RNF128
Description
The RNF128 (ring finger protein 128) is a protein-coding gene located on chromosome X.
RNF128 (RING finger protein 128) is a human gene encoding a type I transmembrane protein that localizes to the endocytic pathway. The protein contains a RING zinc-finger motif and exhibits E3 ubiquitin ligase activity. It is expressed in various tissues, including the liver, adrenal glands, intestines, kidneys, stomach, bladder, and thyroid. Its expression in T cells inhibits cytokine production, suggesting a role in inducing anergy. The RNF128 gene resides on the X chromosome at location Xq22.3, spanning 8 exons and 7 introns. Other aliases for RNF128 include GRAIL (Gene Related to Anergy in Lymphocytes protein), E3 ubiquitin-protein ligase RNF128, FLJ23516, and RING finger protein 128.
RNF128 is an E3 ubiquitin ligase that catalyzes the formation of both 'Lys-48' and 'Lys-63' linked polyubiquitin chains. It functions as an inhibitor of cytokine gene transcription, specifically inhibiting IL2 and IL4 transcription, which is crucial in inducing anergy. Anergy is a state of T-lymphocyte unresponsiveness to antigenic stimulation marked by the suppression of interleukin production. RNF128 ubiquitinates ARPC5 and COR1A, leading to their degradation. This downregulation of cytoskeletal components results in impaired lamellipodium formation and reduced F-actin accumulation at the immunological synapse. RNF128 also plays a role in dorsal ectoderm patterning, increasing the ectoderm's sensitivity to neural-inducing signals.
RNF128 is also known as GRAIL.
Associated Diseases
- neutropenia
- C1 inhibitor deficiency
- common variable immunodeficiency
- autoimmune lymphoproliferative syndrome
- autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency
