RING-CH finger, H2 subclass (C4HC3-type), found in transcriptional repressor NF-X1, NF-X1-type zinc finger protein NFXL1, and similar proteins
NF-X1, also known as nuclear transcription factor, X box-binding protein 1, is a novel cysteine-rich sequence-specific DNA-binding protein that interacts with the conserved X-box motif of the human major histocompatibility complex (MHC) class II genes via a repeated Cys-His domain. It functions as a cytokine-inducible transcriptional repressor that plays an important role in regulating the duration of an inflammatory response by limiting the period in which class II MHC molecules are induced by interferon gamma (IFN- gamma). NFXL1, also known as NF-X1-type zinc finger protein NFXL1 or ovarian zinc finger protein (OZFP), is encoded by a novel human cytoplasm-distribution zinc finger protein (CDZFP) gene. This subfamily also includes NF-X1 homologs from insects, plants, and fungi. Drosophila melanogaster shuttle craft (STC) is a DNA- or RNA-binding protein required for proper axon guidance in the central nervous system. It functions as a putative transcription factor and plays an essential role in the completion of embryonic development. In contrast to NF-X1, STC contains an RD domain. The Arabidopsis genome encodes two NF-X1 homologs, AtNFXL1 and AtNFXL2, both of which function as regulators of salt stress responses. The AtNFXL1 protein is a nuclear factor that positively affects adaptation to salt stress. It also functions as a negative regulator of the type A trichothecene phytotoxin-induced defense response. AtNFXL2 controls abscisic acid (ABA) levels and suppresses ABA responses. It may also prevent unnecessary and costly stress adaptation under favorable conditions. FKBP12-associated protein 1 (FAP1) is a dosage suppressor of rapamycin toxicity in budding yeast. It is localized in the cytoplasm, but upon rapamycin treatment translocates to the nucleus. FAP1 interacts with FKBP12 in a rapamycin-sensitive manner. It is a proline-rich protein containing a novel cysteine-rich DNA-binding motif. Unique structural features of the NFX1 and NFXL proteins are the Cys-rich region and a specific RING-CH finger motif with an unusual arrangement of zinc-coordinating residues. The Cys-rich region is required for binding to specific promoter elements. It frequently comprises more than 500 amino acids and harbors several NFX1-type zinc finger domains, characterized by the pattern C-X(1-6)-H-X-C-X3-C(H/C)-X(3-4)-(H/C)-X(1-10)-C. The RING-CH finger, also known as vRING or RINGv, may have E3 ligase activity. It is characterized by a C4HC3-type Zn ligand signature and additional conserved amino acids, rather than the C3H2C3-type cysteines and histidines arrangement in canonical RING-H2 finger. In addition to the Cys-rich region and RING-CH finger, NFX1 contains a PAM2 motif in the N-terminus and a R3H domain in the C-terminus.
Comment:A RING finger typically binds two zinc atoms, with its Cys and/or His side chains in a unique "cross-brace" arrangement.
Comment:The RING fingers found in NFX1 and its homologs have an unusual arrangement of zinc-coordinating residues: The conserved helix complete with tryptophan at the C-terminal end is present but the cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the typical C3H2C3-type in RING-H2 finger.
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