GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

PMID:23395477

Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.

Recessive human C10orf11/LRMDA loss-of-function alleles segregated with albinism in the studied families.

"The region contains five protein-coding genes, and sequencing of one of these, C10orf11 , revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern."
In human fetal tissue, C10orf11 was detected in melanoblasts and melanocytes but not retinal pigment epithelial cells.

"Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells."
Zebrafish orthologue knockdown reduced pigmentation and apparent pigmented-melanocyte number, and wild-type but not mutant human C10orf11 rescued the morphant phenotype.

"Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11."

PMID:36334630

OCA7 is a melanosome membrane protein that defines pigmentation by regulating early stages of melanosome biogenesis.

OCA7/LRMDA localizes to the limiting membrane of melanosomes in pigment cells.

"Here, we discover that OCA7 localizes to the limiting membrane of melanosomes, the specialized pigment cell organelles where melanin is synthesized."
Recruitment of OCA7/LRMDA depends on the canonical effector-binding surface of melanosomal RAB32 and RAB38.

"We demonstrate that OCA7 is recruited through interaction with a canonical effector-binding surface of melanosome proteins Rab32 and Rab38."
OCA7 knockout in human MNT1 cells altered melanin content by impairing melanosome maturation in a melanocyte-autonomous setting.

"Using newly generated OCA7-KO MNT1 cells, we show OCA7 regulates overall melanin levels in a melanocyte autonomous manner by controlling melanosome maturation."
OCA7 loss perturbed PMEL processing, stage-I-to-stage-II melanosome maturation, and melanosome lumen pH.

"Importantly, we found that OCA7 regulates premelanosome protein (PMEL) processing, impacting fibrillation and the striations that define transition from melanosome stage I to stage II. Furthermore, the melanosome lumen of OCA7-KO cells displays lower pH than control cells."
The 2022 interaction and localization constructs used the 226-residue OCA7 transcript amplified from MNT1 cells; the candidate 198-residue transcript did not amplify in that experiment.

"Attempts to amplify two potential transcript variants of OCA7 encoding a 226 or 198 amino acid protein from MNT1 complementary DNA (cDNA) were only successful for the first, suggesting it is the predominant variant."

PMID:41038817

Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7.

LRMDA can bind Commander and active RAB32 simultaneously, defining a distinct RAB32-LRMDA-Commander assembly.

"Here, we identify leucine rich melanocyte differentiation associated (LRMDA) as a Commander binding protein. We reveal that LRMDA and SNX17 share a common mechanism of Commander association, and that LRMDA simultaneously associates with Commander and active RAB32, establishing distinct RAB32-LRMDA-Commander and SNX17-Commander assemblies."
Functional experiments in melanocytes distinguish an LRMDA-dependent Commander pathway in melanosome biogenesis.

"Functional analysis in melanocytes reveals distinct roles for RAB32-LRMDA-Commander and SNX17-Commander in melanosome biogenesis."
OCA7-causing LRMDA mutations disrupt RAB32 and Commander binding, providing a mechanistic link from variants to defective pigment-organelle biogenesis.

"We reveal how LRMDA mutations, causative for oculocutaneous albinism type 7, a hypopigmentation disorder accompanied by poor visual acuity, uncouple RAB32 and Commander binding thereby establishing the mechanistic basis of this disease."
All experiments in this study used the longer 226-residue LRMDA proteoform represented by unreviewed UniProt accession A0A087WWI0, not the reviewed 198-residue Q9H2I8 record.

"LRMDA-GFP, LRMDA-GFP(ΔC) and LRMDA-GFP(ΔC) in pEGFP-N3 plasmid were a gift from Prof. Santiago di Pietro, and the wild-type sequence encoded the longer LRMDA isoform with Uniprot accession A0A087WWI0. This isoform was used in all experiments."

file:human/LRMDA/LRMDA-uniprot.txt

UniProtKB/Swiss-Prot record for human LRMDA (Q9H2I8)