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GERM CELL-LESS 1, SPERMATOGENESIS-ASSOCIATED; GMCL1

GERM CELL-LESS 1, SPERMATOGENESIS-ASSOCIATED; GMCL1

Alternative titles; symbolsGCLGERM CELL-LESS, DROSOPHILA, HOMOLOG OF, 1GERM CELL-LESS PROTEIN-LIKE 1; GCL1SPERMATOGENESIS-ASSOCIATED 29; SPATA29BTBD13HGNC Approv...

Alternative titles; symbols

  • GCL
  • GERM CELL-LESS, DROSOPHILA, HOMOLOG OF, 1
  • GERM CELL-LESS PROTEIN-LIKE 1; GCL1
  • SPERMATOGENESIS-ASSOCIATED 29; SPATA29
  • BTBD13

HGNC Approved Gene Symbol: GMCL1

Cytogenetic location: 2p13.3 Genomic coordinates (GRCh38): 2:69,829,659-69,881,388 (from NCBI)

▼ Description

GMCL1 encodes a nuclear envelope protein involved in spermatogenesis (summary by Kleiman et al., 2003).

▼ Cloning and Expression

Jongens et al. (1992) cloned Drosophila germ cell-less (gcl), which encodes a 569-amino protein required for embryonic germ cell development. The distribution of gcl during early embryogenesis was specifically associated with the nuclei that became fated to the germ cell lineage.

Kimura et al. (1999) cloned mouse Gcl. The deduced 524-amino acid protein contains a BTB/POZ domain and shares 34% sequence identity with the Drosophila protein. Northern blot analysis detected high expression of Gcl in adult testis, with low expression in 9 other tissues tested. In situ hybridization analysis revealed strong expression of gcl in primary spermatocytes, especially in pachytene stage, but not in spermatogonia or spermatids.

Nili et al. (2001) cloned human GMCL1. The deduced 386-amino acid protein contains a BTB/POZ domain and is highly homologous to the mouse and Drosophila proteins. Northern blot analysis detected high expression of GMCL1 in testis and low expression in pancreas, kidney, liver, heart, and placenta. No expression was detected in adult ovaries.

Nili et al. (2001) found that the mouse Gcl protein contains 2 putative N-terminal nuclear localization signal motifs and a possible tyrosine phosphorylation site in addition to the N-terminal BTB/POZ domain.

Using quantitative RT-PCR analysis, Holaska et al. (2003) showed that GCL was expressed in a tissue-specific manner and present at low levels in heart and skeletal muscle.

▼ Gene Structure

Kimura et al. (1999) determined that the mouse Gcl gene contains 14 exons and spans more than 50 kb.

▼ Mapping

By radiation hybrid analysis, Nili et al. (2001) mapped the GMCL1 gene to chromosome 2p14-p13.

▼ Gene Function

Jongens et al. (1992) showed that female flies with reduced gcl function produced sterile progeny lacking germ cells.

Holaska et al. (2003) found that human emerin (300384) specifically bound to GCL and also to BAF (603811). Two regions in emerin were essential for binding to GCL: one overlapping the LEM motif and the other near the transmembrane domain. Deletion analysis revealed that an emerin mutation known to cause Emery-Dreifuss muscular dystrophy (EDMD1; 310300) disrupted emerin binding to GCL and also to lamin A (see LMNA, 150330). Binding competition studies demonstrated that BAF binding to the LEM domain of emerin displaced GCL by reducing its affinity, since GCL also bound to residues at the C terminus of the LEM domain. However, lamin A did not compete with GCL or BAF, as emerin was capable of binding with lamin A and GCL or lamin A and BAF, simultaneously.

In a study of 67 azoospermic men with normal karyotypes, Kleiman et al. (2003) found that the expression level of GMCL1 correlated with the severity of the testicular impairment. Defective sperm motility was associated with the absence of GMCL1. Likewise, in a study of genes associated with asthenozoospermia, Liu et al. (2018) found that GMCL1 was downregulated, along with ASRGL1 (609212), another spermatocyte-specific gene.

Using a yeast 2-hybrid system, Gjerstorff et al. (2012) found that GCL interacted with GAGE12I (300637). GMCL1 residues 209-320, including the BACK domain, were necessary and sufficient for the interaction. GMCL1 also binds at the nuclear envelope inner membrane, where the authors proposed that GCL, along with other GAGE-related proteins, interact with dsDNA and modify chromatin both in germ cells and in cancer.

In mouse, Nili et al. (2001) found that endogenous Gcl colocalized with Lap2-beta (see TMPO, 188380) to the nuclear envelope (NE). However, as a soluble protein, Gcl was not an integral membrane protein of the NE, but rather a nuclear matrix protein associated with the NE through the interaction with Lap2-beta. Using coexpression analysis, Nili et al. (2001) showed that Gcl and Lap2-beta proteins reduced the transcriptional activity of the heterodimeric E2f5 (600967)-Dp3-alpha complex.

Using yeast 2-hybrid screening, Masuhara et al. (2003) showed that mouse Gcl1 bound to Tsg101 (601387). The Ubc domain of TSG101 interferes with the ubiquitination of MDM2 (164785), and consequently, TSG101 elevates the steady-state level of MDM2 by inhibiting MDM2 decay. Overexpression of mouse Gcl1 altered the subcellular localization of Mdm2 from nucleus to cytoplasm and reduced the amount of Mdm2 in a posttranscriptional manner, likely thorough the binding between Mdm2 and Tgs101. Reduction of Mdm2 increased the amount and the transcriptional activity of p53 (191170).

Tags: 2p13.3