- RING finger domain
Symbol = zf-C3HC4
Name = Zinc finger, C3HC4 type (RING finger)
SCOP = 1chc
PDB=PDB3|1jm7A:24-64 PDB3|1rmd :290-328 PDB3|1bor :57-91PDB3|2csyA:256-293 PDB3|1fbvA:381-419 PDB3|1x4jA:463-503PDB3|1iymA:134-175 PDB3|1u6gB:75-96 PDB3|1ldjB:75-96PDB3|1ldkC:75-96 PDB3|1chc :8-46 PDB3|1v87A:409-469PDB3|2ct2A:20-64 PDB3|1g25A:6-49 PDB3|1vyxA:9-53
The RING finger domain is a type of
zinc fingerwhich contains a Cys3HisCys4 amino acidmotif which binds two zinc cations.cite journal | author = Borden KL, Freemont PS | title = The RING finger domain: a recent example of a sequence-structure family | journal = Curr. Opin. Struct. Biol. | volume = 6 | issue = 3 | pages = 395–401 | year = 1996 | pmid = 8804826 | doi = 10.1016/S0959-440X(96)80060-1 | issn = ] This proteindomain contains from 40 to 60 amino acids. The acronym RING stands for Really Interesting New Gene.cite journal | author = Hanson IM, Poustka A, Trowsdale J | title = New genes in the class II region of the human major histocompatibility complex | journal = Genomics | volume = 10 | issue = 2 | pages = 417–24 | year = 1991 | pmid = 1906426 | doi = | url = http://linkinghub.elsevier.com/retrieve/pii/0888-7543(91)90327-B | issn = ] cite journal | author = Freemont PS, Hanson IM, Trowsdale J | title = A novel cysteine-rich sequence motif | journal = Cell | volume = 64 | issue = 3 | pages = 483–4 | year = 1991 | pmid = 1991318 | doi = | issn = ] cite journal | author = Lovering R, Hanson IM, Borden KL, Martin S, O'Reilly NJ, Evan GI, Rahman D, Pappin DJ, Trowsdale J, Freemont PS | title = Identification and preliminary characterization of a protein motif related to the zinc finger | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 6 | pages = 2112–6 | year = 1993 | pmid = 7681583 | doi = 10.1073/pnas.90.6.2112 | issn = ]
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 lipidsubstrates.cite journal | author = Klug A | title = Zinc finger peptides for the regulation of gene expression | journal = J. Mol. Biol. | volume = 293 | issue = 2 | pages = 215–8 | year = 1999 | pmid = 10529348 | doi = 10.1006/jmbi.1999.3007 | issn = ] cite journal | author = Hall TM | title = Multiple modes of RNA recognition by zinc finger proteins | journal = Curr. Opin. Struct. Biol. | volume = 15 | issue = 3 | pages = 367–73 | year = 2005 | pmid = 15963892 | doi = 10.1016/j.sbi.2005.04.004 | issn = ] cite journal | author = Brown RS | title = Zinc finger proteins: getting a grip on RNA | journal = Curr. Opin. Struct. Biol. | volume = 15 | issue = 1 | pages = 94–8 | year = 2005 | pmid = 15718139 | doi = 10.1016/j.sbi.2005.01.006 | issn = ] cite journal | author = Gamsjaeger R, Liew CK, Loughlin FE, Crossley M, Mackay JP | title = Sticky fingers: zinc-fingers as protein-recognition motifs | journal = Trends Biochem. Sci. | volume = 32 | issue = 2 | pages = 63–70 | year = 2007 | pmid = 17210253 | doi = 10.1016/j.tibs.2006.12.007 | issn = ] cite journal | author = Matthews JM, Sunde M | title = Zinc fingers--folds for many occasions | journal = IUBMB Life | volume = 54 | issue = 6 | pages = 351–5 | year = 2002 | pmid = 12665246 | doi = 10.1080/15216540216035 | issn = ] 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, cytoskeletonorganisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing.cite journal | author = Laity JH, Lee BM, Wright PE | title = Zinc finger proteins: new insights into structural and functional diversity | journal = Curr. Opin. Struct. Biol. | volume = 11 | issue = 1 | pages = 39–46 | year = 2001 | pmid = 11179890 | doi = 10.1016/S0959-440X(00)00167-6 | issn = ] 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.
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.cite journal | author = Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM | title = RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 20 | pages = 11364–9 | year = 1999 | pmid = 10500182 | doi = 10.1073/pnas.96.20.11364 | issn = ] cite journal | author = Joazeiro CA, Weissman AM | title = RING finger proteins: mediators of ubiquitin ligase activity | journal = Cell | volume = 102 | issue = 5 | pages = 549–52 | year = 2000 | pmid = 11007473 | doi = | url = http://linkinghub.elsevier.com/retrieve/pii/S0092-8674(00)00077-5 | issn = ] cite journal | author = Freemont PS | title = RING for destruction? | journal = Curr. Biol. | volume = 10 | issue = 2 | pages = R84–7 | year = 2000 | pmid = 10662664 | doi = | url = http://linkinghub.elsevier.com/retrieve/pii/bb10b10 | issn = ]
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:
* C is a conserved
cysteineresidue involved zinc coordination,
* H is a conserved
histidineinvolved in zinc coordination,
* Zn is zinc atom, and
* X is any amino acid residue.
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
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.
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