Heme transporter HRG (IPR026218)

Short name: HRG

Overlapping homologous superfamilies


Family relationships



Haems are metalloporphyrins that serve as prosthetic groups for a variety of biological processes, including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing. Haem is usually synthesised by a multistep biosynthetic pathway. The cellular pathways and molecules that mediate intracellular haem trafficking are still largely unknown [PMID: 18418376].

Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins. In C.elegans, it has been shown that HRG-1 proteins are essential for haem homeostasis. In worms, depletion of hrg-1, or its paralogue hrg-4, results in the disruption of organismal haem sensing, and an abnormal response to haem analogues [PMID: 18418376].

HRG-1 and HRG-4 are transmembrane (TM) proteins that reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins have been shown to co-localise, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1 [PMID: 18418376].

Sequence analysis of HRG-1 has identified 4 predicted TM domains, and a conserved tyrosine and acidic-di-leucine-based sorting signal in the cytoplasmic C terminus. In addition, residues that could potentially either directly bind haem (H90 in TM2) or interact with the haem side chains (FARKY) are situated in the C-terminal tail [PMID: 18418376].

GO terms

Biological Process

GO:0015886 heme transport

Molecular Function

GO:0015232 heme transporter activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.