Alternative titles; symbols
HGNC Approved Gene Symbol: PSG1
Cytogenetic location: 19q13.2 Genomic coordinates (GRCh38): 19:42,866,464-42,879,713 (from NCBI)
The human placenta is a multihormonal endocrine organ that produces hormones, enzymes, and other molecules that support fetal survival and development. Pregnancy-specific beta-1-glycoprotein (PSBG, PSG) is a major product of the syncytiotrophoblast, reaching concentrations of 100 to 290 mg/l at term in the serum of pregnant women (Horne et al., 1976). PSG is a member of the immunoglobulin (Ig) superfamily (Watanabe and Chou, 1988; Streydio et al., 1988).
Watanabe and Chou (1988) and Streydio et al. (1988) independently reported the isolation of cDNA sequences encoding different members of the PSBG family. Both reports noted a striking similarity to the carcinoembryonic antigen (CEA; 114890)-related proteins, involving the existence of signal peptides, N-terminal domains and tandemly arranged doublets of Ig-like domains.
Niemann et al. (1989) isolated a PSBG cDNA from a human placenta cDNA library, which was similar to one of the clones (PSG93) described by Watanabe and Chou (1988).
As noted by Teglund et al. (1994), all known members of the CEA/PSG family have a similar gene organization. The first exon, denoted L., codes for the 5-prime UTR and part (21 amino acids) of the signal peptide. Exon 2, denoted L/N, codes for the rest of the signal peptide (13 amino acids) and the first domain of the mature protein, termed N domain (107-110 amino acids), which is homologous to the Ig variable domain (IgV). Depending on the gene, this domain is followed by 0 to 6 IgC-like domains (C2 type) denoted A (92 amino acids) and B (86 amino acids), each encoded by a single exon. The PSGs have short and relatively hydrophilic C-terminal ends indicating extracellular secretion. The CEA subgroup molecules, on the other hand, are anchored to the cell membrane.
Khan et al. (1992) estimated the size of the PSG subfamily by identification of N-domain exons from isolated genomic clones and from total genomic DNA through PCR amplification and DNA sequence determination. They found that the PSG subfamily contains at least 11 different genes. For 7 of these, 2 DNA sequences differing from each other in 1 to 4 nucleotides were detected. Most likely they represent different alleles. All of the PSGs except PSG1, PSG4 (176393), and PSG8 (176397) contain the arginine-glycine-aspartic acid sequence at position 93-95 corresponding to the complementarity determining region 3 of immunoglobulin. Parsimony analysis of 24 CEA and PSG sequences using 12 members of the immunoglobulin gene superfamily as out-groups to root the family tree showed that the N-domain of the CEA group genes evolved in one major branch and the PSG group genes in the other.
By Southern analysis of somatic hybrid cell DNAs, Barnett et al. (1989, 1989) assigned a PSBG locus to chromosome 19. They pointed out that because of the relatedness of PSBG to carcinoembryonic antigen (CEA; 114890), which is located on chromosome 19, their finding may not be unexpected.
By Southern blot hybridization of human/rodent somatic cell hybrids, including some with subchromosomal segments of 19q, Niemann et al. (1989) assigned the gene to the distal part of 19q13.1. Close chromosomal location of PSBG1 to the genes for CEA and of normal cross-reacting antigen (163980) is of interest in light of the close homology of these proteins (Niemann et al., 1989).
Streydio et al. (1990) likewise assigned the PSBG1 gene to chromosome 19 by Southern analysis of human-rodent somatic cell hybrids. They made deductions concerning the evolution of the gene family on the basis of gene structure.
Thompson et al. (1990) presented evidence that multiple genes coding for pregnancy-specific glycoproteins are clustered on 19q. Differential splicing of at least 1 of these genes increases further the number of different proteins. By in situ hybridization, they concluded that the PSG genes are located at 19q13.2-q13.3. The coordinated expression of 5 of the PSG genes in a tissue-specific manner suggested that common regulatory elements may control their transcriptional activities. By fluorescence in situ hybridization to metaphase chromosomes, Brandriff et al. (1992) localized the PSG subgroup of carcinoembryonic antigen genes to an area telomeric to the CEA subgroup. Brandriff et al. (1992) estimated that the CEA-PSG gene family region spans 1.1 to 1.2 Mb.
Using a high-resolution restriction fragment fingerprinting technique, Olsen et al. (1994) assembled 256 cosmids spanning the PSG region on 19q13.2 into a single 700-kb contig. FISH to sperm pronuclei and cosmid walking experiments indicated that this PSG contig is telomeric of CGM8 at the telomeric end of the CEA subgroup gene cluster. Detailed restriction mapping and hybridization with gene-specific probes indicated that the order of the 11 PSG genes in the contig is cen--PSG3 (176392)--PSG8--PSG12 (PSG10; 176399)--PSG1--PSG6 (176395)--PSG7 (176396)--PSG13 (PSG11; 176401)--PSG2 (176391)--PSG5 (176394)--PSG4--PSG11 (PSG9; 176398)--tel. The PSG genes are tandemly oriented in a 5-prime to 3-prime direction from telomere to centromere. The CEA subgroup gene CGM11 is located at the telomeric end of the PSG gene cluster, and 6 genes belonging to a third CEA family subgroup, namely CGM13 through CGM18 (later found to be pseudogenes; see 109770), are interspersed among the PSG genes.
Teglund et al. (1994) determined that the PSG1 gene contains 6 exons.
PSBG levels have been found to correlate well with placental function and fetal well-being (Gordon et al., 1977; Bartels and Lindemann, 1988).
Low PSG levels are associated with poor pregnancy outcome (Wurz et al., 1981).
Bartels and Lindemann (1988) found elevated PSBG in the maternal blood in the second trimester of pregnancy when the fetus had trisomy 21.
Elevated levels of PSGs are found in serum of patients with choriocarcinoma and hydatidiform mole (231090) (Tatarinov et al., 1976; Leslie et al., 1990), suggesting their potential utility as tumor markers.
Beauchemin et al. (1999) provided a revised nomenclature for the CEA gene family. Based on this nomenclature, the CEA family is composed of the PSG subfamily, the CEACAM subfamily (see 109770), and the CEACAM pseudogene (CEACAMP) subfamily (see 109770). PSG11, PSG12, and PSG13 were renamed PSG9, PSG10, and PSG11, respectively.
Chan and Qiu (1988) reported multiple genes coding for SP1 by hybridization of an SP1 cDNA probe to multiple bands on Southern blots of human genomic DNA. By analysis of chromosomal DNA dot blots, they demonstrated the presence of sequences on the X chromosome and on chromosome 6. Barnett et al. (1989) and Niemann et al. (1989) could not support the conclusions of Chan and Qiu (1988). No dosage effects were observed in lymphoblastoid cell lines with multiple X chromosomes, whereas positive hybridization signals were seen in all cell hybrids which had retained a human chromosome 19.
Barnett, T., Pickle, W., II, Rae, P. M. M., Hart, J., Kamarck, M., Elting, J. Pregnancy-specific beta-1-glycoproteins are related to carcinoembryonic antigens and map to chromosome 19. (Abstract) Cytogenet. Cell Genet. 51: 958, 1989.
Barnett, T. R., Pickle, W., II, Rae, P. M. M., Hart, J., Kamarck, M., Elting, J. Human pregnancy-specific beta(1)-glycoproteins are coded within chromosome 19. Am. J. Hum. Genet. 44: 890-893, 1989. [PubMed: 2786334]
Bartels, I., Lindemann, A. Maternal levels of pregnancy-specific beta-1-glycoprotein (SP-1) are elevated in pregnancies affected by Down's syndrome. Hum. Genet. 80: 46-48, 1988. [PubMed: 2971018] [Full Text: https://doi.org/10.1007/BF00451454]
Beauchemin, N., Draber, P., Dveksler, G., Gold, P., Gray-Owen, S., Grunert, F., Hammarstrom, S., Holmes, K. V., Karlsson, A., Kuroki, M., Lin, S.-H., Lucka, L., and 13 others. Redefined nomenclature for members of the carcinoembryonic antigen family. Exp. Cell Res. 252: 243-249, 1999. [PubMed: 11501563] [Full Text: https://doi.org/10.1006/excr.1999.4610]
Brandriff, B. F., Gordon, L. A., Tynan, K. T., Olsen, A. S., Mohrenweiser, H. W., Fertitta, A., Carrano, A. V., Trask, B. J. Order and genomic distances among members of the carcinoembryonic antigen (CEA) gene family determined by fluorescence in situ hybridization. Genomics 12: 773-779, 1992. [PubMed: 1572650] [Full Text: https://doi.org/10.1016/0888-7543(92)90308-f]
Chan, W.-Y., Qiu, W.-R. Human pregnancy-specific beta-1 glycoprotein is encoded by multiple genes localized on two chromosomes. Am. J. Hum. Genet. 43: 152-159, 1988. Note: Erratum: Am. J. Hum. Genet. 44: 908 only, 1989. [PubMed: 2840821]
Gordon, Y. B., Jeffrey, D., Grudzinska, J. G., Chard, T., Letchworth, A. T. Concentration of pregnancy-specific beta-1-glycoprotein in maternal blood in normal pregnancy and in intrauterine growth retardation. Lancet 309: 331-333, 1977. Note: Originally Volume I. [PubMed: 64859] [Full Text: https://doi.org/10.1016/s0140-6736(77)91135-7]
Horne, C. H. W., Towler, C. M., Pugh-Humphreys, R. G. P., Thomson, A. W., Bohn, H. Pregnancy-specific beta-1-glycoprotein--a product of the syncytiotrophoblast. Experientia 32: 1197-1199, 1976. [PubMed: 971765] [Full Text: https://doi.org/10.1007/BF01927624]
Khan, W. N., Teglund, S., Bremer, K., Hammarstrom, S. The pregnancy-specific glycoprotein family of the immunoglobulin superfamily: identification of new members and estimation of family size. Genomics 12: 780-787, 1992. [PubMed: 1572651] [Full Text: https://doi.org/10.1016/0888-7543(92)90309-g]
Leslie, K. K., Watanabe, S., Lei, K.-J., Chou, D. Y., Plouzek, C. A., Deng, H.-C., Torres, J., Chou, J. Y. Linkage of two human pregnancy-specific beta 1-glycoprotein genes: one is associated with hydatidiform mole. Proc. Nat. Acad. Sci. 87: 5822-5826, 1990. [PubMed: 2377620] [Full Text: https://doi.org/10.1073/pnas.87.15.5822]
Niemann, S. C., Flake, A., Bohn, H., Bartels, I. Pregnancy-specific beta-1-glycoprotein: cDNA cloning, tissue expression, and species specificity of one member of the PSBG family. Hum. Genet. 82: 239-243, 1989. [PubMed: 2786492] [Full Text: https://doi.org/10.1007/BF00291162]
Niemann, S. C., Schonk, D., van Dijk, P. E., Grzeschik, K.-H., Bartels, I. Chromosomal assignment of a cDNA clone encoding pregnancy-specific beta-1-glycoprotein to chromosome 19. (Abstract) Cytogenet. Cell Genet. 51: 1053, 1989.
Niemann, S. C., Schonk, D., van Dijk, P., Wieringa, B., Grzeschik, K.-H., Bartels, I. Regional localization of the gene encoding pregnancy specific beta-1-glycoprotein 1 (PSBG1) to human chromosome 19q13.1. Cytogenet. Cell Genet. 52: 95-97, 1989. [PubMed: 2612223] [Full Text: https://doi.org/10.1159/000132851]
Olsen, A., Teglund, S., Nelson, D., Gordon, L., Copeland, A., Georgescu, A., Carrano, A., Hammarstrom, S. Gene organization of the pregnancy-specific glycoprotein region on human chromosome 19: assembly and analysis of a 700-kb cosmid contig spanning the region. Genomics 23: 659-668, 1994. [PubMed: 7851895] [Full Text: https://doi.org/10.1006/geno.1994.1555]
Streydio, C., Lacka, K., Swillens, S., Vassart, G. The human pregnancy-specific beta-1-glycoprotein (PS-beta-G) and the carcinoembryonic antigen (CEA)-related proteins are members of the same multigene family. Biochem. Biophys. Res. Commun. 154: 130-137, 1988. [PubMed: 3260773] [Full Text: https://doi.org/10.1016/0006-291x(88)90660-2]
Streydio, C., Swillens, S., Georges, M., Szpirer, C., Vassart, G. Structure, evolution and chromosomal localization of the human pregnancy-specific beta-1 glycoprotein gene family. Genomics 6: 579-592, 1990. Note: Erratum: Genomics 7: 661-662, 1990. [PubMed: 2341148] [Full Text: https://doi.org/10.1016/0888-7543(90)90492-d]
Tatarinov, Y. S., Falaleeva, D. M., Kalashnikov, V. V. Human pregnancy-specific beta-1-globulin and its relation to chorioepithelioma. Int. J. Cancer 17: 626-632, 1976. [PubMed: 57935] [Full Text: https://doi.org/10.1002/ijc.2910170511]
Teglund, S., Olsen, A., Khan, W. N., Frangsmyr, L., Hammarstrom, S. The pregnancy-specific glycoprotein (PSG) gene cluster on human chromosome 19: fine structure of the 11 PSG genes and identification of 6 new genes forming a third subgroup within the carcinoembryonic antigen (CEA) family. Genomics 23: 669-684, 1994. [PubMed: 7851896] [Full Text: https://doi.org/10.1006/geno.1994.1556]
Thompson, J., Koumari, R., Wagner, K., Barnert, S., Schleussner, C., Schrewe, H., Zimmermann, W., Muller, G., Schempp, W., Zaninetta, D., Ammaturo, D., Hardman, N. The human pregnancy-specific glycoprotein genes are tightly linked on the long arm of chromosome 19 and are coordinately expressed. Biochem. Biophys. Res. Commun. 167: 848-859, 1990. Note: Erratum: Biochem. Biophys. Res. Commun. 168: 1325 only, 1990. [PubMed: 1690992] [Full Text: https://doi.org/10.1016/0006-291x(90)92103-7]
Watanabe, S., Chou, J. Y. Isolation and characterization of complementary DNAs encoding human pregnancy-specific beta-1-glycoprotein. J. Biol. Chem. 263: 2049-2054, 1988. [PubMed: 3257488]
Wurz, H., Geiger, W., Kunzig, H. J., Jabs-Lehmann, A., Bohn, H., Luben, G. Radioimmunoassay of SP1 (pregnancy-specific beta-1-glycoprotein) in maternal blood and in amniotic fluid in normal and pathologic pregnancies. J. Perinat. Med. 9: 67-78, 1981. [PubMed: 6787188] [Full Text: https://doi.org/10.1515/jpme.1981.9.2.67]