RING finger domain explained

Symbol:zf-C3HC4
Zinc finger, C3HC4 type (RING finger)
Pfam:PF00097
Pfam Clan:CL0229
Interpro:IPR001841
Smart:SM00184
Prosite:PDOC00449
Scop:1chc

In molecular biology, a RING (short for Really Interesting New Gene) finger domain is a protein structural domain of zinc finger type which contains a C3HC4 amino acid motif which binds two zinc cations (seven cysteines and one histidine arranged non-consecutively).[1] [2] [3] [4] This protein domain contains 40 to 60 amino acids. Many proteins containing a RING finger play a key role in the ubiquitination pathway. Conversely, proteins with RING finger domains are the largest type of ubiquitin ligases in the human genome.[5]

Zinc fingers

See main article: Zinc finger. 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.[6] [7] [8] [9] [10] 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.[11] 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.

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.[12] [13] [14]

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.where:

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

x 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 / \ H C / \ C x x x x x x x x x x x x x x x x x

Examples

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

AMFR, BARD1, BBAP, BFAR, BIRC2, BIRC3, BIRC7, BIRC8, BMI1, BRAP, BRCA1, CBL, CBLB, CBLC, CBLL1, CHFR, CNOT4, COMMD3, DTX1, DTX2, DTX3, DTX3L, DTX4, DZIP3, HCGV, HLTF, HOIL-1, IRF2BP2, LNX1, LNX2, LONRF1, LONRF2, LONRF3, MARCH1, MARCH10, MARCH2, MARCH3, MARCH4, MARCH5, MARCH6, MARCH7, MARCH8, MARCH9, MDM2, 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, PHRF1, 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, RNFT1, 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, TRIM33, 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, UHRF1, UHRF2, VPS11, VPS8, ZNF179, ZNF294, ZNF313, ZNF364, ZNF451, ZNF650, ZNFB7, ZNRF1, ZNRF2, ZNRF3, ZNRF4, and ZSWIM2.

Notes and References

  1. Borden KL, Freemont PS . The RING finger domain: a recent example of a sequence-structure family . Curr. Opin. Struct. Biol. . 6 . 3 . 395–401 . 1996 . 8804826 . 10.1016/S0959-440X(96)80060-1 .
  2. Hanson IM, Poustka A, Trowsdale J . New genes in the class II region of the human major histocompatibility complex . Genomics . 10 . 2 . 417–24 . 1991 . 1906426 . 10.1016/0888-7543(91)90327-B.
  3. Freemont PS, Hanson IM, Trowsdale J . A novel cysteine-rich sequence motif . Cell . 64 . 3 . 483–4 . 1991 . 1991318 . 10.1016/0092-8674(91)90229-R . free .
  4. Lovering R, Hanson IM, Borden KL, Martin S, O'Reilly NJ, Evan GI, Rahman D, Pappin DJ, Trowsdale J, Freemont PS . Identification and preliminary characterization of a protein motif related to the zinc finger . Proc. Natl. Acad. Sci. U.S.A. . 90 . 6 . 2112–6 . 1993 . 7681583 . 10.1073/pnas.90.6.2112 . 46035 . 1993PNAS...90.2112L . free .
  5. Scalia . Pierluigi . Williams . Stephen J. . Suma . Antonio . Carnevale . Vincenzo . 2023-06-21 . The DTX Protein Family: An Emerging Set of E3 Ubiquitin Ligases in Cancer . Cells . 12 . 13 . 1680 . 10.3390/cells12131680 . free . 2073-4409 . 37443713. 10340142 .
  6. Klug A . Zinc finger peptides for the regulation of gene expression . J. Mol. Biol. . 293 . 2 . 215–8 . 1999 . 10529348 . 10.1006/jmbi.1999.3007 .
  7. Hall TM . Multiple modes of RNA recognition by zinc finger proteins . Curr. Opin. Struct. Biol. . 15 . 3 . 367–73 . 2005 . 15963892 . 10.1016/j.sbi.2005.04.004 .
  8. Brown RS . Zinc finger proteins: getting a grip on RNA . Curr. Opin. Struct. Biol. . 15 . 1 . 94–8 . 2005 . 15718139 . 10.1016/j.sbi.2005.01.006 .
  9. Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP . Sticky fingers: zinc-fingers as protein-recognition motifs . Trends Biochem. Sci. . 32 . 2 . 63–70 . 2007 . 17210253 . 10.1016/j.tibs.2006.12.007 .
  10. Matthews JM, Sunde M . Zinc fingers--folds for many occasions . IUBMB Life . 54 . 6 . 351–5 . 2002 . 12665246 . 10.1080/15216540216035 . 22109146 . free .
  11. Laity JH, Lee BM, Wright PE . Zinc finger proteins: new insights into structural and functional diversity . Curr. Opin. Struct. Biol. . 11 . 1 . 39–46 . 2001 . 11179890 . 10.1016/S0959-440X(00)00167-6 .
  12. Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM . RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination . Proc. Natl. Acad. Sci. U.S.A. . 96 . 20 . 11364–9 . 1999 . 10500182 . 10.1073/pnas.96.20.11364 . 18039 . 1999PNAS...9611364L . free .
  13. Joazeiro CA, Weissman AM . RING finger proteins: mediators of ubiquitin ligase activity . Cell . 102 . 5 . 549–52 . 2000 . 11007473 . 10.1016/S0092-8674(00)00077-5. free .
  14. Freemont PS . RING for destruction? . Curr. Biol. . 10 . 2 . R84–7 . 2000 . 10662664 . 10.1016/S0960-9822(00)00287-6. free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "RING finger domain".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.