CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011901
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Sterol regulatory element-binding protein 2 
Protein Synonyms/Alias
 SREBP-2; Class D basic helix-loop-helix protein 2; bHLHd2; Sterol regulatory element-binding transcription factor 2; Processed sterol regulatory element-binding protein 2 
Gene Name
 SREBF2 
Gene Synonyms/Alias
 BHLHD2; SREBP2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
115QAPTLQVKVSPTSVPubiquitination[1]
314GQEKVPIKQVPGGVKubiquitination[1]
340TTHNIIEKRYRSSINubiquitination[1]
349YRSSINDKIIELKDLubiquitination[1]
354NDKIIELKDLVMGTDubiquitination[1, 2, 3]
363LVMGTDAKMHKSGVLubiquitination[1]
366GTDAKMHKSGVLRKAubiquitination[1]
372HKSGVLRKAIDYIKYubiquitination[1]
386YLQQVNHKLRQENMVubiquitination[1]
405NQKNKLLKGIDLGSLubiquitination[1, 2, 3]
464LLDDAKVKDEPDSPPsumoylation[4, 5]
464LLDDAKVKDEPDSPPubiquitination[2]
579VTFWRHRKQADLDLAubiquitination[1]
660AGFEDEAKTSARDAAubiquitination[1, 2, 3, 6]
731LKTRCGGKLGFLASYubiquitination[1]
768LCHPLGQKFFMERSWubiquitination[1]
778MERSWSVKSAAKESLubiquitination[1]
782WSVKSAAKESLYCAQubiquitination[1, 7]
805QVHQAFCKNLLERAIubiquitination[1]
817RAIESLVKPQAKKKAubiquitination[1, 2, 6]
821SLVKPQAKKKAGDQEubiquitination[1]
822LVKPQAKKKAGDQEEubiquitination[1]
823VKPQAKKKAGDQEEEubiquitination[1]
865LSRSSVLKSALGPDIubiquitination[1]
907TKVERIPKALEVTESubiquitination[1, 2]
918VTESPLVKAIFHACRubiquitination[1]
934MHASLPGKADGQQSSubiquitination[1]
989LRTALWQKQASASQAubiquitination[1, 2, 3]
1031SFRPAYRKVFLHEATubiquitination[1, 6]
1067RRTTQSTKHGEVDAWubiquitination[1, 2, 3, 6, 8]
1115EAARTLEKVGDRRSCubiquitination[1, 2, 6]
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] 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]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] Sterol regulatory element-binding proteins are negatively regulated through SUMO-1 modification independent of the ubiquitin/26 S proteasome pathway.
 Hirano Y, Murata S, Tanaka K, Shimizu M, Sato R.
 J Biol Chem. 2003 May 9;278(19):16809-19. [PMID: 12615929]
 [5] Growth factor-induced phosphorylation of sterol regulatory element-binding proteins inhibits sumoylation, thereby stimulating the expression of their target genes, low density lipoprotein uptake, and lipid synthesis.
 Arito M, Horiba T, Hachimura S, Inoue J, Sato R.
 J Biol Chem. 2008 May 30;283(22):15224-31. [PMID: 18403372]
 [6] 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]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [8] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094] 
Functional Description
 Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes. 
Sequence Annotation
 DOMAIN 330 380 bHLH.
 REGION 1 50 Transcriptional activation (acidic).
 REGION 237 491 Interaction with LMNA (By similarity).
 REGION 380 401 Leucine-zipper.
 MOD_RES 1121 1121 Phosphoserine (By similarity).  
Keyword
 3D-structure; Activator; Cholesterol metabolism; Complete proteome; Cytoplasmic vesicle; Direct protein sequencing; DNA-binding; Endoplasmic reticulum; Golgi apparatus; Lipid metabolism; Membrane; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Steroid metabolism; Sterol metabolism; Transcription; Transcription regulation; Transmembrane; Transmembrane helix. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1141 AA 
Protein Sequence
MDDSGELGGL ETMETLTELG DELTLGDIDE MLQFVSNQVG EFPDLFSEQL CSSFPGSGGS 60
GSSSGSSGSS SSSSNGRGSS SGAVDPSVQR SFTQVTLPSF SPSAASPQAP TLQVKVSPTS 120
VPTTPRATPI LQPRPQPQPQ PQTQLQQQTV MITPTFSTTP QTRIIQQPLI YQNAATSFQV 180
LQPQVQSLVT SSQVQPVTIQ QQVQTVQAQR VLTQTANGTL QTLAPATVQT VAAPQVQQVP 240
VLVQPQIIKT DSLVLTTLKT DGSPVMAAVQ NPALTALTTP IQTAALQVPT LVGSSGTILT 300
TMPVMMGQEK VPIKQVPGGV KQLEPPKEGE RRTTHNIIEK RYRSSINDKI IELKDLVMGT 360
DAKMHKSGVL RKAIDYIKYL QQVNHKLRQE NMVLKLANQK NKLLKGIDLG SLVDNEVDLK 420
IEDFNQNVLL MSPPASDSGS QAGFSPYSID SEPGSPLLDD AKVKDEPDSP PVALGMVDRS 480
RILLCVLTFL CLSFNPLTSL LQWGGAHDSD QHPHSGSGRS VLSFESGSGG WFDWMMPTLL 540
LWLVNGVIVL SVFVKLLVHG EPVIRPHSRS SVTFWRHRKQ ADLDLARGDF AAAAGNLQTC 600
LAVLGRALPT SRLDLACSLS WNVIRYSLQK LRLVRWLLKK VFQCRRATPA TEAGFEDEAK 660
TSARDAALAY HRLHQLHITG KLPAGSACSD VHMALCAVNL AECAEEKIPP STLVEIHLTA 720
AMGLKTRCGG KLGFLASYFL SRAQSLCGPE HSAVPDSLRW LCHPLGQKFF MERSWSVKSA 780
AKESLYCAQR NPADPIAQVH QAFCKNLLER AIESLVKPQA KKKAGDQEEE SCEFSSALEY 840
LKLLHSFVDS VGVMSPPLSR SSVLKSALGP DIICRWWTSA ITVAISWLQG DDAAVRSHFT 900
KVERIPKALE VTESPLVKAI FHACRAMHAS LPGKADGQQS SFCHCERASG HLWSSLNVSG 960
ATSDPALNHV VQLLTCDLLL SLRTALWQKQ ASASQAVGET YHASGAELAG FQRDLGSLRR 1020
LAHSFRPAYR KVFLHEATVR LMAGASPTRT HQLLEHSLRR RTTQSTKHGE VDAWPGQRER 1080
ATAILLACRH LPLSFLSSPG QRAVLLAEAA RTLEKVGDRR SCNDCQQMIV KLGGGTAIAA 1140
S 1141 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0012507; C:ER to Golgi transport vesicle membrane; IEA:UniProtKB-SubCell.
 GO:0000139; C:Golgi membrane; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0032937; C:SREBP-SCAP-Insig complex; IDA:UniProtKB.
 GO:0070888; F:E-box binding; IDA:BHF-UCL.
 GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:BHF-UCL.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:Compara.
 GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
 GO:0071499; P:cellular response to laminar fluid shear stress; NAS:BHF-UCL.
 GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
 GO:0090370; P:negative regulation of cholesterol efflux; IDA:BHF-UCL.
 GO:0010886; P:positive regulation of cholesterol storage; IDA:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:2000188; P:regulation of cholesterol homeostasis; IEA:Compara.
 GO:0072368; P:regulation of lipid transport by negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0055098; P:response to low-density lipoprotein particle stimulus; IEP:BHF-UCL.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome.
 GO:0032933; P:SREBP signaling pathway; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR011598; bHLH_dom. 
Pfam
 PF00010; HLH 
SMART
 SM00353; HLH 
PROSITE
 PS50888; BHLH 
PRINTS