FLVCR1

This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein is a heme transporter that may play a critical role in erythropoiesis by protecting developing erythroid cells from heme toxicity. This gene may play a role in posterior column ataxia with retinitis pigmentosa and the hematological disorder Diamond-Blackfan syndrome.

Full Name

feline leukemia virus subgroup C cellular receptor 1

Function

Isoform 1:
Heme transporter that exports cytoplasmic heme. It can also export coproporphyrin and protoporphyrin IX, which are both intermediate products in the heme biosynthetic pathway. Does not export bilirubin. Heme export depends on the presence of HPX and is required to maintain intracellular free heme balance, protecting cells from heme toxicity. Heme export provides protection from heme or ferrous iron toxicities in liver, brain, sensory neurons and during erythtopoiesis, a process in which heme synthesis intensifies. Causes susceptibility to FeLV-C in vitro.

Isoform 2:
Heme transporter that promotes heme efflux from the mitochondrion to the cytoplasm. Essential for erythroid differentiation.

Biological Process

Blood vessel development Source: Ensembl
Cellular iron ion homeostasis Source: Reactome
Embryonic digit morphogenesis Source: Ensembl
Embryonic skeletal system morphogenesis Source: Ensembl
Erythrocyte differentiation Source: MGI
Erythrocyte maturation Source: UniProtKB-KW
Head morphogenesis Source: Ensembl
Heme biosynthetic process Source: Reactome
Heme export Source: UniProtKB
Heme transport Source: MGI
In utero embryonic development Source: Ensembl
Mitochondrial transport Source: MGI
Multicellular organism growth Source: Ensembl
Regulation of organ growth Source: Ensembl
Spleen development Source: Ensembl

Cellular Location

Isoform 1: Cell membrane
Isoform 2: Mitochondrion membrane

Involvement in disease

Posterior column ataxia with retinitis pigmentosa (PCARP):
The disease is caused by variants affecting the gene represented in this entry. Defective neuronal heme transmembrane export due to FLVCR1 mutations may abrogate the neuroprotective effects of neuroglobin and initiate an apoptotic cascade that results in the selective degeneration of photoreceptors in the neurosensory retina and sensory neurons in the posterior spinal cord. A neurodegenerative syndrome beginning in infancy with areflexia and retinitis pigmentosa. Nyctalopia (night blindness) and peripheral visual field loss are usually evident during late childhood or teenage years, with subsequent progressive constriction of the visual fields and loss of central retinal function over time. A sensory ataxia caused by degeneration of the posterior columns of the spinal cord results in a loss of proprioceptive sensation that is clinically evident in the second decade of life and gradually progresses. Scoliosis, camptodactyly, achalasia, gastrointestinal dysmotility, and a sensory peripheral neuropathy are variable features of the disease. Affected individuals have no clinical or radiological evidence of cerebral or cerebellar involvement. Defects in FLVCR1 are a cause of a sensory neuropathy resulting in pain insensitivity. Patients have decreased sensing of pain, temperature and touch. Self-injury, ulcers and amputations are commonly observed in affected individuals.

Topology

Cytoplasmic: 1-107
Helical: 108-128
Extracellular: 129-147
Helical: 148-168
Cytoplasmic: 169-174
Helical: 175-195
Extracellular: 196-199
Helical: 200-220
Cytoplasmic: 221-240
Helical: 241-261
Extracellular: 262-275
Helical: 276-296
Cytoplasmic: 297-331
Helical: 332-352
Extracellular: 353-372
Helical: 373-393
Cytoplasmic: 394-401
Helical: 402-422
Extracellular: 423-424
Helical: 425-445
Cytoplasmic: 446-459
Helical: 460-480
Extracellular: 481-490
Helical: 491-511
Cytoplasmic: 512-555

PTM

N-Glycosylated.