Kelch proteins (and Kelch-like

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s) are a widespread group of proteins that contain multiple

Kelch motif The Kelch motif is a region of protein sequence found widely in proteins from bacteria and eukaryotes. This sequence motif is composed of about 50 amino acid residues which form a structure of a four stranded beta-sheet "blade". This sequen ...

s. The kelch domain generally occurs as a set of five to seven kelch

tandem repeats Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. Several protein domains also form tandem repeats within their amino acid primary structure, such as armadill ...

that form a

β-propeller 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 ...

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.

Structure

The

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

of several Kelch proteins contain other protein domains, including Discoidin,

F-box F-box proteins are proteins containing at least one F-box domain. The first identified F-box protein is one of three components of the SCF complex, which mediates ubiquitination of proteins targeted for degradation by the 26S proteasome. Core co ...

, and Broad-complex, Tramtrack, Bric-a-Brac/Poxvirus Zinc finger (BTB/POZ) domains. Kelch proteins may also only have a β-propeller architecture. The BTB domain of kelch proteins (if present) allows the formation of homo- or heterodimers that mediate

protein–protein interaction Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and th ...

s. The

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

of Kelch proteins contains kelch repeats. Each kelch repeat is a sequence of 44–55

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 ...

s in length, usually occurring in clusters of 4 – 7 repeats. Each kelch repeat forms a "blade" of the β-propeller fold, consisting of a four-stranded antiparallel

β-sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

secondary structure Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...

, arranged radially around a central axis, packed onto its adjoining repeats via hydrophobic contacts. Kelch-repeat β-propellers undergo a variety of binding interactions with other proteins, notably the

actin filaments Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other pr ...

of a cell.

Function

Kelch-like proteins are known to act as substrate adaptors for

Cullin 3 Cullin 3 is a protein that in humans is encoded by the ''CUL3'' gene. Cullin 3 protein belongs to the family of cullins which in mammals contains eight proteins (Cullin 1, Cullin 2, Cullin 3, Cullin 4A, Cullin 4B, Cullin 5, Cullin 7 and Cullin 9) ...

ubiquitin ligases.

Organisms

The first Kelch protein (from which this family derives its name) was isolated from ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

'', in which Kelch-mutant females lay sterile, cup-shaped eggs;UNDERSTANDING THE FUNCTION OF ACTIN-BINDING PROTEINS THROUGH GENETIC ANALYSIS OF ''DROSOPHILA'' OOGENESIS
by Andrew M. Hudson and Lynn Cooley; in the

Annual Review of Genetics The ''Annual Review of Genetics'' is an annual peer-reviewed scientific review journal published by Annual Reviews. It was established in 1967 and covers all topics related to the genetics of viruses, bacteria, fungi, plants, and animals, includi ...

, Vol. 36: 455–488 (Volume publication date December 2002); retrieved 12 December 2013 The word ''Kelch'' is German for 'chalice, cup'. Kelch proteins have also been isolated in many other animals, plants, bacteria, fungi, and even virus (restricted to

Poxviridae ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated wit ...

Human proteins containing Kelch motifs

ATRN Attractin is a protein that in humans is encoded by the ''ATRN'' gene. Attractin is a Group XI C-type lectin A C-type lectin (CLEC) is a type of carbohydrate-binding protein known as a lectin. The C-type designation is from their requirement ...

; ATRNL1; CCIN; ENC1; FBXO42;

GAN The word Gan or the initials GAN may refer to: Places *Gan, a component of Hebrew placenames literally meaning "garden" China * Gan River (Jiangxi) * Gan River (Inner Mongolia), * Gan County, in Jiangxi province * Gansu, abbreviated ''Gā ...

;

HCFC1 Host cell factor 1 (HCFC1, HCF1, or HCF-1), also known as VP16-accessory protein, is a protein that in humans is encoded by the ''HCFC1'' gene. Structure HCF1 is a member of the highly conserved host cell factor family and encodes a protein wi ...

; HCFC2; IPP; IVNS1ABP; KBTBD10; KBTBD11; KBTBD2; KBTBD3; KBTBD4; KBTBD5; KBTBD6; KBTBD7; KBTBD8;

KEAP1 Kelch-like ECH-associated protein 1 is a protein that in humans is encoded by the ''Keap1'' gene. Structure Keap1 has four discrete protein domains. The N-terminal Broad complex, Tramtrack and Bric-à-Brac (BTB) domain contains the Cys151 res ...

; KIAA1900; KLHDC1; KLHDC2; KLHDC3; KLHDC4; KLHDC5; KLHDC6; KLHDC7A; KLHDC7B; KLHDC8A; KLHDC8B; KLHDC9; KLHDC10; KLHL1; KLHL10; KLHL11;

KLHL12 Kelch-like protein 12 is a protein that in humans is encoded by the ''KLHL12'' gene. Interactions KLHL12 has been shown to interact with RIT1 and CUL3 Cullin 3 is a protein that in humans is encoded by the ''CUL3'' gene. Cullin 3 protein be ...

; KLHL13; KLHL14; KLHL15; KLHL17; KLHL18; KLHL2; KLHL20; KLHL21; KLHL22; KLHL23; KLHL24; KLHL25; KLHL26; KLHL28; KLHL29; KLHL3; KLHL30; KLHL31; KLHL32; KLHL34; KLHL4; KLHL40; KLHL5; KLHL6; KLHL7; KLHL8; KLHL9; LZTR1;

MEGF8 ''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 chromosom ...

;

MKLN1 Muskelin is a protein that in humans is encoded by the ''MKLN1'' gene. Interactions MKLN1 has been shown to interact with RANBP9 Ran-binding protein 9 is a protein that in humans is encoded by the ''RANBP9'' gene. Function This gene encodes ...

; RABEPK; SARCOSIN;

References

* * * {{Protein tandem repeats