6hax | pdb_00006hax

Crystal structure of PROTAC 2 in complex with the bromodomain of human SMARCA2 and pVHL:ElonginC:ElonginB

spinqualitylabelsall models 6hax, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6hax is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, EPE, FWZ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [SMCA2_HUMAN] Defects in SMARCA2 are the cause of Nicolaides-Baraitser syndrome (NCBRS) [MIM:601358]. A rare disorder characterized by severe mental retardation with absent or limited speech, seizures, short stature, sparse hair, typical facial characteristics, brachydactyly, prominent finger joints and broad distal phalanges. Some of the features are progressive with time. [VHL_HUMAN] Defects in VHL are a cause of susceptibility to pheochromocytoma (PCC) [MIM:171300]. A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Defects in VHL are the cause of von Hippel-Lindau disease (VHLD) [MIM:193300]. VHLD is a dominantly inherited familial cancer syndrome characterized by the development of retinal angiomatosis, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst). VHL type 2C refers to patients with isolated pheochromocytoma without hemangioblastoma or renal cell carcinoma. The estimated incidence is 3/100000 births per year and penetrance is 97% by age 60 years. [:] Defects in VHL are the cause of familial erythrocytosis type 2 (ECYT2) [MIM:263400]; also called VHL-dependent polycythemia or Chuvash type polycythemia. ECYT2 is an autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events. Defects in VHL are a cause of renal cell carcinoma (RCC) [MIM:144700]. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Function [ELOB_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. [SMCA2_HUMAN] Transcriptional coactivator cooperating with nuclear hormone receptors to potentiate transcriptional activation. Also involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). [ELOC_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. [VHL_HUMAN] Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.

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