| IED ID | IndEnz0002013399 |
| Enzyme Type ID | protease013399 |
| Protein Name |
TNF receptor-associated factor 2 EC 2.3.2.27 E3 ubiquitin-protein ligase TRAF2 RING-type E3 ubiquitin transferase TRAF2 Tumor necrosis factor type 2 receptor-associated protein 3 |
| Gene Name | TRAF2 TRAP3 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAAASVTPPGSLELLQPGFSKTLLGTKLEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPQNCAACVHEGIYEEGISILESSSAFPDNAARREVESLPAVCPSDGCTWKGTLKEYESCHEGRCPLMLTECPACKGLVRLGEKERHLEHECPERSLSCRHCRAPCCGADVKAHHEVCPKFPLTCDGCGKKKIPREKFQDHVKTCGKCRVPCRFHAIGCLETVEGEKQQEHEVQWLREHLAMLLSSVLEAKPLLGDQSHAGSELLQRCESLEKKTATFENIVCVLNREVERVAMTAEACSRQHRLDQDKIEALSSKVQQLERSIGLKDLAMADLEQKVLEMEASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIKAIVDLTGL |
| Enzyme Length | 501 |
| Uniprot Accession Number | Q12933 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Has very low E3 ubiquitin ligase activity in the absence of sphingosine-1-phosphate. E3 ubiquitin ligase activity is strongly activated by cytoplasmic sphingosine-1-phosphate. {ECO:0000269|PubMed:20577214}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; |
| DNA Binding | |
| EC Number | 2.3.2.27 |
| Enzyme Function | FUNCTION: 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. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE. {ECO:0000269|PubMed:10346818, ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:11907583, ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:18981220, ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:19506082, ECO:0000269|PubMed:19810754, ECO:0000269|PubMed:19918265, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20047764, ECO:0000269|PubMed:20064526, ECO:0000269|PubMed:20385093, ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:23453969}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Protein modification; protein ubiquitination. |
| nucleotide Binding | |
| Features | Alternative sequence (3); Beta strand (14); Chain (1); Coiled coil (1); Cross-link (1); Domain (1); Helix (17); Initiator methionine (1); Modified residue (6); Mutagenesis (7); Region (1); Sequence conflict (2); Turn (5); Zinc finger (3) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Apoptosis;Coiled coil;Cytoplasm;Isopeptide bond;Lipid-binding;Metal-binding;Phosphoprotein;Reference proteome;Repeat;Transferase;Ubl conjugation;Ubl conjugation pathway;Zinc;Zinc-finger |
| Interact With | Q9NRN7; Q9UHB7; Q9UHB7-2; O95994; C9JRZ8-2; Q9Y2J4-4; X5D778; Q96IX9; Q9UKG1; P29972; Q15052; Q8N5N6; Q8N9N2; Q8N9N2-2; P54253; O15169; Q8TBE0; B4DE54; Q8N9N5; Q8N9N5-2; Q8N9N5-7; A0A0A0MR97; O95999; P41182; Q9BXY8; Q13490; Q13489; Q8IYS8; Q13895; Q8WYQ4-2; Q53TS8; O75808; Q8NEC5; Q9HC52; E9PSE9; Q9NVL8; Q8TD31-3; F6RF56; P25942; Q86Y33; Q86Y33-5; Q16543; Q99618; Q07002; P46527; Q8IYX8-2; Q9Y6H1; P51800-3; Q02930-3; Q49AN0; P53672; P49711; Q2TBE0; Q6BCY4; Q6BCY4-2; Q8WTU0; P26196; Q08495; O60941; O60941-5; Q92997; Q96JC9; Q9HAK2; Q8WWZ3; Q8N6R0; A0A0S2Z3V1; Q12805; Q5JVL4; P00533; Q08426; Q9H0I2; A0A0A0MR80; O75460; A0A0S2Z3N6; Q01844; Q8N2X6; O95990-4; Q96EK7; Q9H5Z6-2; Q3B820; Q96MY7; Q7L5A3; Q9Y247; Q86YD7; Q8IZU1; O95363; Q9NVF7; Q9BRP7; Q4VC44; Q53EP0-3; O15353; Q06547; Q8NHY3; O95995; P28676; P55040; Q9H8Y8; O95872; Q92917; Q4V328; Q14687; Q2KHT4; P09211; O43708; Q6B0K9; A0A024R8L2; Q5T8I9; P49639; P09067; Q96MM6; P42858; P12268; Q9C086; Q96PC2; Q8NA54; Q6GPH6-2; Q63ZY3; Q5T5P2-6; Q9BVG8; Q9BVG8-5; P57682; Q96BZ8; Q86X59; Q8IXW0; Q8TBB1; Q17RB8; Q496Y0; Q96S90; O75367; Q99558; Q99683; Q7Z434; P55081; Q8IVT4; Q8IVT2; Q13064; Q9UBU8-2; Q6PF18; P00540; Q9Y3D2; Q15742; Q8N6N6; O76041; Q14511-2; Q9HC98-4; Q16649; Q8NI38; Q5HYW2; Q9GZQ4; Q86UR1-2; Q16656; Q16656-4; Q6X4W1-2; Q9BRJ7; Q8N3R9; Q9HBE1-4; P35227; Q86SE9; Q17RL8; Q96JS3; O75928-2; Q4G0R1; Q13526; Q16512; Q9BUI4; Q96HA1-2; O60437; Q6NYC8; Q5T8A7; Q7Z5V6-2; O43741; Q9H875; Q99633; P20618; O00233; Q9GZU8; P47897; Q2TAL8; P54725; Q9Y4B4; Q8WWW0; Q96IZ5; Q9P2K3; P48380; Q13671; Q13546; Q0D2K3; P57055; Q9NTX7; Q9NTX7-2; P78317; Q9UHP6; Q96NU1; Q9BWG6; Q9H788; Q92529; P48751; Q9H0W8; O95863; Q9BV90; Q9UN79; P41225; P35711-4; Q9NZD8; P63165; G2XKQ0; Q9BSW7; Q5T7P8-2; Q92844; Q9H2K8; Q9UHD2; Q9Y4C2-2; O15273; Q15560; Q8N8B7-2; P56279; Q9BXF9; Q9BT49; Q96CV8; Q96CG3; Q8IY51; Q08117; P21580; Q9Y6Q6; Q9Y6Q6-2; Q9NP84; Q92956; P20333; Q9UKE5; Q15628; Q13077; Itself; O00463; Q9Y4K3; Q14142; Q8IWZ5; Q86XT4; Q12815; Q86TN4-2; Q3SY00; Q9NRE2; Q63HK5; Q9Y5U2; Q5W5X9-3; P10599; Q7KZS0; Q5T124; Q5T124-6; P22415; O75604; Q5TAP6; Q9BRU9; Q14119; Q5GFL6; Q92558; P07947; Q05516; O43167; P24278; Q6ZSB9; Q53FD0; Q53FD0-2; Q6FIF0; Q9BRR0; Q96NC0; Q9UJ78-2; P15622-3; P13682; Q86VK4; Q86VK4-3; Q8TAU3; Q7Z4V0; Q96MN9; Q32MK9; Q6NX49; Q7Z3I7; Q6ZN55-2; Q5T619; Q8N720; Q6ZS27-3; A0A0S2Z6P0; Q6NX45; Q3MJ62; Q9NX65; Q96MP5; Q8IYH5; A0A384ME25; B2R8Y4; O08736; P09022; Q62925; P07174; P89055; P0DTD1; P20334; P70191; P88961; Q92956 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:19150425}. |
| Modified Residue | MOD_RES 2; /note="N-acetylalanine"; /evidence="ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"; MOD_RES 5; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 7; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 11; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:18981220, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 22; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21406692"; MOD_RES 117; /note="Phosphothreonine; by PKC"; /evidence="ECO:0000269|PubMed:19150425" |
| Post Translational Modification | PTM: Phosphorylated at several serine residues within the first 128 amino acid residues. Phosphorylated at Thr-117 in response to signaling via TNF and TNFRSF1A. Phosphorylation at Thr-117 is required for 'Lys-63'-linked polyubiquitination, but not for 'Lys-48'-linked polyubiquitination. Phosphorylation at Thr-117 is important for interaction with IKKA and IKKB, activation of IKK and subsequent activation of NF-kappa-B. {ECO:0000269|PubMed:19150425}.; PTM: Undergoes both 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination. Polyubiquitinated via 'Lys-63'-linked ubiquitin in response to TNF signaling; this requires prior phosphorylation at Thr-117. 'Lys-63'-linked polyubiquitination promotes TRAF2-mediated activation of NF-kappa-B. Can be polyubiquitinated at several Lys residues via 'Lys-48'-linked ubiquitin chains in response to TNF signaling, leading to proteasomal degradation. Autoubiquitinated, leading to its subsequent proteasomal degradation. Polyubiquitinated by BIRC2 and SIAH2, leading to its subsequent proteasomal degradation. Deubiquitinated by CYLD, a protease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Ubiquination is inhibited by LRRC19; inhibits proteasomal degradation (PubMed:25026888). {ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:25026888}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (14) |
| Cross Reference PDB | 1CA4; 1CA9; 1CZY; 1CZZ; 1D00; 1D01; 1D0A; 1D0J; 1F3V; 1QSC; 3KNV; 3M06; 3M0A; 3M0D; |
| Mapped Pubmed ID | 10075662; 10421793; 10518213; 10521396; 10797013; 10837247; 11112773; 11181075; 11463813; 11777919; 11798190; 12133833; 12167698; 12221085; 12374738; 12529173; 12571250; 12591926; 12620240; 12721308; 12813029; 12842894; 12887920; 14557256; 14604983; 14743216; 15024054; 15084608; 15208311; 15258597; 15265700; 15308666; 15361868; 15585864; 15644327; 15670977; 15708970; 15743837; 15824857; 15944293; 16009713; 16189514; 16260598; 16260783; 16282325; 16304992; 16311516; 16446357; 16603398; 16611992; 16636664; 16713569; 16876162; 16891304; 16914100; 16936264; 16953224; 17047155; 17327220; 17353931; 17379600; 17446270; 17626074; 17724081; 17981138; 18024283; 18069092; 18178551; 18190721; 18230756; 18256533; 18292192; 18312353; 18362156; 18485876; 18635759; 18671942; 18787502; 18818748; 18827186; 18838202; 18984593; 18990758; 18997792; 18997794; 19019335; 19151112; 19234489; 19243308; 19278658; 19336370; 19336568; 19380743; 19416807; 19426221; 19453261; 19479062; 19524512; 19527514; 19573080; 19666475; 19667091; 19668221; 19690440; 19690564; 19773279; 19815541; 19910467; 20005846; 20056178; 20064372; 20133937; 20138174; 20185725; 20218968; 20237496; 20304918; 20308068; 20333651; 20368287; 20449947; 20562859; 20568250; 20585848; 20628086; 20676093; 20696707; 20732415; 20856938; 21071692; 21078624; 21119000; 21229359; 21235526; 21266470; 21282507; 21289304; 21325409; 21516116; 21525013; 21737330; 21782231; 21793045; 21810480; 21822258; 21822306; 21864338; 21886773; 21903422; 21988832; 22029577; 22078441; 22167321; 22179575; 22297296; 22435550; 22458338; 22619329; 22685297; 22711886; 22817896; 22847298; 22848449; 23007157; 23051914; 23088713; 23142077; 23160117; 23188828; 23301098; 23313255; 23357418; 23414308; 23453971; 23524849; 23595117; 23608757; 23624947; 23638224; 23743189; 23754945; 23774506; 23775076; 23890813; 24098568; 24246475; 24298274; 24362534; 24457959; 24457966; 24658140; 24695225; 24722368; 24841215; 25051892; 25134449; 25152365; 25241761; 25260751; 25299769; 25416956; 25716317; 25797626; 25852190; 25882049; 25911380; 26011589; 26221961; 26331901; 26390021; 26510914; 26521044; 26779844; 26823737; 26993379; 27098354; 27382069; 27534557; 27834853; 28337828; 28482378; 28482915; 28489822; 28499815; 28667915; 28726782; 28855498; 28874458; 28926524; 28972304; 29151113; 29311633; 29681455; 29875129; 29935055; 30054040; 30127245; 30373932; 31477831; 31511692; 31555268; 31986892; 32024699; 32041822; 32898524; 33229071; 33404903; 33582548; 33869626; 33997937; 34070875; 34089727; 34257589; 7544915; 7758105; 8565075; 8612133; 8663299; 8702708; 8943045; 9008162; 9122217; 9689078; 9852070; 9880531; |
| Motif | |
| Gene Encoded By | |
| Mass | 55,859 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |