HUWE1 associated protein modifying stress responses 2 (HAPSTR2)

HAPSTR2 is a functional paralog of HAPSTR1 that emerged approximately 180 million years ago through a retroposition event early in mammalian evolution[1]. It is expressed primarily in neural and germline tissues and certain cancers in a tissue-selective manner[1]. HAPSTR2 functions dually to stabilize HAPSTR1 protein during normal physiological conditions through direct physical interaction and to preserve stress signaling resilience when HAPSTR1 function is compromised[1]. The protein retains key biochemical features of HAPSTR1, including the ability to homo-oligomerize and hetero-oligomerize with HAPSTR1 through conserved HBO domain residues[1]. HAPSTR2 also interacts with the E3 ubiquitin ligase HUWE1, though with lower affinity compared to HAPSTR1, making it approximately 4-fold more stable than HAPSTR1[1]. This mammalian retrogene serves as a molecular buffer that safeguards cellular fitness by augmenting HAPSTR1-dependent stress response pathways and providing functional redundancy during stress conditions including DNA damage, nutrient scarcity, and protein misfolding[1]. The protein demonstrates evolutionary conservation under purifying selection pressure, indicating its beneficial role for organismal fitness[1].

Other names

C16orf72-likeHUWE1-associated protein modifying stress responses 2chromosome 16 open reading frame 72-like