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CNTF_HUMAN
ID   CNTF_HUMAN              Reviewed;         200 AA.
AC   P26441; B2RAB2;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   03-AUG-2022, entry version 201.
DE   RecName: Full=Ciliary neurotrophic factor;
DE            Short=CNTF;
GN   Name=CNTF;
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 [GENOMIC DNA].
RX   PubMed=1861138; DOI=10.1111/j.1471-4159.1991.tb08250.x;
RA   Masiakowski P., Liu H., Radziejewski C., Lottspeich F., Oberthuer W.,
RA   Wong V., Lindsay R.M., Furth M.E., Panayotatos N.;
RT   "Recombinant human and rat ciliary neurotrophic factors.";
RL   J. Neurochem. 57:1003-1012(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1915374; DOI=10.1111/j.1432-1033.1991.tb16286.x;
RA   Negro A., Tolosano E., Skaper S., Martini I., Callegaro L., Silengo L.,
RA   Fiorini F., Altruda F.;
RT   "Cloning and expression of human ciliary neurotrophic factor.";
RL   Eur. J. Biochem. 201:289-294(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Lung;
RX   PubMed=1840538; DOI=10.1016/0378-1119(91)90089-t;
RA   Lam A., Fuller F., Miller J., Kloss J., Manthorpe M., Varon M., Cordell B.;
RT   "Sequence and structural organization of the human gene encoding ciliary
RT   neurotrophic factor.";
RL   Gene 102:271-276(1991).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1883844; DOI=10.1016/0167-4781(91)90038-n;
RA   McDonald J.R., Ko C., Mismer D., Smith D.J., Collins F.;
RT   "Expression and characterization of recombinant human ciliary neurotrophic
RT   factor from Escherichia coli.";
RL   Biochim. Biophys. Acta 1090:70-80(1991).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Sciatic nerve;
RX   PubMed=8075647; DOI=10.1038/ng0594-79;
RA   Takahashi R., Yokoji H., Misawa H., Hayashi M., Hu J., Deguchi T.;
RT   "A null mutation in the human CNTF gene is not causally related to
RT   neurological diseases.";
RL   Nat. Genet. 7:79-84(1994).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
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   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-187.
RX   PubMed=7796798; DOI=10.1002/j.1460-2075.1995.tb07269.x;
RA   McDonald N.Q., Panayotatos N., Hendrickson W.A.;
RT   "Crystal structure of dimeric human ciliary neurotrophic factor determined
RT   by MAD phasing.";
RL   EMBO J. 14:2689-2699(1995).
RN   [10]
RP   VARIANT ARG-182.
RX   PubMed=10391209; DOI=10.1038/10290;
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RT   "Characterization of single-nucleotide polymorphisms in coding regions of
RT   human genes.";
RL   Nat. Genet. 22:231-238(1999).
RN   [11]
RP   ERRATUM OF PUBMED:10391209.
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RL   Nat. Genet. 23:373-373(1999).
CC   -!- FUNCTION: CNTF is a survival factor for various neuronal cell types.
CC       Seems to prevent the degeneration of motor axons after axotomy.
CC   -!- SUBUNIT: Homodimer.
CC   -!- INTERACTION:
CC       P26441; Q96MA6: AK8; NbExp=3; IntAct=EBI-1050897, EBI-8466265;
CC       P26441; P02649: APOE; NbExp=3; IntAct=EBI-1050897, EBI-1222467;
CC       P26441; P05067: APP; NbExp=3; IntAct=EBI-1050897, EBI-77613;
CC       P26441; P26992: CNTFR; NbExp=13; IntAct=EBI-1050897, EBI-743758;
CC       P26441; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1050897, EBI-3867333;
CC       P26441; P40189: IL6ST; NbExp=10; IntAct=EBI-1050897, EBI-1030834;
CC       P26441; Q15323: KRT31; NbExp=3; IntAct=EBI-1050897, EBI-948001;
CC       P26441; Q6A162: KRT40; NbExp=3; IntAct=EBI-1050897, EBI-10171697;
CC       P26441; P42702: LIFR; NbExp=9; IntAct=EBI-1050897, EBI-7702162;
CC       P26441; O14561: NDUFAB1; NbExp=3; IntAct=EBI-1050897, EBI-1246261;
CC       P26441; Q8NG50: RDM1; NbExp=3; IntAct=EBI-1050897, EBI-10288724;
CC       P26441; Q99523: SORT1; NbExp=6; IntAct=EBI-1050897, EBI-1057058;
CC       P26441; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-1050897, EBI-11139477;
CC       P26441; Q15654: TRIP6; NbExp=3; IntAct=EBI-1050897, EBI-742327;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- TISSUE SPECIFICITY: Nervous system.
CC   -!- SIMILARITY: Belongs to the CNTF family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Ciliary neurotrophic factor entry;
CC       URL="https://en.wikipedia.org/wiki/Ciliary_neurotrophic_factor";
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DR   EMBL; X60542; CAA43032.1; -; Genomic_DNA.
DR   EMBL; X60477; CAA43009.1; -; Genomic_DNA.
DR   EMBL; X60478; CAA43009.1; JOINED; Genomic_DNA.
DR   EMBL; X55889; CAA39374.1; -; Genomic_DNA.
DR   EMBL; X55890; CAA39374.1; JOINED; Genomic_DNA.
DR   EMBL; AK314118; BAG36809.1; -; mRNA.
DR   EMBL; CH471076; EAW73819.1; -; Genomic_DNA.
DR   EMBL; BC068030; AAH68030.1; -; mRNA.
DR   EMBL; BC074963; AAH74963.1; -; mRNA.
DR   EMBL; BC074964; AAH74964.1; -; mRNA.
DR   CCDS; CCDS31554.1; -.
DR   PIR; JH0455; UNHUCF.
DR   RefSeq; NP_000605.1; NM_000614.3.
DR   PDB; 1CNT; X-ray; 2.40 A; 1/2/3/4=1-187.
DR   PDBsum; 1CNT; -.
DR   AlphaFoldDB; P26441; -.
DR   SMR; P26441; -.
DR   BioGRID; 107670; 23.
DR   CORUM; P26441; -.
DR   DIP; DIP-5776N; -.
DR   IntAct; P26441; 18.
DR   MINT; P26441; -.
DR   STRING; 9606.ENSP00000355370; -.
DR   PhosphoSitePlus; P26441; -.
DR   BioMuta; CNTF; -.
DR   PaxDb; P26441; -.
DR   PeptideAtlas; P26441; -.
DR   PRIDE; P26441; -.
DR   ProteomicsDB; 54349; -.
DR   Antibodypedia; 34925; 657 antibodies from 41 providers.
DR   DNASU; 1270; -.
DR   Ensembl; ENST00000361987.6; ENSP00000355370.4; ENSG00000242689.3.
DR   GeneID; 1270; -.
DR   KEGG; hsa:1270; -.
DR   MANE-Select; ENST00000361987.6; ENSP00000355370.4; NM_000614.4; NP_000605.1.
DR   UCSC; uc001nna.5; human.
DR   CTD; 1270; -.
DR   DisGeNET; 1270; -.
DR   GeneCards; CNTF; -.
DR   HGNC; HGNC:2169; CNTF.
DR   HPA; ENSG00000242689; Tissue enhanced (bone marrow, brain).
DR   MIM; 118945; gene.
DR   neXtProt; NX_P26441; -.
DR   OpenTargets; ENSG00000242689; -.
DR   PharmGKB; PA26683; -.
DR   VEuPathDB; HostDB:ENSG00000242689; -.
DR   eggNOG; ENOG502S4XX; Eukaryota.
DR   GeneTree; ENSGT00420000029890; -.
DR   HOGENOM; CLU_118647_0_0_1; -.
DR   InParanoid; P26441; -.
DR   OMA; MESYVKH; -.
DR   OrthoDB; 1466128at2759; -.
DR   PhylomeDB; P26441; -.
DR   TreeFam; TF336237; -.
DR   PathwayCommons; P26441; -.
DR   Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions.
DR   SignaLink; P26441; -.
DR   SIGNOR; P26441; -.
DR   BioGRID-ORCS; 1270; 11 hits in 1080 CRISPR screens.
DR   EvolutionaryTrace; P26441; -.
DR   GeneWiki; Ciliary_neurotrophic_factor; -.
DR   GenomeRNAi; 1270; -.
DR   Pharos; P26441; Tbio.
DR   PRO; PR:P26441; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P26441; protein.
DR   Bgee; ENSG00000242689; Expressed in tibial nerve and 96 other tissues.
DR   Genevisible; P26441; HS.
DR   GO; GO:0030424; C:axon; IBA:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005127; F:ciliary neurotrophic factor receptor binding; IBA:GO_Central.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL.
DR   GO; GO:0005138; F:interleukin-6 receptor binding; IPI:BHF-UCL.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:BHF-UCL.
DR   GO; GO:0048143; P:astrocyte activation; IBA:GO_Central.
DR   GO; GO:0070120; P:ciliary neurotrophic factor-mediated signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0048644; P:muscle organ morphogenesis; IEA:Ensembl.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:BHF-UCL.
DR   GO; GO:0046533; P:negative regulation of photoreceptor cell differentiation; IEA:Ensembl.
DR   GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR   GO; GO:0048680; P:positive regulation of axon regeneration; IBA:GO_Central.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL.
DR   GO; GO:0046668; P:regulation of retinal cell programmed cell death; IEA:Ensembl.
DR   GO; GO:0060221; P:retinal rod cell differentiation; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR   GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR   Gene3D; 1.20.1250.10; -; 1.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR000151; Ciliary_neurotrophic_fac_CNTF.
DR   PANTHER; PTHR15196; PTHR15196; 1.
DR   Pfam; PF01110; CNTF; 1.
DR   SUPFAM; SSF47266; SSF47266; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Developmental protein; Differentiation;
KW   Growth factor; Neurogenesis; Reference proteome.
FT   CHAIN           1..200
FT                   /note="Ciliary neurotrophic factor"
FT                   /id="PRO_0000149519"
FT   VARIANT         49
FT                   /note="N -> S (in dbSNP:rs17152779)"
FT                   /id="VAR_033777"
FT   VARIANT         182
FT                   /note="H -> R (in dbSNP:rs6266)"
FT                   /evidence="ECO:0000269|PubMed:10391209"
FT                   /id="VAR_013924"
FT   HELIX           13..41
FT                   /evidence="ECO:0007829|PDB:1CNT"
FT   HELIX           69..95
FT                   /evidence="ECO:0007829|PDB:1CNT"
FT   TURN            96..98
FT                   /evidence="ECO:0007829|PDB:1CNT"
FT   STRAND          99..101
FT                   /evidence="ECO:0007829|PDB:1CNT"
FT   HELIX           104..129
FT                   /evidence="ECO:0007829|PDB:1CNT"
FT   STRAND          138..140
FT                   /evidence="ECO:0007829|PDB:1CNT"
FT   HELIX           152..180
FT                   /evidence="ECO:0007829|PDB:1CNT"
SQ   SEQUENCE   200 AA;  22931 MW;  EDD9D895BDA6F35A CRC64;
     MAFTEHSPLT PHRRDLCSRS IWLARKIRSD LTALTESYVK HQGLNKNINL DSADGMPVAS
     TDQWSELTEA ERLQENLQAY RTFHVLLARL LEDQQVHFTP TEGDFHQAIH TLLLQVAAFA
     YQIEELMILL EYKIPRNEAD GMPINVGDGG LFEKKLWGLK VLQELSQWTV RSIHDLRFIS
     SHQTGIPARG SHYIANNKKM
 
 
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