Nonaka M, Kimura H, Yeul Y, Yokoyama S, Nakayama K, Takahashi M. Identification of the 5'-flanking regulatory region responsible for the difference in transcriptional control between mouse complement C4 and Slp genes. Proc Natl Acad Sci U S A. 1986;83:7883-7 pubmed
    ..the difference in the mode of gene expression between mouse complement C4 (constitutive) and sex-limited protein (Slp) (testosterone-regulated), we compared nucleotide sequences and transcriptional regulatory activities of the 5'-..
  6. Passmore H, Shreffler D. A sex-limited serum protein variant in the mouse: inheritance and association with the H-2 region. Biochem Genet. 1970;4:351-65 pubmed
  7. Passmore H, Shreffler D. A sex-limited serum protein variant in the mouse: hormonal control of phenotypic expression. Biochem Genet. 1971;5:201-9 pubmed
  8. Atkinson J, Karp D, Seeskin E, Killion C, Rosa P, Newell S, et al. H-2 S region determined polymorphic variants of the C4, Slp, C2, and B complement proteins: a compilation. Immunogenetics. 1982;16:617-23 pubmed
  9. Ferreira A, Michaelson J, Nussenzweig V. H-2-controlled polymorphism of the gamma chain of Slp (sex-limited protein). Immunogenetics. 1980;11:491-7 pubmed the O'Farrell two-dimensional technique (isoelectric focusing and SDS-PAGE) of the murine sex-limited protein (Slp) is described and shown to map to the H-2 complex. The Slp charge variation was found to be in the gamma chains...
  10. Roos M, Demant P. Murine complement factor B (BF): sexual dimorphism and H-2-linked polymorphism. Immunogenetics. 1982;15:23-30 pubmed
    ..These data extend the information on the interspecies homology of the MHC and may open new possibilities for studies of the genetic organization and hormonal regulation of the H-2 complex. ..
  11. Miller R, Aizawa Y, Shreffler D. Restriction fragment length polymorphism of the murine C4 and Slp genes: two C4 groups. J Immunol. 1992;149:2926-34 pubmed
    ..have examined the related H-2 genes coding for the fourth component of complement (C4) and the sex-limited protein (Slp) from 30 inbred mouse strains by Southern blot analysis...
  12. Bruisten S, Skamene E, Demant P. Haplotype-specific interactions of non-H-2-linked genetic factors controlling the mouse C4 and Slp protein levels. Genetics. 1989;121:795-801 pubmed
    The influence of non-H-2 linked genes on the plasma levels of the H-2 S-region encoded proteins C4, Slp, and factor B was tested in Recombinant Inbred (RI) strains...
  13. Tachibana M, Adachi W, Kinoshita S, Kobayashi Y, Honma Y, Hiai H, et al. Androgen-dependent hereditary mouse keratoconus: linkage to an MHC region. Invest Ophthalmol Vis Sci. 2002;43:51-7 pubmed to an MHC region on mouse chromosome 17, which includes a locus for the gene for sex-limited protein (Slp)...
  14. Milstone D, Shaw S, Parker K, Szyf M, Seidman J. An element regulating adrenal-specific steroid 21-hydroxylase expression is located within the slp gene. J Biol Chem. 1992;267:21924-7 pubmed
    ..Specifically, the 3' portion of the murine sex-limited protein (slp) gene, located within the class III region of the major histocompatibility complex, contains an element that ..
  15. Poole T, Drinkwater N. Two genes abrogate the inhibition of murine hepatocarcinogenesis by ovarian hormones. Proc Natl Acad Sci U S A. 1996;93:5848-53 pubmed
    ..2 +/- 3.9). In backcross male mice, the double heterozygotes (35 +/- 22) and Hcf1 heterozygotes (28 +/- 12) were 5.4- and 4.3-fold more sensitive than mice homozygous for B6 alleles at both loci (6.5 +/- 5.4). ..
  16. Varin Blank N, Dondi E, Tosi M, Hernandez C, Boucontet L, Gotoh H, et al. Male-specific transcription initiation of the C4-Slp gene in mouse liver follows activation of STAT5. Proc Natl Acad Sci U S A. 1998;95:8750-5 pubmed
    The mouse genes encoding the constitutively expressed complement component C4 and its closely related isoform C4-Slp (sex-limited protein), which is expressed only in male animals of several strains, provide a unique model to study ..
  17. Tosi M, Levi Strauss M, Duponchel C, Meo T. Sequence heterogeneity of murine complementary DNA clones related to the C4 and C4-Slp isoforms of the fourth complement component. Philos Trans R Soc Lond B Biol Sci. 1984;306:389-94 pubmed
    ..That this restriction site indeed discriminates the two non-allelic genes encoding the mouse C4 and C4-Slp isoforms has been demonstrated by Southern blot analysis and nucleotide sequencing at the genomic level...
  18. Brown L, Shreffler D. Female expression of the H-2-linked sex-limited protein (Slp) due to non-H-2 genes. Immunogenetics. 1980;10:19-29 pubmed
    Female mice of 15 inbred strains in which males express the H-2-linked sex-limited protein (Slp) were tested for the production of this protein...
  19. Nonaka M, Nakayama K, Yeul Y, Takahashi M. Complete nucleotide and derived amino acid sequences of sex-limited protein (Slp), nonfunctional isotype of the fourth component of mouse complement (C4). J Immunol. 1986;136:2989-93 pubmed
    The nucleotide sequence coding for sex-limited protein (Slp), the testosterone-regulated isotype of the fourth component of mouse complement (C4), has been determined from cloned genomic DNA and cDNA fragments...
  20. Levi Strauss M, Tosi M, Steinmetz M, Klein J, Meo T. Multiple duplications of complement C4 gene correlate with H-2-controlled testosterone-independent expression of its sex-limited isoform, C4-Slp. Proc Natl Acad Sci U S A. 1985;82:1746-50 pubmed
    Mouse liver cDNA clones related to the C4 and C4-Slp isoforms of the fourth component of complement differ by few nucleotide changes within a region of substantial divergence from human C4...
  21. Chaplin D, Woods D, Whitehead A, Goldberger G, Colten H, Seidman J. Molecular map of the murine S region. Proc Natl Acad Sci U S A. 1983;80:6947-51 pubmed
    ..duplication that contains the structural gene for mouse C4 and, we presume, for the sex-limited protein variant, Slp. RNA transfer blot analysis of total liver RNA from high C4- and low C4-producing strains showed that steady-state ..
  22. Pattanakitsakul S, Zheng J, Natsuume Sakai S, Takahashi M, Nonaka M. Aberrant splicing caused by the insertion of the B2 sequence into an intron of the complement C4 gene is the basis for low C4 production in H-2k mice. J Biol Chem. 1992;267:7814-20 pubmed
  23. Amor M, Tosi M, Duponchel C, Steinmetz M, Meo T. Liver mRNA probes disclose two cytochrome P-450 genes duplicated in tandem with the complement C4 loci of the mouse H-2S region. Proc Natl Acad Sci U S A. 1985;82:4453-7 pubmed
    ..Sequences hybridizing with liver poly(A)+ RNA were found within a cosmid covering a region 3' to the C4-Slp gene (the gene encoding the hemolytically inactive isoform of the fourth component of serum complement)...
  24. Beurskens F, Kuenen J, Hofhuis F, Fluit A, Robins D, Van Dijk H. Sex-limited protein: in vitro and in vivo functions. Clin Exp Immunol. 1999;116:395-400 pubmed
    ..C4 exists in two isoforms, C4 and a protein with expression restricted to male animals called sex-limited protein (Slp)...
  25. Yang Z, Yu C. Organizations and gene duplications of the human and mouse MHC complement gene clusters. Exp Clin Immunogenet. 2000;17:1-17 pubmed
    ..intron 4 of mouse RP1 is an endogenous retrovirus that probably confers the androgen-responsive expression of the Slp protein in certain male mice...
  26. Dodds A, Law S. The complement component C4 of mammals. Biochem J. 1990;265:495-502 pubmed, but only one gene produces active C4, while the other codes for the closely related sex-limited protein (Slp)...
  27. Ogata R. Structure and expression of murine fourth complement component (C4) and sex-limited protein (Slp). Immunol Rev. 1985;87:101-22 pubmed
    ..years we have used recombinant DNA technology to build upon previous genetic and biochemical studies of the C4 and Slp genes and their products...
  28. Ogata R, Sepich D. Murine sex-limited protein: complete cDNA sequence and comparison with murine fourth complement component. J Immunol. 1985;135:4239-44 pubmed
    Murine sex-limited protein (Slp) is a structural homologue of the murine fourth complement component (C4) that lacks C4 activity and has no known function...
  29. Robins D, Malissen M, Hood L, Ferreira A, Walthall D, Mitchell M. Multiple C4/Slp genes distinguished by expression after transfection. Mol Cell Biol. 1986;6:134-41 pubmed
    ..histocompatibility complex contains two closely related genes: C4, encoding the fourth component of complement, and Slp, encoding sex-limited protein. We cloned these genes from a cosmid library of the B10...
  30. Scarlett C, Scheller A, Thompson E, Robins D. Involvement of an octamer-like sequence within a crucial region of the androgen-dependent Slp enhancer. DNA Cell Biol. 1997;16:45-57 pubmed
    Androgen dependence of the mouse sex-limited protein (Slp) gene is conferred by an enhancer encompassing a consensus hormone response element (HRE) and sites for several nonreceptor factors...
  31. Muller U, Stephan D, Philippsen P, Steinmetz M. Orientation and molecular map position of the complement genes in the mouse MHC. EMBO J. 1987;6:369-73 pubmed
    ..The distances between the E alpha and 21-OHB genes is 430 kb and between the C2 and TNF-alpha genes at least 420 kb. ..
  32. Hemenway C, Kalff M, Stavenhagen J, Walthall D, Robins D. Sequence comparison of alleles of the fourth component of complement (C4) and sex-limited protein (Slp). Nucleic Acids Res. 1986;14:2539-54 pubmed
    ..specific for the fourth component of complement (C4) and its androgen-regulated isotype, sex-limited protein (Slp), have been isolated from two mouse haplotypes (H-2d and H-2w7) that show differential C4 activity and differential ..
  33. Robins D, Samuelson L. Retrotransposons and the evolution of mammalian gene expression. Genetica. 1992;86:191-201 pubmed
    ..The first example, concerning the mouse sex-limited protein (Slp), clearly establishes that ancient retroviral enhancer sequences now confer hormonal dependence on the adjacent ..
  34. Yokomori N, Moore R, Negishi M. Sexually dimorphic DNA demethylation in the promoter of the Slp (sex-limited protein) gene in mouse liver. Proc Natl Acad Sci U S A. 1995;92:1302-6 pubmed
    Mouse Slp, a duplicate of the fourth complement component (C4) gene, exhibits EDTA-independent complement activity with a hepatic expression that is male specific...
  35. Robins D. Multiple mechanisms of male-specific gene expression: lessons from the mouse sex-limited protein (Slp) gene. Prog Nucleic Acid Res Mol Biol. 2004;78:1-36 pubmed
  36. Sekar A, Bialas A, de Rivera H, Davis A, Hammond T, Kamitaki N, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530:177-83 pubmed publisher
    ..These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia. ..
  37. Takahashi M, Natsuume Sakai S, Nonaka M, Tanaka S, Shimizu A, Honjo T. Isolation of cDNA clones specifying the fourth component of mouse complement and its isotype, sex-limited protein. Proc Natl Acad Sci U S A. 1984;81:6822-6 pubmed
    ..for the fourth component of mouse complement (C4) and its hormonally regulated isotype, sex-linked protein (Slp), were isolated using as a probe a 20-mer synthetic oligonucleotide corresponding to a known sequence of human C4 ..
  38. Nakayama K, Nonaka M, Yokoyama S, Yeul Y, Pattanakitsakul S, Takahashi M. Recombination of two homologous MHC class III genes of the mouse (C4 and Slp) that accounts for the loss of testosterone dependence of sex-limited protein expression. J Immunol. 1987;138:620-7 pubmed
    In most mouse strains, expression of a gene encoding sex-limited protein (Slp), an isotype of the fourth component of complement (C4), is induced by testosterone, or the gene is not expressed at all; however, in some wild-derived strains ..
  39. Aldrich C, Rodgers J, Rich R. Regulation of Qa-1 expression and determinant modification by an H-2D-linked gene, Qdm. Immunogenetics. 1988;28:334-44 pubmed
    ..Mechanisms of Qdm function may include either a novel protein modification system or an unprecedented case of antigen recognition restricted by a nonclassical major histocompatibility complex molecule. ..
  40. Pattanakitsakul S, Nakayama K, Takahashi M, Nonaka M. Three extra copies of a C4-related gene in H-2w7 mice are C4/Slp hybrid genes generated by multiple recombinational events. Immunogenetics. 1990;32:431-9 pubmed
    Mice bearing the H-2w7 haplotype have five C4-related genes and constitutively express the Slp antigen. To understand the structure and evolution of the five C4-related genes of the C3H...
  41. Carroll M, Passmore H, Capra J. Structural studies on the murine fourth component of complement (C4). IV. Demonstration that C4 and Slp are encoded by separate loci. J Immunol. 1980;124:1745-9 pubmed
    ..for the fourth complement component (C4) and controls C4 serum levels and expression of the sex-limited protein (Slp)...
  42. Nonaka M, Nakayama K, Yeul Y, Shimizu A, Takahashi M. Molecular cloning and characterization of complementary and genomic DNA clones for mouse C4 and Slp. Immunol Rev. 1985;87:81-99 pubmed
  43. Demant P, Capkova J, Hinzová E, Voracova B. The role of the histocompatibility-2-linked Ss-Slp region in the control of mouse complement. Proc Natl Acad Sci U S A. 1973;70:863-4 pubmed
    The Ss-Slp region of the mouse genome is located between the two loci, H-2K and H-2D, of the major histocompatibility system...
  44. Hansen T, Krasteff T, Shreffler D. Quantitative variations in the expression of the mouse serum antigen Ss and its sex-limited allotype Slp. Biochem Genet. 1974;12:281-93 pubmed
  45. Rosa P, Sepich D, Robins D, Ogata R. Constitutive expression of Slp genes in mouse strain B10.WR directed by C4 regulatory sequences. J Immunol. 1987;139:1568-77 pubmed
    The murine fourth component of complement (C4) and sex-limited protein (Slp) are two closely related serum proteins that exhibit very disparate patterns of gene expression: all mice constitutively express C4, whereas only adult male mice ..
  46. Ogata R, Zepf N. The murine Slp gene. Additional evidence that sex-limited protein has no biologic function. J Immunol. 1991;147:2756-63 pubmed
    Sex-limited protein (Slp) is a mouse serum protein of unknown function that has approximately 95% amino acid sequence identity with murine complement component C4 but is inactive in the complement pathway...