ID   CDNF_HUMAN              Reviewed;         187 AA.
AC   Q49AH0; A2RUU0; B4DVW3;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 2.
DT   19-JAN-2010, entry version 30.
DE   RecName: Full=Cerebral dopamine neurotrophic factor;
DE   AltName: Full=Conserved dopamine neurotrophic factor;
DE   AltName: Full=ARMET-like protein 1;
DE   Flags: Precursor;
GN   Name=CDNF; Synonyms=ARMETL1;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Spleen;
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   [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Testis;
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   [4]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=17611540; DOI=10.1038/nature05957;
RA   Lindholm P., Voutilainen M.H., Lauren J., Peraenen J.,
RA   Leppaenen V.-M., Andressoo J.-O., Lindahl M., Janhunen S.,
RA   Kalkkinen N., Timmusk T., Tuominen R.K., Saarma M.;
RT   "Novel neurotrophic factor CDNF protects and rescues midbrain dopamine
RT   neurons in vivo.";
RL   Nature 448:73-77(2007).
RN   [5]
RP   SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=18561914; DOI=10.1016/j.yexcr.2008.05.001;
RA   Apostolou A., Shen Y., Liang Y., Luo J., Fang S.;
RT   "Armet, a UPR-upregulated protein, inhibits cell proliferation and ER
RT   stress-induced cell death.";
RL   Exp. Cell Res. 314:2454-2467(2008).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 32-133, AND DISULFIDE BONDS.
RX   PubMed=19258449; DOI=10.1093/protein/gzn080;
RA   Parkash V., Lindholm P., Peranen J., Kalkkinen N., Oksanen E.,
RA   Saarma M., Leppanen V.-M., Goldman A.;
RT   "The structure of the conserved neurotrophic factors MANF and CDNF
RT   explains why they are bifunctional.";
RL   Protein Eng. Des. Sel. 22:233-241(2009).
CC   -!- FUNCTION: Trophic factor for dopamine neurons. Prevents the 6-
CC       hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic
CC       neurons. When administered after 6-OHDA-lesioning, restores the
CC       dopaminergic function and prevents the degeneration of
CC       dopaminergic neurons in substantia nigra (By similarity).
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q49AH0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q49AH0-2; Sequence=VSP_023986;
CC         Note=No experimental confirmation available;
CC   -!- TISSUE SPECIFICITY: Widely expressed in neuronal and non-neuronal
CC       tissues. In the brain, highest levels in the optic nerve and
CC       corpus callosum.
CC   -!- INDUCTION: Not induced by endoplasmic reticulum (ER) stress.
CC   -!- SIMILARITY: Belongs to the ARMET family.
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DR   EMBL; AK301259; BAG62825.1; -; mRNA.
DR   EMBL; CH471072; EAW86264.1; -; Genomic_DNA.
DR   EMBL; BC037872; AAH37872.1; -; mRNA.
DR   EMBL; BC133042; AAI33043.1; -; mRNA.
DR   EMBL; BC133044; AAI33045.1; -; mRNA.
DR   IPI; IPI00646351; -.
DR   IPI; IPI00647956; -.
DR   RefSeq; NP_001025125.2; -.
DR   UniGene; Hs.559067; -.
DR   PDB; 2W50; X-ray; 1.60 A; A/B=32-133.
DR   PDBsum; 2W50; -.
DR   STRING; Q49AH0; -.
DR   PhosphoSite; Q49AH0; -.
DR   PRIDE; Q49AH0; -.
DR   Ensembl; ENST00000465530; ENSP00000419395; ENSG00000185267; Homo sapiens.
DR   GeneID; 441549; -.
DR   KEGG; hsa:441549; -.
DR   UCSC; uc001inb.1; human.
DR   UCSC; uc001inc.1; human.
DR   CTD; 441549; -.
DR   GeneCards; GC10M014866; -.
DR   HGNC; HGNC:24913; CDNF.
DR   MIM; 611233; gene.
DR   PharmGKB; PA134870440; -.
DR   eggNOG; prNOG08973; -.
DR   InParanoid; Q49AH0; -.
DR   OMA; GADCEVC; -.
DR   OrthoDB; EOG9CZF3T; -.
DR   PhylomeDB; Q49AH0; -.
DR   NextBio; 110303; -.
DR   ArrayExpress; Q49AH0; -.
DR   Bgee; Q49AH0; -.
DR   CleanEx; HS_ARMETL1; -.
DR   Genevestigator; Q49AH0; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   InterPro; IPR019345; Armet_prot.
DR   Pfam; PF10208; Armet; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Complete proteome; Disulfide bond;
KW   Growth factor; Secreted; Signal.
FT   SIGNAL        1     24       Potential.
FT   CHAIN        25    187       Cerebral dopamine neurotrophic factor.
FT                                /FTId=PRO_0000281137.
FT   DISULFID     37    124
FT   DISULFID     40    113
FT   DISULFID     71     82
FT   VAR_SEQ       1    102       Missing (in isoform 2).
FT                                /FTId=VSP_023986.
FT   HELIX        38     53
FT   HELIX        60     71
FT   HELIX        78     84
FT   HELIX        93    103
FT   TURN        104    106
FT   HELIX       109    117
FT   HELIX       121    124
SQ   SEQUENCE   187 AA;  20964 MW;  87460391592A10CA CRC64;
     MWCASPVAVV AFCAGLLVSH PVLTQGQEAG GRPGADCEVC KEFLNRFYKS LIDRGVNFSL
     DTIEKELISF CLDTKGKENR LCYYLGATKD AATKILSEVT RPMSVHMPAM KICEKLKKLD
     SQICELKYEK TLDLASVDLR KMRVAELKQI LHSWGEECRA CAEKTDYVNL IQELAPKYAA
     THPKTEL
//