IL6RA_PIG
ID IL6RA_PIG Reviewed; 467 AA.
AC O18796;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 25-MAY-2022, entry version 125.
DE RecName: Full=Interleukin-6 receptor subunit alpha;
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;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Morris K.R., Strom A.D.G.;
RT "Cloning and expression of biologically active porcine IL-6 receptor alpha
RT chain.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 123-186.
RC TISSUE=Liver;
RA Klir J.J., Matteri R.L.;
RT "Partial cDNA sequence of porcine interleukin 6 receptor.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
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 -!- TISSUE SPECIFICITY: Expressed in liver.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF147881; AAF73109.1; -; mRNA.
DR EMBL; AF015116; AAB70916.1; -; mRNA.
DR RefSeq; NP_999568.1; NM_214403.1.
DR AlphaFoldDB; O18796; -.
DR SMR; O18796; -.
DR STRING; 9823.ENSSSCP00000006981; -.
DR PRIDE; O18796; -.
DR GeneID; 399522; -.
DR KEGG; ssc:399522; -.
DR CTD; 3570; -.
DR InParanoid; O18796; -.
DR OrthoDB; 783799at2759; -.
DR ChiTaRS; IL6R; pig.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005896; C:interleukin-6 receptor complex; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0004915; F:interleukin-6 receptor activity; ISS:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0010536; P:positive regulation of activation of Janus kinase activity; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IBA:GO_Central.
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; -; 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 Pfam; PF00047; ig; 1.
DR Pfam; PF09240; IL6Ra-bind; 1.
DR SMART; SM00060; FN3; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 2.
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; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000250"
FT CHAIN 20..467
FT /note="Interleukin-6 receptor subunit alpha"
FT /id="PRO_0000010897"
FT CHAIN 20..355
FT /note="Soluble interleukin-6 receptor subunit alpha"
FT /evidence="ECO:0000250|UniProtKB:P08887"
FT /id="PRO_0000450732"
FT TOPO_DOM 20..365
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 366..386
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 387..467
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 20..112
FT /note="Ig-like C2-type"
FT DOMAIN 113..217
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 218..316
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 315..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 303..307
FT /note="WSXWS motif"
FT COMPBIAS 315..338
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 433..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 355..356
FT /note="Cleavage; by ADAM10 and ADAM17"
FT /evidence="ECO:0000250|UniProtKB:P08887"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P08887"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P08887"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P08887"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P08887"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P08887"
FT CARBOHYD 352
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P08887"
FT DISULFID 25..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 47..96
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 121..132
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 165..176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 467 AA; 51067 MW; A2B0B884EF21C502 CRC64;
MLAVGCALLT ALLAAPGMAL APRGCSKLEV AQDVLTSLPG ASVTLTCPGG EPGDNATIHW
VLRNQVTGSP DGRPAGVGRR LLLKSVQLSD SGNYSCYQDG VPAGSVRLLV DAPPEEPQLS
CFRKSPLSNV GCEWRPRSPP SPTTKAVLLV RKFQNSPVED FQEPCQYSLE AQRFFCQLAV
PEGDNSFHIV TLCVANSAGS QSSTPQTFEG YGILQPDPPV NITVSAVDRN PRWLSVTWQD
PPSWNSYFYR LQFELRYRAE RSKTFTTWMV KELQHHCIIH DAWSGMRHVV QLRAQEEFGH
GLWSEWSQEV TGIPWTESRS SPAETELPLS TQAPTTNEDD EDISSKESAN ATSLPVQDSA
SVPLPTFLVA GGSLAFGTLL CIGIILRFKK TGQLQALKEG KTNMHPPYSL GQLVPERPKS
TPVLVPLISP PVSPNSLGDN TSRNSRPEAR GPQSPYDVSN RDYFFPR
