Kelch motif

Last updated
Kelch motif
PDB 1gof EBI.jpg
Structure of Galactose oxidase containing kelch repeats. [1]
Identifiers
SymbolKelch_1
Pfam PF01344
InterPro IPR006652
SMART Kelch
SCOP2 1gof / SCOPe / SUPFAM
OPM superfamily 319
OPM protein 3ii7
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Kelch motif
Identifiers
SymbolKelch_2
Pfam PF07646
Pfam clan CL0186
InterPro IPR011498
SCOP2 1gof / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Galactose oxidase, central domain
Identifiers
SymbolKelch_3
Pfam PF13415
Pfam clan CL0186
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Galactose oxidase, central domain
Identifiers
SymbolKelch_4
Pfam PF13418
Pfam clan CL0186
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Kelch motif
Identifiers
SymbolKelch_5
Pfam PF13854
Pfam clan CL0186
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Kelch motif
Identifiers
SymbolKelch_6
Pfam PF13964
Pfam clan CL0186
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

The Kelch motif is a region of protein sequence found widely in proteins from bacteria and eukaryotes. [2] This sequence motif is composed of about 50 amino acid residues which form a structure of a four stranded beta-sheet "blade". This sequence motif is found in between five and eight tandem copies per protein which fold together to form a larger circular solenoid structure called a beta-propeller domain.

Contents

Proteins containing Kelch motifs

The Kelch motif is widely found in eukaryotic and bacterial species. Notably the human genome contains around 100 proteins containing the Kelch motif. Within individual proteins the motif occurs multiple times. For example, the motif appears 6 times in Drosophila egg-chamber regulatory protein. The motif is also found in mouse protein MIPP [3] and in a number of poxviruses. In addition, kelch repeats have been recognised in alpha- and beta-scruin, [4] [5] in galactose oxidase from the fungus Dactylium dendroides , [6] [7] and in the Escherichia coli NanM protein, a sialic acid mutarotase. [8]

Structure

The structure of galactose oxidase reveals that the repeated Kelch sequence motif corresponds to a 4-stranded anti-parallel beta-sheet motif that forms the repeat unit in a super-barrel structural fold commonly known as a beta propeller. [9]

Function

The known functions of kelch-containing proteins are diverse:

See also

Related Research Articles

<span class="mw-page-title-main">Beta-propeller</span> Toroid protein structure formed from beta sheets

In structural biology, a beta-propeller (β-propeller) is a type of all-β protein architecture characterized by 4 to 8 highly symmetrical blade-shaped beta sheets arranged toroidally around a central axis. Together the beta-sheets form a funnel-like active site.

<span class="mw-page-title-main">Armadillo repeat</span>

An armadillo repeat is a characteristic, repetitive amino acid sequence of about 42 residues in length that is found in many proteins. Proteins that contain armadillo repeats typically contain several tandemly repeated copies. Each armadillo repeat is composed of a pair of alpha helices that form a hairpin structure. Multiple copies of the repeat form what is known as an alpha solenoid structure.

<span class="mw-page-title-main">Sialyltransferase</span> Class of enzymes

Sialyltransferases are enzymes that transfer sialic acid to nascent oligosaccharide. Each sialyltransferase is specific for a particular sugar substrate. Sialyltransferases add sialic acid to the terminal portions of the sialylated glycolipids (gangliosides) or to the N- or O-linked sugar chains of glycoproteins.

<span class="mw-page-title-main">Kelch protein</span>

Kelch proteins are a widespread group of proteins that contain multiple Kelch motifs. The kelch domain generally occurs as a set of five to seven kelch tandem repeats that form a β-propeller tertiary structure. Kelch-repeat β-propellers are generally involved in protein–protein interactions, though the large diversity of domain architectures and limited sequence identity between kelch motifs make characterisation of the kelch superfamily difficult.

<span class="mw-page-title-main">FLNA</span> Protein-coding gene in humans

Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene.

<span class="mw-page-title-main">CORO1A</span> Protein-coding gene in the species Homo sapiens

Coronin-1A is a protein that in humans is encoded by the CORO1A gene. It has been implicated in both T-cell mediated immunity and mitochondrial apoptosis. In a recent genome-wide longevity study, its expression levels were found to be negatively associated both with age at the time of blood sample and the survival time after blood draw.

<span class="mw-page-title-main">CMP-sialic acid transporter</span> Protein-coding gene in the species Homo sapiens

CMP-sialic acid transporter is a protein that in humans is encoded by the SLC35A1 gene.

<span class="mw-page-title-main">ST6GALNAC4</span> Protein-coding gene in the species Homo sapiens

ST6 (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 4, also known as sialyltransferase 3C (SIAT3-C) or sialyltransferase 7D (SIAT7-D) is a sialyltransferase enzyme that in humans is encoded by the ST6GALNAC4 gene.

<span class="mw-page-title-main">Kelch-like protein 20</span> Protein-coding gene in the species Homo sapiens

Kelch-like protein 20 is a protein that in humans is encoded by the KLHL20 gene.

Coronin is an actin binding protein which also interacts with microtubules and in some cell types is associated with phagocytosis. Coronin proteins are expressed in a large number of eukaryotic organisms from yeast to humans.

YWTD repeats are four-stranded beta-propeller repeats found in low-density lipoprotein receptors (LDLR). The six YWTD repeats together fold into a six-bladed beta-propeller. Each blade of the propeller consists of four antiparallel beta-strands; the innermost strand of each blade is labeled 1 and the outermost strand, 4. The sequence repeats are offset with respect to the blades of the propeller, such that any given 40-residue YWTD repeat spans strands 24 of one propeller blade and strand 1 of the subsequent blade. This offset ensures circularization of the propeller because the last strand of the final sequence repeat acts as an innermost strand 1 of the blade that harbors strands 24 from the first sequence repeat. The repeat is found in a variety of proteins that include, vitellogenin receptor from Drosophila melanogaster, low-density lipoprotein (LDL) receptor, preproepidermal growth factor, and nidogen (entactin).

<span class="mw-page-title-main">BTB/POZ domain</span>

The BTB/POZ domain is a structural domain found in proteins across the domain Eukarya. Given its prevalence in eukaryotes and its absence in Archaea and bacteria, it likely arose after the origin of eukaryotes. While primarily a protein-protein interaction domain, some BTB domains have additional functionality in transcriptional regulation, cytoskeletal mobility, protein ubiquitination and degradation, and ion channel formation and operation. BTB domains have traditionally been classified by the other structural features present in the protein.

<span class="mw-page-title-main">Beta thymosins</span>

Beta thymosins are a family of proteins which have in common a sequence of about 40 amino acids similar to the small protein thymosin β4. They are found almost exclusively in multicellular animals. Thymosin β4 was originally obtained from the thymus in company with several other small proteins which although named collectively "thymosins" are now known to be structurally and genetically unrelated and present in many different animal tissues.

WH1 domain is an evolutionary conserved protein domain found on WASP proteins, which are often involved in actin polymerization.

<span class="mw-page-title-main">F-actin capping protein</span>

In molecular biology, the F-actin capping protein is a protein complex which binds in a calcium-independent manner to the fast-growing ends of actin filaments, thereby blocking the exchange of subunits at these ends. Unlike gelsolin and severin this protein does not sever actin filaments. The F-actin capping protein is a heterodimer composed of two unrelated subunits: alpha and beta. Neither of the subunits shows sequence similarity to other filament-capping proteins. The alpha subunit is a protein of about 268 to 286 amino acid residues and the beta subunit is approximately 280 amino acids, their sequences are well conserved in eukaryotic species.

<span class="mw-page-title-main">BNR/Asp-box repeat</span>

BNR/Asp-box repeat is a repetitive sequence of amino acids contained in some proteins. Many of these proteins contain multiple BNR repeats or Asp-boxes.

<span class="mw-page-title-main">Solenoid protein domain</span>

Solenoid protein domains are a highly modular type of protein domain. They consist of a chain of nearly identical folds, often simply called tandem repeats. They are extremely common among all types of proteins, though exact figures are unknown.

<span class="mw-page-title-main">Multiple Epidermal Growth Factor-like Domains 8</span> Protein-coding gene in the species Homo sapiens

Megf8 also known as Multiple Epidermal Growth Factor-like Domains 8, is a protein coding gene that encodes a single pass membrane protein, known to participate in developmental regulation and cellular communication. It is located on chromosome 19 at the 49th open reading frame in humans (19q13.2). There are two isoform constructs known for MEGF8, which differ by a 67 amino acid indel. The isoform 2 splice version is 2785 amino acids long, and predicted to be 296.6 kdal in mass. Isoform 1 is composed of 2845 amino acids and predicted to weigh 303.1 kdal. Using BLAST searches, orthologs were found primarily in mammals, but MEGF8 is also conserved in invertebrates and fishes, and rarely in birds, reptiles, and amphibians. A notably important paralog to multiple epidermal growth factor-like domains 8 is ATRNL1, which is also a single pass transmembrane protein, with several of the same key features and motifs as MEGF8, as indicated by Simple Modular Architecture Research Tool (SMART) which is hosted by the European Molecular Biology Laboratory located in Heidelberg, Germany. MEGF8 has been predicted to be a key player in several developmental processes, such as left-right patterning and limb formation. Currently, researchers have found MEGF8 SNP mutations to be the cause of Carpenter syndrome subtype 2.

<span class="mw-page-title-main">Galactose oxidase</span>

Galactose oxidase is an enzyme that catalyzes the oxidation of D-galactose in some species of fungi.

<span class="mw-page-title-main">Toroid repeat proteins</span>

A toroid repeat is a protein fold composed of repeating subunits, arranged in circular fashion to form a closed structure.

References

  1. Ito N, Phillips SE, Stevens C, et al. (March 1991). "Novel thioether bond revealed by a 1.7 A crystal structure of galactose oxidase". Nature. 350 (6313): 87–90. doi:10.1038/350087a0. PMID   2002850. S2CID   4345713.
  2. Adams J, Kelso R, Cooley L (January 2000). "The kelch repeat superfamily of proteins: propellers of cell function". Trends Cell Biol. 10 (1): 17–24. doi:10.1016/S0962-8924(99)01673-6. PMID   10603472.
  3. Xue F, Cooley L (1993). "kelch encodes a component of intercellular bridges in Drosophila egg chambers". Cell. 72 (5): 681–693. doi: 10.1016/0092-8674(93)90397-9 . PMID   8453663.
  4. 1 2 Way M, Sanders M, Matsudaira P, Chafel M, Knight A, Tu YH (1995). "beta-Scruin, a homologue of the actin crosslinking protein scruin, is localized to the acrosomal vesicle of Limulus sperm". J. Cell Sci. 108: 3155–3162. PMID   7593276.
  5. Way M, Sakai J, Sanders M, Garcia C, Matsudaira P (1995). "Sequence and domain organization of scruin, an actin-cross-linking protein in the acrosomal process of Limulus sperm". J. Cell Biol. 128 (1): 51–60. doi:10.1083/jcb.128.1.51. PMC   2120335 . PMID   7822422.
  6. Doolittle RF, Bork P (1994). "Drosophila kelch motif is derived from a common enzyme fold". J. Mol. Biol. 236 (5): 1277–1282. doi:10.1016/0022-2836(94)90056-6. PMID   8126718.
  7. Keen JN, Ito N, Phillips SE, Stevens C, Ogel ZB, McPherson MJ, Yadav KD, Knowles PF (1991). "Novel thioether bond revealed by a 1.7 A crystal structure of galactose oxidase". Nature. 350 (6313): 87–90. doi:10.1038/350087a0. PMID   2002850. S2CID   4345713.
  8. Severi E, Müller A, Potts JR, Leech A, Williamson D, Wilson KS, Thomas GH (2008). "Sialic acid mutarotation is catalyzed by the Escherichia coli beta-propeller protein YjhT". J. Biol. Chem. 283 (8): 4841–4849. doi: 10.1074/jbc.m707822200 . PMID   18063573.
  9. Ito N, Phillips SE, Yadav KD, Knowles PF (1994). "Crystal structure of a free radical enzyme, galactose oxidase". J. Mol. Biol. 238 (5): 794–814. doi:10.1006/jmbi.1994.1335. PMID   8182749.
This article incorporates text from the public domain Pfam and InterPro: IPR006652
This article incorporates text from the public domain Pfam and InterPro: IPR011498