This domain can be found in a group of archaeal proteins that function as electron transfer proteins. They consist of a small (~35 amino acids) C- terminal metal-binding (MB) domain containing four cysteine residues arranged in a Cys-X(2)-Cys-X(14-19)-Cys-X(1-4)-Cys motif. The archaeal CBS proteins (ACP)-type MB domain can bind several metals, with iron and zinc being the most abundant metals [].The ACP-type MB domain consists of three short β-strands forming a compact anti-parallel β-sheet that packs against the CBS domains [].
The TSSC4 (for tumor-suppressing STF cDNA 4) gene is located in the centre of a 1 Mb gene cluster which contains several imprinted genes; however in humans the TSSC4 gene is not imprinted [, ]. This same cluster is associated with the Beckwith-Wiedermann syndrome []. Proteins in the TSSC4 family are found in eukaryotes, and contain a conserved YSL sequence motif.
CECR5 (cat eye syndrome critical region protein 5 also known as haloacid dehalogenase-like hydrolase domain-containing 5) gene is a candidate gene for the Cat Eye Syndrome (CES), a developmental disorder associated with the duplication of a 2 Mb region of 22q11.2 []. Its function isnot clear.
This entry represents the human Cat eye syndrome critical region protein 6 (also known as transmembrane protein 121B) and its homologues [, ]. Cat Eye Syndrome (CES) is characterised clinically by the combination of coloboma of the iris and anal atresia with fistula. CES is a rare condition caused by the duplication of a 2 Mb region of human 22q11.2 resulting in four copies of the region rather than the usual two copies [].
Chromatin remodeling regulator CECR2 is part of the CERF (CECR2-containing-remodeling factor) complex, which is a chromatin remodelling complex that plays important roles in embryogenesis and neurulation [, , , ]. It may also contribute to spermatogenesis and form complexes with SNF2H in the testis [].CECR2 gene is a candidate gene for the Cat Eye Syndrome (CES), a developmental disorder associated with the duplication of a 2 Mb region of 22q11.2 [].
Globins are haem-containing proteins involved in binding and/or transporting oxygen. They belong to a very large and well studied family that is widely distributed in many organisms []. Globins have evolved from a common ancestor and can be divided into three groups: single-domainglobins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three types of globins, while archaea lack flavohaemoglobins, and eukaryotes lack globin-coupled sensors []. Several functionally different haemoglobins can coexist in the same species. The major types of globins include:Haemoglobin (Hb): tetramer of two alpha and two beta chains, although embryonic and foetal forms can substitute the alpha or beta chain for ones with higher oxygen affinity, such as gamma, delta, epsilon or zeta chains. Hb transports oxygen from lungs to other tissues in vertebrates []. Hb proteins are also present in unicellular organisms where they act as enzymes or sensors [].Myoglobin (Mb): monomeric protein responsible for oxygen storage in vertebrate muscle [].Neuroglobin: a myoglobin-like haemprotein expressed in vertebrate brain and retina, where it is involved in neuroprotection from damage due to hypoxia or ischemia []. Neuroglobin belongs to a branch of the globin family that diverged early in evolution. Cytoglobin: an oxygen sensor expressed in multiple tissues. Related to neuroglobin [].Erythrocruorin: highly cooperative extracellular respiratory proteins found in annelids and arthropods that are assembled from as many as 180 subunit into hexagonal bilayers [].Leghaemoglobin (legHb or symbiotic Hb): occurs in the root nodules of leguminous plants, where itfacilitates the diffusion of oxygen to symbiotic bacteriods in order to promote nitrogen fixation.Non-symbiotic haemoglobin (NsHb): occurs in non-leguminous plants, and can be over-expressed in stressed plants [].Flavohaemoglobins (FHb): chimeric, with an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD/FAD-binding domain. FHb provides protection against nitric oxide via its C-terminal domain, which transfers electrons to haem in the globin [].Globin-coupled sensors: chimeric, with an N-terminal myoglobin-like domain and a C-terminal domain that resembles the cytoplasmic signalling domain of bacterial chemoreceptors. They bind oxygen, and act to initiate an aerotactic response or regulate gene expression [, ]. Protoglobin: a single domain globin found in archaea that is related to the N-terminal domain of globin-coupled sensors [].Truncated 2/2 globin: lack the first helix, giving them a 2-over-2 instead of the canonical 3-over-3 α-helical sandwich fold. Can be divided into three main groups (I, II and II) based on structural features [].This entry represents myoglobin (Mb). Mb is an intracellular haemoprotein expressed in the heart and oxidative skeletal myofibres of vertebrates that reversibly binds molecular oxygen by its haem. Mb functions as an oxygen storage protein in muscle that is capable of releasing oxygen during periods of hypoxia or anoxia []. Mb is also believed to facilitate oxygen transport from erythrocytes to mitochondria to maintain cellular respiration during periods of high physiological demand, however, mice lacking myoglobin appear to function normally []. Mb does appear to have an additional function scavenging nitric oxide and reactive oxygen species in the heart []. Mb binds oxygen in the reduced [Fe(II)]state. The Mb molecule exists as a monomer that binds haem. The 3D structures of a great number of vertebrate Mb proteins in various states are known. The protein is largely α-helical, eight conserved helices (A to H) providing the scaffold for a well-defined haem-binding pocket. The imidazole ring of the 'proximal' His residue provides the fifth haem iron ligand; the other axial haem iron position remains essentially free for oxygen coordination. Oxygen binding results in a transition from high-spin to low-spin iron, with accompanying changes in the Fe-N bond lengths and coordination geometry.
Diphthamide is a unique post-translationally modified histidine residue found only in translation elongation factor 2 (eEF-2). It is conserved from archaea to humans and serves as the target for diphteria toxin and Pseudomonas exotoxin A. These two toxins catalyse the transfer of ADP-ribose to diphtamide on eEF-2, thus inactivating eEF-2, halting cellular protein synthesis, and causing cell death []. The biosynthesis of diphtamide is dependent on at least five proteins, DPH1 to -5, and a still unidentified amidating enzyme. DPH3 and DPH4 share a conserved region, which encode a putative zinc finger, the DPH-type or CSL-type (after the the final conserved cysteine of the zinc finger and the next two residues) MB domain contains a Cys-X-Cys...Cys-X2-Cys motif which tetrahedrically coordinates both Fe and Zn. The Fe containing DPH-type MBD has an electron transfer activity [, , , , , ].This entry includes DPH3, DPH4 and their homologues.
Diphthamide is a unique post-translationallymodified histidine residue found only in translation elongation factor 2 (eEF-2). It is conserved from archaea to humans and serves as the target for diphteria toxin and Pseudomonas exotoxin A. These two toxins catalyse the transfer of ADP-ribose to diphtamide on eEF-2, thus inactivating eEF-2, halting cellular protein synthesis, and causing cell death []. The biosynthesis of diphtamide is dependent on at least five proteins, DPH1 to -5, and a still unidentified amidating enzyme. DPH3 and DPH4 share a conserved region, which encode a putative zinc finger, the DPH-type or CSL-type (after the the final conserved cysteine of the zinc finger and the next two residues) MB domain contains a Cys-X-Cys...Cys-X2-Cys motif which tetrahedrically coordinates both Fe and Zn. The Fe containing DPH-type MBD has an electron transfer activity [, , , , , ].This entry represents the DPH-type metal binding domain consists of a three-stranded β-sandwich with one sheet comprising two parallel strands: (i) β1 and (ii) β6 and one antiparallel strand: β5. The second sheet in the β-sandwich is comprised of strands β2, β3, and β4 running anti-parallel to each other. The two β-sheets are separated by a short stretch α-helix. It can be found in proteins such as DPH3 and DPH4. This domain is also found associated with N-terminal domain of heat shock protein DnaJ domain [, , ].
