| IED ID | IndEnz0002015323 |
| Enzyme Type ID | protease015323 |
| Protein Name |
Interleukin-6 receptor subunit alpha IL-6 receptor subunit alpha IL-6R subunit alpha IL-6R-alpha IL-6RA IL-6R 1 Membrane glycoprotein 80 gp80 CD antigen CD126 Cleaved into: Soluble interleukin-6 receptor subunit alpha sIL6R |
| Gene Name | IL6R |
| 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 | MLAVGCALLAALLAAPGAALAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHWVLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLSCFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAVPEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQDPHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQGEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPVQDSSSVPLPTFLVAGGSLAFGTLLCIAIVLRFKKTWKLRALKEGKTSMHPPYSLGQLVPERPRPTPVLVPLISPPVSPSSLGSDNTSSHNRPDARDPRSPYDISNTDYFFPR |
| Enzyme Length | 468 |
| Uniprot Accession Number | P08887 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Classic and trans-signaling are both inhibited by tocilizumab, a humanized monoclonal antibody that blocks interleukin IL6R signaling. {ECO:0000269|PubMed:21990364}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis (PubMed:30995492, PubMed:31235509). The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable). {ECO:0000269|PubMed:28265003, ECO:0000269|PubMed:31235509, ECO:0000305|PubMed:30995492}.; FUNCTION: [Isoform 1]: Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000305|PubMed:30995492}.; FUNCTION: [Isoform 2]: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the proinflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:21990364}.; FUNCTION: [Soluble interleukin-6 receptor subunit alpha]: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the proinflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:21990364}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Beta strand (23); Chain (2); Compositional bias (1); Disulfide bond (4); Domain (3); Glycosylation (6); Helix (2); Motif (1); Mutagenesis (35); Natural variant (4); Region (2); Sequence conflict (1); Signal peptide (1); Site (2); Topological domain (2); Transmembrane (1); Turn (3) |
| Keywords | 3D-structure;Alternative splicing;Cell membrane;Direct protein sequencing;Disulfide bond;Glycoprotein;Immunoglobulin domain;Membrane;Receptor;Reference proteome;Repeat;Secreted;Signal;Transmembrane;Transmembrane helix |
| Interact With | P05231; Q96EQ0; Q92673; Q2HRC7; O00233 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000250|UniProtKB:P22272}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000269|PubMed:28060820}.; SUBCELLULAR LOCATION: [Soluble interleukin-6 receptor subunit alpha]: Secreted {ECO:0000269|PubMed:28060820}. |
| Modified Residue | |
| Post Translational Modification | PTM: A short soluble form is released from the membrane by proteolysis (PubMed:26876177). The sIL6R is formed mostly by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding, but is also directly secreted from the cells after alternative mRNA splicing (PubMed:26876177, PubMed:28060820). mIL6R is cleaved by the proteases ADAM10 and ADAM17 (PubMed:26876177, PubMed:28060820). {ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:28060820}.; PTM: Glycosylated. Glycosylation is dispensable for transport, signaling, and cell-surface turnover. Glycosylation at Asn-55 is a protease-regulatory exosite. Glycosylation is required for ADAM17-mediated proteolysis. {ECO:0000269|PubMed:28060820}. |
| Signal Peptide | SIGNAL 1..19; /evidence=ECO:0000269|PubMed:2529343 |
| Structure 3D | NMR spectroscopy (1); X-ray crystallography (4) |
| Cross Reference PDB | 1N26; 1P9M; 2ARW; 5FUC; 7DC8; |
| Mapped Pubmed ID | 10777583; 10851062; 11084045; 11121117; 11238858; 11356008; 11557047; 11884403; 12002769; 12008038; 12079407; 12372336; 12414855; 12419823; 12445803; 12472176; 12483717; 12553038; 12553555; 12574959; 12633863; 12643274; 12748171; 12748876; 12789531; 12832423; 12857602; 12917504; 14592826; 15041717; 15100312; 15166129; 15213442; 15284182; 15297310; 15306846; 15456942; 15561970; 15562008; 15579373; 15625895; 15641051; 15816827; 15895091; 16034137; 16127269; 16372246; 16557588; 16606674; 16731080; 16794539; 16817825; 16868551; 16899024; 16912152; 16972794; 16973585; 17160948; 17310346; 17346257; 17519976; 17570254; 17619842; 17652155; 17671508; 17703412; 17898129; 17903307; 17908769; 17984249; 18065760; 18276608; 18320358; 18439548; 18464913; 18490707; 18508242; 18519587; 18538149; 18543249; 18676680; 18781131; 18784373; 18818748; 18852330; 18853133; 18980999; 19019335; 19026125; 19088723; 19124510; 19170196; 19258923; 19277666; 19280716; 19336475; 19396608; 19406470; 19420002; 19422646; 19453261; 19495883; 19503017; 19505916; 19527514; 19567438; 19573080; 19625176; 19633828; 19665805; 19671870; 19692168; 19713205; 19733878; 19773279; 19773451; 19790045; 19913121; 19914334; 19926672; 19966016; 20017315; 20026129; 20031577; 20083667; 20140262; 20145925; 20157327; 20159251; 20186139; 20197062; 20237496; 20379614; 20423763; 20438838; 20452482; 20453000; 20463041; 20484876; 20493732; 20503287; 20551110; 20568250; 20599261; 20600579; 20661738; 20673868; 20698883; 20727736; 20800603; 20811626; 20823887; 20839491; 20856253; 20951753; 20974296; 21102457; 21159831; 21173340; 21196890; 21220034; 21229891; 21255427; 21282511; 21295508; 21401300; 21490132; 21496483; 21515913; 21748280; 21813064; 21835044; 21846873; 21851175; 21879314; 21907864; 21968316; 21981268; 21989726; 21994466; 22072558; 22079540; 22128229; 22133618; 22209080; 22295972; 22421339; 22449275; 22552503; 22554704; 22575642; 2261637; 22642608; 22742541; 22911828; 22984080; 23078005; 23094986; 23199226; 23242610; 23375120; 23428306; 23433353; 23479153; 23564454; 23582566; 23582716; 23593036; 23594084; 23648090; 23658720; 23677452; 23771909; 23782174; 23902164; 23926072; 23935104; 23945879; 24032723; 24118365; 24140252; 24152848; 24165468; 24285489; 24285563; 24346288; 24429361; 24445140; 24498998; 24642471; 24668548; 24699044; 24710939; 24717336; 24743777; 24772425; 24790088; 24791950; 24802752; 24806843; 24878322; 24886605; 24898204; 24940886; 24971337; 24978393; 24986424; 24993179; 25041016; 25052265; 25058889; 25176527; 25183374; 25245339; 25335739; 25345743; 25491772; 25524550; 25658637; 25781951; 25792278; 25813875; 25846075; 25910182; 25930193; 25973020; 26080005; 26086344; 26200663; 26205065; 26329582; 26359498; 26424054; 26455324; 26551279; 26561568; 26563755; 26699882; 26705936; 26712690; 26714766; 26725994; 26782593; 26932604; 26955245; 26981890; 26986049; 26997259; 27062409; 27068103; 27078193; 27344294; 27460086; 27461244; 27510094; 27527594; 27563232; 27629486; 27698010; 27744141; 27809289; 27810997; 27824145; 27825119; 2788034; 27908732; 27958380; 28049968; 28106546; 28128332; 28134246; 28235765; 28276471; 28334838; 28346858; 28388577; 28442395; 28466804; 28741286; 28769070; 28774868; 28779573; 28821817; 28918391; 28928101; 29117539; 29120300; 29157669; 29197507; 29200018; 29357923; 29510423; 29559558; 29752408; 29775600; 29777792; 29784660; 29797122; 29976575; 30098545; 30110560; 30132982; 30206163; 30228077; 30249138; 30291142; 30419338; 30787661; 30885232; 30913495; 30965356; 31021550; 31086276; 31148212; 31219249; 31219767; 31322277; 31328584; 31386885; 31413087; 31515941; 31524180; 31611269; 31655158; 31679401; 31707836; 31778705; 31836512; 31875623; 31883124; 31914141; 31918059; 31983174; 32162496; 32222277; 32306778; 32319395; 32364816; 32456348; 32472750; 32494918; 32519679; 32561314; 32643523; 32733444; 32898607; 32933994; 33001866; 33006190; 33126846; 33248276; 33314148; 33327352; 33350884; 33357423; 33414408; 33471392; 33492708; 33555431; 33575324; 33579000; 33610555; 34198336; 34253862; 34281231; 34353696; 34389747; 34687791; 7812050; 7871433; 8134389; 8140422; 8272873; 8388392; 8662591; 8662795; 9285712; 9382798; 9743535; 9794795; |
| Motif | MOTIF 303..307; /note=WSXWS motif |
| Gene Encoded By | |
| Mass | 51,548 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |