| Zinc finger, C3HC4 type (RING finger) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Structure of the C3HC4 domain.[1] Zinc ions are black spheres, coordinated by cysteines residues (blue). | |||||||||
| Identifiers | |||||||||
| Symbol | zf-C3HC4 | ||||||||
| Pfam | PF00097 | ||||||||
| Pfam clan | CL0229 | ||||||||
| ECOD | 376.1.1 | ||||||||
| InterPro | IPR001841 | ||||||||
| SMART | SM00184 | ||||||||
| PROSITE | PDOC00449 | ||||||||
| SCOP2 | 1chc /SCOPe /SUPFAM | ||||||||
| |||||||||
Inmolecular biology, aRING (short forReallyInterestingNewGene)finger domain is a proteinstructural domain ofzinc finger type which contains a C3HC4amino acid motif which binds twozinc cations (sevencysteines and onehistidine arranged non-consecutively).[2][3][4][5] This protein domain contains 40 to 60 amino acids. Many proteins containing a RING finger play a key role in theubiquitination pathway. Conversely, proteins with RING finger domains are the largest type ofubiquitin ligases in the human genome.[6]
Zinc finger (Znf)domains are relatively smallprotein 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 bindDNA,RNA, protein and/orlipid substrates.[7][8][9][10][11] 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 ingene transcription, translation, mRNA trafficking,cytoskeleton organisation, epithelial development,cell adhesion,protein folding, chromatin remodelling and zinc sensing.[12] 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 bindubiquitination enzymes and their substrates and hence function asligases. Ubiquitination in turn targets the substrate protein for degradation.[13][14][15]
Duringmeiosis,crossing over betweenhomologous chromosomes (homologs) promotes accuratechromosome segregation.[16] In mammals, the ring-domain proteins RNF212,HEI10 and RNF212B facilitate crossing over between each pair of homologs during meiosis.[16] Studies in the mouse showed that these pro-crossover ring-domain proteins have distinct, but interdependent functions, in facilitating thehomologous recombination andDNA repair processes that produce crossovers.[16]
The RING finger domain has the consensus sequenceC-X2-C-X[9-39]-C-X[1-3]-H-X[2-3]-C-X2-C-X[4-48]-C-X2-C.[2]where:
The following is a schematic representation of the structure of the RING finger domain:[2]
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 of humangenes 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,MARCH2,MARCH3,MARCH4,MARCH5,MARCH6,MARCH7,MARCH8,MARCH9,MARCH10,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, andZSWIM2.