This entry represents the testis-determining factor Sry (Sex-determining Region Y). Sry is a transcriptional activator that regulates a genetic switch inmale development. It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells []. Sry is involved in different aspects of gene regulation including promoter activation or repression and contains a high-mobility-group (HMG) box that recognises DNA by partial intercalation in the minor groove []. It binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'. Sry also facilitates DNA bending and is involved in pre-mRNA splicing. It is also involved in maintenance of motor functions of dopaminergic neurons in the male adult brain. Sry interacts with a number of partners, including CALM, EP300 (modulates Sry DNA-binding activity), HDAC3, KPNB1, ZNF208 isoform KRAB-O, PARP1 (impaired Sry DNA-binding activity), SLC9A3R2 and WT1. The C-terminal nuclear localization signal in Sry HMG-box domain mediates nuclear import through importin beta 1 [].Defects in Sry can cause gonadal dysgenesis XY female type (GDXY) (OMIM:306100), which is also known as 'XY females' or Swyer syndrome []. Patients suffer rapid and early degeneration of their gonads, which prevents the development secondary sexual characteristics at puberty. Defects in Sry are also found Turner's Syndrome, a disease characterised by gonadal dysgenesis in a 45,X female type []. Defects in Sry can also cause true hermaphroditism (OMIM:235600), genetically heterogeneous condition whre patients have both mature ovarian and mature testicular tissue (46,XX, 46,XY or a mosaic of 46,XX/46,XY) [].
SOX-3 is a HMG box transcription factor. The SOX-3 gene is an X-linked gene related to SRY (sex-determining region Y) []. SOX-3 may play a role in neural development []. Mutations in SOX-3 gene cause several diseases, such as panhypopituitarism X-linked (PHPX) [], mental retardation, X-linked, with isolated growth hormone deficiency (MRXGH) [], and 46,XX sex reversal 3 (SRXX3) [].
TFCP2 (CP2 transcription factor) is a critical regulator of erythroid gene expression [, ]. It also regulates the expressison of the male-dominant sex-determining gene SRY []. TFCP2 can interact with NF-E4 proteins forming heteromeric stage selector protein complex (SSP); this complex is able to bind stage selector element (SSE) and regulate embryonic globin expression in fetal-erythroid cells [].TFCP2 has an N-terminal DNA-binding CP2 domain, a central predicted SAM domain and a C-terminal dimerization domain. This entry represents the SAM domain.
High mobility group (HMG) box domains are involved in binding DNA, and may be involved in protein-protein interactions as well. The structure of the HMG-box domain consists of three helices in an irregular array. HMG-box domains are found in one or more copies in HMG-box proteins, which form a large, diverse family involved in the regulation of DNA-dependent processes such as transcription, replication, and strand repair, all of which require the bending and unwinding of chromatin. Many of these proteins are regulators of gene expression. HMG-box proteins are found in a variety of eukaryotic organisms, and can be broadly divided into two groups, based on sequence-dependent and sequence-independent DNA recognition; the former usually contain one HMG-box motif, while the latter can contain multiple HMG-box motifs.HMG-box domains can be found in single or multiple copies in the following protein classes: HMG1 and HMG2 non-histone components of chromatin; SRY (sex determining region Y protein) involved in differential gonadogenesis; the SOX family of transcription factors []; sequence-specific LEF1 (lymphoid enhancer binding factor 1) and TCF-1 (T-cell factor 1) involved in regulation of organogenesis and thymocyte differentiation []; structure-specific recognition protein SSRP involved in transcription and replication; MTF1 mitochondrial transcription factor; nucleolar transcription factors UBF 1/2 (upstream binding factor) involved in transcription by RNA polymerase I; Abf2 yeast ARS-binding factor []; yeast transcription factors lxr1, Rox1, Nhp6b and Spp41; mating type proteins (MAT) involved in the sexual reproduction of fungi []; and the YABBY plant-specific transcription factors.
High mobility group (HMG) box domains are involved in binding DNA, and may be involved in protein-protein interactions as well. The structure of the HMG-box domain consists of three helices in an irregular array. HMG-box domains are found in one or more copies in HMG-box proteins, which form a large, diverse family involved in the regulation of DNA-dependent processes such as transcription, replication, and strand repair, all of which require the bending and unwinding of chromatin. Many of these proteins are regulators of gene expression. HMG-box proteins are found in a variety of eukaryotic organisms, and can be broadly divided into two groups, based on sequence-dependent and sequence-independent DNA recognition; the former usually contain one HMG-box motif, while the latter can contain multiple HMG-box motifs.HMG-box domains can be found in single or multiple copies in the following protein classes: HMG1 and HMG2 non-histone components of chromatin; SRY (sex determining region Y protein) involved in differential gonadogenesis; the SOX family of transcription factors []; sequence-specific LEF1 (lymphoid enhancer binding factor 1) and TCF-1 (T-cell factor 1) involved in regulation of organogenesis and thymocyte differentiation []; structure-specific recognition protein SSRP involved in transcription and replication; MTF1 mitochondrial transcription factor; nucleolar transcription factors UBF 1/2 (upstream binding factor) involved in transcription by RNA polymerase I; Abf2 yeast ARS-binding factor []; yeast transcription factors lxr1, Rox1, Nhp6b and Spp41; mating type proteins (MAT) involved in the sexual reproduction of fungi []; and the YABBY plant-specific transcription factors. Structurally, the HMG box domain is composed of three helices.
