2h8r | pdb_00002h8r

Hepatocyte Nuclear Factor 1b bound to DNA: MODY5 Gene Product

Loading... Status: waiting for Mol* initialization Structural highlights 2h8r is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease HNF1B_HUMAN Defects in HNF1B are the cause of renal cysts and diabetes syndrome (RCAD) [MIM:137920; also called maturity-onset diabetes of the young type 5 (MODY5) or familial hypoplastic glomerulocystic kidney disease (GCKD). RCAD is an autosomal dominant disorder comprising non-diabetic renal disease resulting from abnormal renal development, and diabetes, which in some cases occurs earlier than age 25 years and is thus consistent with a diagnosis of maturity-onset diabetes of the young (MODY5). The renal disease is highly variable and includes renal cysts, glomerular tufts, aberrant nephrogenesis, primitive tubules, irregular collecting systems, oligomeganephronia, enlarged renal pelves, abnormal calyces, small kidney, single kidney, horseshoe kidney, and hyperuricemic nephropathy. Defects in HNF1B may be rare genetic risk factor contributing to the development of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance. Defects in HNF1B may be a cause of susceptibility to prostate cancer hereditary type 11 (HPC11) [MIM:611955. It is a condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Function HNF1B_HUMAN Transcription factor, probably binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed HNF1beta is an atypical POU transcription factor that participates in a hierarchical network of transcription factors controlling the development and proper function of vital organs such as liver, pancreas, and kidney. Many inheritable mutations on HNF1beta are the monogenic causes of diabetes and several kidney diseases. To elucidate the molecular mechanism of its function and the structural basis of mutations, we have determined the crystal structure of human HNF1beta DNA binding domain in complex with a high-affinity promoter. Disease-causing mutations have been mapped to our structure, and their predicted effects have been tested by a set of biochemical/ functional studies. These findings together with earlier findings with a homologous protein HNF1alpha, help us to understand the structural basis of promoter recognition by these atypical POU transcription factors and the site-specific functional disruption by disease-causing mutations. Structural basis of disease-causing mutations in hepatocyte nuclear factor 1beta.,Lu P, Rha GB, Chi YI Biochemistry. 2007 Oct 30;46(43):12071-80. Epub 2007 Oct 9. PMID:17924661 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA