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   25-JAN-2012, entry version 126.
DE   RecName: Full=Ciliary neurotrophic factor;
DE            Short=CNTF;
GN   Name=CNTF;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=91318259; PubMed=1861138;
RX   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   MEDLINE=92007888; PubMed=1915374;
RX   DOI=10.1111/j.1432-1033.1991.tb16286.x;
RA   Negro A., Tolosano E., Skaper S., Martini I., Callegaro L.,
RA   Silengo L., 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   MEDLINE=91340164; PubMed=1840538; DOI=10.1016/0378-1119(91)90089-T;
RA   Lam A., Fuller F., Miller J., Kloss J., Manthorpe M., Varon M.,
RA   Cordell B.;
RT   "Sequence and structural organization of the human gene encoding
RT   ciliary neurotrophic factor.";
RL   Gene 102:271-276(1991).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=91355232; 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
RT   neurotrophic 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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   MEDLINE=95317288; PubMed=7796798;
RA   McDonald N.Q., Panayotatos N., Hendrickson W.A.;
RT   "Crystal structure of dimeric human ciliary neurotrophic factor
RT   determined by MAD phasing.";
RL   EMBO J. 14:2689-2699(1995).
RN   [10]
RP   VARIANT ARG-182.
RX   MEDLINE=99318093; 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
RT   of human genes.";
RL   Nat. Genet. 22:231-238(1999).
RN   [11]
RP   ERRATUM.
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
CC       types. Seems to prevent the degeneration of motor axons after
CC       axotomy.
CC   -!- SUBUNIT: Homodimer.
CC   -!- INTERACTION:
CC       P60228:EIF3E; NbExp=1; IntAct=EBI-1050897, EBI-347740;
CC       Q16394:EXT1; NbExp=1; IntAct=EBI-1050897, EBI-1046007;
CC       Q93063:EXT2; NbExp=1; IntAct=EBI-1050897, EBI-1047761;
CC       Q05084:ICA1; NbExp=1; IntAct=EBI-1050897, EBI-1046751;
CC       O75716:STK16; NbExp=1; IntAct=EBI-1050897, EBI-749295;
CC       P40337:VHL; NbExp=1; IntAct=EBI-1050897, EBI-301246;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- TISSUE SPECIFICITY: Nervous system.
CC   -!- SIMILARITY: Belongs to the CNTF family.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Ciliary neurotrophic factor
CC       entry;
CC       URL="http://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   IPI; IPI00032298; -.
DR   PIR; JH0455; UNHUCF.
DR   RefSeq; NP_000605.1; NM_000614.3.
DR   UniGene; Hs.524920; -.
DR   PDB; 1CNT; X-ray; 2.40 A; 1/2/3/4=1-187.
DR   PDBsum; 1CNT; -.
DR   ProteinModelPortal; P26441; -.
DR   SMR; P26441; 11-187.
DR   DIP; DIP-5776N; -.
DR   MINT; MINT-205057; -.
DR   STRING; P26441; -.
DR   PhosphoSite; P26441; -.
DR   DMDM; 116585; -.
DR   PRIDE; P26441; -.
DR   Ensembl; ENST00000361987; ENSP00000355370; ENSG00000242689.
DR   GeneID; 1270; -.
DR   KEGG; hsa:1270; -.
DR   UCSC; uc001nna.2; human.
DR   CTD; 1270; -.
DR   GeneCards; GC11P058390; -.
DR   H-InvDB; HIX0009648; -.
DR   HGNC; HGNC:2169; CNTF.
DR   HPA; HPA019654; -.
DR   MIM; 118945; gene.
DR   neXtProt; NX_P26441; -.
DR   PharmGKB; PA26683; -.
DR   eggNOG; prNOG19298; -.
DR   GeneTree; ENSGT00420000029890; -.
DR   HOVERGEN; HBG005362; -.
DR   OrthoDB; EOG4M65JM; -.
DR   NextBio; 5143; -.
DR   ArrayExpress; P26441; -.
DR   CleanEx; HS_CNTF; -.
DR   Genevestigator; P26441; -.
DR   GermOnline; ENSG00000205003; Homo sapiens.
DR   GO; GO:0005615; C:extracellular space; IC:BHF-UCL.
DR   GO; GO:0005127; F:ciliary neurotrophic factor receptor binding; TAS:ProtInc.
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:0070120; P:ciliary neurotrophic factor-mediated signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0040007; P:growth; IEA:InterPro.
DR   GO; GO:0043524; P:negative regulation of neuron apoptosis; IDA:BHF-UCL.
DR   GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IDA:BHF-UCL.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR012351; 4_helix_cytokine_core.
DR   InterPro; IPR000151; Ciliary_neurotrophic_fac_CNTF.
DR   Gene3D; G3DSA:1.20.1250.10; 4_helix_cytokine_core; 1.
DR   KO; K05420; -.
DR   Pfam; PF01110; CNTF; 1.
DR   SUPFAM; SSF47266; 4_helix_cytokine; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Complete proteome; Cytoplasm; Developmental protein;
KW   Differentiation; Growth factor; Neurogenesis; Polymorphism;
KW   Reference proteome.
FT   CHAIN         1    200       Ciliary neurotrophic factor.
FT                                /FTId=PRO_0000149519.
FT   VARIANT      49     49       N -> S (in dbSNP:rs17152779).
FT                                /FTId=VAR_033777.
FT   VARIANT     182    182       H -> R (in dbSNP:rs6266).
FT                                /FTId=VAR_013924.
FT   HELIX        13     41
FT   HELIX        69     95
FT   TURN         96     98
FT   STRAND       99    101
FT   HELIX       104    129
FT   STRAND      138    140
FT   HELIX       152    180
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
//