CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011951
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 TNF receptor-associated factor 2 
Protein Synonyms/Alias
 E3 ubiquitin-protein ligase TRAF2; Tumor necrosis factor type 2 receptor-associated protein 3 
Gene Name
 TRAF2 
Gene Synonyms/Alias
 TRAP3 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
21LLQPGFSKTLLGTKLubiquitination[1]
27SKTLLGTKLEAKYLCubiquitination[2, 3, 4]
31LGTKLEAKYLCSACRubiquitination[4, 5]
119CTWKGTLKEYESCHEubiquitination[3, 4]
140LTECPACKGLVRLGEubiquitination[1, 2, 4]
176PCCGADVKAHHEVCPubiquitination[4]
201KKKIPREKFQDHVKTubiquitination[4]
207EKFQDHVKTCGKCRVubiquitination[4]
231LETVEGEKQQEHEVQubiquitination[4, 6]
255LSSVLEAKPLLGDQSubiquitination[1, 2, 4, 7, 8, 9]
278RCESLEKKTATFENIubiquitination[4]
313QHRLDQDKIEALSSKubiquitination[1, 2, 4]
320KIEALSSKVQQLERSubiquitination[1, 2, 4]
331LERSIGLKDLAMADLubiquitination[1, 2, 4]
481PVSKMEAKNSYVRDDubiquitination[1, 2, 3, 4]
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] 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] 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]
 [4] 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]
 [5] 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]
 [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] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [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]
 [9] 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] 
Functional Description
 Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'- linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin- protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. 
Sequence Annotation
 DOMAIN 351 496 MATH.
 ZN_FING 34 73 RING-type.
 ZN_FING 124 180 TRAF-type 1.
 ZN_FING 177 233 TRAF-type 2.
 REGION 283 293 Important for interaction with BIRC2 and
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 7 7 Phosphothreonine.
 MOD_RES 11 11 Phosphoserine.
 MOD_RES 22 22 Phosphothreonine.
 MOD_RES 117 117 Phosphothreonine; by PKC.
 CROSSLNK 31 31 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Alternative splicing; Apoptosis; Coiled coil; Complete proteome; Cytoplasm; Isopeptide bond; Ligase; Lipid-binding; Metal-binding; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 501 AA 
Protein Sequence
MAAASVTPPG SLELLQPGFS KTLLGTKLEA KYLCSACRNV LRRPFQAQCG HRYCSFCLAS 60
ILSSGPQNCA ACVHEGIYEE GISILESSSA FPDNAARREV ESLPAVCPSD GCTWKGTLKE 120
YESCHEGRCP LMLTECPACK GLVRLGEKER HLEHECPERS LSCRHCRAPC CGADVKAHHE 180
VCPKFPLTCD GCGKKKIPRE KFQDHVKTCG KCRVPCRFHA IGCLETVEGE KQQEHEVQWL 240
REHLAMLLSS VLEAKPLLGD QSHAGSELLQ RCESLEKKTA TFENIVCVLN REVERVAMTA 300
EACSRQHRLD QDKIEALSSK VQQLERSIGL KDLAMADLEQ KVLEMEASTY DGVFIWKISD 360
FARKRQEAVA GRIPAIFSPA FYTSRYGYKM CLRIYLNGDG TGRGTHLSLF FVVMKGPNDA 420
LLRWPFNQKV TLMLLDQNNR EHVIDAFRPD VTSSSFQRPV NDMNIASGCP LFCPVSKMEA 480
KNSYVRDDAI FIKAIVDLTG L 501 
Gene Ontology
 GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0009898; C:internal side of plasma membrane; ISS:BHF-UCL.
 GO:0005174; F:CD40 receptor binding; ISS:BHF-UCL.
 GO:0004871; F:signal transducer activity; NAS:ProtInc.
 GO:0046625; F:sphingolipid binding; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; TAS:Reactome.
 GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IMP:UniProtKB.
 GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
 GO:0043623; P:cellular protein complex assembly; ISS:BHF-UCL.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB.
 GO:0043507; P:positive regulation of JUN kinase activity; IDA:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0090073; P:positive regulation of protein homodimerization activity; IMP:UniProtKB.
 GO:0050870; P:positive regulation of T cell activation; IC:UniProtKB.
 GO:0002726; P:positive regulation of T cell cytokine production; IMP:UniProtKB.
 GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
 GO:0030163; P:protein catabolic process; IEA:Compara.
 GO:0070207; P:protein homotrimerization; IPI:UniProtKB.
 GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
 GO:0051023; P:regulation of immunoglobulin secretion; IEA:Compara.
 GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB. 
Interpro
 IPR002083; MATH.
 IPR012227; TNF_rcpt--assoc_TRAF.
 IPR008974; TRAF-like.
 IPR027133; TRAF2.
 IPR018957; Znf_C3HC4_RING-type.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS.
 IPR001293; Znf_TRAF. 
Pfam
 PF00917; MATH
 PF00097; zf-C3HC4 
SMART
 SM00061; MATH
 SM00184; RING 
PROSITE
 PS50144; MATH
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2
 PS50145; ZF_TRAF 
PRINTS