Q9GZT9 (EGLN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	426 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.8 Ref.9 Ref.14 Ref.17 Ref.22
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.11 Ref.19
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.14 Ref.18 Ref.23 Ref.24
Subcellular location	Cytoplasm. Nucleus. Note: Mainly cytoplasmic. Shuttles between the nucleus and cytoplasm. Nuclear export requires functional XPO1. Ref.12 Ref.16 Ref.17
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.9 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.10 Ref.11
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	Familial erythrocytosis 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.27 Ref.28
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 component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Congenital erythrocytosis Disease mutation
Domain	Zinc-finger
Ligand	Iron Metal-binding Vitamin C Zinc
Molecular function	Dioxygenase Oxidoreductase
PTM	Phosphoprotein S-nitrosylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle tissue morphogenesis Inferred from electronic annotation. Source: Compara heart trabecula formation Inferred from electronic annotation. Source: Compara labyrinthine layer development Inferred from electronic annotation. Source: Compara 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 nitric oxide Inferred from direct assay Ref.26. Source: UniProtKB ventricular septum morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW iron ion binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-proline 4-dioxygenase activity Inferred from direct assay PubMed 11598268. Source: FlyBase zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
OS9	Q13438	4	EBI-1174818,EBI-1174342

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 426

426

Egl nine homolog 1

PRO_0000206661

Regions

Domain

291 – 392

102

Fe2OG dioxygenase

Zinc finger

21 – 58

38

MYND-type

Region

6 – 20

15

Required for nuclear export

Region

241 – 251

11

Beta(2)beta(3) 'finger-like' loop

Sites

Metal binding

313

1

Iron

Metal binding

315

1

Iron

Metal binding

374

1

Iron

Binding site

383

1

2-oxoglutarate Probable

Amino acid modifications

Modified residue

125

1

Phosphoserine Ref.20

Modified residue

201

1

S-nitrosocysteine Ref.26

Modified residue

208

1

S-nitrosocysteine Ref.26

Modified residue

302

1

S-nitrosocysteine Ref.26

Modified residue

323

1

S-nitrosocysteine; alternate Ref.26

Modified residue

326

1

S-nitrosocysteine; alternate Ref.26

Natural variations

Alternative sequence

58 – 175

118

CQGSE…DALSP → LLGGYRFAFSWNSDERA in isoform 3.

VSP_042191

Alternative sequence

338 – 359

22

Missing in isoform 2.

VSP_007569

Natural variant

317

1

P → R in ECYT3; marked decrease in enzyme activity. Ref.27

VAR_027371

Natural variant

371

1

R → H in ECYT3; decreased interaction with HIF1A and HIF2A and decreased enzyme activity. Ref.28

VAR_045902

Experimental info

Mutagenesis

201

1

C → A: Little change in enzyme activity. Ref.26

Mutagenesis

208

1

C → A: Little change in enzyme activity. Ref.26

Mutagenesis

252

1

R → A: Reduced C-terminal ODD domain (CODD) hydroxylation of HIF1A.

Mutagenesis

254

1

D → A or K: Reduced C-terminal ODD domain (CODD) hxdroxylation of HIF1A.

Mutagenesis

266

1

C → A: Little change in enzyme activity. Ref.26

Mutagenesis

283

1

C → A: Little change in enzyme activity. Ref.26

Mutagenesis

302

1

C → A: Slight increase in enzyme activity. Ref.26

Mutagenesis

303

1

Y → F: No effect. Ref.24

Mutagenesis

323

1

C → A: Little change in enzyme activity. Ref.26

Mutagenesis

326

1

C → A: Slight increase in enzyme activity. Ref.26

Mutagenesis

383

1

R → A: Reduces enzyme activity by 95%. Ref.24

Secondary structure

1

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426

Helix Strand Turn

Details...

Helix

190 – 196

7

Helix

198 – 204

7

Beta strand

206 – 214

9

Helix

216 – 231

16

Beta strand

240 – 242

3

Beta strand

245 – 247

3

Helix

248 – 250

3

Beta strand

255 – 259

5

Helix

267 – 282

16

Turn

283 – 286

4

Beta strand

287 – 289

3

Beta strand

292 – 295

4

Beta strand

298 – 303

6

Beta strand

305 – 307

3

Beta strand

310 – 313

4

Beta strand

315 – 318

4

Beta strand

321 – 329

9

Helix

336 – 339

4

Beta strand

343 – 345

3

Beta strand

348 – 351

4

Beta strand

354 – 356

3

Beta strand

362 – 367

6

Beta strand

374 – 376

3

Beta strand

379 – 381

3

Beta strand

383 – 392

10

Helix

393 – 402

10

Helix

407 – 409

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 81A97FF772CAA14C	FASTA	426	46,021
	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
	Isoform 2 [UniParc]. Checksum: 32B08D27CD89A8B9	FASTA	404	43,666
	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 NKDWDAKFDR LLFFWSDRRN PHEVQPAYAT 370 380 390 400 RYAITVWYFD ADERARAKVK YLTGEKGVRV ELNKPSDSVG KDVF
	Isoform 3 [UniParc]. Checksum: 116F684A91222E6A	FASTA	325	36,486
	10 20 30 40 50 60 MANDSGGPGG PSPSERDRQY CELCGKMENL LRCSRCRSSF YCCKEHQRQD WKKHKLVLLG 70 80 90 100 110 120 GYRFAFSWNS DERAGGGLRP NGQTKPLPAL KLALEYIVPC MNKHGICVVD DFLGKETGQQ 130 140 150 160 170 180 IGDEVRALHD TGKFTDGQLV SQKSDSSKDI RGDKITWIEG KEPGCETIGL LMSSMDDLIR 190 200 210 220 230 240 HCNGKLGSYK INGRTKAMVA CYPGNGTGYV RHVDNPNGDG RCVTCIYYLN KDWDAKVSGG 250 260 270 280 290 300 ILRIFPEGKA QFADIEPKFD RLLFFWSDRR NPHEVQPAYA TRYAITVWYF DADERARAKV 310 320 KYLTGEKGVR VELNKPSDSV GKDVF

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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, MASS SPECTROMETRY, MUTAGENESIS OF 237-ASP--ILE-251.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[21]	"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].
[22]	"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.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	"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, 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.
[27]	"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.
[28]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00004928.
IPI00328822.

RefSeq

NP_071334.1. NM_022051.2.

UniGene

Hs.444450.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2G19	X-ray	1.70	A	181-417	[»]
2G1M	X-ray	2.20	A	181-426	[»]
2HBT	X-ray	1.60	A	188-426	[»]
2HBU	X-ray	1.85	A	188-426	[»]
2Y33	X-ray	2.00	A	181-426	[»]
2Y34	X-ray	2.01	A	181-426	[»]
3HQR	X-ray	2.00	A	181-426	[»]
3HQU	X-ray	2.30	A	181-426	[»]
3OUH	X-ray	2.51	A	181-416	[»]
3OUI	X-ray	1.70	A	181-392	[»]
3OUJ	X-ray	2.30	A	181-416	[»]

ProteinModelPortal

Q9GZT9.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-37495N.

IntAct

Q9GZT9. 6 interactions.

MINT

MINT-1206232.

STRING

9606.ENSP00000355601.

PTM databases

PhosphoSite

Q9GZT9.

Polymorphism databases

DMDM

32129514.

Proteomic databases

PaxDb

Q9GZT9.

PRIDE

Q9GZT9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366641; ENSP00000355601; ENSG00000135766.

GeneID

54583.

KEGG

hsa:54583.

UCSC

uc001huv.2. human.

Organism-specific databases

CTD

54583.

GeneCards

GC01M231499.

H-InvDB

HIX0159985.

HGNC

HGNC:1232. EGLN1.

HPA

HPA022129.

MIM

606425. gene.
609820. phenotype.

neXtProt

NX_Q9GZT9.

Orphanet

247511. Autosomal dominant secondary polycythemia.

PharmGKB

PA27670.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3751.

HOGENOM

HOG000004818.

HOVERGEN

HBG051455.

InParanoid

Q9GZT9.

KO

K09592.

OMA

LVCQGSE.

OrthoDB

EOG4320ZT.

PhylomeDB

Q9GZT9.

Enzyme and pathway databases

BRENDA

1.14.11.2. 2681.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.
hif1apathway. Hypoxic and oxygen homeostasis regulation of HIF-1-alpha.

Reactome

REACT_120956. Cellular responses to stress.

Gene expression databases

ArrayExpress

Q9GZT9.

Bgee

Q9GZT9.

CleanEx

HS_EGLN1.

Genevestigator

Q9GZT9.

GermOnline

ENSG00000135766. Homo sapiens.

Family and domain databases

InterPro

IPR005123. Oxoglu/Fe-dep_dioxygenase.
IPR006620. Pro_4_hyd_alph.
IPR002893. Znf_MYND.
[Graphical view]

Pfam

PF13640. 2OG-FeII_Oxy_3. 1 hit.
PF01753. zf-MYND. 1 hit.
[Graphical view]

SMART

SM00702. P4Hc. 1 hit.
[Graphical view]

PROSITE

PS51471. FE2OG_OXY. 1 hit.
PS01360. ZF_MYND_1. 1 hit.
PS50865. ZF_MYND_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9GZT9.

ChEMBL

CHEMBL5697.

DrugBank

DB00126. Vitamin C.

EvolutionaryTrace

Q9GZT9.

GenomeRNAi

54583.

NextBio

57101.

SOURCE

Search...

Entry information

Entry name

EGLN1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.