HEAT Repeat

From Proteopedia

HEAT repeat motif

The protein domain HEAT is found in a number of diverse eukaryotic cytoplasmic proteins, including the four that give rise to the acronym HEAT (Huntingtin, elongation factor 3 (EF3) 1, protein phosphatase 2A (PP2A) 2, and the yeast PI3‐kinase TOR1). The HEAT domain consists of repeats of ~47 residues that form two anti‐parallel α‐helices and two turns arranged about a common axis. These repeats are linked by flexible inter‐unit loops. A signature motif of the HEAT repeats is the presence of conserved Asp and Arg residues at positions 19 and 25, respectively. Thus, repeats form rod‐like helical structures, which are involved in intracellular transport.

The HEAT repeat family is related to armadillo/beta‐catenin‐like repeats. Similarities between HEAT and Armadillo (ARM) repeat families are found in the conserved residues that form the hydrophobic cores. In contrast to ARM repeats, HEAT repeats are more variable in length, amino acid sequence and 3D-structure.

Family of HEAT repeats are divided into three classes: IMB, AAA and ADB based on similarities. Mainly, HEAT containing proteins are found in proteins such as importins and exportins that bind Ran‐GTP implicating their role in cargo transport. A substantial number of HEAT repeats have been detected in proteins involved in translation including eIF4Gs, p97/DAP5, Paip‐1, GCN1 and FRAP/mTOR, also.

Reference: 1. Andrade MA, Bork P (October 1995). "HEAT repeats in the Huntington's disease protein". Nat. Genet. 11 (2): 115–6. doi:10.1038/ng1095‐115 PMID 7550332 2. Groves MR, Hanlon N, Turowski P, Hemmings BA, Barford D (January 1999). "The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs". Cell 96 (1): 99–110. doi:10.1016/S0092‐8674(00)80963‐0 PMID 9989501