CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-023001
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ISG15--protein ligase HERC5 
Protein Synonyms/Alias
 Cyclin-E-binding protein 1; HECT domain and RCC1-like domain-containing protein 5 
Gene Name
 HERC5 
Gene Synonyms/Alias
 CEB1; CEBP1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
27AAATQPAKSPGAQLWubiquitination[1, 2]
138FESILQEKKIIQITCubiquitination[3]
397TLNEGTVKRWIADVEubiquitination[3]
406WIADVETKRWQSTKRubiquitination[3]
447PVYLDLNKARNIFKEubiquitination[3, 4]
643FNNLSKIKLLHTDTLubiquitination[3]
652LHTDTLLKIESKKHKubiquitination[3]
867NKRDYVSKYINYIFNubiquitination[3, 5]
890EFRRGFYKMCDEDIIubiquitination[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] 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]
 [4] 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]
 [5] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572] 
Functional Description
 Major E3 ligase for ISG15 conjugation. Acts as a positive regulator of innate antiviral response in cells induced by interferon. Makes part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant- negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15. 
Sequence Annotation
 REPEAT 96 155 RCC1 1.
 REPEAT 156 208 RCC1 2.
 REPEAT 209 260 RCC1 3.
 REPEAT 262 312 RCC1 4.
 REPEAT 314 364 RCC1 5.
 DOMAIN 702 1024 HECT.
 ACT_SITE 994 994 Glycyl thioester intermediate (By  
Keyword
 Antiviral defense; Complete proteome; Cytoplasm; Immunity; Innate immunity; Ligase; Polymorphism; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1024 AA 
Protein Sequence
MERRSRRKSR RNGRSTAGKA AATQPAKSPG AQLWLFPSAA GLHRALLRRV EVTRQLCCSP 60
GRLAVLERGG AGVQVHQLLA GSGGARTPKC IKLGKNMKIH SVDQGAEHML ILSSDGKPFE 120
YDNYSMKHLR FESILQEKKI IQITCGDYHS LALSKGGELF AWGQNLHGQL GVGRKFPSTT 180
TPQIVEHLAG VPLAQISAGE AHSMALSMSG NIYSWGKNEC GQLGLGHTES KDDPSLIEGL 240
DNQKVEFVAC GGSHSALLTQ DGLLFTFGAG KHGQLGHNST QNELRPCLVA ELVGYRVTQI 300
ACGRWHTLAY VSDLGKVFSF GSGKDGQLGN GGTRDQLMPL PVKVSSSEEL KLESHTSEKE 360
LIMIAGGNQS ILLWIKKENS YVNLKRTIPT LNEGTVKRWI ADVETKRWQS TKREIQEIFS 420
SPACLTGSFL RKRRTTEMMP VYLDLNKARN IFKELTQKDW ITNMITTCLK DNLLKRLPFH 480
SPPQEALEIF FLLPECPMMH ISNNWESLVV PFAKVVCKMS DQSSLVLEEY WATLQESTFS 540
KLVQMFKTAV ICQLDYWDES AEENGNVQAL LEMLKKLHRV NQVKCQLPES IFQVDELLHR 600
LNFFVEVCRR YLWKMTVDAS ENVQCCVIFS HFPFIFNNLS KIKLLHTDTL LKIESKKHKA 660
YLRSAAIEEE RESEFALRPT FDLTVRRNHL IEDVLNQLSQ FENEDLRKEL WVSFSGEIGY 720
DLGGVKKEFF YCLFAEMIQP EYGMFMYPEG ASCMWFPVKP KFEKKRYFFF GVLCGLSLFN 780
CNVANLPFPL ALFKKLLDQM PSLEDLKELS PDLGKNLQTL LDDEGDNFEE VFYIHFNVHW 840
DRNDTNLIPN GSSITVNQTN KRDYVSKYIN YIFNDSVKAV YEEFRRGFYK MCDEDIIKLF 900
HPEELKDVIV GNTDYDWKTF EKNARYEPGY NSSHPTIVMF WKAFHKLTLE EKKKFLVFLT 960
GTDRLQMKDL NNMKITFCCP ESWNERDPIR ALTCFSVLFL PKYSTMETVE EALQEAINNN 1020
RGFG 1024 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IBA:RefGenome.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
 GO:0042296; F:ISG15 ligase activity; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IBA:RefGenome.
 GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
 GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0032020; P:ISG15-protein conjugation; IDA:UniProtKB.
 GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
 GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc.
 GO:0050688; P:regulation of defense response to virus; IDA:UniProtKB. 
Interpro
 IPR000569; HECT.
 IPR009091; RCC1/BLIP-II.
 IPR000408; Reg_chr_condens. 
Pfam
 PF00632; HECT
 PF00415; RCC1 
SMART
 SM00119; HECTc 
PROSITE
 PS50237; HECT
 PS00625; RCC1_1
 PS00626; RCC1_2
 PS50012; RCC1_3 
PRINTS
 PR00633; RCCNDNSATION.