SMART: ZnF_C2HC domain annotation

ZnF_C2HC zinc finger

SMART accession number:	SM00343
Description:
Interpro abstract (IPR001878):	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 were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis, however they are now recognised to bind DNA, RNA, protein and/or lipid substrates (PUBMED:10529348), (PUBMED:15963892), (PUBMED:15718139), (PUBMED:17210253), (PUBMED:12665246). 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, to name but a few (PUBMED:11179890). Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. (Note that in certain cases, some Znf 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. These domains can show strong sequence identity to zinc-binding motifs, and may therefore be included in Znf entries). This entry represents the CysCysHisCys (CCHC) type zinc finger domains, and have the sequence: C-X2-C-X4-H-X4-C where X can be any amino acid, and number indicates the number of residues. These 18 residues CCHC zinc finger domains are mainly found in the nucleocapsid protein of retroviruses. It is required for viral genome packaging and for early infection process (PUBMED:17416621), (PUBMED:17202191), (PUBMED:17029416). It is also found in eukaryotic proteins involved in RNA binding or single-stranded DNA binding (PUBMED:15937226). More information about these proteins can be found at Protein of the Month: Zinc Fingers.
GO function:	zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676)
Family alignment:	View or

There are 16634 ZnF_C2HC domains in 11038 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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This tree shows only several representative species. The complete taxonomic breakdown of all proteins with ZnF_C2HC domain is also avaliable.

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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Curtis D, Treiber DK, Tao F, Zamore PD, Williamson JR, Lehmann R
- A CCHC metal-binding domain in Nanos is essential for translational regulation.
- EMBO J. 1997; 16: 834-43
- Display abstract
- The Drosophila Nanos protein is a localized repressor of hunchback mRNA translation in the early embryo, and is required for the establishment of the anterior-posterior body axis. Analysis of nanos mutants reveals that a small, evolutionarily conserved, C-terminal region is essential for Nanos function in vivo, while no other single portion of the Nanos protein is absolutely required. Within the C-terminal region are two unusual Cys-Cys-His-Cys (CCHC) motifs that are potential zinc-binding sites. Using absorption spectroscopy and NMR we demonstrate that the CCHC motifs each bind one equivalent of zinc with high affinity. nanos mutations disrupting metal binding at either of these two sites in vitro abolish Nanos translational repression activity in vivo. We show that full-length and C-terminal Nanos proteins bind to RNA in vitro with high affinity, but with little sequence specificity. Mutations affecting the hunchback mRNA target sites for Nanos-dependent translational repression were found to disrupt translational repression in vivo, but had little effect on Nanos RNA binding in vitro. Thus, the Nanos zinc domain does not specifically recognize target hunchback RNA sequences, but might interact with RNA in the context of a larger ribonucleoprotein complex.
- Webb JR, McMaster WR
- Molecular cloning and expression of a Leishmania major gene encoding a single-stranded DNA-binding protein containing nine "CCHC" zinc finger motifs.
- J Biol Chem. 1993; 268: 13994-4002
- Display abstract
- The genes encoding GP63, the major surface glycoprotein of the protozoan parasite Leishmania, are highly conserved across diverse species of Leishmania both within the protein coding region and in the immediate 5'-untranslated region. Located between the 3' trans-spliced leader acceptor site and the translational initiation codon of the GP63 gene is an area of conserved hexanucleotide direct repeats (CTCGCC) which vary in number according to species. To determine whether these repeats represent a site of protein DNA interaction, a Leishmania major lambda gt11 expression library was screened with a radiolabeled synthetic oligodeoxynucleotide probe containing multiple CTCGCC repeats to detect clones expressing functional DNA-binding proteins. Using this approach a gene was isolated which encodes a sequence-specific DNA-binding protein referred to as HEXBP (hexamer-binding protein). Sequence analysis of the HEXBP gene showed that HEXBP contains nine cysteine-rich motifs which are identical to a consensus sequence known as the "CCHC type" zinc finger. This motif is present in a number of nucleic acid-binding proteins including the nucleocapsid protein of retroviruses. In accordance with the activity exhibited by other proteins containing the "CCHC" motif, HEXBP binds to single-stranded nucleic acids as demonstrated by gel mobility shift assays and Southwestern blot assays.
- Summers MF, South TL, Kim B, Hare DR
- High-resolution structure of an HIV zinc fingerlike domain via a new NMR-based distance geometry approach.
- Biochemistry. 1990; 29: 329-40
- Display abstract
- A new method is described for determining molecular structures from NMR data. The approach utilizes 2D NOESY back-calculations to generate simulated spectra for structures obtained from distance geometry (DG) computations. Comparison of experimental and back-calculated spectra, including analysis of cross-peak buildup and auto-peak decay with increasing mixing time, provides a quantitative measure of the consistence between the experimental data and generated structures and allows for use of tighter interproton distance constraints. For the first time, the "goodness" of the generated structures is evaluated on the basis of their consistence with the actual experimental data rather than on the basis of consistence with other generated structures. This method is applied to the structure determination of an 18-residue peptide with an amino acid sequence comprising the first zinc fingerlike domain from the gag protein p55 of HIV. This is the first structure determination to atomic resolution for a retroviral zinc fingerlike complex. The peptide [Zn(p55F1)] exhibits a novel folding pattern that includes type I and type II NH-S tight turns and is stabilized both by coordination of the three Cys and one His residues to zinc and by extensive internal hydrogen bonding. The backbone folding is significantly different from that of a "classical" DNA-binding zinc finger. Residues C(1)-F(2)-N(3)-C(4)-G(5)-K(6) fold in a manner virtually identical with the folding observed by X-ray crystallography for related residues in the iron domain of rubredoxin; superposition of all main-chain and Cys side-chain atoms of residues C(1)-K(6) of Zn(p55F1) onto residues C(6)-Y(11) and C(39)-V(44) of rubredoxin gives RMSDs of 0.46 and 0.35 A, respectively. The side chains of conservatively substituted Phe and Ile residues implicated in genomic RNA recognition form a hydrophobic patch on the peptide surface.
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

3D Structures of ZnF_C2HC domains in PDB

PDB code	Main view	Title
1a1t		Structure of the hiv-1 nucleocapsid protein bound to the sl3 psi-rna recognition element, nmr, 25 structures
1a6b		Nmr structure of the complex between the zinc finger protein ncp10 of moloney murine leukemia virus and a sequence of the psi-packaging domain of hiv-1, 20 structures
1aaf		Nucleocapsid zinc fingers detected in retroviruses: exafs studies on intact viruses and the solution-state structure of the nucleocapsid protein from hiv-1
1bj6		1h nmr of (12-53) ncp7/d(acgcc) complex, 10 structures
1cl4		Nucleocapsid protein from mason-pfizer monkey virus (mpmv)
1dsq		Structure of the mmtv nucleocapsid protein (zinc finger 1)
1dsv		Structure of the mmtv nucleocapsid protein (c-terminal zinc finger)
1esk		Solution structure of ncp7 from hiv-1
1f6u		Nmr structure of the hiv-1 nucleocapsid protein bound to stem-loop sl2 of the psi-rna packaging signal. implications for genome recognition
1hvn		Zinc-and sequence-dependent binding to nucleic acids by the n-terminal zinc finger domain of the hiv-1 nucleocapsid protein: nmr structure of the complex with the psi-site analog, d/acgcc
1hvo		Zinc-and sequence-dependent binding to nucleic acids by the n-terminal zinc finger domain of the hiv-1 nucleocapsid protein: nmr structure of the complex with the psi-site analog, d/acgcc
1mfs		Dynamical behavior of the hiv-1 nucleocapsid protein; nmr, structures
1nc8		High-resolution solution nmr structure of the minimal active domain of the human immunodeficiency virus type-2 nucleocapsid protein, 15 structures
1ncp		Structural characterization of a 39 residue synthetic peptide containing the two zinc binding domains from the hiv-1 p7 nucleocapsid protein by cd and nmr spectroscopy
1q3y		Nmr structure of the cys28his mutant (d form) of the nucleocapsid protein ncp7 of hiv-1.
1q3z		Nmr structure of the cys28his mutant (e form) of the nucleocapsid protein ncp7 of hiv-1.
1u6p		Nmr structure of the mlv encapsidation signal bound to the nucleocapsid protein
1wwd		Nmr structure determined for mlv nc complex with rna sequence aacagu
1wwe		Nmr structure determined for mlv nc complex with rna sequence uuuugcu
1wwf		Nmr structure determined for mlv nc complex with rna sequence ccuccgu
1wwg		Nmr structure determined for mlv nc complex with rna sequence uaucug
2a51		Structure of the (13-51) domain of the nucleocapsid protein ncp8 from sivlhoest
2bl6		Solution structure of the zn complex of eiav ncp11(22-58) peptide, including two cchc zn-binding motifs.
2cqf		Solution structure of the zinc-finger domain in lin-28
2di2		Nmr structure of the hiv-2 nucleocapsid protein
2e1x		Nmr structure of the hiv-2 nucleocapsid protein
2ec7		Solution structure of human immunodificiency virus type-2 nucleocapsid protein
2exf		Solution structure of the hiv-1 nucleocapsid (ncp7(12-55)) complexed with the dna (-) primer binding site
2hqh		Crystal structure of p150glued and clip-170
2ihx		Solution structure of the rous sarcoma virus nucleocapsid protein:upsi rna packaging signal complex
2iwj		Solution structure of the zn complex of hiv-2 ncp(23-49) peptide, encompassing protein cchc-linker, distal cchc zn- binding motif and c-terminal tail.
2jzw
2k2c		Solution nmr structure of n-terminal domain of human pirh2. northeast structural genomics consortium (nesg) target ht2a
2ysa		Solution structure of the zinc finger cchc domain from the human retinoblastoma-binding protein 6 (retinoblastoma- binding q protein 1, rbq-1)
2znf		High-resolution structure of an hiv zinc fingerlike domain via a new nmr-based distance geometry approach
3e2u		Crystal structure of the zink-knuckle 2 domain of human clip-170 in complex with cap-gly domain of human dynactin- (p150-glued)

Links (links to other resources describing this domain)
PFAM zf-CCHC
INTERPRO IPR001878

PFAM	zf-CCHC
INTERPRO	IPR001878