A HEAT repeat is a
protein tandem repeat structural motif
In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated molecules. A structural motif does not have t ...
composed of two
alpha helices
An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix).
The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
linked by a short loop. HEAT repeats can form
alpha solenoid
An alpha solenoid (sometimes also known as an alpha horseshoe or as stacked pairs of alpha helices, abbreviated SPAH) is a protein fold composed of repeating alpha helix subunits, commonly helix-turn-helix motifs, arranged in antiparallel fash ...
s, a type of
solenoid protein domain
Solenoid protein domains are a highly modular type of protein domain. They consist of a chain of nearly identical Protein structure, folds, often simply called Protein tandem repeats, tandem repeats. They are extremely common among all types of pr ...
found in a number of
cytoplasm
The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
ic proteins. The name "HEAT" is an acronym for four proteins in which this repeat structure is found:
Huntingtin, elongation factor 3 (
EF3),
protein phosphatase 2
Protein phosphatase 2 (PP2), also known as PP2A, is an enzyme that in humans is encoded by the ''PPP2CA'' gene. The PP2A heterotrimeric protein phosphatase is ubiquitously expressed, accounting for a large fraction of phosphatase activity in ...
A (PP2
A),
and the yeast kinase
TOR1.
HEAT repeats form extended superhelical structures which are often involved in intracellular transport; they are structurally related to
armadillo repeats
An armadillo repeat is a characteristic, repetitive amino acid peptide sequence, sequence of about 42 residue (chemistry)#biochemistry, residues in length that is found in many proteins. Proteins that contain armadillo repeats typically contain sev ...
. The nuclear transport protein
importin beta
Importin is a type of karyopherin that transports protein molecules from the cell's cytoplasm to the nucleus. It does so by binding to specific recognition sequences, called nuclear localization sequences (NLS).
Importin has two subunits, impor ...
contains 19 HEAT repeats.
Various HEAT repeat proteins and their structures
Representative examples of HEAT repeat proteins include
importin
Importin is a type of karyopherin that transports protein molecules from the Eukaryotic Cell, cell's cytoplasm to the cell nucleus, nucleus. It does so by binding to specific recognition sequences, called nuclear localization sequences (NLS).
I ...
β (also known as karyopherin β) family,
regulatory subunits of
condensin
Condensins are large protein complexes that play a central role in chromosome condensation and segregation during mitosis and meiosis (Figure 1). Their subunits were originally identified as major components of mitotic chromosomes assembled in ' ...
and
cohesin
Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...
,
separase,
PIKKs (phosphatidylinositol 3-kinase-related protein kinases) such as ATM (
Ataxia telangiectasia mutated
ATM serine/threonine kinase or Ataxia-telangiectasia mutated, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA repair#Double-strand breaks, DNA double-strand breaks (Canonical pathway, canonical pathway), o ...
) and ATR (
Ataxia telangiectasia and Rad3 related
Serine/threonine-protein kinase ATR, also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein 1 (FRP1), is an enzyme that, in humans, is encoded by the ''ATR'' gene. It is a large kinase of about 301.66 kDa. ATR ...
),
and the microtubule-binding protein XMAP215/Dis1/TOG
and CLASP.
Thus, cellular functions of HEAT repeat proteins are highly variable.
The structure of the following HEAT repeat proteins have been determined so far:
*Protein modification and degradation
**A subunit
and holoenzyme
of PP2A
**SCF
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 19 ...
ligase regulator Cand1
**Hsm3, a molecular chaperon involved in the assembly of 26S
proteasome
Proteasomes are essential protein complexes responsible for the degradation of proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are found inside all e ...
*Nucleo-cytoplasmic transport
**
Importin
Importin is a type of karyopherin that transports protein molecules from the Eukaryotic Cell, cell's cytoplasm to the cell nucleus, nucleus. It does so by binding to specific recognition sequences, called nuclear localization sequences (NLS).
I ...
β
**Exportin Cse1
**Transportin 1
**Nuleoporin Gle1;
Nup188;
Nup192
*
Transcriptional regulation
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from al ...
**TFIID subunit TAF6
**TBP regulator Mot1 (Modifier of transcription 1)
**Transcriptional initiation factor Rrn3
*
Translational regulation Translational regulation refers to the control of the levels of protein synthesized from its mRNA. This regulation is vastly important to the cellular response to stressors, growth cues, and differentiation. In comparison to transcriptional regula ...
**Elongation factor eEF3
**Initiation factor eIF4G
**
Aminoacyl tRNA synthetase
An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA. It does so by catalyzing the transesterification of a specific cognate amino acid or its pre ...
transfer protein Cex1p
*DNA repair
**DNA-PK (
DNA-dependent protein kinase)
**
Fanconi anemia
Fanconi anemia (FA) is a rare, autosomal recessive genetic disease characterized by aplastic anemia, congenital defects, endocrinological abnormalities, and an increased incidence of developing cancer. The study of Fanconi anemia has improve ...
responsible protein FANCF (
FANCF
Fanconi anemia group F protein is a protein that in humans is encoded by the ''FANCF'' gene.
Interactions
FANCF has been shown to interact with Fanconi anemia, complementation group C, FANCG, FANCA and FANCE.
Function
FANCF is an adaptor ...
)
**Damaged DNA-binding protein AlkD (Alkylpurin DNA glycosylase)
**PIKKs chaperone Tel2
*Chromosomal regulation
**
Cohesin
Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...
subunit SA2
/Scc3
**
Cohesin
Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...
regulator Wapl
**
Cohesin
Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...
regulator Pds5
**
Cohesin
Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...
loading factor Scc2
**
Cohesin
Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...
protease Separase
**
Condensin
Condensins are large protein complexes that play a central role in chromosome condensation and segregation during mitosis and meiosis (Figure 1). Their subunits were originally identified as major components of mitotic chromosomes assembled in ' ...
subunit CAP-G/ycg1
**
Condensin
Condensins are large protein complexes that play a central role in chromosome condensation and segregation during mitosis and meiosis (Figure 1). Their subunits were originally identified as major components of mitotic chromosomes assembled in ' ...
subunit CAP-D2/ycs4
*Cytoskeletal regulation
**
Microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nanometer, nm and have an inner diameter bet ...
-binding protein TOG
/Stu2
*Cell proliferation regulation
**TOR (
target of rapamycin)
*Others
**API5 (Apoptosis inhibitor 5)
**V-type ATPase H subunit
References
External links
*
*
{{Protein tandem repeats