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Protein

Egl nine homolog 1

Gene

EGLN1

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

Functioni

Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferencially recognized via a LXXLAP motif.7 Publications

Catalytic activityi

Hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2.1 Publication

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells.2 Publications

Kineticsi

  1. KM=70 nM for HIF2A1 Publication
  2. KM=150 µM for O21 Publication
  3. KM=1.3 µM for 2-oxoglutarate1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi313 – 3131Iron2 Publications
    Metal bindingi315 – 3151Iron2 Publications
    Metal bindingi374 – 3741Iron2 Publications
    Binding sitei383 – 38312-oxoglutarate1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri21 – 5838MYND-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Ligandi

    Iron, Metal-binding, Vitamin C, Zinc

    Enzyme and pathway databases

    BRENDAi1.14.11.2. 2681.
    1.14.11.29. 2681.
    ReactomeiREACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Egl nine homolog 1 (EC:1.14.11.291 Publication)
    Alternative name(s):
    Hypoxia-inducible factor prolyl hydroxylase 2
    Short name:
    HIF-PH2
    Short name:
    HIF-prolyl hydroxylase 2
    Short name:
    HPH-2
    Prolyl hydroxylase domain-containing protein 2
    Short name:
    PHD2
    SM-20
    Gene namesi
    Name:EGLN1Imported
    Synonyms:C1orf12
    ORF Names:PNAS-118, PNAS-137
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:1232. EGLN1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: Reactome
    • nucleus Source: UniProtKB-SubCell
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Erythrocytosis, familial, 3 (ECYT3)2 Publications

    The disease is caused by mutations affecting the gene represented in this entry.

    Disease descriptionAn autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels.

    See also OMIM:609820
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti317 – 3171P → R in ECYT3; marked decrease in enzyme activity. 1 Publication
    VAR_027371
    Natural varianti371 – 3711R → H in ECYT3; decreased interaction with HIF1A and HIF2A and decreased enzyme activity. 1 Publication
    VAR_045902

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi201 – 2011C → A: Little change in enzyme activity. 1 Publication
    Mutagenesisi208 – 2081C → A: Little change in enzyme activity. 1 Publication
    Mutagenesisi252 – 2521R → A: Reduced C-terminal ODD domain (CODD) hydroxylation of HIF1A.
    Mutagenesisi254 – 2541D → A or K: Reduced C-terminal ODD domain (CODD) hxdroxylation of HIF1A.
    Mutagenesisi266 – 2661C → A: Little change in enzyme activity. 1 Publication
    Mutagenesisi283 – 2831C → A: Little change in enzyme activity. 1 Publication
    Mutagenesisi302 – 3021C → A: Slight increase in enzyme activity. 1 Publication
    Mutagenesisi303 – 3031Y → F: No effect. 1 Publication
    Mutagenesisi323 – 3231C → A: Little change in enzyme activity. 1 Publication
    Mutagenesisi326 – 3261C → A: Slight increase in enzyme activity. 1 Publication
    Mutagenesisi383 – 3831R → A: Reduces enzyme activity by 95%. 1 Publication

    Keywords - Diseasei

    Congenital erythrocytosis, Disease mutation

    Organism-specific databases

    MIMi609820. phenotype.
    Orphaneti247511. Autosomal dominant secondary polycythemia.
    PharmGKBiPA27670.

    Chemistry

    DrugBankiDB00126. Vitamin C.

    Polymorphism and mutation databases

    BioMutaiEGLN1.
    DMDMi32129514.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed2 Publications
    Chaini2 – 426425Egl nine homolog 1PRO_0000206661Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine2 Publications
    Modified residuei125 – 1251Phosphoserine1 Publication
    Modified residuei201 – 2011S-nitrosocysteine1 Publication
    Modified residuei208 – 2081S-nitrosocysteine1 Publication
    Modified residuei302 – 3021S-nitrosocysteine1 Publication
    Modified residuei323 – 3231S-nitrosocysteine1 Publication
    Modified residuei326 – 3261S-nitrosocysteine1 Publication

    Post-translational modificationi

    S-nitrosylation inhibits the enzyme activity up to 60% under aerobic conditions. Chelation of Fe2+ has no effect on the S-nitrosylation. It is uncertain whether nitrosylation occurs on Cys-323 or Cys-326.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein, S-nitrosylation

    Proteomic databases

    MaxQBiQ9GZT9.
    PaxDbiQ9GZT9.
    PRIDEiQ9GZT9.

    PTM databases

    PhosphoSiteiQ9GZT9.

    Expressioni

    Tissue specificityi

    According to PubMed:11056053, widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain (dopaminergic neurons of adult and fetal substantia nigra) and kidney, and lower levels in lung and liver. According to PubMed:12351678 widely expressed with highest levels in brain, kidney and adrenal gland. Expressed in cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle. According to PubMed:12788921; expressed in adult and fetal heart, brain, liver, lung, skeletal muscle and kidney. Also expressed in placenta. Highest levels in adult heart, brain, lung and liver and fetal brain, heart spleen and skeletal muscle.5 Publications

    Gene expression databases

    BgeeiQ9GZT9.
    CleanExiHS_EGLN1.
    ExpressionAtlasiQ9GZT9. baseline and differential.
    GenevisibleiQ9GZT9. HS.

    Organism-specific databases

    HPAiHPA022129.

    Interactioni

    Subunit structurei

    Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIF alpha proteins. Interacts with PTGES3 (via PXLE motif); thereby recruiting EGLN1 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 and CUL2. Interacts with EPAS1.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    EPAS1Q998142EBI-1174818,EBI-447470
    FKBP8Q143186EBI-1174818,EBI-724839
    HIF1AQ166654EBI-1174818,EBI-447269
    OS9Q134384EBI-1174818,EBI-725454

    Protein-protein interaction databases

    BioGridi120060. 28 interactions.
    DIPiDIP-37495N.
    IntActiQ9GZT9. 10 interactions.
    MINTiMINT-1206232.
    STRINGi9606.ENSP00000355601.

    Structurei

    Secondary structure

    1
    426
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi190 – 1967Combined sources
    Helixi198 – 2058Combined sources
    Beta strandi206 – 2149Combined sources
    Helixi216 – 23116Combined sources
    Beta strandi240 – 2423Combined sources
    Helixi247 – 2493Combined sources
    Beta strandi255 – 2595Combined sources
    Helixi267 – 28317Combined sources
    Turni284 – 2863Combined sources
    Beta strandi287 – 2893Combined sources
    Beta strandi292 – 2954Combined sources
    Beta strandi298 – 3036Combined sources
    Beta strandi305 – 3139Combined sources
    Beta strandi315 – 3184Combined sources
    Beta strandi321 – 3299Combined sources
    Beta strandi331 – 3333Combined sources
    Helixi336 – 3394Combined sources
    Beta strandi343 – 3453Combined sources
    Beta strandi348 – 3514Combined sources
    Beta strandi354 – 3563Combined sources
    Beta strandi362 – 3676Combined sources
    Beta strandi374 – 3818Combined sources
    Beta strandi383 – 39210Combined sources
    Helixi393 – 40210Combined sources
    Helixi407 – 4093Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2G19X-ray1.70A181-417[»]
    2G1MX-ray2.20A181-426[»]
    2HBTX-ray1.60A188-426[»]
    2HBUX-ray1.85A188-426[»]
    2Y33X-ray2.00A181-426[»]
    2Y34X-ray2.01A181-426[»]
    3HQRX-ray2.00A181-426[»]
    3HQUX-ray2.30A181-426[»]
    3OUHX-ray2.51A181-416[»]
    3OUIX-ray1.70A181-392[»]
    3OUJX-ray2.30A181-416[»]
    4BQWX-ray1.79A181-426[»]
    4BQXX-ray1.79A181-426[»]
    4BQYX-ray1.53A181-426[»]
    4JZRX-ray2.10A189-399[»]
    4KBZX-ray2.15A184-419[»]
    4UWDX-ray1.72A181-426[»]
    ProteinModelPortaliQ9GZT9.
    SMRiQ9GZT9. Positions 20-58, 188-403.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9GZT9.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini291 – 392102Fe2OG dioxygenasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni6 – 2015Required for nuclear exportAdd
    BLAST
    Regioni241 – 25111Beta(2)beta(3) 'finger-like' loop1 PublicationAdd
    BLAST

    Domaini

    The beta2beta3 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity.1 Publication

    Sequence similaritiesi

    Contains 1 Fe2OG dioxygenase domain.PROSITE-ProRule annotation
    Contains 1 MYND-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri21 – 5838MYND-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiCOG3751.
    HOGENOMiHOG000004818.
    HOVERGENiHBG051455.
    InParanoidiQ9GZT9.
    KOiK09592.
    OMAiLVCQGSE.
    OrthoDBiEOG7TBC2W.
    PhylomeDBiQ9GZT9.
    TreeFamiTF314595.

    Family and domain databases

    InterProiIPR005123. Oxoglu/Fe-dep_dioxygenase.
    IPR006620. Pro_4_hyd_alph.
    IPR002893. Znf_MYND.
    [Graphical view]
    PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
    PF01753. zf-MYND. 1 hit.
    [Graphical view]
    SMARTiSM00702. P4Hc. 1 hit.
    [Graphical view]
    PROSITEiPS51471. FE2OG_OXY. 1 hit.
    PS01360. ZF_MYND_1. 1 hit.
    PS50865. ZF_MYND_2. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9GZT9-1) [UniParc]FASTAAdd to basket

    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
    MANDSGGPGG PSPSERDRQY CELCGKMENL LRCSRCRSSF YCCKEHQRQD
    60 70 80 90 100
    WKKHKLVCQG SEGALGHGVG PHQHSGPAPP AAVPPPRAGA REPRKAAARR
    110 120 130 140 150
    DNASGDAAKG KVKAKPPADP AAAASPCRAA AGGQGSAVAA EAEPGKEEPP
    160 170 180 190 200
    ARSSLFQEKA NLYPPSNTPG DALSPGGGLR PNGQTKPLPA LKLALEYIVP
    210 220 230 240 250
    CMNKHGICVV DDFLGKETGQ QIGDEVRALH DTGKFTDGQL VSQKSDSSKD
    260 270 280 290 300
    IRGDKITWIE GKEPGCETIG LLMSSMDDLI RHCNGKLGSY KINGRTKAMV
    310 320 330 340 350
    ACYPGNGTGY VRHVDNPNGD GRCVTCIYYL NKDWDAKVSG GILRIFPEGK
    360 370 380 390 400
    AQFADIEPKF DRLLFFWSDR RNPHEVQPAY ATRYAITVWY FDADERARAK
    410 420
    VKYLTGEKGV RVELNKPSDS VGKDVF
    Length:426
    Mass (Da):46,021
    Last modified:March 1, 2001 - v1
    Checksum:i81A97FF772CAA14C
    GO
    Isoform 2 (identifier: Q9GZT9-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         338-359: Missing.

    Note: Inactive isoform.
    Show »
    Length:404
    Mass (Da):43,666
    Checksum:i32B08D27CD89A8B9
    GO
    Isoform 3 (identifier: Q9GZT9-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         58-175: CQGSEGALGH...SNTPGDALSP → LLGGYRFAFSWNSDERA

    Note: No experimental confirmation available.
    Show »
    Length:325
    Mass (Da):36,486
    Checksum:i116F684A91222E6A
    GO

    Sequence cautioni

    The sequence AAK07534.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence AAK07536.1 differs from that shown. Reason: Frameshift at position 239. Curated

    Polymorphismi

    Variations in EGLN1 are associated with adaptation to high altitude (PubMed:20838600, PubMed:20466884, PubMed:24711448, PubMed:25129147). High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body and leads to an elevation of hematocrit levels and an increased number of erythrocytes (polycythemia) in non-adapted individuals. Genetic variations in EGLN1 contribute to adaptation to high altitute by maintaining hematocrit levels comparable to those for populations living at sea level and are present in two high-altitude regions where humans have lived for millennia, the Andean Altiplano and the Tibetan Plateau (PubMed:20838600, PubMed:20466884). Variants Glu-4 and Ser-127, which are frequently associated together and are present in the majority of Tibetan populations, participate to adaptation to high altitude (PubMed:24711448, PubMed:25129147). Molecular mechanisms explaining this adaptation are however unclear. According to a report, variants Glu-4 and Ser-127 lead to decreased interaction with PTGES3 and subsequent decrease of HIF alpha proteins degradation (PubMed:24711448). According to a second report, Glu-4 and Ser-127 haplotype enhances the catalytic activity under hypoxic conditions, promoting increased HIF alpha proteins degradation, thereby abrogating hypoxia-induced and HIF alpha-mediated augmentation of erythropoiesis and protecting Tibetans from polycythemia at high altitude (PubMed:25129147).Curated4 Publications

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti4 – 41D → E Polymorphism present in the majority of Tibetans; increased protection from polycythemia at high altitude; when associated with S-127. 2 Publications
    VAR_071858
    Natural varianti127 – 1271C → S Polymorphism present in the majority of Tibetans; increased protection from polycythemia at high altitude; when associated with E-4. 2 Publications
    VAR_071859
    Natural varianti317 – 3171P → R in ECYT3; marked decrease in enzyme activity. 1 Publication
    VAR_027371
    Natural varianti371 – 3711R → H in ECYT3; decreased interaction with HIF1A and HIF2A and decreased enzyme activity. 1 Publication
    VAR_045902

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei58 – 175118CQGSE…DALSP → LLGGYRFAFSWNSDERA in isoform 3. 1 PublicationVSP_042191Add
    BLAST
    Alternative sequencei338 – 35922Missing in isoform 2. 1 PublicationVSP_007569Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF246631, AF246630 Genomic DNA. Translation: AAG34568.1.
    AF229245 mRNA. Translation: AAG33965.1.
    AJ310543 mRNA. Translation: CAC42509.1.
    AL833885 mRNA. Translation: CAD38741.2.
    AF277174 mRNA. Translation: AAK07534.1. Different initiation.
    AF277176 mRNA. Translation: AAK07536.1. Frameshift.
    AL117352, AL445524 Genomic DNA. Translation: CAI23092.1.
    AL445524, AL117352 Genomic DNA. Translation: CAH72105.1.
    CCDSiCCDS1595.1. [Q9GZT9-1]
    RefSeqiNP_071334.1. NM_022051.2. [Q9GZT9-1]
    UniGeneiHs.444450.

    Genome annotation databases

    EnsembliENST00000366641; ENSP00000355601; ENSG00000135766. [Q9GZT9-1]
    GeneIDi54583.
    KEGGihsa:54583.
    UCSCiuc001huv.2. human. [Q9GZT9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF246631, AF246630 Genomic DNA. Translation: AAG34568.1.
    AF229245 mRNA. Translation: AAG33965.1.
    AJ310543 mRNA. Translation: CAC42509.1.
    AL833885 mRNA. Translation: CAD38741.2.
    AF277174 mRNA. Translation: AAK07534.1. Different initiation.
    AF277176 mRNA. Translation: AAK07536.1. Frameshift.
    AL117352, AL445524 Genomic DNA. Translation: CAI23092.1.
    AL445524, AL117352 Genomic DNA. Translation: CAH72105.1.
    CCDSiCCDS1595.1. [Q9GZT9-1]
    RefSeqiNP_071334.1. NM_022051.2. [Q9GZT9-1]
    UniGeneiHs.444450.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2G19X-ray1.70A181-417[»]
    2G1MX-ray2.20A181-426[»]
    2HBTX-ray1.60A188-426[»]
    2HBUX-ray1.85A188-426[»]
    2Y33X-ray2.00A181-426[»]
    2Y34X-ray2.01A181-426[»]
    3HQRX-ray2.00A181-426[»]
    3HQUX-ray2.30A181-426[»]
    3OUHX-ray2.51A181-416[»]
    3OUIX-ray1.70A181-392[»]
    3OUJX-ray2.30A181-416[»]
    4BQWX-ray1.79A181-426[»]
    4BQXX-ray1.79A181-426[»]
    4BQYX-ray1.53A181-426[»]
    4JZRX-ray2.10A189-399[»]
    4KBZX-ray2.15A184-419[»]
    4UWDX-ray1.72A181-426[»]
    ProteinModelPortaliQ9GZT9.
    SMRiQ9GZT9. Positions 20-58, 188-403.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi120060. 28 interactions.
    DIPiDIP-37495N.
    IntActiQ9GZT9. 10 interactions.
    MINTiMINT-1206232.
    STRINGi9606.ENSP00000355601.

    Chemistry

    BindingDBiQ9GZT9.
    ChEMBLiCHEMBL5697.
    DrugBankiDB00126. Vitamin C.
    GuidetoPHARMACOLOGYi2833.

    PTM databases

    PhosphoSiteiQ9GZT9.

    Polymorphism and mutation databases

    BioMutaiEGLN1.
    DMDMi32129514.

    Proteomic databases

    MaxQBiQ9GZT9.
    PaxDbiQ9GZT9.
    PRIDEiQ9GZT9.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000366641; ENSP00000355601; ENSG00000135766. [Q9GZT9-1]
    GeneIDi54583.
    KEGGihsa:54583.
    UCSCiuc001huv.2. human. [Q9GZT9-1]

    Organism-specific databases

    CTDi54583.
    GeneCardsiGC01M231499.
    H-InvDBHIX0159985.
    HGNCiHGNC:1232. EGLN1.
    HPAiHPA022129.
    MIMi606425. gene.
    609820. phenotype.
    neXtProtiNX_Q9GZT9.
    Orphaneti247511. Autosomal dominant secondary polycythemia.
    PharmGKBiPA27670.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG3751.
    HOGENOMiHOG000004818.
    HOVERGENiHBG051455.
    InParanoidiQ9GZT9.
    KOiK09592.
    OMAiLVCQGSE.
    OrthoDBiEOG7TBC2W.
    PhylomeDBiQ9GZT9.
    TreeFamiTF314595.

    Enzyme and pathway databases

    BRENDAi1.14.11.2. 2681.
    1.14.11.29. 2681.
    ReactomeiREACT_120916. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.

    Miscellaneous databases

    ChiTaRSiEGLN1. human.
    EvolutionaryTraceiQ9GZT9.
    GeneWikiiEGLN1.
    GenomeRNAii54583.
    NextBioi57101.
    PROiQ9GZT9.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9GZT9.
    CleanExiHS_EGLN1.
    ExpressionAtlasiQ9GZT9. baseline and differential.
    GenevisibleiQ9GZT9. HS.

    Family and domain databases

    InterProiIPR005123. Oxoglu/Fe-dep_dioxygenase.
    IPR006620. Pro_4_hyd_alph.
    IPR002893. Znf_MYND.
    [Graphical view]
    PfamiPF13640. 2OG-FeII_Oxy_3. 1 hit.
    PF01753. zf-MYND. 1 hit.
    [Graphical view]
    SMARTiSM00702. P4Hc. 1 hit.
    [Graphical view]
    PROSITEiPS51471. FE2OG_OXY. 1 hit.
    PS01360. ZF_MYND_1. 1 hit.
    PS50865. ZF_MYND_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Mapping, characterization, and expression analysis of the SM-20 human homologue, C1orf12, and identification of a novel related gene, SCAND2."
      Dupuy D., Aubert I., Duperat V.G., Petit J., Taine L., Stef M., Bloch B., Arveiler B.
      Genomics 69:348-354(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    2. "Characterization and comparative analysis of the EGLN gene family."
      Taylor M.S.
      Gene 275:125-132(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
    3. "Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor."
      Hirsila M., Koivunen P., Gunzler V., Kivirikko K.I., Myllyharju J.
      J. Biol. Chem. 278:30772-30780(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, SUBSTRATE SPECIFICITY.
      Tissue: Aorta, Colon and Lung.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 160-426 (ISOFORM 1).
      Tissue: Amygdala.
    5. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "Human acute promyelocytic leukemia cell line NB4's apoptosis related genes."
      Yu W.-Q., Sun B.-Z., Chai Y.-B., Zhu F., Liu X.-S., Li Z., Lu F., Yan W., Yang H., Zhao Z.-L.
      Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 136-426 (ISOFORM 2).
      Tissue: Promyelocytic leukemia.
    7. "HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus."
      Semenza G.L.
      Cell 107:1-3(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    8. Cited for: FUNCTION.
    9. "Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3."
      Huang J., Zhao Q., Mooney S.M., Lee F.S.
      J. Biol. Chem. 277:39792-39800(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBSTRATE RECOGNITION MOTIF.
    10. "Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor."
      Ivan M., Haberberger T., Gervasi D.C., Michelson K.S., Guenzler V., Kondo K., Yang H., Sorokina I., Conaway R.C., Conaway J.W., Kaelin W.G. Jr.
      Proc. Natl. Acad. Sci. U.S.A. 99:13459-13464(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors."
      Oehme F., Ellinghaus P., Kolkhof P., Smith T.J., Ramakrishnan S., Huetter J., Schramm M., Flamme I.
      Biochem. Biophys. Res. Commun. 296:343-349(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    12. "Differential regulation of HIF-1alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells."
      Cioffi C.L., Qin Liu X., Kosinski P.A., Garay M., Bowen B.R.
      Biochem. Biophys. Res. Commun. 303:947-953(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, ENZYME REGULATION.
    13. Cited for: SUBCELLULAR LOCATION, INDUCTION.
    14. "Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor."
      Appelhoff R.J., Tian Y.M., Raval R.R., Turley H., Harris A.L., Pugh C.W., Ratcliffe P.J., Gleadle J.M.
      J. Biol. Chem. 279:38458-38465(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, SUBSTRATE SPECIFICITY.
    15. "The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF)."
      Ozer A., Wu L.C., Bruick R.K.
      Proc. Natl. Acad. Sci. U.S.A. 102:7481-7486(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ING4, FUNCTION.
    16. "Kinetic rationale for selectivity toward N- and C-terminal oxygen-dependent degradation domain substrates mediated by a loop region of hypoxia-inducible factor prolyl hydroxylases."
      Flashman E., Bagg E.A., Chowdhury R., Mecinovic J., Loenarz C., McDonough M.A., Hewitson K.S., Schofield C.J.
      J. Biol. Chem. 283:3808-3815(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBSTRATE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF 237-ASP--ILE-251, DOMAIN.
    17. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    18. "Cellular oxygen sensing: Importins and exportins are mediators of intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2."
      Steinhoff A., Pientka F.K., Mockel S., Kettelhake A., Hartmann E., Kohler M., Depping R.
      Biochem. Biophys. Res. Commun. 387:705-711(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    19. "Role of the intracellular localization of HIF-prolyl hydroxylases."
      Yasumoto K., Kowata Y., Yoshida A., Torii S., Sogawa K.
      Biochim. Biophys. Acta 1793:792-797(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, FUNCTION.
    20. "Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline."
      Furlow P.W., Percy M.J., Sutherland S., Bierl C., McMullin M.F., Master S.R., Lappin T.R., Lee F.S.
      J. Biol. Chem. 284:9050-9058(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPAS1.
    21. "Evidence for the slow reaction of hypoxia-inducible factor prolyl hydroxylase 2 with oxygen."
      Flashman E., Hoffart L.M., Hamed R.B., Bollinger J.M. Jr., Krebs C., Schofield C.J.
      FEBS J. 277:4089-4099(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    22. "Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data."
      Bigham A., Bauchet M., Pinto D., Mao X., Akey J.M., Mei R., Scherer S.W., Julian C.G., Wilson M.J., Lopez Herraez D., Brutsaert T., Parra E.J., Moore L.G., Shriver M.D.
      PLoS Genet. 6:E1001116-E1001116(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: POLYMORPHISM.
    23. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    24. Cited for: POLYMORPHISM.
    25. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    26. "Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in pancreatic cancer."
      Su Y., Loos M., Giese N., Metzen E., Buchler M.W., Friess H., Kornberg A., Buchler P.
      Cancer 118:960-972(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION.
    27. Cited for: INTERACTION WITH LIMD1, IDENTIFICATION IN A COMPLEX WITH LIMD1; VHL; TCEB2 AND CUL2.
    28. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    29. "SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha hydroxylation."
      Seo K.S., Park J.H., Heo J.Y., Jing K., Han J., Min K.N., Kim C., Koh G.Y., Lim K., Kang G.Y., Uee Lee J., Yim Y.H., Shong M., Kwak T.H., Kweon G.R.
      Oncogene 34:1354-1362(2015) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIF1A.
    30. Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 181-417 IN COMPLEXES WITH IRON AND COMPETITIVE INHIBITOR, METAL-BINDING SITES, MUTAGENESIS OF TYR-303 AND ARG-383, SUBUNIT, COFACTOR.
    31. "Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases."
      Chowdhury R., McDonough M.A., Mecinovic J., Loenarz C., Flashman E., Hewitson K.S., Domene C., Schofield C.J.
      Structure 17:981-989(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 181-426 OF WILD TYPE AND MUTANTS ALA-252; ALA-254; LYS-254 AND ALA-398 IN COMPLEX WITH HIF1A, IRON, N-OXALYGLYCINE AND MANGANESE, METAL-BINDING SITES, COFACTOR.
    32. "Studies on the reaction of nitric oxide with the hypoxia-inducible factor prolyl hydroxylase domain 2 (EGLN1)."
      Chowdhury R., Flashman E., Mecinovic J., Kramer H.B., Kessler B.M., Frapart Y.M., Boucher J.L., Clifton I.J., McDonough M.A., Schofield C.J.
      J. Mol. Biol. 410:268-279(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 181-426 IN COMPLEX WITH NITRIC OXIDE OR A NITRIC OXIDE TRANSFER REAGENT, IDENTIFICATION BY MASS SPECTROMETRY, S-NITROSYLATION AT CYS-201; CYS-208; CYS-302; CYS-323 AND CYS-326, MUTAGENESIS OF CYS-201; CYS-208; CYS-266; CYS-283; CYS-302; CYS-323 AND CYS-326.
    33. "A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis."
      Percy M.J., Zhao Q., Flores A., Harrison C., Lappin T.R., Maxwell P.H., McMullin M.F., Lee F.S.
      Proc. Natl. Acad. Sci. U.S.A. 103:654-659(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ECYT3 ARG-317, CHARACTERIZATION OF VARIANT ECYT3 ARG-317.
    34. "A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove."
      Percy M.J., Furlow P.W., Beer P.A., Lappin T.R.J., McMullin M.F., Lee F.S.
      Blood 110:2193-2196(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ECYT3 HIS-371, CHARACTERIZATION OF VARIANT EXCYT3 HIS-371.
    35. "Defective Tibetan PHD2 binding to p23 links high altitude adaption to altered oxygen sensing."
      Song D., Li L.S., Arsenault P.R., Tan Q., Bigham A.W., Heaton-Johnson K.J., Master S.R., Lee F.S.
      J. Biol. Chem. 289:14656-14665(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS GLU-4 AND SER-127, POLYMORPHISM, INTERACTION WITH PTGES3, CHARACTERIZATION OF VARIANTS GLU-4 AND SER-127.
    36. Cited for: VARIANTS GLU-4 AND SER-127, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, POLYMORPHISM, CHARACTERIZATION OF VARIANTS GLU-4 AND SER-127.

    Entry informationi

    Entry nameiEGLN1_HUMAN
    AccessioniPrimary (citable) accession number: Q9GZT9
    Secondary accession number(s): Q8N3M8, Q9BZS8, Q9BZT0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 16, 2003
    Last sequence update: March 1, 2001
    Last modified: June 24, 2015
    This is version 143 of the entry and version 1 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

    Caution

    It was previously reported that this protein was the ortholog of rat SM-20. However, EGLN3 is now considered the true ortholog of rat SM-20 since it shows substantially greater similarity.Curated

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: 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

    External Data

    Dasty 3

    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 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.