CNTFR_HUMAN
ID CNTFR_HUMAN Reviewed; 372 AA.
AC P26992; Q5U050;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Ciliary neurotrophic factor receptor subunit alpha;
DE Short=CNTF receptor subunit alpha;
DE Short=CNTFR-alpha;
DE Flags: Precursor;
GN Name=CNTFR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1648265; DOI=10.1126/science.1648265;
RA Davis S., Aldrich T.H., Valenzuela D.M., Wong V., Furth M.E., Squinto S.P.,
RA Yancopoulos G.D.;
RT "The receptor for ciliary neurotrophic factor.";
RL Science 253:59-63(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7774913; DOI=10.1016/0888-7543(95)80121-2;
RA Valenzuela D.M., Rojas E., le Beau M.M., Espinosa R., Brannan C.I.,
RA McClain J., Masiakowski P., Ip N.Y., Copeland N.G., Jenkins N.A.,
RA Yancopoulos G.D.;
RT "Genomic organization and chromosomal localization of the human and mouse
RT genes encoding the alpha receptor component for ciliary neurotrophic
RT factor.";
RL Genomics 25:157-163(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, AND IDENTIFICATION IN HUMANIN RECEPTOR COMPLEX.
RX PubMed=19386761; DOI=10.1091/mbc.e09-02-0168;
RA Hashimoto Y., Kurita M., Aiso S., Nishimoto I., Matsuoka M.;
RT "Humanin inhibits neuronal cell death by interacting with a cytokine
RT receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130.";
RL Mol. Biol. Cell 20:2864-2873(2009).
RN [8]
RP FUNCTION, AND INTERACTION WITH CLCF1; CRLF1 AND SORL1.
RX PubMed=26858303; DOI=10.1128/mcb.00917-15;
RA Larsen J.V., Kristensen A.M., Pallesen L.T., Bauer J., Vaegter C.B.,
RA Nielsen M.S., Madsen P., Petersen C.M.;
RT "Cytokine-like factor 1, an essential facilitator of cardiotrophin-like
RT cytokine:ciliary neurotrophic factor receptor alpha signaling and sorLA-
RT mediated turnover.";
RL Mol. Cell. Biol. 36:1272-1286(2016).
RN [9]
RP STRUCTURE BY NMR OF 202-305.
RX PubMed=12707266; DOI=10.1074/jbc.m301976200;
RA Man D., He W., Sze K.H., Gong K., Smith D.K., Zhu G., Ip N.Y.;
RT "Solution structure of the C-terminal domain of the ciliary neurotrophic
RT factor (CNTF) receptor and ligand free associations among components of the
RT CNTF receptor complex.";
RL J. Biol. Chem. 278:23285-23294(2003).
CC -!- FUNCTION: Binds to CNTF. The alpha subunit provides the receptor
CC specificity. Receptor for heterodimeric neurotropic cytokine composed
CC of CLCF1/CLC and CRLF1/CLF-1 (PubMed:26858303). Acts as a receptor for
CC the neuroprotective peptide humanin as part of a complex with
CC IL6ST/GP130 and IL27RA/WSX1 (PubMed:19386761).
CC {ECO:0000269|PubMed:19386761, ECO:0000269|PubMed:26858303}.
CC -!- SUBUNIT: Forms a heterotrimer with LIFR and IL6ST. Interacts with
CC heterodimeric neurotropic cytokine composed of CLCF1/CLC and CRLF1/CLF-
CC 1 (PubMed:26858303). Either alone or in complex with the heterodimer
CC CLCF1-CRLF1 interacts with SORL1; this interaction may promote
CC internalization and lysosomal degradation (PubMed:26858303). Component
CC of a receptor complex composed of IL6ST/GP130, IL27RA/WSX1 and CNTFR
CC which interacts with the neuroprotective peptide humanin
CC (PubMed:19386761). {ECO:0000269|PubMed:19386761,
CC ECO:0000269|PubMed:26858303}.
CC -!- INTERACTION:
CC P26992; PRO_0000015616 [Q9UBD9]: CLCF1; NbExp=3; IntAct=EBI-743758, EBI-25298664;
CC P26992; P26441: CNTF; NbExp=13; IntAct=EBI-743758, EBI-1050897;
CC P26992; Q92673: SORL1; NbExp=7; IntAct=EBI-743758, EBI-1171329;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.
CC -!- TISSUE SPECIFICITY: Nervous system and skeletal muscle.
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 -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 3
CC subfamily. {ECO:0000305}.
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DR EMBL; M73238; AAA35707.1; -; mRNA.
DR EMBL; L38025; AAA91337.1; -; Genomic_DNA.
DR EMBL; L38022; AAA91337.1; JOINED; Genomic_DNA.
DR EMBL; L38023; AAA91337.1; JOINED; Genomic_DNA.
DR EMBL; L38024; AAA91337.1; JOINED; Genomic_DNA.
DR EMBL; BT019824; AAV38627.1; -; mRNA.
DR EMBL; AL160270; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58445.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58446.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58447.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58448.1; -; Genomic_DNA.
DR EMBL; BC001492; AAH01492.1; -; mRNA.
DR CCDS; CCDS6558.1; -.
DR PIR; A40854; UHHUCN.
DR RefSeq; NP_001193940.1; NM_001207011.1.
DR RefSeq; NP_001833.1; NM_001842.4.
DR RefSeq; NP_671693.1; NM_147164.2.
DR RefSeq; XP_016869752.1; XM_017014263.1.
DR RefSeq; XP_016869753.1; XM_017014264.1.
DR RefSeq; XP_016869754.1; XM_017014265.1.
DR PDB; 1UC6; NMR; -; A=202-305.
DR PDBsum; 1UC6; -.
DR AlphaFoldDB; P26992; -.
DR BMRB; P26992; -.
DR SMR; P26992; -.
DR BioGRID; 107671; 16.
DR CORUM; P26992; -.
DR DIP; DIP-5777N; -.
DR IntAct; P26992; 14.
DR MINT; P26992; -.
DR STRING; 9606.ENSP00000368265; -.
DR GlyGen; P26992; 4 sites.
DR PhosphoSitePlus; P26992; -.
DR BioMuta; CNTFR; -.
DR DMDM; 1352099; -.
DR EPD; P26992; -.
DR jPOST; P26992; -.
DR MassIVE; P26992; -.
DR PaxDb; P26992; -.
DR PeptideAtlas; P26992; -.
DR PRIDE; P26992; -.
DR ProteomicsDB; 54371; -.
DR Antibodypedia; 25488; 334 antibodies from 39 providers.
DR DNASU; 1271; -.
DR Ensembl; ENST00000351266.8; ENSP00000242338.4; ENSG00000122756.15.
DR Ensembl; ENST00000378980.8; ENSP00000368265.3; ENSG00000122756.15.
DR Ensembl; ENST00000610543.4; ENSP00000480451.1; ENSG00000122756.15.
DR GeneID; 1271; -.
DR KEGG; hsa:1271; -.
DR MANE-Select; ENST00000378980.8; ENSP00000368265.3; NM_147164.3; NP_671693.1.
DR UCSC; uc003zup.2; human.
DR CTD; 1271; -.
DR DisGeNET; 1271; -.
DR GeneCards; CNTFR; -.
DR HGNC; HGNC:2170; CNTFR.
DR HPA; ENSG00000122756; Tissue enhanced (brain, skeletal muscle).
DR MIM; 118946; gene.
DR neXtProt; NX_P26992; -.
DR OpenTargets; ENSG00000122756; -.
DR PharmGKB; PA26684; -.
DR VEuPathDB; HostDB:ENSG00000122756; -.
DR eggNOG; ENOG502QUDK; Eukaryota.
DR GeneTree; ENSGT00940000158864; -.
DR InParanoid; P26992; -.
DR OMA; KICDTGE; -.
DR OrthoDB; 741136at2759; -.
DR PhylomeDB; P26992; -.
DR TreeFam; TF331210; -.
DR PathwayCommons; P26992; -.
DR Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions.
DR SignaLink; P26992; -.
DR SIGNOR; P26992; -.
DR BioGRID-ORCS; 1271; 7 hits in 1061 CRISPR screens.
DR ChiTaRS; CNTFR; human.
DR EvolutionaryTrace; P26992; -.
DR GenomeRNAi; 1271; -.
DR Pharos; P26992; Tbio.
DR PRO; PR:P26992; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P26992; protein.
DR Bgee; ENSG00000122756; Expressed in ventricular zone and 98 other tissues.
DR ExpressionAtlas; P26992; baseline and differential.
DR Genevisible; P26992; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IDA:CACAO.
DR GO; GO:0070110; C:ciliary neurotrophic factor receptor complex; IDA:BHF-UCL.
DR GO; GO:0097059; C:CNTFR-CLCF1 complex; IDA:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0004897; F:ciliary neurotrophic factor receptor activity; TAS:ProtInc.
DR GO; GO:0019955; F:cytokine binding; IPI:HGNC-UCL.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR GO; GO:0003360; P:brainstem development; IEA:Ensembl.
DR GO; GO:0070120; P:ciliary neurotrophic factor-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0007548; P:sex differentiation; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0060538; P:skeletal muscle organ development; IEA:Ensembl.
DR GO; GO:0001967; P:suckling behavior; IEA:Ensembl.
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 Pfam; PF00041; fn3; 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 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor;
KW Immunoglobulin domain; Lipoprotein; Membrane; Receptor; Reference proteome;
KW Repeat; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..342
FT /note="Ciliary neurotrophic factor receptor subunit alpha"
FT /id="PRO_0000010991"
FT PROPEP 343..372
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010992"
FT DOMAIN 27..104
FT /note="Ig-like C2-type"
FT DOMAIN 108..205
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 206..306
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 301..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 290..294
FT /note="WSXWS motif"
FT COMPBIAS 312..330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 342
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 46..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT STRAND 208..214
FT /evidence="ECO:0007829|PDB:1UC6"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:1UC6"
FT TURN 235..239
FT /evidence="ECO:0007829|PDB:1UC6"
FT STRAND 242..251
FT /evidence="ECO:0007829|PDB:1UC6"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:1UC6"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:1UC6"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:1UC6"
FT STRAND 276..281
FT /evidence="ECO:0007829|PDB:1UC6"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:1UC6"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:1UC6"
SQ SEQUENCE 372 AA; 40633 MW; B2F3F73DE8F8750E CRC64;
MAAPVPWACC AVLAAAAAVV YAQRHSPQEA PHVQYERLGS DVTLPCGTAN WDAAVTWRVN
GTDLAPDLLN GSQLVLHGLE LGHSGLYACF HRDSWHLRHQ VLLHVGLPPR EPVLSCRSNT
YPKGFYCSWH LPTPTYIPNT FNVTVLHGSK IMVCEKDPAL KNRCHIRYMH LFSTIKYKVS
ISVSNALGHN ATAITFDEFT IVKPDPPENV VARPVPSNPR RLEVTWQTPS TWPDPESFPL
KFFLRYRPLI LDQWQHVELS DGTAHTITDA YAGKEYIIQV AAKDNEIGTW SDWSVAAHAT
PWTEEPRHLT TEAQAAETTT STTSSLAPPP TTKICDPGEL GSGGGPSAPF LVSVPITLAL
AAAAATASSL LI
