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Protein

FAD-linked sulfhydryl oxidase ALR

Gene

GFER

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Isoform 1: 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.
Isoform 2: May act as an autocrine hepatotrophic growth factor promoting liver regeneration.

Catalytic activityi

2 R'C(R)SH + O2 = R'C(R)S-S(R)CR' + H2O2.2 Publications

Cofactori

FADPROSITE-ProRule annotation2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei111FAD1 Publication1
Binding sitei140FAD1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi99 – 107FAD1 Publication9
Nucleotide bindingi171 – 183FAD1 PublicationAdd BLAST13
Nucleotide bindingi194 – 195FAD1 Publication2

GO - Molecular functioni

  • flavin adenine dinucleotide binding Source: UniProtKB
  • flavin-linked sulfhydryl oxidase activity Source: GO_Central
  • protein disulfide oxidoreductase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Oxidoreductase

Keywords - Ligandi

FAD, Flavoprotein

Enzyme and pathway databases

BioCyciZFISH:HS05112-MONOMER.
BRENDAi1.8.3.2. 2681.
ReactomeiR-HSA-1268020. Mitochondrial protein import.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:4236. GFER.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Secreted

Pathology & Biotechi

Involvement in diseasei

Myopathy, mitochondrial progressive, with congenital cataract, hearing loss and developmental delay (MPMCHD)1 Publication
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.
See also OMIM:613076
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063435194R → 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 rs121908192dbSNPEnsembl.1

Keywords - Diseasei

Cataract, Disease mutation

Organism-specific databases

DisGeNETi2671.
MalaCardsiGFER.
MIMi613076. phenotype.
OpenTargetsiENSG00000127554.
Orphaneti330054. Congenital cataract - progressive muscular hypotonia - hearing loss - developmental delay.
PharmGKBiPA28648.

Chemistry databases

ChEMBLiCHEMBL1741189.
DrugBankiDB03147. Flavin adenine dinucleotide.

Polymorphism and mutation databases

BioMutaiGFER.
DMDMi218511915.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002085481 – 205FAD-linked sulfhydryl oxidase ALRAdd BLAST205

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei59PhosphoserineCombined sources1
Disulfide bondi95Interchain (with C-204)
Disulfide bondi142 ↔ 145Redox-active
Disulfide bondi171 ↔ 188
Disulfide bondi204Interchain (with C-95)

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP55789.
MaxQBiP55789.
PaxDbiP55789.
PeptideAtlasiP55789.
PRIDEiP55789.

PTM databases

iPTMnetiP55789.
PhosphoSitePlusiP55789.

Expressioni

Tissue specificityi

Ubiquitously expressed. Highest expression in the testis and liver and low expression in the muscle.1 Publication

Gene expression databases

BgeeiENSG00000127554.
CleanExiHS_GFER.
ExpressionAtlasiP55789. baseline and differential.
GenevisibleiP55789. HS.

Organism-specific databases

HPAiHPA041227.
HPA063553.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. May form heterodimers of isoform 1 and isoform 2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PLEKHF2Q9H8W43EBI-718281,EBI-742388

Protein-protein interaction databases

BioGridi108939. 33 interactors.
IntActiP55789. 4 interactors.
MINTiMINT-263560.
STRINGi9606.ENSP00000248114.

Structurei

Secondary structure

1205
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi86 – 88Combined sources3
Beta strandi93 – 95Combined sources3
Helixi99 – 115Combined sources17
Helixi123 – 139Combined sources17
Helixi143 – 155Combined sources13
Helixi163 – 180Combined sources18
Helixi188 – 190Combined sources3
Helixi191 – 195Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MBGX-ray1.85A/B/C81-205[»]
3O55X-ray1.90A81-205[»]
3TK0X-ray1.61A81-205[»]
3U2LX-ray1.95A91-205[»]
3U2MX-ray2.00A91-205[»]
3U5SX-ray1.50A82-203[»]
4LDKX-ray2.04A81-205[»]
ProteinModelPortaliP55789.
SMRiP55789.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55789.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini95 – 195ERV/ALR sulfhydryl oxidasePROSITE-ProRule annotationAdd BLAST101

Sequence similaritiesi

Contains 1 ERV/ALR sulfhydryl oxidase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3355. Eukaryota.
COG5054. LUCA.
GeneTreeiENSGT00390000001979.
HOGENOMiHOG000195924.
HOVERGENiHBG000235.
InParanoidiP55789.
KOiK17783.
OMAiHGGNLFF.
OrthoDBiEOG091G0TRW.
PhylomeDBiP55789.
TreeFamiTF105271.

Family and domain databases

Gene3Di1.20.120.310. 1 hit.
InterProiIPR017905. ERV/ALR_sulphydryl_oxidase.
[Graphical view]
PfamiPF04777. Evr1_Alr. 1 hit.
[Graphical view]
SUPFAMiSSF69000. SSF69000. 1 hit.
PROSITEiPS51324. ERV_ALR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P55789-1) [UniParc]FASTAAdd to basket
Also known as: HPO-205, lfALR

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:205
Mass (Da):23,449
Last modified:December 16, 2008 - v2
Checksum:i43CBF8CCB5BA91C8
GO
Isoform 2 (identifier: P55789-2) [UniParc]FASTAAdd to basket
Also known as: HPO-125, sfALR

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: Missing.

Show »
Length:125
Mass (Da):15,029
Checksum:i3F0B927DC64EF606
GO

Sequence cautioni

The sequence AAA96390 differs from that shown. Reason: Frameshift at position 70.Curated
The sequence AAD36986 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAD56538 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH02429 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH28348 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti30L → S in AAA96390 (PubMed:10712775).Curated1
Sequence conflicti127Q → R in AAG38105 (Ref. 3) Curated1
Sequence conflicti180K → E in AAG38105 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_061994166F → L.Corresponds to variant rs36041021dbSNPEnsembl.1
Natural variantiVAR_063435194R → 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 rs121908192dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0403931 – 80Missing in isoform 2. 2 PublicationsAdd BLAST80

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.
CCDSiCCDS32368.1. [P55789-1]
RefSeqiNP_005253.3. NM_005262.2. [P55789-1]
UniGeneiHs.27184.

Genome annotation databases

EnsembliENST00000248114; ENSP00000248114; ENSG00000127554. [P55789-1]
GeneIDi2671.
KEGGihsa:2671.
UCSCiuc002cob.4. human. [P55789-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS32368.1. [P55789-1]
RefSeqiNP_005253.3. NM_005262.2. [P55789-1]
UniGeneiHs.27184.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MBGX-ray1.85A/B/C81-205[»]
3O55X-ray1.90A81-205[»]
3TK0X-ray1.61A81-205[»]
3U2LX-ray1.95A91-205[»]
3U2MX-ray2.00A91-205[»]
3U5SX-ray1.50A82-203[»]
4LDKX-ray2.04A81-205[»]
ProteinModelPortaliP55789.
SMRiP55789.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108939. 33 interactors.
IntActiP55789. 4 interactors.
MINTiMINT-263560.
STRINGi9606.ENSP00000248114.

Chemistry databases

ChEMBLiCHEMBL1741189.
DrugBankiDB03147. Flavin adenine dinucleotide.

PTM databases

iPTMnetiP55789.
PhosphoSitePlusiP55789.

Polymorphism and mutation databases

BioMutaiGFER.
DMDMi218511915.

Proteomic databases

EPDiP55789.
MaxQBiP55789.
PaxDbiP55789.
PeptideAtlasiP55789.
PRIDEiP55789.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000248114; ENSP00000248114; ENSG00000127554. [P55789-1]
GeneIDi2671.
KEGGihsa:2671.
UCSCiuc002cob.4. human. [P55789-1]

Organism-specific databases

CTDi2671.
DisGeNETi2671.
GeneCardsiGFER.
H-InvDBHIX0012707.
HGNCiHGNC:4236. GFER.
HPAiHPA041227.
HPA063553.
MalaCardsiGFER.
MIMi600924. gene.
613076. phenotype.
neXtProtiNX_P55789.
OpenTargetsiENSG00000127554.
Orphaneti330054. Congenital cataract - progressive muscular hypotonia - hearing loss - developmental delay.
PharmGKBiPA28648.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3355. Eukaryota.
COG5054. LUCA.
GeneTreeiENSGT00390000001979.
HOGENOMiHOG000195924.
HOVERGENiHBG000235.
InParanoidiP55789.
KOiK17783.
OMAiHGGNLFF.
OrthoDBiEOG091G0TRW.
PhylomeDBiP55789.
TreeFamiTF105271.

Enzyme and pathway databases

BioCyciZFISH:HS05112-MONOMER.
BRENDAi1.8.3.2. 2681.
ReactomeiR-HSA-1268020. Mitochondrial protein import.

Miscellaneous databases

EvolutionaryTraceiP55789.
GeneWikiiGFER.
GenomeRNAii2671.
PROiP55789.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127554.
CleanExiHS_GFER.
ExpressionAtlasiP55789. baseline and differential.
GenevisibleiP55789. HS.

Family and domain databases

Gene3Di1.20.120.310. 1 hit.
InterProiIPR017905. ERV/ALR_sulphydryl_oxidase.
[Graphical view]
PfamiPF04777. Evr1_Alr. 1 hit.
[Graphical view]
SUPFAMiSSF69000. SSF69000. 1 hit.
PROSITEiPS51324. ERV_ALR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiALR_HUMAN
AccessioniPrimary (citable) accession number: P55789
Secondary accession number(s): Q53YM6
, Q8TAH6, Q9H290, Q9UK40
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 16, 2008
Last modified: November 2, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.