RING finger domain

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Zinc finger, C3HC4 type (RING finger)
Identifiers
Symbol zf-C3HC4
Pfam PF00097
InterPro IPR001841
PROSITE PDOC00449
SCOP 1chc
Available PDB structures:

1jm7A:24-64 1rmd :290-328 1bor :57-91 2csyA:256-293 1fbvA:381-419 1x4jA:463-503 1iymA:134-175 1u6gB:75-96 1ldjB:75-96 1ldkC:75-96 1chc :8-46 1v87A:409-469 2ct2A:20-64 1g25A:6-49 1vyxA:9-53

The RING finger domain is a type of zinc finger which contains a Cys3HisCys4 amino acid motif which binds two zinc cations.[1] This protein domain contains from 40 to 60 amino acids. The acronym RING stands for Really Interesting New Gene.[2][3][4]

Contents

[edit] Zinc fingers

Zinc finger (Znf) domains are relatively small protein motifs that bind one or more zinc atoms, and which usually contain multiple finger-like protrusions that make tandem contacts with their target molecule. They bind DNA, RNA, protein and/or lipid substrates.[5][6][7][8][9] Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing.[10] Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

Some Zn finger domains have diverged such that they still maintain their core structure, but have lost their ability to bind zinc, using other means such as salt bridges or binding to other metals to stabilise the finger-like folds.

[edit] Function

Many RING finger domains simultaneously bind ubiquitination enzymes and their substrates and hence function as ligases. Ubiquitination in turn targets the substrate protein for degradation.[11][12][13]

[edit] Structure

The RING finger domain has the consensus sequence C-X2-C-X[9-39]-C-X[1-3]-H-X[2-3]-C-X2-C-X[4-48]-C-X2-C.[1] where:

  • C is a conserved cysteine residue involved zinc coordination,
  • H is a conserved histidine involved in zinc coordination,
  • Zn is zinc atom, and
  • X is any amino acid residue.

The following is a schematic representation of the structure of the RING finger domain:[1]

                              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

[edit] Examples

Examples of human genes which encode proteins containing a RING finger domain include:

AMFR, BBAP, BFAR, BIRC2, BIRC3, BIRC7, BIRC8, BMI1, BRAP, BRCA1, CBL, CBLB, CBLC, CHFR, COMMD3, DTX1, DTX2, DTX3, DTX3L, DTX4, DZIP3, HCGV, HLTF, HOIL-1, IRF2BP2, KIAA1542, LNX1, LNX2, LOC51136, LONRF1, LONRF2, LONRF3, MARCH1, MARCH10, MARCH2, MARCH3, MARCH4, MARCH5, MARCH6, MARCH7, MARCH8, MARCH9, MEX3A, MEX3B, MEX3C, MEX3D, MGRN1, MIB1, MID1, MID2, MKRN1, MKRN2, MKRN3, MKRN4, MNAT1, MYLIP, NFX1, NFX2, PCGF1, PCGF2, PCGF3, PCGF4, PCGF5, PCGF6, PDZRN3, PDZRN4, PEX10, PJA1, PJA2, PML, PML-RAR, PXMP3, RAD18, RAG1, RAPSN, RBCK1, RBX1, RC3H1, RC3H2, RCHY1, RFP2, RFPL1, RFPL2, RFPL3, RFPL4B, RFWD2, RFWD3, RING1, RNF2, RNF4, RNF5, RNF6, RNF7, RNF8, RNF10, RNF11, RNF12, RNF13, RNF14, RNF19A, RNF20, RNF24, RNF25, RNF26, RNF32, RNF38, RNF39, RNF40, RNF41, RNF43, RNF44, RNF55, RNF71, RNF103, RNF111, RNF113A, RNF113B, RNF121, RNF122, RNF123, RNF125, RNF126, RNF128, RNF130, RNF133, RNF135, RNF138, RNF139, RNF141, RNF144A, RNF145, RNF146, RNF148, RNF149, RNF150, RNF151, RNF152, RNF157, RNF165, RNF166, RNF167, RNF168, RNF169, RNF170, RNF175, RNF180, RNF181, RNF182, RNF185, RNF207, RNF213, RNF215, SH3MD4, SH3RF1, SH3RF2, SYVN1, TIF1, TMEM118, TOPORS, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7, TRAIP, TRIM2, TRIM3, TRIM4, TRIM5, TRIM6, TRIM7, TRIM8, TRIM9, TRIM10, TRIM11, TRIM13, TRIM15, TRIM17, TRIM21, TRIM22, TRIM23, TRIM24, TRIM25, TRIM26, TRIM27, TRIM28, TRIM31, TRIM32, TRIM34, TRIM35, TRIM36, TRIM38, TRIM39, TRIM40, TRIM41, TRIM42, TRIM43, TRIM45, TRIM46, TRIM47, TRIM48, TRIM49, TRIM50, TRIM52, TRIM54, TRIM55, TRIM56, TRIM58, TRIM59, TRIM60, TRIM61, TRIM62, TRIM63, TRIM65, TRIM67, TRIM68, TRIM69, TRIM71, TRIM72, TRIM73, TRIM74, TRIML1, TTC3, UHRF2, VPS11, VPS8, ZNF179, ZNF294, ZNF313, ZNF364, ZNF650, ZNFB7, ZNRF1, ZNRF2, ZNRF3, ZNRF4, and ZSWIM2.

[edit] References

  1. ^ a b c Borden KL, Freemont PS (1996). "The RING finger domain: a recent example of a sequence-structure family". Curr. Opin. Struct. Biol. 6 (3): 395–401. doi:10.1016/S0959-440X(96)80060-1. PMID 8804826. 
  2. ^ Hanson IM, Poustka A, Trowsdale J (1991). "New genes in the class II region of the human major histocompatibility complex". Genomics 10 (2): 417–24. PMID 1906426. 
  3. ^ Freemont PS, Hanson IM, Trowsdale J (1991). "A novel cysteine-rich sequence motif". Cell 64 (3): 483–4. PMID 1991318. 
  4. ^ Lovering R, Hanson IM, Borden KL, Martin S, O'Reilly NJ, Evan GI, Rahman D, Pappin DJ, Trowsdale J, Freemont PS (1993). "Identification and preliminary characterization of a protein motif related to the zinc finger". Proc. Natl. Acad. Sci. U.S.A. 90 (6): 2112–6. doi:10.1073/pnas.90.6.2112. PMID 7681583. 
  5. ^ Klug A (1999). "Zinc finger peptides for the regulation of gene expression". J. Mol. Biol. 293 (2): 215–8. doi:10.1006/jmbi.1999.3007. PMID 10529348. 
  6. ^ Hall TM (2005). "Multiple modes of RNA recognition by zinc finger proteins". Curr. Opin. Struct. Biol. 15 (3): 367–73. doi:10.1016/j.sbi.2005.04.004. PMID 15963892. 
  7. ^ Brown RS (2005). "Zinc finger proteins: getting a grip on RNA". Curr. Opin. Struct. Biol. 15 (1): 94–8. doi:10.1016/j.sbi.2005.01.006. PMID 15718139. 
  8. ^ Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP (2007). "Sticky fingers: zinc-fingers as protein-recognition motifs". Trends Biochem. Sci. 32 (2): 63–70. doi:10.1016/j.tibs.2006.12.007. PMID 17210253. 
  9. ^ Matthews JM, Sunde M (2002). "Zinc fingers--folds for many occasions". IUBMB Life 54 (6): 351–5. doi:10.1080/15216540216035. PMID 12665246. 
  10. ^ Laity JH, Lee BM, Wright PE (2001). "Zinc finger proteins: new insights into structural and functional diversity". Curr. Opin. Struct. Biol. 11 (1): 39–46. doi:10.1016/S0959-440X(00)00167-6. PMID 11179890. 
  11. ^ Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM (1999). "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11364–9. doi:10.1073/pnas.96.20.11364. PMID 10500182. 
  12. ^ Joazeiro CA, Weissman AM (2000). "RING finger proteins: mediators of ubiquitin ligase activity". Cell 102 (5): 549–52. PMID 11007473. 
  13. ^ Freemont PS (2000). "RING for destruction?". Curr. Biol. 10 (2): R84–7. PMID 10662664. 

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