| IED ID | IndEnz0002011118 |
| Enzyme Type ID | protease011118 |
| Protein Name |
E3 ubiquitin-protein ligase XIAP EC 2.3.2.27 Baculoviral IAP repeat-containing protein 4 IAP-like protein ILP hILP Inhibitor of apoptosis protein 3 IAP-3 hIAP-3 hIAP3 RING-type E3 ubiquitin transferase XIAP X-linked inhibitor of apoptosis protein X-linked IAP |
| Gene Name | XIAP API3 BIRC4 IAP3 |
| 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 | MTFNSFEGSKTCVPADINKEEEFVEEFNRLKTFANFPSGSPVSASTLARAGFLYTGEGDTVRCFSCHAAVDRWQYGDSAVGRHRKVSPNCRFINGFYLENSATQSTNSGIQNGQYKVENYLGSRDHFALDRPSETHADYLLRTGQVVDISDTIYPRNPAMYSEEARLKSFQNWPDYAHLTPRELASAGLYYTGIGDQVQCFCCGGKLKNWEPCDRAWSEHRRHFPNCFFVLGRNLNIRSESDAVSSDRNFPNSTNLPRNPSMADYEARIFTFGTWIYSVNKEQLARAGFYALGEGDKVKCFHCGGGLTDWKPSEDPWEQHAKWYPGCKYLLEQKGQEYINNIHLTHSLEECLVRTTEKTPSLTRRIDDTIFQNPMVQEAIRMGFSFKDIKKIMEEKIQISGSNYKSLEVLVADLVNAQKDSMQDESSQTSLQKEISTEEQLRRLQEEKLCKICMDRNIAIVFVPCGHLVTCKQCAEAVDKCPMCYTVITFKQKIFMS |
| Enzyme Length | 497 |
| Uniprot Accession Number | P98170 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| 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: Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinating COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Ubiquitinates and therefore mediates the proteosomal degradation of BCL2 in response to apoptosis (PubMed:29020630). Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program. {ECO:0000269|PubMed:11447297, ECO:0000269|PubMed:12121969, ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:17560374, ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:20154138, ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:22103349, ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:29020630, ECO:0000269|PubMed:9230442}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (17); Chain (1); Cross-link (2); Helix (28); Metal binding (4); Modified residue (1); Mutagenesis (22); Natural variant (4); Region (4); Repeat (3); Sequence conflict (1); Turn (10); Zinc finger (1) |
| Keywords | 3D-structure;Apoptosis;Cytoplasm;Isopeptide bond;Metal-binding;Nucleus;Phosphoprotein;Protease inhibitor;Reference proteome;Repeat;S-nitrosylation;Thiol protease inhibitor;Transferase;Ubl conjugation;Ubl conjugation pathway;Wnt signaling pathway;Zinc;Zinc-finger |
| Interact With | Q9Y3E2; A0A087WZT3; Q92851; Q92851-4; P42574; P55210; P55211; O14618; P61024; Q9NR28; Q9NR28-1; Q96FJ2; P19447; Q96CN9; P07686; O43464; P83110; P83110-1; P83110-2; P83105; Q17RB8; Q96EZ8; Q9HC98; P46531; Q96HA8; Q4G0R1; O43447; Q8N3J5; P47897; P63000; P40937; O43353; P57078; Q06455-2; O43236-6; Q8IUQ4; Q9Y2D8; Q15750; Q5W5X9-3; P0CG48; P51668; P62837; P61077; P61088; Q13404; A5D8V6; Itself; Q9JIQ3; Q9JIY5 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=TLE3 promotes its nuclear localization. |
| Modified Residue | MOD_RES 450; /note=S-nitrosocysteine; /evidence=ECO:0000269|PubMed:20670888 |
| Post Translational Modification | PTM: S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase activity. {ECO:0000269|PubMed:20670888}.; PTM: Autoubiquitinated. {ECO:0000269|PubMed:12747801}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (7); X-ray crystallography (59) |
| Cross Reference PDB | 1C9Q; 1F9X; 1G3F; 1G73; 1I3O; 1I4O; 1I51; 1KMC; 1NW9; 1TFQ; 1TFT; 2ECG; 2JK7; 2KNA; 2OPY; 2OPZ; 2POI; 2POP; 2QRA; 2VSL; 3CLX; 3CM2; 3CM7; 3EYL; 3G76; 3HL5; 3UW4; 3UW5; 4EC4; 4HY0; 4IC2; 4IC3; 4J3Y; 4J44; 4J45; 4J46; 4J47; 4J48; 4KJU; 4KJV; 4KMP; 4MTZ; 4OXC; 4WVS; 4WVT; 4WVU; 5C0K; 5C0L; 5C3H; 5C3K; 5C7A; 5C7B; 5C7C; 5C7D; 5C83; 5C84; 5M6E; 5M6F; 5M6H; 5M6L; 5M6M; 5O6T; 5OQW; 6EY2; 6GJW; 6QCI; |
| Mapped Pubmed ID | 10206961; 10929711; 10934209; 10972280; 11084335; 11140638; 11230124; 11242052; 11257230; 11257232; 11546791; 11583623; 11597143; 11602612; 11701129; 11752425; 11801603; 11927604; 11972398; 12048196; 12121983; 12167698; 12218061; 12243753; 12388702; 12482981; 12592339; 12624662; 12691733; 12725530; 12824163; 12835328; 12851723; 12855663; 12874265; 12970762; 14512414; 14523016; 14532997; 14570909; 14759516; 14960576; 15037009; 15044484; 15173080; 15207275; 15258597; 15282301; 15292176; 15297970; 15337764; 15359644; 15531913; 15570290; 15580265; 15650747; 15677500; 15749826; 16142363; 16189514; 16211302; 16260783; 16278380; 16282325; 16343440; 16344307; 16394139; 16543147; 16603398; 16603637; 16732928; 16799641; 16868249; 16869888; 16887178; 16916640; 16932741; 16953224; 16964381; 16972754; 16983704; 17008917; 17016456; 17035597; 17050666; 17069460; 17094439; 17144666; 17179183; 17218260; 17218261; 17287399; 17291493; 17318174; 17331366; 17332680; 17339366; 17350081; 17437405; 17440816; 17450518; 17471152; 17534699; 17537996; 17579071; 17611394; 17613533; 17626072; 17630106; 17721914; 17724022; 17936246; 17947468; 17951200; 17993464; 18022123; 18022362; 18024305; 18041764; 18068526; 18071906; 18178551; 18187663; 18251743; 18309651; 18415656; 18432259; 18438971; 18520160; 18521960; 18560353; 18566024; 18570872; 18590777; 18619610; 18645029; 18647593; 18666224; 18703998; 18704457; 18717598; 18755525; 18761086; 18767116; 18795889; 18807090; 18820704; 18829553; 18831009; 18851976; 18954041; 18992220; 19001278; 19011619; 19171073; 19273858; 19288545; 19289587; 19355825; 19369629; 19393243; 19397802; 19398375; 19411066; 19492850; 19506533; 19524512; 19531477; 19549727; 19562673; 19590513; 19615732; 19649722; 19654940; 19667203; 19670614; 19698783; 19723899; 19726736; 19738422; 19758744; 19763917; 19782107; 19854829; 19859091; 19875445; 19877056; 19885569; 19897582; 19910467; 19913121; 19916060; 19946707; 19949310; 20005846; 20067634; 20185725; 20213810; 20304918; 20381828; 20385093; 20395960; 20406824; 20406946; 20431038; 20484174; 20515940; 20517649; 20582956; 20625944; 20632385; 20676365; 20677802; 20682709; 20711500; 20712893; 20819778; 20856198; 20862799; 20938744; 20959405; 20979872; 20980180; 21102524; 21119115; 21185211; 21317880; 21325798; 21354220; 21364655; 21367892; 21387310; 21402697; 21442307; 21518480; 21532586; 21535957; 21543760; 21559296; 21674762; 21707856; 21712378; 21737330; 21869827; 21903422; 21908615; 21935275; 21949740; 22039248; 22072751; 22083305; 22117219; 22179575; 22194841; 22273571; 22297296; 22320973; 22333553; 22393046; 22403616; 22413863; 22427670; 22435550; 22459568; 22465666; 22493164; 22532870; 22584050; 22607974; 22653317; 22653319; 22683311; 22696161; 22733138; 22776562; 22811387; 22815893; 22817896; 22848449; 22867709; 22886722; 22896709; 22934750; 23074197; 23156805; 23166698; 23222509; 23223428; 23251006; 23259674; 23298277; 23306356; 23313255; 23354694; 23397285; 23418891; 23492187; 23553333; 23640046; 23650375; 23669290; 23720779; 23742934; 23749209; 23817665; 23818254; 23828693; 23891189; 23955808; 23973892; 23979166; 23999295; 24038028; 24043286; 24083380; 24083782; 24093940; 24098568; 24124924; 24145606; 24173770; 24176845; 24188482; 24194568; 24246475; 24247248; 24344018; 24371121; 24422988; 24425875; 24446252; 24552816; 24572142; 24603802; 24623724; 24698088; 24733578; 24799195; 24802394; 24841289; 24853184; 24942515; 24975362; 25003840; 25005847; 25074812; 25079909; 25080938; 25151142; 25216527; 25241761; 25260751; 25273171; 25292199; 25293521; 25359904; 25389989; 25394481; 25416956; 25436288; 25501831; 25501832; 25549803; 25578648; 25619915; 25666262; 25669656; 25686839; 25695766; 25707849; 25744037; 25776486; 25801017; 25824780; 25888903; 25943627; 25974735; 26071313; 26134559; 26172506; 26182687; 26218264; 26313705; 26314849; 26404623; 26496610; 26507126; 26521691; 26638075; 26676658; 26707189; 26733262; 26779627; 26821068; 27025967; 27048285; 27048361; 27070757; 27072230; 27188727; 27210546; 27221209; 27259577; 27317434; 27416006; 27447744; 27498621; 27607580; 27697095; 27841661; 27865841; 27927753; 28039474; 28040451; 28057023; 28186968; 28204942; 28224479; 28324269; 28404814; 28414080; 28492317; 28656888; 28661476; 28666324; 28667026; 28691642; 28721806; 28772220; 28851536; 28952057; 28976632; 28977846; 29037837; 29048653; 29053960; 29115633; 29124675; 29170254; 29236891; 29250796; 29255093; 29351901; 29501442; 29530788; 29556337; 29631059; 29678905; 29681455; 29695633; 30014630; 30055105; 30066913; 30249882; 30395908; 30421089; 30446907; 30522111; 30528232; 30671387; 30688097; 30706710; 30778852; 30819044; 30819803; 30867140; 31004702; 31011505; 31018043; 31064412; 31127027; 31228514; 31240993; 31266830; 31350258; 31493422; 31539130; 31635307; 31744505; 31842909; 32019552; 32020226; 32050753; 32301277; 32373947; 32462369; 32485270; 32540394; 32788347; 32797709; 32994395; 33097010; 33138314; 33328332; 33460440; 33941563; 34247143; 34546853; 34739338; 9390557; 9525868; 9922454; |
| Motif | |
| Gene Encoded By | |
| Mass | 56,685 |
| Kinetics | |
| Metal Binding | METAL 300; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00029; METAL 303; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00029; METAL 320; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00029; METAL 327; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00029 |
| Rhea ID | |
| Cross Reference Brenda |