CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-021181
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Egl nine homolog 1 
Protein Synonyms/Alias
 Hypoxia-inducible factor prolyl hydroxylase 2; HIF-PH2; HIF-prolyl hydroxylase 2; HPH-2; Prolyl hydroxylase domain-containing protein 2; PHD2; SM-20 
Gene Name
 EGLN1 
Gene Synonyms/Alias
 C1orf12; PNAS-118; PNAS-137 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
234RALHDTGKFTDGQLVubiquitination[1, 2]
408VKYLTGEKGVRVELNacetylation[3]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 291 392 Fe2OG dioxygenase.
 ZN_FING 21 58 MYND-type.
 REGION 6 20 Required for nuclear export.
 REGION 241 251 Beta(2)beta(3) 'finger-like' loop.
 METAL 313 313 Iron.
 METAL 315 315 Iron.
 METAL 374 374 Iron.
 BINDING 383 383 2-oxoglutarate (Probable).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 125 125 Phosphoserine.
 MOD_RES 201 201 S-nitrosocysteine.
 MOD_RES 208 208 S-nitrosocysteine.
 MOD_RES 302 302 S-nitrosocysteine.
 MOD_RES 323 323 S-nitrosocysteine.
 MOD_RES 326 326 S-nitrosocysteine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Congenital erythrocytosis; Cytoplasm; Dioxygenase; Disease mutation; Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; S-nitrosylation; Vitamin C; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 426 AA 
Protein Sequence
MANDSGGPGG PSPSERDRQY CELCGKMENL LRCSRCRSSF YCCKEHQRQD WKKHKLVCQG 60
SEGALGHGVG PHQHSGPAPP AAVPPPRAGA REPRKAAARR DNASGDAAKG KVKAKPPADP 120
AAAASPCRAA AGGQGSAVAA EAEPGKEEPP ARSSLFQEKA NLYPPSNTPG DALSPGGGLR 180
PNGQTKPLPA LKLALEYIVP CMNKHGICVV DDFLGKETGQ QIGDEVRALH DTGKFTDGQL 240
VSQKSDSSKD IRGDKITWIE GKEPGCETIG LLMSSMDDLI RHCNGKLGSY KINGRTKAMV 300
ACYPGNGTGY VRHVDNPNGD GRCVTCIYYL NKDWDAKVSG GILRIFPEGK AQFADIEPKF 360
DRLLFFWSDR RNPHEVQPAY ATRYAITVWY FDADERARAK VKYLTGEKGV RVELNKPSDS 420
VGKDVF 426 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005506; F:iron ion binding; IEA:InterPro.
 GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
 GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:UniProtKB-KW.
 GO:0031545; F:peptidyl-proline 4-dioxygenase activity; IDA:FlyBase.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0055008; P:cardiac muscle tissue morphogenesis; IEA:Compara.
 GO:0060347; P:heart trabecula formation; IEA:Compara.
 GO:0060711; P:labyrinthine layer development; IEA:Compara.
 GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:HGNC.
 GO:0032364; P:oxygen homeostasis; IDA:HGNC.
 GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IDA:FlyBase.
 GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
 GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
 GO:0071731; P:response to nitric oxide; IDA:UniProtKB.
 GO:0060412; P:ventricular septum morphogenesis; IEA:Compara. 
Interpro
 IPR005123; Oxoglu/Fe-dep_dioxygenase.
 IPR006620; Pro_4_hyd_alph.
 IPR002893; Znf_MYND. 
Pfam
 PF13640; 2OG-FeII_Oxy_3
 PF01753; zf-MYND 
SMART
 SM00702; P4Hc 
PROSITE
 PS51471; FE2OG_OXY
 PS01360; ZF_MYND_1
 PS50865; ZF_MYND_2 
PRINTS