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P55789 (ALR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
FAD-linked sulfhydryl oxidase ALR

EC=1.8.3.2
Alternative name(s):
Augmenter of liver regeneration
Short name=hERV1
Hepatopoietin
Gene names
Name:GFER
Synonyms:ALR, HERV1, HPO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length205 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.12 Ref.14 Ref.15 Ref.16 Ref.17

Isoform 2:May act as an autocrine hepatotrophic growth factor promoting liver regeneration. Ref.12 Ref.14 Ref.15 Ref.16 Ref.17

Catalytic activity

2 R'C(R)SH + O2 = R'C(R)S-S(R)CR' + H2O2. Ref.15 Ref.17

Cofactor

FAD. Ref.16

Subunit structure

Homodimer; disulfide-linked. May form heterodimers of isoform 1 and isoform 2. Ref.9 Ref.15 Ref.16 Ref.17

Subcellular location

Isoform 1: Mitochondrion intermembrane space Ref.12 Ref.14.

Isoform 2: Cytoplasm. Secreted Ref.12 Ref.14.

Tissue specificity

Ubiquitously expressed. Highest expression in the testis and liver and low expression in the muscle. Ref.18

Involvement in disease

Myopathy, mitochondrial progressive, with congenital cataract, hearing loss and developmental delay (MPMCHD) [MIM:613076]: A disease characterized by progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.18

Sequence similarities

Contains 1 ERV/ALR sulfhydryl oxidase domain.

Sequence caution

The sequence AAA96390.2 differs from that shown. Reason: Frameshift at position 70.

The sequence AAD36986.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAD56538.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAH02429.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAH28348.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P55789-1)

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.
Isoform 2 (identifier: P55789-2)

Also known as: HPO-125; sfALR;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 205205FAD-linked sulfhydryl oxidase ALR
PRO_0000208548

Regions

Domain95 – 195101ERV/ALR sulfhydryl oxidase
Nucleotide binding99 – 1079FAD
Nucleotide binding171 – 18313FAD
Nucleotide binding194 – 1952FAD

Sites

Binding site1111FAD
Binding site1401FAD

Amino acid modifications

Modified residue591Phosphoserine Ref.11
Disulfide bond95Interchain (with C-204) Ref.15 Ref.16 Ref.17
Disulfide bond142 ↔ 145Redox-active Ref.15 Ref.16 Ref.17
Disulfide bond171 ↔ 188 Ref.15 Ref.16 Ref.17
Disulfide bond204Interchain (with C-95) Ref.15 Ref.16 Ref.17

Natural variations

Alternative sequence1 – 8080Missing in isoform 2.
VSP_040393
Natural variant1661F → L.
Corresponds to variant rs36041021 [ dbSNP | Ensembl ].
VAR_061994
Natural variant1941R → H in MPMCHD; less stable than the wild-type protein within the mitochondria, increased rate of dissociation of FAD by about 45-fold. Ref.15 Ref.18
Corresponds to variant rs121908192 [ dbSNP | Ensembl ].
VAR_063435

Experimental info

Sequence conflict301L → S in AAA96390. Ref.7
Sequence conflict1271Q → R in AAG38105. Ref.3
Sequence conflict1801K → E in AAG38105. Ref.3

Secondary structure

................ 205
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (HPO-205) (lfALR) [UniParc].

Last modified December 16, 2008. Version 2.
Checksum: 43CBF8CCB5BA91C8

FASTA20523,449
        10         20         30         40         50         60 
MAAPGERGRF HGGNLFFLPG GARSEMMDDL ATDARGRGAG RRDAAASAST PAQAPTSDSP 

        70         80         90        100        110        120 
VAEDASRRRP CRACVDFKTW MRTQQKRDTK FREDCPPDRE ELGRHSWAVL HTLAAYYPDL 

       130        140        150        160        170        180 
PTPEQQQDMA QFIHLFSKFY PCEECAEDLR KRLCRNHPDT RTRACFTQWL CHLHNEVNRK 

       190        200 
LGKPDFDCSK VDERWRDGWK DGSCD 

« Hide

Isoform 2 (HPO-125) (sfALR) [UniParc].

Checksum: 3F0B927DC64EF606
Show »

FASTA12515,029

References

« Hide 'large scale' references
[1]"Genomic structure, chromosomal localization, and characterization of a functional promoter for human hepatopoietin (HPO) gene."
Liu M.-M., He F.-C., Wei H.-D., Zhou W.-Q.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"HERV different transcription sequence."
Li Y., Xing G.-C., He F.-C., Wei H.-D., Zhang C.-G., Zhu L., Yu Y.-T.
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Liver.
[3]"Isolation of human HPO cDNA from human liver tissue."
Jun L., Wangxiang X., Xiaoming Y.
Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal liver.
[4]"Human augmenter of liver regeneration/hepatopoietin gene open reading frame sequence."
Dai W.-J., Jiang H.-C.
Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-205.
Tissue: Placenta and Skin.
[7]"Cloning and sequence analysis of human genomic DNA of augmenter of liver regeneration hepatitis."
Cheng J., Zhong Y.
Zhonghua Gan Zang Bing Za Zhi 8:12-14(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-205.
[8]"A new human gene located in the PKD1 region of chromosome 16 is a functional homologue to ERV1 of yeast."
Lisowsky T., Weinstat-Saslow D.L., Barton N., Reeders S.T., Schneider M.C.
Genomics 29:690-697(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-205.
Tissue: Renal cyst lining cell.
[9]"Identification of hepatopoietin dimerization, its interacting regions and alternative splicing of its transcription."
Li Y., Wei K., Lu C., Li Y., Li M., Xing G., Wei H., Wang Q., Chen J., Wu C., Chen H., Yang S., He F.
Eur. J. Biochem. 269:3888-3893(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, SUBUNIT.
[10]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space."
Daithankar V.N., Farrell S.R., Thorpe C.
Biochemistry 48:4828-4837(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[13]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40."
Sztolsztener M.E., Brewinska A., Guiard B., Chacinska A.
Traffic 14:309-320(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[15]"Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy."
Daithankar V.N., Schaefer S.A., Dong M., Bahnson B.J., Thorpe C.
Biochemistry 49:6737-6745(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 81-205, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, DISULFIDE BONDS, FAD-BINDING SITES, CHARACTERIZATION OF VARIANT MPMCHD HIS-194.
[16]"Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR."
Banci L., Bertini I., Calderone V., Cefaro C., Ciofi-Baffoni S., Gallo A., Kallergi E., Lionaki E., Pozidis C., Tokatlidis K.
Proc. Natl. Acad. Sci. U.S.A. 108:4811-4816(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 81-205 IN COMPLEX WITH FAD, FUNCTION, COFACTOR, SUBUNIT, DISULFIDE BONDS, INTERACTION WITH CHCHD4.
[17]"An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR."
Banci L., Bertini I., Calderone V., Cefaro C., Ciofi-Baffoni S., Gallo A., Tokatlidis K.
J. Am. Chem. Soc. 134:1442-1445(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 91-205, FUNCTION, CATALYTIC ACTIVITY, DISULFIDE BONDS, SUBUNIT.
[18]"The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency."
Di Fonzo A., Ronchi D., Lodi T., Fassone E., Tigano M., Lamperti C., Corti S., Bordoni A., Fortunato F., Nizzardo M., Napoli L., Donadoni C., Salani S., Saladino F., Moggio M., Bresolin N., Ferrero I., Comi G.P.
Am. J. Hum. Genet. 84:594-604(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MPMCHD HIS-194, CHARACTERIZATION OF VARIANT MPMCHD HIS-194, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_005253.3. NM_005262.2.
UniGeneHs.27184.

3D structure databases

PDBe
RCSB PDB
PDBj
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-ray1.50A81-205[»]
ProteinModelPortalP55789.
SMRP55789. Positions 63-205.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108939. 9 interactions.
IntActP55789. 3 interactions.
MINTMINT-263560.
STRING9606.ENSP00000248114.

Chemistry

ChEMBLCHEMBL1741189.

PTM databases

PhosphoSiteP55789.

Polymorphism databases

DMDM218511915.

Proteomic databases

PaxDbP55789.
PRIDEP55789.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000248114; ENSP00000248114; ENSG00000127554. [P55789-1]
GeneID2671.
KEGGhsa:2671.
UCSCuc002cob.3. human. [P55789-1]

Organism-specific databases

CTD2671.
GeneCardsGC16P002095.
H-InvDBHIX0012707.
HGNCHGNC:4236. GFER.
HPAHPA041227.
MIM600924. gene.
613076. phenotype.
neXtProtNX_P55789.
Orphanet330054. Congenital cataract - progressive muscular hypotonia - hearing loss - developmental delay.
PharmGKBPA28648.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5054.
HOGENOMHOG000195924.
HOVERGENHBG000235.
InParanoidP55789.
KOK17783.
OMAQKRDSKF.
PhylomeDBP55789.
TreeFamTF105271.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressP55789.
BgeeP55789.
CleanExHS_GFER.
GenevestigatorP55789.

Family and domain databases

Gene3D1.20.120.310. 1 hit.
InterProIPR017905. ERV/ALR_sulphydryl_oxidase.
[Graphical view]
PfamPF04777. Evr1_Alr. 1 hit.
[Graphical view]
SUPFAMSSF69000. SSF69000. 1 hit.
PROSITEPS51324. ERV_ALR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP55789.
GeneWikiGFER.
GenomeRNAi2671.
NextBio10542.
PROP55789.
SOURCESearch...

Entry information

Entry nameALR_HUMAN
AccessionPrimary (citable) accession number: P55789
Secondary accession number(s): Q53YM6 expand/collapse secondary AC list , Q8TAH6, Q9H290, Q9UK40
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 16, 2008
Last modified: April 16, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM