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A number of eukaryotic and viral proteins contain a conserved cysteine-rich
domain of 40 to 60 residues (called C3HC4 zinc-finger or 'RING' finger) 
that binds two atoms of zinc. There are two different variants, the C3HC4-type
and the C3H2C3-type, which is clearly related despite the different
cysteine/histidine pattern. The latter type is sometimes referred to as
The 3D structure  of the zinc ligation system is referred to as the "cross-brace" motif. This atypical conformation is also shared by the FYVE (see
<PDOC50178>) and PHD (see <PDOC50016>) domains. The way the "cross-brace"
motif is binding two atoms of zinc is illustrated in the following schematic
x x x x x x
x x x x
x x x
x x x x
C C C C
x \ / x x \ / x
x Zn x x Zn x
C / \ C H / \ C
x x x x
x x x x x x x x x x x x x
Many proteins containing a RING finger play a key role in the ubiquitination
pathway. The ubiquitination pathway generally involves three types of enzyme,
know as E1, E2 and E3. E1 and E2 are ubiquitin conjugating enzymes. E1 acts
first and passes ubiquitin to E2. E3 are ubiquitin protein ligases,
responsible for substrate recognition. It has been shown [3,4] that several
RING fingers act as E3 enzymes in the ubiquitination process.
Some proteins known to include a RING finger are listed below:
Mammalian V(D)J recombination activating protein (gene RAG1). RAG1
activates the rearrangement of immunoglobulin and T-cell receptor genes.
Mouse rpt-1. Rpt-1 is a trans-acting factor that regulates gene expression
directed by the promoter region of the interleukin-2 receptor α chain
or the LTR promoter region of HIV-1.
Human rfp. Rfp is a developmentally regulated protein that may function in
male germ cell development. Recombination of the N-terminal section of rfp
with a protein tyrosine kinase produces the ret transforming protein.
Human 52 Kd Ro/SS-A protein. A protein of unknown function from the Ro/SS-A
ribonucleoprotein complex. Sera from patients with systemic lupus
erythematosus or primary Sjogren's syndrome often contain antibodies that
react with the Ro proteins.
Human histocompatibility locus protein RING1.
Human PML, a probable transcription factor. Chromosomal translocation of
PML with retinoic receptor α creates a fusion protein which is the
cause of acute promyelocytic leukemia (APL).
Mammalian breast cancer type 1 susceptibility protein (BRCA1).
Mammalian cbl proto-oncogene.
Mammalian bmi-1 proto-oncogene.
Vertebrate CDK-activating kinase (CAK) assembly factor MAT1, a protein that
stabilizes the complex between the CDK7 kinase and cyclin H (MAT1 stands
for 'Menage A Trois').
Mammalian mel-18 protein. Mel-18 which is expressed in a variety of tumor
cells is a transcriptional repressor that recognizes and bind a specific
Mammalian peroxisome assembly factor-1 (PAF-1) (PMP35), which is somewhat
involved in the biogenesis of peroxisomes. In humans, defects in PAF-1 are
responsible for a form of Zellweger syndrome, an autosomal recessive
disorder associated with peroxisomal deficiencies.
Xenopus XNF7 protein, a probable transcription factor.
Trypanosoma protein ESAG-8 (T-LR), which may be involved in the
postranscriptional regulation of genes in VSG expression sites or may
interact with adenylate cyclase to regulate its activity.
Drosophila proteins Posterior Sex Combs (Psc) and Suppressor two of zeste
(Su(z)2). The two proteins belong to the Polycomb group of genes needed to
maintain the segment-specific repression of homeotic selector genes.
Drosophila protein male-specific msl-2, a DNA-binding protein which is
involved in X chromosome dosage compensation (the elevation of
transcription of the male single X chromosome).
Arabidopsis thaliana protein COP1 which is involved in the regulation of
Fungal DNA repair proteins RAD5, RAD16, RAD18 and rad8.
Herpesviruses trans-acting transcriptional protein ICP0/IE110. This protein
which has been characterized in many different herpesviruses is a trans-
activator and/or -repressor of the expression of many viral and cellular
Baculoviruses protein CG30.
Baculoviruses major immediate early protein (PE-38).
Baculoviruses immediate-early regulatory protein IE-N/IE-2.
Caenorhabditis elegans hypothetical proteins F54G8.4, R05D3.4 and T02C1.1.
Yeast hypothetical proteins YER116c and YKR017c.
We developed a pattern that specifically recognized the C3HC4-type. We also
developed a profile for C3HC4-type and RING-H2 type.
December 2001 / Text revised; profile added.
PROSITE methods (with tools and information) covered by this documentation:
Borden K.L.B., Freemont P.S.
The RING finger domain: a recent example of a sequence-structure family.
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