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Q9GZT9 (EGLN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Egl nine homolog 1

EC=1.14.11.29
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 names
Name:EGLN1
Synonyms:C1orf12
ORF Names:PNAS-118, PNAS-137
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length426 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9 Ref.10 Ref.15 Ref.19 Ref.24

Catalytic activity

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

Cofactor

Binds 1 Fe2+ ion per subunit.

Ascorbate.

Enzyme regulation

Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells. Ref.12 Ref.21

Subunit structure

Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIFs. Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2. Interacts with EPAS1. Ref.15 Ref.20 Ref.25 Ref.27

Subcellular location

Cytoplasm. Nucleus. Note: Mainly cytoplasmic. Shuttles between the nucleus and cytoplasm. Nuclear export requires functional XPO1. Ref.13 Ref.18 Ref.19

Tissue specificity

According to Ref.1, 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 Ref.10 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 Ref.3; 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. Ref.1 Ref.3 Ref.11 Ref.12

Domain

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

Post-translational modification

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.

Involvement in disease

Erythrocytosis, familial, 3 (ECYT3) [MIM:609820]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.30 Ref.31

Sequence similarities

Contains 1 Fe2OG dioxygenase domain.

Contains 1 MYND-type zinc finger.

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.

Sequence caution

The sequence AAK07534.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAK07536.1 differs from that shown. Reason: Frameshift at position 239.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseCongenital erythrocytosis
Disease mutation
   DomainZinc-finger
   LigandIron
Metal-binding
Vitamin C
Zinc
   Molecular functionDioxygenase
Oxidoreductase
   PTMAcetylation
Phosphoprotein
S-nitrosylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle tissue morphogenesis

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Traceable author statement. Source: Reactome

heart trabecula formation

Inferred from electronic annotation. Source: Ensembl

labyrinthine layer development

Inferred from electronic annotation. Source: Ensembl

negative regulation of cAMP catabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cyclic-nucleotide phosphodiesterase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 16956324. Source: HGNC

oxygen homeostasis

Inferred from direct assay PubMed 16956324. Source: HGNC

peptidyl-proline hydroxylation to 4-hydroxy-L-proline

Inferred from direct assay PubMed 11598268. Source: FlyBase

regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter in response to hypoxia

Traceable author statement. Source: Reactome

response to hypoxia

Inferred from direct assay PubMed 16956324. Source: HGNC

response to nitric oxide

Inferred from direct assay Ref.29. Source: UniProtKB

ventricular septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.13. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionL-ascorbic acid binding

Inferred from electronic annotation. Source: UniProtKB-KW

enzyme binding

Inferred from sequence or structural similarity. Source: BHF-UCL

iron ion binding

Inferred from electronic annotation. Source: InterPro

peptidyl-proline 4-dioxygenase activity

Inferred from direct assay PubMed 11598268. Source: FlyBase

peptidyl-proline dioxygenase activity

Traceable author statement PubMed 16956324. Source: HGNC

protein binding

Inferred from physical interaction Ref.20Ref.25PubMed 24681946. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9GZT9-1)

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: Q9GZT9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     338-359: Missing.
Note: Inactive isoform.
Isoform 3 (identifier: Q9GZT9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     58-175: CQGSEGALGH...SNTPGDALSP → LLGGYRFAFSWNSDERA
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.17
Chain2 – 426425Egl nine homolog 1
PRO_0000206661

Regions

Domain291 – 392102Fe2OG dioxygenase
Zinc finger21 – 5838MYND-type
Region6 – 2015Required for nuclear export
Region241 – 25111Beta(2)beta(3) 'finger-like' loop

Sites

Metal binding3131Iron
Metal binding3151Iron
Metal binding3741Iron
Binding site38312-oxoglutarate Probable

Amino acid modifications

Modified residue21N-acetylalanine Ref.17 Ref.26
Modified residue1251Phosphoserine Ref.22
Modified residue2011S-nitrosocysteine Ref.29
Modified residue2081S-nitrosocysteine Ref.29
Modified residue3021S-nitrosocysteine Ref.29
Modified residue3231S-nitrosocysteine Ref.29
Modified residue3261S-nitrosocysteine Ref.29

Natural variations

Alternative sequence58 – 175118CQGSE…DALSP → LLGGYRFAFSWNSDERA in isoform 3.
VSP_042191
Alternative sequence338 – 35922Missing in isoform 2.
VSP_007569
Natural variant3171P → R in ECYT3; marked decrease in enzyme activity. Ref.30
VAR_027371
Natural variant3711R → H in ECYT3; decreased interaction with HIF1A and HIF2A and decreased enzyme activity. Ref.31
VAR_045902

Experimental info

Mutagenesis2011C → A: Little change in enzyme activity. Ref.29
Mutagenesis2081C → A: Little change in enzyme activity. Ref.29
Mutagenesis2521R → A: Reduced C-terminal ODD domain (CODD) hydroxylation of HIF1A.
Mutagenesis2541D → A or K: Reduced C-terminal ODD domain (CODD) hxdroxylation of HIF1A.
Mutagenesis2661C → A: Little change in enzyme activity. Ref.29
Mutagenesis2831C → A: Little change in enzyme activity. Ref.29
Mutagenesis3021C → A: Slight increase in enzyme activity. Ref.29
Mutagenesis3031Y → F: No effect. Ref.27
Mutagenesis3231C → A: Little change in enzyme activity. Ref.29
Mutagenesis3261C → A: Slight increase in enzyme activity. Ref.29
Mutagenesis3831R → A: Reduces enzyme activity by 95%. Ref.27

Secondary structure

............................................... 426
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 81A97FF772CAA14C

FASTA42646,021
        10         20         30         40         50         60 
MANDSGGPGG PSPSERDRQY CELCGKMENL LRCSRCRSSF YCCKEHQRQD WKKHKLVCQG 

        70         80         90        100        110        120 
SEGALGHGVG PHQHSGPAPP AAVPPPRAGA REPRKAAARR DNASGDAAKG KVKAKPPADP 

       130        140        150        160        170        180 
AAAASPCRAA AGGQGSAVAA EAEPGKEEPP ARSSLFQEKA NLYPPSNTPG DALSPGGGLR 

       190        200        210        220        230        240 
PNGQTKPLPA LKLALEYIVP CMNKHGICVV DDFLGKETGQ QIGDEVRALH DTGKFTDGQL 

       250        260        270        280        290        300 
VSQKSDSSKD IRGDKITWIE GKEPGCETIG LLMSSMDDLI RHCNGKLGSY KINGRTKAMV 

       310        320        330        340        350        360 
ACYPGNGTGY VRHVDNPNGD GRCVTCIYYL NKDWDAKVSG GILRIFPEGK AQFADIEPKF 

       370        380        390        400        410        420 
DRLLFFWSDR RNPHEVQPAY ATRYAITVWY FDADERARAK VKYLTGEKGV RVELNKPSDS 


VGKDVF 

« Hide

Isoform 2 [UniParc].

Checksum: 32B08D27CD89A8B9
Show »

FASTA40443,666
Isoform 3 [UniParc].

Checksum: 116F684A91222E6A
Show »

FASTA32536,486

References

« Hide 'large scale' references
[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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation."
Epstein A.C.R., Gleadle J.M., McNeill L.A., Hewitson K.S., O'Rourke J., Mole D.R., Mukherji M., Metzen E., Wilson M.I., Dhanda A., Tian Y.M., Masson N., Hamilton D.L., Jaakkola P., Barstead R., Hodgkin J., Maxwell P.H., Pugh C.W., Schofield C.J., Ratcliffe P.J.
Cell 107:43-54(2001) [PubMed] [Europe PMC] [Abstract]
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]"Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing."
Metzen E., Berchner-Pfannschmidt U., Stengel P., Marxsen J.H., Stolze I., Klinger M., Huang W.Q., Wotzlaw C., Hellwig-Burgel T., Jelkmann W., Acker H., Fandrey J.
J. Cell Sci. 116:1319-1326(2003) [PubMed] [Europe PMC] [Abstract]
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.
[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]"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.
[23]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"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.
[25]"The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity."
Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y., Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S., Ratcliffe P.J., Longmore G.D., Sharp T.V.
Nat. Cell Biol. 14:201-208(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LIMD1, IDENTIFICATION IN A COMPLEX WITH LIMD1; VHL; TCEB2 AND CUL2.
[26]"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: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"Cellular oxygen sensing: crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)."
McDonough M.A., Li V., Flashman E., Chowdhury R., Mohr C., Lienard B.M.R., Zondlo J., Oldham N.J., Clifton I.J., Lewis J., McNeill L.A., Kurzeja R.J., Hewitson K.S., Yang E., Jordan S., Syed R.S., Schofield C.J.
Proc. Natl. Acad. Sci. U.S.A. 103:9814-9819(2006) [PubMed] [Europe PMC] [Abstract]
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.
[28]"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.
[29]"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.
[30]"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.
[31]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS1595.1. [Q9GZT9-1]
RefSeqNP_071334.1. NM_022051.2. [Q9GZT9-1]
UniGeneHs.444450.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9GZT9.
SMRQ9GZT9. Positions 20-58, 188-403.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120060. 22 interactions.
DIPDIP-37495N.
IntActQ9GZT9. 9 interactions.
MINTMINT-1206232.
STRING9606.ENSP00000355601.

Chemistry

BindingDBQ9GZT9.
ChEMBLCHEMBL5697.
DrugBankDB00126. Vitamin C.

PTM databases

PhosphoSiteQ9GZT9.

Polymorphism databases

DMDM32129514.

Proteomic databases

MaxQBQ9GZT9.
PaxDbQ9GZT9.
PRIDEQ9GZT9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366641; ENSP00000355601; ENSG00000135766. [Q9GZT9-1]
GeneID54583.
KEGGhsa:54583.
UCSCuc001huv.2. human. [Q9GZT9-1]

Organism-specific databases

CTD54583.
GeneCardsGC01M231499.
H-InvDBHIX0159985.
HGNCHGNC:1232. EGLN1.
HPAHPA022129.
MIM606425. gene.
609820. phenotype.
neXtProtNX_Q9GZT9.
Orphanet247511. Autosomal dominant secondary polycythemia.
PharmGKBPA27670.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3751.
HOGENOMHOG000004818.
HOVERGENHBG051455.
InParanoidQ9GZT9.
KOK09592.
OMALVCQGSE.
OrthoDBEOG7TBC2W.
PhylomeDBQ9GZT9.
TreeFamTF314595.

Enzyme and pathway databases

BRENDA1.14.11.2. 2681.
ReactomeREACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpressQ9GZT9.
BgeeQ9GZT9.
CleanExHS_EGLN1.
GenevestigatorQ9GZT9.

Family and domain databases

InterProIPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
IPR002893. Znf_MYND.
[Graphical view]
PfamPF13640. 2OG-FeII_Oxy_3. 1 hit.
PF01753. zf-MYND. 1 hit.
[Graphical view]
SMARTSM00702. P4Hc. 1 hit.
[Graphical view]
PROSITEPS51471. FE2OG_OXY. 1 hit.
PS01360. ZF_MYND_1. 1 hit.
PS50865. ZF_MYND_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9GZT9.
GeneWikiEGLN1.
GenomeRNAi54583.
NextBio57101.
PROQ9GZT9.
SOURCESearch...

Entry information

Entry nameEGLN1_HUMAN
AccessionPrimary (citable) accession number: Q9GZT9
Secondary accession number(s): Q8N3M8, Q9BZS8, Q9BZT0
Entry history
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 132 of the entry and version 1 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 1

Human chromosome 1: entries, gene names and cross-references to MIM