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{PDOC00449}
{PS00518; ZF_RING_1}
{PS50089; ZF_RING_2}
{BEGIN}
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* Zinc finger RING-type signature and profile *
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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) [1]
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
"RING-H2 finger".

The 3D structure [2] 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
representation:

                               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

'C': conserved cysteine involved zinc binding.
'H': conserved histidine involved in zinc binding.
'Zn': zinc atom.

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  alpha 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 alpha  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
   DNA sequence.
 - 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
   photomorphogenesis.
 - 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
   promoters.
 - 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.

-Consensus pattern: C-x-H-x-[LIVMFY]-C-x(2)-C-[LIVMYA]
-Sequences known to belong to this class detected by the profile: A majority.
-Other sequence(s) detected in Swiss-Prot: 1.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: December 2001 / Text revised; profile added.

[ 1] Borden K.L.B., Freemont P.S.
     "The RING finger domain: a recent example of a sequence-structure
     family."
     Curr. Opin. Struct. Biol. 6:395-401(1996).
     PubMed=8804826
[ 2] Borden K.L., Boddy M.N., Lally J., O'Reilly N.J., Martin S., Howe K.,
     Solomon E., Freemont P.S.
     "The solution structure of the RING finger domain from the acute
     promyelocytic leukaemia proto-oncoprotein PML."
     EMBO J. 14:1532-1541(1995).
     PubMed=7729428
[ 3] Lorick K.L., Jensen J.P., Fang S., Ong A.M., Hatakeyama S., Weissman A.M.
     "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent
     ubiquitination."
     Proc. Natl. Acad. Sci. U.S.A. 96:11364-11369(1999).
     PubMed=10500182
[ 4] Yokouchi M., Kondo T., Houghton A., Bartkiewicz M., Horne W.C.,
     Zhang H., Yoshimura A., Baron R.
     "Ligand-induced ubiquitination of the epidermal growth factor receptor
     involves the interaction of the c-Cbl RING finger and UbcH7."
     J. Biol. Chem. 274:31707-31712(1999).
     PubMed=10531381

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