CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022279
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Hypoxia-inducible factor 1-alpha inhibitor 
Protein Synonyms/Alias
 Factor inhibiting HIF-1; FIH-1; Hypoxia-inducible factor asparagine hydroxylase 
Gene Name
 HIF1AN 
Gene Synonyms/Alias
 FIH1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
106KFLYYDEKKMANFQNubiquitination[1, 2]
115MANFQNFKPRSNREEubiquitination[1, 3, 4]
131KFHEFVEKLQDIQQRubiquitination[1, 3]
311KRIEYPLKAHQKVAIubiquitination[1, 2]
345PLLNTMIKGRYN***ubiquitination[4]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] 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]
 [3] 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]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
Functional Description
 Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300- interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation. 
Sequence Annotation
 DOMAIN 142 312 JmjC.
 REGION 2 125 Interaction with VHL.
 REGION 181 183 Substrate binding.
 REGION 201 203 Substrate binding.
 REGION 238 239 Substrate binding.
 METAL 199 199 Iron; via tele nitrogen; catalytic.
 METAL 199 199 Zinc; via tele nitrogen.
 METAL 201 201 Iron; via tele nitrogen; catalytic.
 METAL 201 201 Zinc; via tele nitrogen.
 METAL 279 279 Iron; via tele nitrogen; catalytic.
 METAL 279 279 Zinc; via tele nitrogen.
 BINDING 145 145 2-oxoglutarate.
 BINDING 152 152 Substrate.
 BINDING 196 196 2-oxoglutarate.
 BINDING 205 205 2-oxoglutarate.
 BINDING 214 214 2-oxoglutarate.
 BINDING 294 294 2-oxoglutarate.
 BINDING 300 300 Substrate; via amide nitrogen.
 BINDING 321 321 Substrate.
 MOD_RES 2 2 N-acetylalanine.  
Keyword
 3D-structure; Acetylation; Complete proteome; Cytoplasm; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase; Polymorphism; Reference proteome; Transcription; Transcription regulation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 349 AA 
Protein Sequence
MAATAAEAVA SGSGEPREEA GALGPAWDES QLRSYSFPTR PIPRLSQSDP RAEELIENEE 60
PVVLTDTNLV YPALKWDLEY LQENIGNGDF SVYSASTHKF LYYDEKKMAN FQNFKPRSNR 120
EEMKFHEFVE KLQDIQQRGG EERLYLQQTL NDTVGRKIVM DFLGFNWNWI NKQQGKRGWG 180
QLTSNLLLIG MEGNVTPAHY DEQQNFFAQI KGYKRCILFP PDQFECLYPY PVHHPCDRQS 240
QVDFDNPDYE RFPNFQNVVG YETVVGPGDV LYIPMYWWHH IESLLNGGIT ITVNFWYKGA 300
PTPKRIEYPL KAHQKVAIMR NIEKMLGEAL GNPQEVGPLL NTMIKGRYN 349 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
 GO:0031406; F:carboxylic acid binding; IDA:UniProtKB.
 GO:0048037; F:cofactor binding; IDA:UniProtKB.
 GO:0005506; F:iron ion binding; IDA:UniProtKB.
 GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:UniProtKB-KW.
 GO:0019826; F:oxygen sensor activity; NAS:UniProtKB.
 GO:0036140; F:peptidyl-asparagine 3-dioxygenase activity; IDA:UniProtKB.
 GO:0036139; F:peptidyl-histidine dioxygenase activity; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0045746; P:negative regulation of Notch signaling pathway; IDA:UniProtKB.
 GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; IDA:UniProtKB.
 GO:0042265; P:peptidyl-asparagine hydroxylation; IDA:UniProtKB.
 GO:0042264; P:peptidyl-aspartic acid hydroxylation; IDA:UniProtKB.
 GO:0036138; P:peptidyl-histidine hydroxylation; IDA:UniProtKB.
 GO:0045663; P:positive regulation of myoblast differentiation; IDA:UniProtKB.
 GO:2001214; P:positive regulation of vasculogenesis; NAS:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR027445; FIH-1.
 IPR027452; FIH-1_domII.
 IPR003347; JmjC_dom. 
Pfam
  
SMART
 SM00558; JmjC 
PROSITE
 PS51184; JMJC 
PRINTS