| IED ID | IndEnz0002015349 |
| Enzyme Type ID | protease015349 |
| Protein Name |
NF-kappa-B inhibitor alpha I-kappa-B-alpha IkB-alpha IkappaBalpha Major histocompatibility complex enhancer-binding protein MAD3 |
| Gene Name | NFKBIA IKBA MAD3 NFKBI |
| 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 | MFQAAERPQEWAMEGPRDGLKKERLLDDRHDSGLDSMKDEEYEQMVKELQEIRLEPQEVPRGSEPWKQQLTEDGDSFLHLAIIHEEKALTMEVIRQVKGDLAFLNFQNNLQQTPLHLAVITNQPEIAEALLGAGCDPELRDFRGNTPLHLACEQGCLASVGVLTQSCTTPHLHSILKATNYNGHTCLHLASIHGYLGIVELLVSLGADVNAQEPCNGRTALHLAVDLQNPDLVSLLLKCGADVNRVTYQGYSPYQLTWGRPSTRIQQQLGQLTLENLQMLPESEDEESYDTESEFTEFTEDELPYDDCVFGGQRLTL |
| Enzyme Length | 317 |
| Uniprot Accession Number | P25963 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription. {ECO:0000269|PubMed:7479976}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (2); Chain (1); Compositional bias (1); Cross-link (3); Helix (14); Modified residue (10); Motif (3); Mutagenesis (19); Natural variant (1); Region (1); Repeat (5); Turn (5) |
| Keywords | 3D-structure;ANK repeat;Cytoplasm;Disease variant;Ectodermal dysplasia;Host-virus interaction;Hydroxylation;Isopeptide bond;Nucleus;Phosphoprotein;Reference proteome;Repeat;Ubl conjugation |
| Interact With | O15111; Q8N668; P35221; Q9H0I2; Q9UKB1; P25098; P34947; Q9NWT6; O14920; Q9Y6K9; Q14511; Q14511-2; P19838; Q00653; Itself; Q96HA1-2; O43242; Q04864; Q04206; Q04206-2; P23396; P56279; P0CG48; Q60680-2; Q9J0X9; P14340; P14340; P21530; Q9E7P0 |
| Induction | INDUCTION: Induced in adherent monocytes. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export. {ECO:0000250}. |
| Modified Residue | MOD_RES 32; /note="Phosphoserine; by IKKA and IKKE"; /evidence="ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10882136"; MOD_RES 36; /note="Phosphoserine; by IKKA, IKKB, IKKE and TBK1"; /evidence="ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10882136"; MOD_RES 42; /note="Phosphotyrosine; by Tyr-kinases"; /evidence="ECO:0000269|PubMed:8797825"; MOD_RES 210; /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"; /evidence="ECO:0000269|PubMed:17003112"; MOD_RES 244; /note="(3S)-3-hydroxyasparagine; by HIF1AN; partial"; /evidence="ECO:0000269|PubMed:17003112"; MOD_RES 283; /note="Phosphoserine; by CK2"; /evidence="ECO:0000269|PubMed:8622692, ECO:0000269|PubMed:8657113"; MOD_RES 288; /note="Phosphoserine; by CK2"; /evidence="ECO:0000269|PubMed:8622692"; MOD_RES 291; /note="Phosphothreonine; by CK2"; /evidence="ECO:0000269|PubMed:8622692, ECO:0000269|PubMed:8657113"; MOD_RES 293; /note="Phosphoserine; by CK2"; /evidence="ECO:0000269|PubMed:8622692"; MOD_RES 299; /note="Phosphothreonine; by CK2"; /evidence="ECO:0000269|PubMed:8657113" |
| Post Translational Modification | PTM: Phosphorylated; disables inhibition of NF-kappa-B DNA-binding activity. Phosphorylation at positions 32 and 36 is prerequisite to recognition by UBE2D3 leading to polyubiquitination and subsequent degradation. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10882136, ECO:0000269|PubMed:20504922}.; PTM: Sumoylated; sumoylation requires the presence of the nuclear import signal. Sumoylation blocks ubiquitination and proteasome-mediated degradation of the protein thereby increasing the protein stability. {ECO:0000269|PubMed:11124955, ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:20504922}.; PTM: Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3. Ubiquitin chain elongation is then performed by CDC34 in cooperation with the SCF(FBXW11) E3 ligase complex, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. The resulting polyubiquitination leads to protein degradation. Also ubiquitinated by SCF(BTRC) following stimulus-dependent phosphorylation at Ser-32 and Ser-36. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10882136, ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:20504922, ECO:0000269|PubMed:7479976}.; PTM: Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (3) |
| Cross Reference PDB | 1IKN; 1NFI; 6TTU; 6Y1J; |
| Mapped Pubmed ID | 10066434; 10066435; 10075690; 10230406; 10321728; 10336492; 10384135; 10398585; 10409681; 10490984; 10498867; 10514424; 10514433; 10527519; 10542212; 10574930; 10593898; 10644755; 10722693; 10723127; 10733566; 10754328; 10764587; 10823818; 10918611; 10930537; 10973957; 10982547; 11231305; 11254493; 11279241; 11408488; 11673497; 11752211; 11799106; 11815618; 11913973; 11994255; 12028809; 12054687; 12084717; 12086926; 12138192; 12167702; 12189195; 12193729; 12244195; 12297126; 12377412; 12388747; 12406554; 12419806; 12429743; 12432072; 12433922; 12486103; 12518988; 12589049; 12620896; 12651903; 12704657; 12711606; 12730857; 12748192; 12791687; 12897149; 12909638; 12921778; 12944982; 12972430; 14514672; 14576361; 14623898; 14685242; 14743216; 14961554; 15068390; 15073126; 15093615; 15128824; 15145317; 15173174; 15184376; 15202778; 15208311; 15308505; 15330761; 15337789; 15368357; 15371334; 15389633; 15536134; 15613239; 15671028; 15695387; 15799966; 15811852; 15843586; 15858823; 15880609; 15979856; 16007147; 16015604; 16046415; 16105840; 16126728; 16169070; 16189514; 16258173; 16271147; 16286467; 16291755; 16319058; 16365431; 16407234; 16426569; 16540234; 16619039; 16683270; 16737960; 16818647; 16919536; 16931600; 16951195; 16955245; 17047224; 17062574; 17115186; 17148610; 17284228; 17307728; 17316064; 17318178; 17318773; 17333217; 17351338; 17354114; 17363905; 17409387; 17463416; 17492467; 17533369; 17593226; 17607549; 17612295; 17681786; 17701919; 17703412; 17910475; 17914462; 17942396; 17991436; 18045535; 18071880; 18199400; 18207244; 18215193; 18255255; 18260825; 18356846; 18434448; 18436431; 18444250; 18453612; 18455150; 18468507; 18474597; 18511071; 18515365; 18539148; 18555796; 18600435; 18606063; 18636124; 18636537; 18657515; 18660489; 18716880; 18818748; 18922877; 18950845; 18981184; 19019440; 19046417; 19074556; 19187648; 19213954; 19223558; 19258923; 19296948; 19297320; 19345327; 19363678; 19453261; 19456861; 19500386; 19507254; 19522780; 19527514; 19543524; 19554506; 19573080; 19591507; 19648161; 19673747; 19733238; 19758175; 19773279; 19773451; 19797428; 19798070; 19816602; 19874889; 19879840; 19886988; 19891769; 19913121; 19941056; 19948975; 20068069; 20080849; 20132559; 20164548; 20191354; 20193848; 20195357; 20304615; 20335171; 20379146; 20379614; 20385620; 20388715; 20448286; 20453000; 20495844; 20503287; 20546338; 20563630; 20568250; 20628086; 20628624; 20652762; 20659425; 20674643; 20696864; 20711500; 20797629; 20811626; 20836841; 20890592; 20953189; 20953190; 21048031; 21175304; 21217772; 21220295; 21228035; 21263074; 21376060; 21399639; 21454528; 21606193; 21765415; 21778941; 21988832; 22014111; 22022389; 22037600; 22078572; 22156201; 22184009; 22302838; 22393418; 22509384; 22935973; 23046941; 23054188; 23250755; 23274114; 23285182; 23322360; 23377923; 23422506; 23439505; 23453579; 23457512; 23487427; 23555990; 23563313; 23602409; 23697845; 23708964; 23850221; 23996241; 24083678; 24085292; 24101387; 24248593; 24270572; 24295474; 24324738; 24330732; 24361600; 24367071; 24457201; 24463357; 24504166; 24578542; 24634218; 24855949; 24973451; 25112903; 25215581; 25326706; 25352423; 25361605; 25367031; 25374080; 25416956; 25577468; 25609649; 25609694; 25759022; 25881508; 25930675; 25937534; 25974152; 26068031; 26075620; 26161396; 26239140; 26252270; 26295305; 26463447; 26488500; 26496610; 26520440; 26547583; 26647777; 26691317; 27041570; 27052952; 27053111; 27151455; 27312547; 27420950; 27458801; 27529070; 27538656; 27701768; 27806331; 27882436; 28122985; 28167786; 28249778; 28389768; 28417298; 28467781; 28670959; 28674224; 28766683; 28963466; 28970077; 29039556; 29093318; 29743966; 29980729; 30176044; 30464509; 30496749; 30621631; 30804118; 30887112; 31077459; 31115225; 31125555; 31322783; 31344550; 31484794; 31612070; 31683054; 31815120; 31964975; 32017069; 32026471; 32051583; 32085715; 32201828; 32750042; 32912968; 33160813; 33161109; 33851594; 33857149; 34030642; 34224210; 34614173; 7479848; 7575604; 7628694; 7809113; 7831327; 7862124; 7878466; 7957109; 8550590; 8601309; 8604224; 8622650; 8655651; 8660357; 8668171; 8887633; 8940099; 9135156; 9154800; 9214631; 9244310; 9252186; 9261139; 9315679; 9346484; 9346485; 9362451; 9520446; 9573057; 9632633; 9632806; 9689078; 9707608; 9721103; 9734360; 9789032; 9792644; 9859996; 9892650; 9914500; 9990852; 9990853; |
| Motif | MOTIF 30..36; /note=Destruction motif; MOTIF 45..54; /note=Nuclear export signal; MOTIF 110..120; /note=Nuclear import signal |
| Gene Encoded By | |
| Mass | 35,609 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |