In
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
, a RING (short for Really Interesting New Gene) finger domain is a protein
structural domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
of
zinc finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...
type which contains a C
3HC
4 amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
motif which binds two
zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
cations (seven
cysteines and one
histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...
arranged non-consecutively).
This protein domain contains 40 to 60 amino acids. Many proteins containing a RING finger play a key role in the
ubiquitination
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
pathway.
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
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
, protein and/or
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
substrates.
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
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...
, translation, mRNA trafficking,
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
organisation, epithelial development,
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
,
protein folding
Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...
, chromatin remodelling and zinc sensing.
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
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
ation enzymes and their substrates and hence function as
ligase
In biochemistry, a ligase is an enzyme that can catalyze the joining (ligation) of two large molecules by forming a new chemical bond. This is typically via hydrolysis of a small pendant chemical group on one of the larger molecules or the enzym ...
s. Ubiquitination in turn targets the substrate protein for degradation.
Structure
The RING finger domain has the consensus sequence C-X
2-C-X
-39/sub>-C-X -3/sub>-H-X -3/sub>-C-X2-C-X -48/sub>-C-X2-C.
where:
* C is a conserved cysteine residue involved zinc coordination,
* H is a conserved histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...
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:
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 gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s which encode proteins containing a RING finger domain include:
AMFR, BBAP, BFAR, BIRC2
Baculoviral IAP repeat-containing protein 2 (also known as cIAP1) is a protein that in humans is encoded by the ''BIRC2'' gene.
Function
cIAP1 is a member of the Inhibitor of Apoptosis family that inhibit apoptosis by interfering with the acti ...
, BIRC3
Baculoviral IAP repeat-containing protein3 (also known as cIAP2) is a protein that in humans is encoded by the ''BIRC3'' gene.
cIAP2 is a member of the inhibitor of apoptosis family that inhibit apoptosis by interfering with the activation of ca ...
, BIRC7
Baculoviral IAP repeat-containing protein 7 is a protein that in humans is encoded by the ''BIRC7'' gene.
The protein encoded by this gene is a member of the family of inhibitor of apoptosis proteins (IAP) and contains a single copy of a baculo ...
, BIRC8, BMI1
Polycomb complex protein BMI-1 also known as polycomb group RING finger protein 4 (PCGF4) or RING finger protein 51 (RNF51) is a protein that in humans is encoded by the ''BMI1'' gene (B cell-specific Moloney murine leukemia virus integration ...
, BRAP, BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a ...
, CBL, CBLB, CBLC
Signal transduction protein CBL-C is a protein that in humans is encoded by the ''CBLC'' gene.
CBL proteins, such as CBLC, are phosphorylated upon activation of a variety of receptors that signal via protein tyrosine kinases. Through interactions ...
, CBLL1, CHFR, CNOT4
CCR4-NOT transcription complex, subunit 4 is a protein that in humans is encoded by the CNOT4 gene.
Function
The protein encoded by this gene is a subunit of the CCR4-Not complex, a global transcriptional regulator gene, regulator and deadenyla ...
, COMMD3, DTX1, DTX2, DTX3, DTX3L, DTX4, DZIP3, HCGV, HLTF
Helicase-like transcription factor is an enzyme that in humans is encoded by the HLTF gene.
Function
This gene encodes a member of the SWI/SNF family. Members of this family have helicase and ATPase activities and are thought to regulate trans ...
, HOIL-1, IRF2BP2, LNX1
E3 ubiquitin-protein ligase LNX is an enzyme that in humans is encoded by the ''LNX1'' gene.
Interactions
LNX1 has been shown to interact with NAGK, NUMB and PAFAH1B3
Platelet-activating factor acetylhydrolase IB subunit gamma is an enzym ...
, LNX2, LONRF1, LONRF2, LONRF3, MARCH1, MARCH10, MARCH2
E3 ubiquitin-protein ligase MARCH2 is an enzyme that in humans is encoded by the ''MARCH2'' gene. It is a member of the MARCH family of E3 ligases, and plays an important role in the turnover of membrane proteins. MARCH2 has been shown to negativ ...
, MARCH3, MARCH4, MARCH5, MARCH6, MARCH7
E3 ubiquitin-protein ligase MARCH7 is an enzyme that in humans is encoded by the ''MARCH7'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''gener ...
, MARCH8, MARCH9, MDM2, MEX3A, MEX3B
RNA-binding protein MEX3B is a protein that in humans is encoded by the ''MEX3B'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ...
, MEX3C, MEX3D
Mex-3 homolog D (C. elegans), also known as MEX3D, is a protein that in humans is encoded by the ''MEX3D'' gene.
Function
MEX3D is an RNA binding protein that interacts with AU-rich elements of Bcl-2. Upon binding, MEX3D has a negative regulat ...
, MGRN1, MIB1, MID1, MID2, MKRN1, MKRN2, MKRN3, MKRN4, MNAT1
CDK-activating kinase assembly factor MAT1 is an enzyme that in humans is encoded by the ''MNAT1'' gene.
Function
Cyclin-dependent kinases (CDKs), which play an essential role in cell cycle control of eukaryotic cells, are phosphorylated and ...
, MYLIP
Myosin regulatory light chain interacting protein, also known as MYLIP, is a protein that in humans is encoded by the ''MYLIP'' gene.
MYLIP is also known as IDOL "Inducible Degrader of the LDL receptor" based on its involvement in cholesterol reg ...
, NFX1, NFX2, PCGF1
Polycomb group RING finger protein 1, PCGF1, also known as NSPC1 or RNF68 is a RING finger domain protein that in humans is encoded by the ''PCGF1'' gene.
PCGF1 is a component defining the non-canonical Polycomb repressive complex 1, polycomb repr ...
, PCGF2, PCGF3, PCGF4, PCGF5, PCGF6, PDZRN3, PDZRN4, PEX10
Peroxisome biogenesis factor 10 is a protein that in humans is encoded by the ''PEX10'' gene. Alternative splicing results in two transcript variants encoding different isoforms.
Function
Peroxisome biogenesis factor 10 is involved in import o ...
, PHRF1, PJA1
E3 ubiquitin-protein ligase Praja1 is an enzyme that in humans is encoded by the ''PJA1'' gene.
Interactions
PJA1 has been shown to interact with UBE2D2
Ubiquitin-conjugating enzyme E2 D2 is a protein that in humans is encoded by the ''UBE2D ...
, PJA2
E3 ubiquitin-protein ligase Praja2 is an enzyme that in humans is encoded by the ''PJA2'' gene.
Interactions
PJA2 has been shown to interact with UBE2D2
Ubiquitin-conjugating enzyme E2 D2 is a protein that in humans is encoded by the ''UBE2D2 ...
, PML, PML-RAR, PXMP3, RAD18
E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the ''RAD18'' gene.
Function
The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through interact ...
, RAG1
Recombination activating gene 1 also known as RAG-1 is a protein that in humans is encoded by the ''RAG1'' gene.
The RAG1 and RAG2 genes are largely conserved in humans. 55.99% and 55.98% of the encoded amino acids contain no reported variants, re ...
, RAPSN, RBCK1, RBX1
RING-box protein 1 is a protein that in humans is encoded by the ''RBX1'' gene.
Function
This gene encodes an evolutionarily conserved protein that interacts with cullins. The protein plays a unique role in the ubiquitination reaction by heter ...
, RC3H1, RC3H2, RCHY1, RFP2, RFPL1, RFPL2, RFPL3, RFPL4B, RFWD2, RFWD3, RING1, RNF2
E3 ubiquitin-protein ligase RING2 is an enzyme that in humans is encoded by the ''RNF2'' gene.
Polycomb group (PcG) of proteins form the multiprotein complexes that are important for the transcription repression of various genes involved in deve ...
, RNF4, RNF5, RNF6, RNF7
RING-box protein 2 is a protein that in humans is encoded by the ''RNF7'' gene.
The protein encoded by this gene is a highly conserved ring finger protein. It is an essential subunit of SKP1-cullin/CDC53-F box protein ubiquitin ligases, which are ...
, RNF8
E3 ubiquitin-protein ligase RNF8 is an enzyme that in humans is encoded by the ''RNF8'' gene. RNF8 has activity both in immune system functions and in DNA repair.
Function
The protein encoded by this gene contains a RING finger motif and an ...
, RNF10, RNF11
RING finger protein 11 is a protein that in humans is encoded by the ''RNF11'' gene.
Function
The protein encoded by this gene contains a RING-H2 finger motif, which is known to be important for protein-protein interactions. The expression of ...
, RNF12
E3 ubiquitin-protein ligase RLIM is an enzyme that in humans is encoded by the ''RLIM'' gene.
Function
The protein encoded by this gene is a RING-H2 zinc finger protein. It has been shown to be a ubiquitin protein ligase that targets LIM domai ...
, RNF13, RNF14
E3 ubiquitin-protein ligase RNF14 is an enzyme that in humans is encoded by the ''RNF14'' gene.
Function
The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This protein i ...
, RNF19A, RNF20
E3 ubiquitin-protein ligase BRE1A is an enzyme that in humans is encoded by the ''RNF20'' gene.
The protein encoded by this gene shares similarity with BRE1 of S. cerevisiae. Yeast BRE1 is a ubiquitin ligase required for the ubiquitination of his ...
, RNF24
Ring finger protein 24 is a protein that in humans is encoded by the ''RNF24'' gene.
RNF24 binds TRPC6 (603652) and other transient receptor potential cation channel (TRPC) family members and is involved in regulation of intracellular traffickin ...
, RNF25
E3 ubiquitin-protein ligase RNF25 is an enzyme that in humans is encoded by the ''RNF25'' gene.
Function
The protein encoded by this gene contains a RING finger motif. The mouse counterpart of this protein has been shown to interact with Rela, ...
, RNF26, RNF32, RNF38, RNF39, RNF40
E3 ubiquitin-protein ligase BRE1B is an enzyme that in humans is encoded by the ''RNF40'' gene.
Function
The protein encoded by this gene contains a RING finger, a motif known to be involved in protein-protein and protein-DNA interactions. Thi ...
, RNF41
E3 ubiquitin-protein ligase NRDP1 is an enzyme that in humans is encoded by the ''RNF41'' gene.
Function
The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be inv ...
, RNF43
Ring finger protein 43 is a protein that in humans is encoded by the RNF43 gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''bi ...
, RNF44, RNF55, RNF71, RNF103, RNF111, RNF113A, RNF113B, RNF121, RNF122, RNF123, RNF125, RNF126, RNF128, RNF130, RNF133, RNF135, RNF138, RNF139, RNF141, RNF144A, RNF145, RNF146
RING finger protein 146 is a protein that in humans is encoded by the ''RNF146'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ...
, RNF148, RNF149, RNF150, RNF151, RNF152, RNF157, RNF165, RNF166, RNF167, RNF168, RNF169, RNF170, RNF175, RNF180, RNF181, RNF182, RNF185, RNF207, RNF213
Ring finger protein 213 is a protein that in humans is encoded by the ''RNF213'' gene. RNF213 is a 591kDa cytosolic E3 Ubiquitin-ligase with RING finger and AAA+ ATPase domains.
Clinical relevance
Chromosome-wide linkage analysis found that moya ...
, RNF215, RNFT1, SH3MD4, SH3RF1
Putative E3 ubiquitin-protein ligase SH3RF1 is an enzyme that in humans is encoded by the ''SH3RF1'' gene.
Function
This gene encodes a protein containing an N-terminus RING-finger, four SH3 domains, and a region implicated in binding of the Rh ...
, SH3RF2, SYVN1, TIF1, TMEM118, TOPORS, TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene.
Function
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, an ...
, TRAF3
TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.
Function
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate wit ...
, TRAF4
TNF receptor-associated factor 4 (TRAF4) also known as RING finger protein 83 (RNF83) is a protein that in humans is encoded by the ''TRAF4'' gene.
TRAF4 is a member of the TNF receptor associated factor (TRAF) family, a family of scaffold protein ...
, TRAF5
TNF receptor-associated factor 5 is a protein that in humans is encoded by the ''TRAF5'' gene.
Function
The scaffold protein encoded by this gene is a member of the tumor necrosis factor receptor-associated factor (TRAF) protein family and con ...
, TRAF6
TRAF6 is a TRAF human protein.
Function
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF recep ...
, TRAF7, TRAIP, TRIM2
Trim or TRIM may refer to:
Cutting
* Cutting or wiktionary:trim#English, trimming small pieces off something to remove them
** Book trimming, a stage of the publishing process
** Pruning, trimming as a form of pruning often used on trees
Decora ...
, TRIM3
Tripartite motif-containing protein 3 is a protein that in humans is encoded by the ''TRIM3'' gene.
The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also called the 'RING-B-box-coiled-coil' (RBCC) subgroup of RIN ...
, TRIM4, TRIM5
Tripartite motif-containing protein 5 also known as RING finger protein 88 is a protein that in humans is encoded by the ''TRIM5'' gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates a species-specif ...
, TRIM6, TRIM7, TRIM8, TRIM9
Tripartite motif-containing protein 9 is a protein that in humans is encoded by the ''TRIM9'' gene.
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a ...
, TRIM10, TRIM11, TRIM13, TRIM15, TRIM17, TRIM21
Tripartite motif-containing protein 21, also known as E3 ubiquitin-protein ligase TRIM21, is a protein that in humans is encoded by the ''TRIM21'' gene. Alternatively spliced transcript variants for this gene have been described but the full-length ...
, TRIM22
Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the ''TRIM22'' gene.
Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three z ...
, TRIM23, TRIM24
Tripartite motif-containing 24 (TRIM24) also known as transcriptional intermediary factor 1α (TIF1α) is a protein that, in humans, is encoded by the ''TRIM24'' gene.
Function
The protein encoded by this gene mediates transcriptional control b ...
, TRIM25
Tripartite motif-containing protein 25 is a protein that in humans is encoded by the ''TRIM25'' gene.
Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family grouping more than 70 TRIMs. TRIM proteins primari ...
, TRIM26, TRIM27, TRIM28
Tripartite motif-containing 28 (TRIM28), also known as transcriptional intermediary factor 1β (TIF1β) and KAP1 (KRAB-associated protein-1), is a protein that in humans is encoded by the ''TRIM28'' gene.
Function
The protein encoded by this ge ...
, TRIM31, TRIM32
Tripartite motif-containing protein 32 is a protein that in humans is encoded by the ''TRIM32'' gene. Since its discovery in 1995, TRIM32 has been shown to be implicated in a number of diverse biological pathways.
Structure
The protein encoded ...
, TRIM33
E3 ubiquitin-protein ligase TRIM33, also known as (ectodermin homolog and tripartite motif-containing 33) is a protein encoded in the human by the gene ''TRIM33'', a member of the tripartite motif family.
TRIM33 is thought to be a transcriptional ...
, 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
E3 ubiquitin-protein ligase TRIM63, also known as "MuRF1" (Muscle Ring-Finger Protein-1), is an enzyme that in humans is encoded by the ''TRIM63'' gene.
This gene encodes a member of the RING zinc finger protein family found in striated muscle a ...
, TRIM65, TRIM67, TRIM68, TRIM69
Tripartite motif containing 69 is a protein that in humans is encoded by the TRIM69 gene.
Function
This gene encodes a member of the RING-B-box-coiled-coil (RBCC) family and encodes a protein with an N-terminal RING finger motif, a PRY domain ...
, TRIM71, TRIM72, TRIM73, TRIM74, TRIML1, TTC3, UHRF1
Ubiquitin-like, containing PHD and RING finger domains, 1, also known as UHRF1, is a protein which in humans is encoded by the ''UHRF1'' gene.
Function
This gene encodes a member of a subfamily of RING finger domain, RING-finger type E3 ubiqui ...
, UHRF2, VPS11, VPS8, ZNF179, ZNF294, ZNF313, ZNF364, ZNF451
Zinc finger protein 451 is a novel nuclear protein that in humans is encoded by the ''ZNF451'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''g ...
, ZNF650, ZNFB7, ZNRF1, ZNRF2, ZNRF3, ZNRF4, and ZSWIM2.
References
External links
*
{{InterPro content, IPR001841
Protein structural motifs
RING finger proteins