UniProtKB - P55789 (ALR_HUMAN)
Protein
FAD-linked sulfhydryl oxidase ALR
Gene
GFER
Organism
Homo sapiens (Human)
Status
Functioni
FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen.6 Publications
May act as an autocrine hepatotrophic growth factor promoting liver regeneration.
Catalytic activityi
- EC:1.8.3.22 Publications
Cofactori
FADPROSITE-ProRule annotation2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 111 | FAD1 Publication | 1 | |
Binding sitei | 140 | FAD1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 99 – 107 | FAD1 Publication | 9 | |
Nucleotide bindingi | 171 – 183 | FAD1 PublicationAdd BLAST | 13 | |
Nucleotide bindingi | 194 – 195 | FAD1 Publication | 2 |
GO - Molecular functioni
- flavin adenine dinucleotide binding Source: UniProtKB
- flavin-linked sulfhydryl oxidase activity Source: GO_Central
- growth factor activity Source: UniProtKB-KW
- protein disulfide oxidoreductase activity Source: UniProtKB
GO - Biological processi
- liver development Source: GO_Central
Keywordsi
Molecular function | Growth factor, Oxidoreductase |
Ligand | FAD, Flavoprotein |
Enzyme and pathway databases
BRENDAi | 1.8.3.2, 2681 |
PathwayCommonsi | P55789 |
Reactomei | R-HSA-1268020, Mitochondrial protein import |
SIGNORi | P55789 |
Names & Taxonomyi
Protein namesi | Recommended name: FAD-linked sulfhydryl oxidase ALR (EC:1.8.3.2)Alternative name(s): Augmenter of liver regeneration Short name: hERV1 Hepatopoietin |
Gene namesi | Name:GFER Synonyms:ALR, HERV1, HPO |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000127554.12 |
HGNCi | HGNC:4236, GFER |
MIMi | 600924, gene |
neXtProti | NX_P55789 |
Subcellular locationi
Mitochondrion
- Mitochondrion intermembrane space
- Mitochondrion 1 Publication
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Mitochondrion
- mitochondrial intermembrane space Source: UniProtKB-SubCell
- mitochondrion Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Mitochondrion, SecretedPathology & Biotechi
Involvement in diseasei
Myopathy, mitochondrial progressive, with congenital cataract, hearing loss and developmental delay (MPMCHD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_063435 | 194 | R → H in MPMCHD; less stable than the wild-type protein within the mitochondria, increased rate of dissociation of FAD by about 45-fold. 2 PublicationsCorresponds to variant dbSNP:rs121908192EnsemblClinVar. | 1 |
Keywords - Diseasei
Cataract, Deafness, Disease mutation, Primary mitochondrial diseaseOrganism-specific databases
DisGeNETi | 2671 |
MalaCardsi | GFER |
MIMi | 613076, phenotype |
OpenTargetsi | ENSG00000127554 |
Orphaneti | 330054, Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome |
PharmGKBi | PA28648 |
Miscellaneous databases
Pharosi | P55789, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1741189 |
DrugBanki | DB03147, Flavin adenine dinucleotide |
DrugCentrali | P55789 |
Polymorphism and mutation databases
BioMutai | GFER |
DMDMi | 218511915 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000208548 | 1 – 205 | FAD-linked sulfhydryl oxidase ALRAdd BLAST | 205 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 59 | PhosphoserineCombined sources | 1 | |
Disulfide bondi | 95 | Interchain (with C-204) | ||
Disulfide bondi | 142 ↔ 145 | Redox-active | ||
Disulfide bondi | 171 ↔ 188 | |||
Disulfide bondi | 204 | Interchain (with C-95) |
Keywords - PTMi
Disulfide bond, PhosphoproteinProteomic databases
EPDi | P55789 |
jPOSTi | P55789 |
MassIVEi | P55789 |
MaxQBi | P55789 |
PaxDbi | P55789 |
PeptideAtlasi | P55789 |
PRIDEi | P55789 |
ProteomicsDBi | 56865 [P55789-1] 56866 [P55789-2] |
PTM databases
iPTMneti | P55789 |
MetOSitei | P55789 |
PhosphoSitePlusi | P55789 |
Expressioni
Tissue specificityi
Ubiquitously expressed. Highest expression in the testis and liver and low expression in the muscle.1 Publication
Gene expression databases
Bgeei | ENSG00000127554, Expressed in dorsal plus ventral thalamus and 189 other tissues |
ExpressionAtlasi | P55789, baseline and differential |
Genevisiblei | P55789, HS |
Organism-specific databases
HPAi | ENSG00000127554, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
P55789
With | #Exp. | IntAct |
---|---|---|
PLEKHF2 [Q9H8W4] | 3 | EBI-718281,EBI-742388 |
GO - Molecular functioni
- growth factor activity Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 108939, 63 interactors |
IntActi | P55789, 28 interactors |
MINTi | P55789 |
STRINGi | 9606.ENSP00000248114 |
Miscellaneous databases
RNActi | P55789, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P55789 |
SMRi | P55789 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P55789 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 95 – 195 | ERV/ALR sulfhydryl oxidasePROSITE-ProRule annotationAdd BLAST | 101 |
Phylogenomic databases
eggNOGi | KOG3355, Eukaryota |
GeneTreei | ENSGT00390000001979 |
HOGENOMi | CLU_070631_1_1_1 |
InParanoidi | P55789 |
OMAi | KPCRSCT |
OrthoDBi | 1537996at2759 |
PhylomeDBi | P55789 |
TreeFami | TF105271 |
Family and domain databases
Gene3Di | 1.20.120.310, 1 hit |
InterProi | View protein in InterPro IPR039799, ALR/ERV IPR036774, ERV/ALR_sulphydryl_oxid_sf IPR017905, ERV/ALR_sulphydryl_oxidase |
PANTHERi | PTHR12645, PTHR12645, 1 hit |
Pfami | View protein in Pfam PF04777, Evr1_Alr, 1 hit |
SUPFAMi | SSF69000, SSF69000, 1 hit |
PROSITEi | View protein in PROSITE PS51324, ERV_ALR, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P55789-1) [UniParc]FASTAAdd to basket
Also known as: HPO-205, lfALR
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAAPGERGRF HGGNLFFLPG GARSEMMDDL ATDARGRGAG RRDAAASAST
60 70 80 90 100
PAQAPTSDSP VAEDASRRRP CRACVDFKTW MRTQQKRDTK FREDCPPDRE
110 120 130 140 150
ELGRHSWAVL HTLAAYYPDL PTPEQQQDMA QFIHLFSKFY PCEECAEDLR
160 170 180 190 200
KRLCRNHPDT RTRACFTQWL CHLHNEVNRK LGKPDFDCSK VDERWRDGWK
DGSCD
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BRD2 | H3BRD2_HUMAN | Sulfhydryl oxidase | GFER | 139 | Annotation score: | ||
H3BQQ4 | H3BQQ4_HUMAN | Sulfhydryl oxidase | GFER hCG_42694 | 130 | Annotation score: | ||
H3BRW3 | H3BRW3_HUMAN | FAD-linked sulfhydryl oxidase ALR | GFER | 109 | Annotation score: |
Sequence cautioni
The sequence AAA96390 differs from that shown. Reason: Frameshift.Curated
The sequence AAD36986 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAD56538 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAH02429 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAH28348 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 30 | L → S in AAA96390 (PubMed:10712775).Curated | 1 | |
Sequence conflicti | 127 | Q → R in AAG38105 (Ref. 3) Curated | 1 | |
Sequence conflicti | 180 | K → E in AAG38105 (Ref. 3) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_061994 | 166 | F → L. Corresponds to variant dbSNP:rs36041021EnsemblClinVar. | 1 | |
Natural variantiVAR_063435 | 194 | R → H in MPMCHD; less stable than the wild-type protein within the mitochondria, increased rate of dissociation of FAD by about 45-fold. 2 PublicationsCorresponds to variant dbSNP:rs121908192EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_040393 | 1 – 80 | Missing in isoform 2. 2 PublicationsAdd BLAST | 80 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF183892 Genomic DNA Translation: AAD56538.1 Different initiation. AF124604 mRNA Translation: AAD17328.1 AF306863 mRNA Translation: AAG38105.1 AY550027 mRNA Translation: AAS55642.1 AC005606 Genomic DNA No translation available. BC002429 mRNA Translation: AAH02429.1 Different initiation. BC028348 mRNA Translation: AAH28348.2 Different initiation. AF146394 Genomic DNA Translation: AAD36986.1 Different initiation. U31176 mRNA Translation: AAA96390.2 Frameshift. |
CCDSi | CCDS32368.1 [P55789-1] |
RefSeqi | NP_005253.3, NM_005262.2 [P55789-1] |
Genome annotation databases
Ensembli | ENST00000248114; ENSP00000248114; ENSG00000127554 [P55789-1] |
GeneIDi | 2671 |
KEGGi | hsa:2671 |
UCSCi | uc002cob.4, human [P55789-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF183892 Genomic DNA Translation: AAD56538.1 Different initiation. AF124604 mRNA Translation: AAD17328.1 AF306863 mRNA Translation: AAG38105.1 AY550027 mRNA Translation: AAS55642.1 AC005606 Genomic DNA No translation available. BC002429 mRNA Translation: AAH02429.1 Different initiation. BC028348 mRNA Translation: AAH28348.2 Different initiation. AF146394 Genomic DNA Translation: AAD36986.1 Different initiation. U31176 mRNA Translation: AAA96390.2 Frameshift. |
CCDSi | CCDS32368.1 [P55789-1] |
RefSeqi | NP_005253.3, NM_005262.2 [P55789-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3MBG | X-ray | 1.85 | A/B/C | 81-205 | [»] | |
3O55 | X-ray | 1.90 | A | 81-205 | [»] | |
3TK0 | X-ray | 1.61 | A | 81-205 | [»] | |
3U2L | X-ray | 1.95 | A | 91-205 | [»] | |
3U2M | X-ray | 2.00 | A | 91-205 | [»] | |
3U5S | X-ray | 1.50 | A | 82-203 | [»] | |
4LDK | X-ray | 2.04 | A | 81-205 | [»] | |
BMRBi | P55789 | |||||
SMRi | P55789 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108939, 63 interactors |
IntActi | P55789, 28 interactors |
MINTi | P55789 |
STRINGi | 9606.ENSP00000248114 |
Chemistry databases
ChEMBLi | CHEMBL1741189 |
DrugBanki | DB03147, Flavin adenine dinucleotide |
DrugCentrali | P55789 |
PTM databases
iPTMneti | P55789 |
MetOSitei | P55789 |
PhosphoSitePlusi | P55789 |
Polymorphism and mutation databases
BioMutai | GFER |
DMDMi | 218511915 |
Proteomic databases
EPDi | P55789 |
jPOSTi | P55789 |
MassIVEi | P55789 |
MaxQBi | P55789 |
PaxDbi | P55789 |
PeptideAtlasi | P55789 |
PRIDEi | P55789 |
ProteomicsDBi | 56865 [P55789-1] 56866 [P55789-2] |
Protocols and materials databases
Antibodypediai | 42516, 256 antibodies |
Genome annotation databases
Ensembli | ENST00000248114; ENSP00000248114; ENSG00000127554 [P55789-1] |
GeneIDi | 2671 |
KEGGi | hsa:2671 |
UCSCi | uc002cob.4, human [P55789-1] |
Organism-specific databases
CTDi | 2671 |
DisGeNETi | 2671 |
EuPathDBi | HostDB:ENSG00000127554.12 |
GeneCardsi | GFER |
HGNCi | HGNC:4236, GFER |
HPAi | ENSG00000127554, Low tissue specificity |
MalaCardsi | GFER |
MIMi | 600924, gene 613076, phenotype |
neXtProti | NX_P55789 |
OpenTargetsi | ENSG00000127554 |
Orphaneti | 330054, Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome |
PharmGKBi | PA28648 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3355, Eukaryota |
GeneTreei | ENSGT00390000001979 |
HOGENOMi | CLU_070631_1_1_1 |
InParanoidi | P55789 |
OMAi | KPCRSCT |
OrthoDBi | 1537996at2759 |
PhylomeDBi | P55789 |
TreeFami | TF105271 |
Enzyme and pathway databases
BRENDAi | 1.8.3.2, 2681 |
PathwayCommonsi | P55789 |
Reactomei | R-HSA-1268020, Mitochondrial protein import |
SIGNORi | P55789 |
Miscellaneous databases
BioGRID-ORCSi | 2671, 527 hits in 857 CRISPR screens |
EvolutionaryTracei | P55789 |
GeneWikii | GFER |
GenomeRNAii | 2671 |
Pharosi | P55789, Tchem |
PROi | PR:P55789 |
RNActi | P55789, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000127554, Expressed in dorsal plus ventral thalamus and 189 other tissues |
ExpressionAtlasi | P55789, baseline and differential |
Genevisiblei | P55789, HS |
Family and domain databases
Gene3Di | 1.20.120.310, 1 hit |
InterProi | View protein in InterPro IPR039799, ALR/ERV IPR036774, ERV/ALR_sulphydryl_oxid_sf IPR017905, ERV/ALR_sulphydryl_oxidase |
PANTHERi | PTHR12645, PTHR12645, 1 hit |
Pfami | View protein in Pfam PF04777, Evr1_Alr, 1 hit |
SUPFAMi | SSF69000, SSF69000, 1 hit |
PROSITEi | View protein in PROSITE PS51324, ERV_ALR, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ALR_HUMAN | |
Accessioni | P55789Primary (citable) accession number: P55789 Secondary accession number(s): Q53YM6 Q9UK40 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | December 16, 2008 | |
Last modified: | December 2, 2020 | |
This is version 176 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations