HEAT repeat

HEAT repeat
An example of an alpha solenoid structure composed of 15 HEAT repeats. The protein phosphatase 2A regulatory subunit is shown with the N-terminus in blue at bottom and the C-terminus in red at top. A single helix-turn-helix motif is shown in the center with the outer helix in pink, the inner helix in green, and the turn in white. From PDB: 2IAE​.[1][2]
Identifiers
Symbol	HEAT
Pfam	PF02985
InterPro	IPR000357
PROSITE	PDOC50077
SCOP2	1b3u / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1b3u​, 1f59​, 1gcj​, 1ibr​, 1m5n​, 1o6o​, 1o6p​, 1qbk​, 1qgr​, 1u6g​, 1ukl​, 2bku​

A HEAT repeat is a protein tandem repeat structural motif composed of two alpha helices linked by a short loop. HEAT repeats can form alpha solenoids, a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" is an acronym for four proteins in which this repeat structure is found: Huntingtin, elongation factor 3 (EF3), protein phosphatase 2A (PP2A),^[3] and the yeast kinase TOR1.^[4] HEAT repeats form extended superhelical structures which are often involved in intracellular transport; they are structurally related to armadillo repeats. The nuclear transport protein importin beta contains 19 HEAT repeats.

Various HEAT repeat proteins and their structures

Representative examples of HEAT repeat proteins include importin β (also known as karyopherin β) family,^[5] regulatory subunits of condensin and cohesin,^[6] separase,^[7] PIKKs (phosphatidylinositol 3-kinase-related protein kinases) such as ATM (Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3 related),^[8][9] and the microtubule-binding protein XMAP215/Dis1/TOG^[10] and CLASP.^[11] 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^[2] and holoenzyme^[12][13] of PP2A
  • SCFubiquitin ligase regulator Cand1^[14]
  • Hsm3, a molecular chaperon involved in the assembly of 26Sproteasome^[15]
• Nucleo-cytoplasmic transport
  • Importin β^[16][17][18]
  • Exportin Cse1^[19]
  • Transportin 1^[20]
  • Nuleoporin Gle1;^[21] Nup188;^[22] Nup192^[23]
• Transcriptional regulation
  • TFIID subunit TAF6^[24]
  • TBP regulator Mot1 (Modifier of transcription 1)^[25]
  • Transcriptional initiation factor Rrn3^[26]
• Translational regulation
  • Elongation factor eEF3^[27]
  • Initiation factor eIF4G^[28]
  • Aminoacyl tRNA synthetase transfer protein Cex1p^[29]
• DNA repair
  • DNA-PK (DNA-dependent protein kinase)^[30]
  • Fanconi anemia responsible protein FANCF (FANCF)^[31]
  • Damaged DNA-binding protein AlkD (Alkylpurin DNA glycosylase)^[32]
  • PIKKs chaperone Tel2^[33]
• Chromosomal regulation
  • Cohesin subunit SA2^[34]/Scc3^[35][36]
  • Cohesin regulator Wapl^[37][38]
  • Cohesin regulator Pds5^[39][40][41]
  • Cohesin loading factor Scc2^[42][43]
  • Cohesin protease Separase^[44][45][46]
  • Condensin subunit CAP-G/ycg1^[47][48]
  • Condensin subunit CAP-D2/ycs4^[49]
• Cytoskeletal regulation
  • Microtubule-binding protein TOG^[50][51]/Stu2^[52]
• Cell proliferation regulation
  • TOR (target of rapamycin)^[53]
• Others
  • API5 (Apoptosis inhibitor 5)^[54]
  • V-type ATPase H subunit^[55]

References

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External links

• Eukaryotic Linear Motif resource motif class LIG_PIKK_1
• Eukaryotic Linear Motif resource motif class DOC_PIKK_1