ALR_RAT
ID ALR_RAT Reviewed; 198 AA.
AC Q63042;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=FAD-linked sulfhydryl oxidase ALR;
DE EC=1.8.3.2;
DE AltName: Full=Augmenter of liver regeneration;
GN Name=Gfer; Synonyms=Alr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION IN LIVER REGENERATION.
RC STRAIN=Fischer 344; TISSUE=Liver;
RX PubMed=8058770; DOI=10.1073/pnas.91.17.8142;
RA Hagiya M., Francavilla A., Polimeno L., Ihara I., Sakai H., Seki T.,
RA Shimonishi M., Porter K.A., Starzl T.E.;
RT "Cloning and sequence analysis of the rat augmenter of liver regeneration
RT (ALR) gene: expression of biologically active recombinant ALR and
RT demonstration of tissue distribution.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:8142-8146(1994).
RN [2]
RP ERRATUM OF PUBMED:8058770.
RX PubMed=7708779; DOI=10.1073/pnas.92.7.3076d;
RA Hagiya M., Francavilla A., Polimeno L., Ihara I., Sakai H., Seki T.,
RA Shimonishi M., Porter K.A., Starzl T.E.;
RL Proc. Natl. Acad. Sci. U.S.A. 92:3076-3076(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Wistar;
RX PubMed=12906155;
RA Dong J., Cheng J., Wang Q., Shi S., Wang G., Si C.;
RT "Cloning and analysis of the genomic DNA sequence of augmenter of liver
RT regeneration from rat.";
RL Chin. Med. Sci. J. 17:63-67(2002).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH FAD, SUBUNIT,
RP COFACTOR, AND DISULFIDE BONDS.
RX PubMed=12717032; DOI=10.1110/ps.0238103;
RA Wu C.-K., Dailey T.A., Dailey H.A., Wang B.-C., Rose J.P.;
RT "The crystal structure of augmenter of liver regeneration: a mammalian FAD-
RT dependent sulfhydryl oxidase.";
RL Protein Sci. 12:1109-1118(2003).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 74-198 IN COMPLEX WITH FAD, AND
RP SUBUNIT.
RX PubMed=22948913; DOI=10.1107/s0907444912022561;
RA Florence Q., Wu C.K., Habel J., Swindell J.T. II, Wang B.C., Rose J.P.;
RT "The structure of augmenter of liver regeneration crystallized in the
RT presence of 50 mM CdCl2 reveals a novel Cd2Cl4O6 cluster that aids in
RT crystal packing.";
RL Acta Crystallogr. D 68:1128-1133(2012).
CC -!- FUNCTION: FAD-dependent sulfhydryl oxidase that regenerates the redox-
CC active disulfide bonds in CHCHD4/MIA40, a chaperone essential for
CC disulfide bond formation and protein folding in the mitochondrial
CC intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient
CC intermolecular disulfide bridge with GFER/ERV1, resulting in
CC regeneration of the essential disulfide bonds in CHCHD4/MIA40, while
CC GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or
CC molecular oxygen. May have a function in liver regeneration and
CC spermatogenesis. {ECO:0000269|PubMed:8058770}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + 2 R'C(R)SH = H2O2 + R'C(R)S-S(R)CR';
CC Xref=Rhea:RHEA:17357, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:16520, ChEBI:CHEBI:17412; EC=1.8.3.2;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00654,
CC ECO:0000269|PubMed:12717032};
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:12717032,
CC PubMed:22948913). Interacts with CHCHD4/MIA40 (By similarity).
CC {ECO:0000250|UniProtKB:P55789, ECO:0000269|PubMed:12717032,
CC ECO:0000269|PubMed:22948913}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:P55789}. Mitochondrion
CC {ECO:0000250|UniProtKB:P55789}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF12808.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA06399.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D30735; BAA06399.1; ALT_INIT; mRNA.
DR EMBL; AF197192; AAF12808.1; ALT_INIT; Genomic_DNA.
DR PIR; I80184; I80184.
DR RefSeq; NP_037354.2; NM_013222.2.
DR PDB; 1OQC; X-ray; 1.80 A; A/B/C/D=74-198.
DR PDB; 3R7C; X-ray; 2.40 A; A/B/C/D=74-198.
DR PDBsum; 1OQC; -.
DR PDBsum; 3R7C; -.
DR AlphaFoldDB; Q63042; -.
DR SMR; Q63042; -.
DR STRING; 10116.ENSRNOP00000017917; -.
DR PhosphoSitePlus; Q63042; -.
DR PaxDb; Q63042; -.
DR PRIDE; Q63042; -.
DR Ensembl; ENSRNOT00000017917; ENSRNOP00000017917; ENSRNOG00000013370.
DR GeneID; 27100; -.
DR KEGG; rno:27100; -.
DR UCSC; RGD:61845; rat.
DR CTD; 2671; -.
DR RGD; 61845; Gfer.
DR eggNOG; KOG3355; Eukaryota.
DR GeneTree; ENSGT00390000001979; -.
DR HOGENOM; CLU_070631_1_1_1; -.
DR InParanoid; Q63042; -.
DR OMA; KPCRSCT; -.
DR OrthoDB; 1537996at2759; -.
DR PhylomeDB; Q63042; -.
DR TreeFam; TF105271; -.
DR BRENDA; 1.8.3.2; 5301.
DR EvolutionaryTrace; Q63042; -.
DR PRO; PR:Q63042; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000013370; Expressed in testis and 20 other tissues.
DR Genevisible; Q63042; RN.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR GO; GO:0016971; F:flavin-linked sulfhydryl oxidase activity; IDA:RGD.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0015035; F:protein-disulfide reductase activity; ISS:UniProtKB.
DR GO; GO:0072717; P:cellular response to actinomycin D; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0097237; P:cellular response to toxic substance; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0001889; P:liver development; IBA:GO_Central.
DR GO; GO:0097421; P:liver regeneration; IMP:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IDA:RGD.
DR GO; GO:1903204; P:negative regulation of oxidative stress-induced neuron death; IDA:RGD.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IDA:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR Gene3D; 1.20.120.310; -; 1.
DR InterPro; IPR039799; ALR/ERV.
DR InterPro; IPR036774; ERV/ALR_sulphydryl_oxid_sf.
DR InterPro; IPR017905; ERV/ALR_sulphydryl_oxidase.
DR PANTHER; PTHR12645; PTHR12645; 1.
DR Pfam; PF04777; Evr1_Alr; 1.
DR SUPFAM; SSF69000; SSF69000; 1.
DR PROSITE; PS51324; ERV_ALR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; FAD; Flavoprotein; Growth factor;
KW Mitochondrion; Oxidoreductase; Reference proteome.
FT CHAIN 1..198
FT /note="FAD-linked sulfhydryl oxidase ALR"
FT /id="PRO_0000208550"
FT DOMAIN 88..188
FT /note="ERV/ALR sulfhydryl oxidase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..45
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 92..100
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12717032,
FT ECO:0000269|PubMed:22948913"
FT BINDING 104
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12717032,
FT ECO:0000269|PubMed:22948913"
FT BINDING 133
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12717032,
FT ECO:0000269|PubMed:22948913"
FT BINDING 164..176
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12717032,
FT ECO:0000269|PubMed:22948913"
FT BINDING 187..188
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12717032,
FT ECO:0000269|PubMed:22948913"
FT DISULFID 88
FT /note="Interchain (with C-197)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654,
FT ECO:0000269|PubMed:12717032"
FT DISULFID 135..138
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654,
FT ECO:0000269|PubMed:12717032"
FT DISULFID 164..181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654,
FT ECO:0000269|PubMed:12717032"
FT DISULFID 197
FT /note="Interchain (with C-88)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00654,
FT ECO:0000269|PubMed:12717032"
FT HELIX 92..108
FT /evidence="ECO:0007829|PDB:1OQC"
FT HELIX 116..132
FT /evidence="ECO:0007829|PDB:1OQC"
FT HELIX 136..148
FT /evidence="ECO:0007829|PDB:1OQC"
FT HELIX 156..173
FT /evidence="ECO:0007829|PDB:1OQC"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:1OQC"
FT HELIX 184..188
FT /evidence="ECO:0007829|PDB:1OQC"
SQ SEQUENCE 198 AA; 22837 MW; 46AD9BEC2EF0C393 CRC64;
MAAPSEPAGF PRGSRFSFLP GGAHSEMTDD LVTDARGRGA RHRKDNAPAA APAPKGLEHG
KRPCRACVDF KSWMRTQQKR DIKFREDCPQ DREELGRNTW AFLHTLAAYY PDMPTPEQQQ
DMAQFIHIFS KFYPCEECAE DIRKRIDRSQ PDTSTRVSFS QWLCRLHNEV NRKLGKPDFD
CSRVDERWRD GWKDGSCD
