CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023679
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Hypoxia-inducible factor 3-alpha 
Protein Synonyms/Alias
 HIF-3-alpha; HIF3-alpha; Basic-helix-loop-helix-PAS protein MOP7; Class E basic helix-loop-helix protein 17; bHLHe17; HIF3-alpha-1; Inhibitory PAS domain protein; IPAS; Member of PAS protein 7; PAS domain-containing protein 7 
Gene Name
 HIF3A 
Gene Synonyms/Alias
 BHLHE17; MOP7; PASD7 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
467HRLFTSGKDTEAVETubiquitination[1]
570SPMAGARKRTLAQSSubiquitination[1]
Reference
 [1] 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
Functional Description
 Involved in adaptive response to hypoxia. Suppresses hypoxia-inducible expression of HIF1A and EPAS1. Binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. The complex HIF3A-ARNT activates the transcription of reporter genes driven by HRE. Isoform 4 has a dominant-negative function of inactivating HIF1A-mediated transcription. Isoform 4 attenuates the binding of HIF1A to hypoxia-responsive elements (HRE), thus inhibiting HRE-driven transcription. Hypoxia induces down-regulation of isoform 4, leading to activation of HIF1A in hypoxia. Conversely, upon restoring normoxia, the expression of isoform 4 increases and thereby secure an inhibition of HIF1A activity. Isoform 4 may be a negative regulator of hypoxia-inducible gene expression in the kidney and may be involved in renal tumorigenesis. Functions as an inhibitor of angiogenesis in the cornea (By similarity). 
Sequence Annotation
 DOMAIN 14 67 bHLH.
 DOMAIN 82 154 PAS 1.
 DOMAIN 227 297 PAS 2.
 REGION 452 581 ODD.
 REGION 454 506 NTAD.
 MOTIF 414 418 LRRLL.
 MOTIF 490 497 LAPYISMD.
 MOD_RES 492 492 4-hydroxyproline.
 CROSSLNK 467 467 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 570 570 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 Alternative splicing; Complete proteome; Cytoplasm; DNA-binding; Hydroxylation; Isopeptide bond; Nucleus; Polymorphism; Reference proteome; Repeat; Transcription; Transcription regulation; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 669 AA 
Protein Sequence
MALGLQRARS TTELRKEKSR DAARSRRSQE TEVLYQLAHT LPFARGVSAH LDKASIMRLT 60
ISYLRMHRLC AAGEWNQVGA GGEPLDACYL KALEGFVMVL TAEGDMAYLS ENVSKHLGLS 120
QLELIGHSIF DFIHPCDQEE LQDALTPQQT LSRRKVEAPT ERCFSLRMKS TLTSRGRTLN 180
LKAATWKVLN CSGHMRAYKP PAQTSPAGSP DSEPPLQCLV LICEAIPHPG SLEPPLGRGA 240
FLSRHSLDMK FTYCDDRIAE VAGYSPDDLI GCSAYEYIHA LDSDAVSKSI HTLLSKGQAV 300
TGQYRFLARS GGYLWTQTQA TVVSGGRGPQ SESIVCVHFL ISQVEETGVV LSLEQTEQHS 360
RRPIQRGAPS QKDTPNPGDS LDTPGPRILA FLHPPSLSEA ALAADPRRFC SPDLRRLLGP 420
ILDGASVAAT PSTPLATRHP QSPLSADLPD ELPVGTENVH RLFTSGKDTE AVETDLDIAQ 480
DADALDLEML APYISMDDDF QLNASEQLPR AYHRPLGAVP RPRARSFHGL SPPALEPSLL 540
PRWGSDPRLS CSSPSRGDPS ASSPMAGARK RTLAQSSEDE DEGVELLGVR PPKRSPSPEH 600
ENFLLFPLSL SFLLTGGPAP GSLQDPSTPL LNLNEPLGLG PSLLSPYSDE DTTQPGGPFQ 660
PRAGSAQAD 669 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:Compara.
 GO:0004871; F:signal transducer activity; IEA:InterPro.
 GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
 GO:0006366; P:transcription from RNA polymerase II promoter; IEA:Compara. 
Interpro
 IPR011598; bHLH_dom.
 IPR021537; HIF_alpha_subunit.
 IPR001610; PAC.
 IPR000014; PAS.
 IPR013767; PAS_fold.
 IPR013655; PAS_fold_3. 
Pfam
 PF11413; HIF-1
 PF00989; PAS
 PF08447; PAS_3 
SMART
 SM00353; HLH
 SM00086; PAC
 SM00091; PAS 
PROSITE
 PS50888; BHLH
 PS50112; PAS 
PRINTS