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Database: UniProt
Entry: P22273
LinkDB: P22273
Original site: P22273 
ID   IL6RA_RAT               Reviewed;         462 AA.
AC   P22273;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 2.
DT   24-JAN-2024, entry version 167.
DE   RecName: Full=Interleukin-6 receptor subunit alpha {ECO:0000305};
DE            Short=IL-6 receptor subunit alpha;
DE            Short=IL-6R subunit alpha;
DE            Short=IL-6R-alpha;
DE            Short=IL-6RA;
DE   AltName: Full=IL-6R 1;
DE   AltName: CD_antigen=CD126;
DE   Contains:
DE     RecName: Full=Soluble interleukin-6 receptor subunit alpha {ECO:0000305};
DE              Short=sIL6R {ECO:0000305};
DE   Flags: Precursor;
GN   Name=Il6r {ECO:0000312|RGD:2902}; Synonyms=Il6ra;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Fischer 344; TISSUE=Liver;
RX   PubMed=2174054; DOI=10.1016/s0021-9258(17)45451-2;
RA   Baumann M., Baumann H., Fey G.H.;
RT   "Molecular cloning, characterization and functional expression of the rat
RT   liver interleukin 6 receptor.";
RL   J. Biol. Chem. 265:19853-19862(1990).
RN   [2]
RP   IDENTIFICATION OF PROBABLE FRAMESHIFT IN 227-261.
RA   Gibson T.;
RL   Unpublished observations (FEB-1995).
CC   -!- FUNCTION: Part of the receptor for interleukin 6. Binds to IL6 with low
CC       affinity, but does not transduce a signal. Signal activation
CC       necessitate an association with IL6ST. Activation leads to the
CC       regulation of the immune response, acute-phase reactions and
CC       hematopoiesis. The interaction with membrane-bound IL6R and IL6ST
CC       stimulates 'classic signaling', the restricted expression of the IL6R
CC       limits classic IL6 signaling to only a few tissues such as the liver
CC       and some cells of the immune system. Whereas the binding of IL6 and
CC       soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively,
CC       'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on
CC       transmitter cells activate IL6ST receptors on neighboring receiver
CC       cells. {ECO:0000250|UniProtKB:P22272}.
CC   -!- FUNCTION: [Interleukin-6 receptor subunit alpha]: Signaling via the
CC       membrane-bound IL6R is mostly regenerative and anti-inflammatory.
CC       Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster
CC       signaling' by dendritic cells. {ECO:0000250|UniProtKB:P22272}.
CC   -!- FUNCTION: [Soluble interleukin-6 receptor subunit alpha]: Soluble form
CC       of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (By
CC       similarity). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on
CC       cell surfaces and induces signaling also on cells that do not express
CC       membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is
CC       causative for the pro-inflammatory properties of IL6 and an important
CC       player in the development of chronic inflammatory diseases. In complex
CC       with IL6, is required for induction of VEGF production (By similarity).
CC       Plays a protective role during liver injury, being required for
CC       maintenance of tissue regeneration. 'Trans-signaling' in central
CC       nervous system regulates energy and glucose homeostasis (By
CC       similarity). {ECO:0000250|UniProtKB:P08887,
CC       ECO:0000250|UniProtKB:P22272}.
CC   -!- ACTIVITY REGULATION: Classic and trans-signaling are both inhibited by
CC       tocilizumab, a humanized monoclonal antibody that blocks interleukin
CC       IL6R signaling. {ECO:0000250|UniProtKB:P08887}.
CC   -!- SUBUNIT: Component of a hexamer of two molecules each of IL6, IL6R and
CC       IL6ST; first binds to IL6 to associate with the signaling subunit
CC       IL6ST. Interacts (via N-terminal ectodomain) with SORL1; this
CC       interaction may affect IL6-binding to IL6R, hence decrease IL6
CC       'classic-signaling'. {ECO:0000250|UniProtKB:P22272}.
CC   -!- SUBUNIT: [Soluble interleukin-6 receptor subunit alpha]: Also interacts
CC       with SORL1; this interaction leads to soluble IL6R internalization. May
CC       form a trimeric complex with the soluble SORL1 ectodomain and
CC       circulating IL6 receptor; this interaction might stabilize circulating
CC       IL6, hence promote IL6 'trans-signaling'.
CC       {ECO:0000250|UniProtKB:P08887}.
CC   -!- SUBCELLULAR LOCATION: [Interleukin-6 receptor subunit alpha]: Cell
CC       membrane {ECO:0000250|UniProtKB:P22272}; Single-pass type I membrane
CC       protein {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: [Soluble interleukin-6 receptor subunit alpha]:
CC       Secreted {ECO:0000250|UniProtKB:P22272}.
CC   -!- DOMAIN: The two fibronectin type-III-like domains contained in the C-
CC       terminal part form together a cytokine-binding domain.
CC   -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC       folding and thereby efficient intracellular transport and cell-surface
CC       receptor binding.
CC   -!- PTM: A short soluble form is also released from the membrane by
CC       proteolysis. The sIL6R is formed by limited proteolysis of membrane-
CC       bound receptors, a process referred to as ectodomain shedding. mIL6R is
CC       cleaved by the proteases ADAM10 and ADAM17.
CC       {ECO:0000250|UniProtKB:P22272}.
CC   -!- PTM: Glycosylated. Glycosylation is dispensable for transport,
CC       signaling, and cell-surface turnover. Glycosylation at Asn-55 is a
CC       protease-regulatory exosite. Glycosylation is required for ADAM17-
CC       mediated proteolysis. {ECO:0000250|UniProtKB:P08887}.
CC   -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 3
CC       subfamily. {ECO:0000305}.
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DR   EMBL; M58587; AAA41431.1; -; mRNA.
DR   PIR; A37986; A37986.
DR   STRING; 10116.ENSRNOP00000028234; -.
DR   BindingDB; P22273; -.
DR   ChEMBL; CHEMBL4289; -.
DR   GlyCosmos; P22273; 5 sites, No reported glycans.
DR   GlyGen; P22273; 5 sites.
DR   PhosphoSitePlus; P22273; -.
DR   PaxDb; 10116-ENSRNOP00000028234; -.
DR   UCSC; RGD:2902; rat.
DR   AGR; RGD:2902; -.
DR   RGD; 2902; Il6r.
DR   eggNOG; ENOG502RY0M; Eukaryota.
DR   InParanoid; P22273; -.
DR   PhylomeDB; P22273; -.
DR   Reactome; R-RNO-1059683; Interleukin-6 signaling.
DR   Reactome; R-RNO-110056; MAPK3 (ERK1) activation.
DR   Reactome; R-RNO-112411; MAPK1 (ERK2) activation.
DR   PRO; PR:P22273; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR   GO; GO:0070110; C:ciliary neurotrophic factor receptor complex; ISO:RGD.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; ISO:RGD.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0005896; C:interleukin-6 receptor complex; ISS:UniProtKB.
DR   GO; GO:0032809; C:neuronal cell body membrane; IDA:RGD.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0070119; F:ciliary neurotrophic factor binding; ISO:RGD.
DR   GO; GO:0004896; F:cytokine receptor activity; ISO:RGD.
DR   GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR   GO; GO:0019970; F:interleukin-11 binding; IBA:GO_Central.
DR   GO; GO:0004921; F:interleukin-11 receptor activity; IBA:GO_Central.
DR   GO; GO:0019981; F:interleukin-6 binding; ISO:RGD.
DR   GO; GO:0004915; F:interleukin-6 receptor activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR   GO; GO:0070120; P:ciliary neurotrophic factor-mediated signaling pathway; ISO:RGD.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR   GO; GO:0048589; P:developmental growth; IMP:RGD.
DR   GO; GO:0031018; P:endocrine pancreas development; ISO:RGD.
DR   GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISS:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR   GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR   GO; GO:0072126; P:positive regulation of glomerular mesangial cell proliferation; ISO:RGD.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
DR   GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR   GO; GO:0034097; P:response to cytokine; ISO:RGD.
DR   GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR   GO; GO:0010332; P:response to gamma radiation; IEP:RGD.
DR   GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR   GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProtKB.
DR   GO; GO:0010573; P:vascular endothelial growth factor production; ISS:UniProtKB.
DR   CDD; cd00063; FN3; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 3.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR003530; Hematopoietin_rcpt_L_F3_CS.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR013151; Immunoglobulin.
DR   InterPro; IPR015321; TypeI_recpt_CBD.
DR   PANTHER; PTHR23037:SF35; -; 1.
DR   PANTHER; PTHR23037; CYTOKINE RECEPTOR; 1.
DR   Pfam; PF00047; ig; 1.
DR   Pfam; PF09240; IL6Ra-bind; 1.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00408; IGc2; 1.
DR   SUPFAM; SSF49265; Fibronectin type III; 2.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   PROSITE; PS50853; FN3; 1.
DR   PROSITE; PS01354; HEMATOPO_REC_L_F3; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW   Membrane; Receptor; Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..19
FT   CHAIN           20..462
FT                   /note="Interleukin-6 receptor subunit alpha"
FT                   /id="PRO_0000010898"
FT   CHAIN           20..354
FT                   /note="Soluble interleukin-6 receptor subunit alpha"
FT                   /evidence="ECO:0000250|UniProtKB:P08887"
FT                   /id="PRO_0000450733"
FT   TOPO_DOM        20..364
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        365..385
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        386..462
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          20..108
FT                   /note="Ig-like C2-type"
FT   DOMAIN          215..313
FT                   /note="Fibronectin type-III"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   REGION          420..462
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           300..304
FT                   /note="WSXWS motif"
FT   COMPBIAS        422..455
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            354..355
FT                   /note="Cleavage; by ADAM10 and ADAM17"
FT                   /evidence="ECO:0000250|UniProtKB:P08887"
FT   CARBOHYD        32
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        55
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000250|UniProtKB:P08887"
FT   CARBOHYD        85
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        150
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        218
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000250|UniProtKB:P08887"
FT   DISULFID        25..190
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        47..92
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        117..128
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        162..173
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   CONFLICT        227..261
FT                   /note="XPRWLKVSWQDPESWDPSYYLLQFELRYRPVWSKX -> SLVGSKSVGKTLS
FT                   PGTQVTTCCNSSFDTDLYGQRT (in Ref. 1; AAA41431)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   462 AA;  50401 MW;  A4D6064CEDC0537D CRC64;
     MLAVGCTLLV ALLAAPAVAL VLGSCRALEV ANGTVTSLPG ATVTLICPGK EAAGNATIHW
     VYSGSQSREW TTTGNTLVLR AVQVNDTGHY LCFLDDHLVG TVPLLVDVPP EEPKLSCFRK
     NPLVNAFCEW HPSSTPSPTT KAVMFAKKIN TTNGKSDFQV PCQYSQQLKS FSCEVEILEG
     DKVYHIVSLC VANSVGSRSS HNVVFQSLKM VQPDPPANLV VSAIPGXPRW LKVSWQDPES
     WDPSYYLLQF ELRYRPVWSK XFTVWPLQVA QHQCVIHDAL RGVKHVVQVR GKEEFDIGQW
     SKWSPEVTGT PWLAEPRTTP AGIPGNPTQV SVEDYDNHED QYGSSTEATS VLAPVQGSSP
     IPLPTFLVAG GSLAFGLLLC VFIILRLKKK WKSQAEKESK TTSPPPYPLG PLKPTFLLVP
     LLTPSGSHNS SGTDNTGSHS CLGVRDPQCP NDNSNRDYLF PR
//
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