DLC1

2DKY, 2GYT, 2KAP, 2LOZ, 3KUQ, 5FZT1039550768ENSG00000164741ENSG00000285265ENSMUSG00000031523Q96QB1Q9R0Z9NM_001348081NM_001348082NM_001348083NM_001348084NM_001194940NM_001194941NM_015802NM_178735NP_001335010NP_001335011NP_001335012NP_001335013NP_001181869NP_001181870NP_056617Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.2dky: Solution structure of the SAM-domain of Rho-GTPase-activating protein 72gyt: Solution structure of the SAM (sterile alpha motif) domain of DLC1 (deleted in liver cancer 1) Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene. This gene is deleted in the primary tumor of hepatocellular carcinoma. It maps to 8p22-p21.3, a region frequently deleted in solid tumors. It is suggested that this gene is a candidate tumor suppressor gene for human liver cancer, as well as for prostate, lung, colorectal, and breast cancers. The human DLC1 gene is located on the short arm of chromosome 8 (8p21.3-22), within a region that frequently undergoes loss of heterozygosity by either genomic deletion or epigenetic silencing mechanisms in several types of solid cancers. The gene contains 14 exons and produces an mRNA transcript that is 6.3 kb in length; the second AUG present in the open reading frame is the major translational start site, and produces a polypeptide which is 1091 amino acids long. The promoter region of the DLC1 gene contains a CpG island containing several CpG sites which can be methylated to promote gene silencing and prevent transcription. DLC1 is frequently inactivated in human hepatocellular carcinoma, as well as some nasopharyngeal, lung, breast, prostate, kidney, colon, uterine, ovarian, and gastric cancers. The DLC1 protein contains four major functional domains: an N-terminal sterile α motif (SAM), a serine-rich (SR) region, a Rho-GAP domain, and a C-terminal steroidogenic acute regulatory protein related lipid-transfer (START) domain. DLC1 is localized to focal adhesions located at the periphery of cells. The SAM domain (stretching from amino acids 11-78) is believed to be involved in protein-protein interactions. The exact function of the DLC1 SAM domain has not yet been determined. The relatively unstructured and unconserved SR region (amino acids 86-638) contains a focal adhesion targeting (FAT) domain, including a tyrosine residue at position 442, which interacts with SH2 domains of tensin1 and cten. These interactions allow DLC1 to co-localize along with these proteins to focal adhesions at the periphery of the cell, where it is able to carry out its function as a Rho-GAP protein. The highly conserved Rho-GAP domain (amino acids 639-847) functions to enhance the GTPase activity of the Rho-GTPase proteins RhoA and Cdc42, promoting the hydrolysis of their bound GTP to GDP and thus “shutting off” these proteins. DLC1 contains a conserved “arginine finger” arginine residue at position 677, which is located within the active site of the protein and is essential for catalyzation of the GTP hydrolysis. Rho-GTPases are involved in regulating cell morphology (through cytoskeletal organization) and migration (through focal adhesion formation).