| IED ID | IndEnz0002002621 |
| Enzyme Type ID | protease002621 |
| Protein Name |
B-cell lymphoma/leukemia 10 B-cell CLL/lymphoma 10 Bcl-10 CARD-containing molecule enhancing NF-kappa-B CARD-like apoptotic protein hCLAP CED-3/ICH-1 prodomain homologous E10-like regulator CIPER Cellular homolog of vCARMEN cCARMEN Cellular-E10 c-E10 Mammalian CARD-containing adapter molecule E10 mE10 |
| Gene Name | BCL10 CIPER CLAP |
| 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 | MEPTAPSLTEEDLTEVKKDALENLRVYLCEKIIAERHFDHLRAKKILSREDTEEISCRTSSRKRAGKLLDYLQENPKGLDTLVESIRREKTQNFLIQKITDEVLKLRNIKLEHLKGLKCSSCEPFPDGATNNLSRSNSDESNFSEKLRASTVMYHPEGESSTTPFFSTNSSLNLPVLEVGRTENTIFSSTTLPRPGDPGAPPLPPDLQLEEEGTCANSSEMFLPLRSRTVSRQ |
| Enzyme Length | 233 |
| Uniprot Accession Number | O95999 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation (PubMed:10187770, PubMed:10364242, PubMed:10400625, PubMed:25365219, PubMed:24074955). Acts by channeling adaptive and innate immune signaling downstream of CARD domain-containing proteins CARD9, CARD11 and CARD14 to activate NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:24074955). Recruited by activated CARD domain-containing proteins: homooligomerized CARD domain-containing proteins form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10, subsequent recruitment of MALT1 and formation of a CBM complex (PubMed:24074955). This leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:18287044, PubMed:27777308, PubMed:24074955). Activated by CARD9 downstream of C-type lectin receptors; CARD9-mediated signals are essential for antifungal immunity (PubMed:26488816). Activated by CARD11 downstream of T-cell receptor (TCR) and B-cell receptor (BCR) (PubMed:18264101, PubMed:18287044, PubMed:27777308, PubMed:24074955). Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK (PubMed:10187815). {ECO:0000269|PubMed:10187770, ECO:0000269|PubMed:10187815, ECO:0000269|PubMed:10364242, ECO:0000269|PubMed:10400625, ECO:0000269|PubMed:18264101, ECO:0000269|PubMed:18287044, ECO:0000269|PubMed:24074955, ECO:0000269|PubMed:25365219, ECO:0000269|PubMed:26488816, ECO:0000269|PubMed:27777308}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (2); Chain (1); Compositional bias (1); Cross-link (3); Domain (1); Helix (8); Modified residue (2); Mutagenesis (20); Natural variant (20); Region (1); Site (1); Turn (3) |
| Keywords | 3D-structure;Acetylation;Adaptive immunity;Apoptosis;Chromosomal rearrangement;Cytoplasm;Disease variant;Immunity;Innate immunity;Isopeptide bond;Membrane;Phosphoprotein;Reference proteome;Tumor suppressor;Ubl conjugation |
| Interact With | P31749; Itself; P20749; Q9BXL7; Q9H257; Q9Y2V7; Q9Y6K9; Q9UDY8; Q05513; Q12933; Q66677 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000269|PubMed:17287217}. Membrane raft {ECO:0000269|PubMed:17287217}. Note=Appears to have a perinuclear, compact and filamentous pattern of expression. Also found in the nucleus of several types of tumor cells. Colocalized with DPP4 in membrane rafts. {ECO:0000269|PubMed:17287217}. |
| Modified Residue | MOD_RES 1; /note=N-acetylmethionine; /evidence=ECO:0007744|PubMed:19413330; MOD_RES 138; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:21406692 |
| Post Translational Modification | PTM: Phosphorylated. Phosphorylation results in dissociation from TRAF2 and binding to BIRC2/c-IAP2 (PubMed:11466612). Phosphorylated by IKBKB/IKKB (PubMed:17213322). {ECO:0000269|PubMed:11466612, ECO:0000269|PubMed:17213322}.; PTM: Ubiquitinated via both 'Lys-63'-linked and linear ('Met-1'-linked) polyubiquitin chains in response to T-cell receptor (TCR) activation (PubMed:18287044, PubMed:27777308). Ubiquitination is recognized by IKBKG/NEMO, the regulatory subunit of I-kappa-B kinase (IKK), and is required for TCR-induced NF-kappa-B activation (PubMed:18287044, PubMed:27777308). Linear ubiquitination at Lys-17, Lys-31 and Lys-63 is mediated by RNF31/HOIP; linear ubiquitination is recognized with much higher affinity than 'Lys-63'-linked ubiquitin by IKBKG/NEMO (PubMed:27777308). CARD11 is required for linear ubiquitination by HOIP by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308). {ECO:0000269|PubMed:18287044, ECO:0000269|PubMed:27777308}.; PTM: Proteolytically cleaved by MALT1; required for T-cell activation. {ECO:0000269|PubMed:18264101}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (1); Electron microscopy (2) |
| Cross Reference PDB | 2MB9; 6BZE; 6GK2; |
| Mapped Pubmed ID | 10557068; 10702308; 10838074; 10882101; 11053425; 11057907; 11090634; 11262391; 11325957; 11460167; 11830492; 11836626; 11960389; 12017308; 14514672; 14523480; 14638696; 14674990; 14695475; 14754896; 15122200; 15125833; 15207693; 15327770; 15637807; 15878976; 16056267; 16123224; 16127295; 16186825; 16229939; 16280327; 16301747; 16341151; 16356855; 16432253; 16775419; 16785131; 16818229; 16831874; 17047224; 17052756; 17101977; 17135271; 17158449; 17179215; 17199743; 17332413; 17353931; 17363905; 17371994; 17428801; 17468049; 17496917; 17502353; 17540779; 17728323; 17893875; 17948050; 18231929; 18307945; 18346354; 18349075; 18625728; 18772140; 18806265; 18949449; 19035248; 19112107; 19279678; 19309400; 19336552; 19444310; 19573080; 19690445; 19709433; 19773279; 19897484; 19909372; 20038579; 20237496; 20300203; 20439115; 20449947; 20466000; 20538596; 20695076; 21048031; 21157432; 21406399; 21513986; 21674474; 21700900; 21896478; 21966355; 21988832; 22069318; 22267217; 22474286; 22564715; 22579587; 22708078; 22812606; 22818167; 22880103; 23153494; 23530562; 23784377; 24412244; 24681956; 24702227; 24732096; 25011391; 25105596; 25384343; 25416956; 25849213; 26038114; 26496610; 26638075; 26668357; 26711259; 26771713; 26774590; 27071417; 28717989; 29358699; 29382759; 30206119; 30279415; 30283440; 30336982; 30514565; 31047877; 31178130; 32008135; 32799824; 9744859; |
| Motif | |
| Gene Encoded By | |
| Mass | 26,252 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |