2EZD, 2EZE, 2EZF, 2EZG
3159
15361
ENSG00000137309
ENSMUSG00000046711
P17096
P17095
NM_145904NM_145905NM_001319077NM_001319078NM_001319079NM_001319080NM_001319081NM_001319082
NM_001166539NM_001166540NM_001166541NM_001166542NM_001166543NM_001166544NM_001166545NM_001166546NM_016660
NP_001306011NP_002122NP_665906NP_665908NP_665909NP_665910NP_665912
NP_001160008NP_001160009NP_001160011NP_001160012NP_001160013NP_001160014NP_001160015NP_001160016NP_001160017NP_001160018NP_057869
High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.[5][6]
This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transcription, DNA replication, heterochromatin organization, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells.
HMGA1 proteins are quite small (~10-12 kDa) and basic molecules, and consist of three AT-hooks with the RGRP (Arg-Gly-Arg-Pro) core motif, a novel cross-linking domain located between the second and third AT-hook, and a C-terminal acidic tail characteristic for the HMG family comprising HMGA, HMGB and HMGN proteins.
HMGA1-GFP fusion proteins are highly dynamic in vivo (determined using FRAP analysis), but in contrast also show nanomolar affinity to AT-rich DNA in vitro (determined biochemically), which might be explained due to the extensive post-transcriptional modifications in vivo. HMGA1 preferentially binds to the minor groove of AT-rich regions in double-stranded DNA using its AT-hooks. It has little secondary structure in solution but assumes distinct conformations when bound to substrates such as DNA or other proteins. HMGA1 proteins have high amounts of diverse posttranslational modifications and are located mainly in the nucleus, especially in heterochromatin, but also in mitochondria and the cytoplasm.
Recently it has been shown that HMGA1 proteins, HMGA1a and HMGA1b, can cross-link DNA fibers in vitro and can induce chromatin clustering in vivo suggesting a structural role of HMGA1 proteins in heterochromatin organization.[7]
At least seven transcript variants encoding two different isoforms (HMGA1a, HMGA1b) have been found for this gene.[8] The splice variant HMGA1c with only two AT hooks and no acidic tail is in discussion to be a real member of the HMGA family.
Mice lacking their variant of HMGA1, i.e., Hmga1-/- mice, are diabetic, show a cardiac hypertrophy and express low levels of the insulin receptor.[9]
HMGA1 has been shown to interact with CEBPB[10] and Sp1 transcription factor.[10]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Lokasi Pengunjung: 3.144.12.96