Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Suppression of peroxisomal membrane protein defects by peroxisomal ATP binding cassette (ABC) proteins.
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Expression of PMP70 restores VLCFA beta-oxidation in X-ALD fibroblasts
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PMP70 and ALDP expression restores peroxisome biogenesis in PEX2-deficient cells
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Indicates overlapping functions between peroxisomal ABC transporters
Restoration of PEX2 peroxisome assembly defects by overexpression of PMP70.
Peroxisome synthesis in the absence of preexisting peroxisomes.
Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters.
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ABCD3 (PMP70) homo- and heterodimerizes with ABCD1 (ALDP) and ABCD2 (ALDRP)
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Demonstrated by yeast two-hybrid and co-immunoprecipitation
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C-terminal halves mediate dimerization
PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis.
Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p.
Characterization and functional analysis of the nucleotide binding fold in human peroxisomal ATP binding cassette transporters.
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PMP70 NBF binds ATP with KM of 8.2 uM
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ATP-specific, no GTPase activity
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G478R mutation decreases ATP binding; S572I decreases ATPase activity
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NBF mutations do not affect dimerization
Targeting elements in the amino-terminal part direct the human 70-kDa peroxisomal integral membrane protein (PMP70) to peroxisomes.
Two different targeting signals direct human peroxisomal membrane protein 22 to peroxisomes.
Two splice variants of human PEX19 exhibit distinct functions in peroxisomal assembly.
PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins.
Role of Pex19p in the targeting of PMP70 to peroxisome.
Adrenoleukodystrophy: subcellular localization and degradation of adrenoleukodystrophy protein (ALDP/ABCD1) with naturally occurring missense mutations.
Live cell FRET microscopy: homo- and heterodimerization of two human peroxisomal ABC transporters, the adrenoleukodystrophy protein (ALDP, ABCD1) and PMP70 (ABCD3).
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ABCD3 forms homodimers in living cells (FRET microscopy)
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Also forms ABCD1/ABCD3 heterodimers, but ABCD1 homodimers predominate
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C-terminal 87 amino acids harbor the key dimerization domain
Hydrophobic regions adjacent to transmembrane domains 1 and 5 are important for the targeting of the 70-kDa peroxisomal membrane protein.
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PMP70 has two distinct peroxisomal targeting signals
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Hydrophobic regions adjacent to TMD1 and TMD5 are critical
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L21Q/L22Q/L23Q, I70N/L71Q, I307A/L308A mutations abolish targeting
Pex3p-dependent peroxisomal biogenesis initiates in the endoplasmic reticulum of human fibroblasts.
Defining the membrane proteome of NK cells.
Multiple organelle-targeting signals in the N-terminal portion of peroxisomal membrane protein PMP70.
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N-terminal 80aa segment alone targets to outer mitochondrial membrane
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TM1 segment alone targets to ER
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Full N80-TM1-TM2 region targets exclusively to peroxisomes
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N80 segment suppresses ER-targeting function of TM1
Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p.
A role for the human peroxisomal half-transporter ABCD3 in the oxidation of dicarboxylic acids.
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Each peroxisomal half-transporter can function as homodimer
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ABCD3 preferentially transports hydrophilic substrates including long-chain unsaturated, branched-chain, and dicarboxylic fatty acids
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Substrate specificities of ABCD1, ABCD2, and ABCD3 are overlapping but distinct
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All substrates transported as CoA esters
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ABCD3 has a specific role in dicarboxylic acid oxidation
A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3.
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First ABCD3-deficient patient identified with CBAS5
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Accumulation of C27-bile acid intermediates in plasma
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Normal C26:0 beta-oxidation but reduced pristanic acid beta-oxidation
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Abcd3 KO mice accumulate phytanic acid and C27-bile acid intermediates
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ABCD3 transports branched-chain fatty acids and C27 bile acids into peroxisomes
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Critical step in bile acid biosynthesis
Characterization of human ATP-binding cassette protein subfamily D reconstituted into proteoliposomes.
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ABCD3 displays stable ATPase activity inhibited by AlF3
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ABCD3 possesses acyl-CoA thioesterase activity equal to ABCD1/2/4
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Reconstituted in proteoliposomes for functional characterization
The peroxisomal transporter ABCD3 plays a major role in hepatic dicarboxylic fatty acid metabolism and lipid homeostasis.
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Abcd3 KO mice show increased hepatic long-chain DCAs (C14-C18)
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Elevated urinary medium-chain DCAs
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Hepatomegaly, lipodystrophic phenotype
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Elevated C27 bile acid precursors DHCA and THCA
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Deficient ketone body production during fasting
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Enhanced cholesterol synthesis with decreased de novo lipogenesis
Structural insights into human ABCD3-mediated peroxisomal acyl-CoA translocation.
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Cryo-EM structures of ABCD3 bound to phytanoyl-CoA (2.9 A) and ATP (3.2 A)
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Inward-facing and outward-facing conformational states captured
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Two phytanoyl-CoA molecules bind individually to each TMD
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DHCA-CoA and THCA-CoA are ABCD3-specific substrates
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ATP binding causes scissor-like movement expanding translocation cavity
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PDB codes 8Z0F and 8Z9X
Molecular mechanism of substrate transport by human peroxisomal ABCD3.
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Cryo-EM structures of full-length ABCD3 apo (3.33 A) and phytanoyl-CoA-bound (3.13 A)
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Both inward-facing conformations as homodimer
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Substrate binding induces 5-fold increase in ATPase activity
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Substrate binding reduces NBD separation from 38.18 to 34.28 A
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Proposed transport cycle with substrate-induced NBD closure
ABCD1-3 dimers transfer LCFAs from cytosol to peroxisomal matrix
PEX-19 docks ABCD1/D2/D3 to peroximal membrane
PEX3:PEX19:class I PMP dissociates
PEX19:class I PMP binds PEX3
PEX19 binds class I peroxisomal membrane proteins