CDNF_HUMAN
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 03-AUG-2022, entry version 112.
DE RecName: Full=Cerebral dopamine neurotrophic factor;
DE AltName: Full=ARMET-like protein 1;
DE AltName: Full=Conserved dopamine neurotrophic factor;
DE Flags: Precursor;
GN Name=CDNF; Synonyms=ARMETL1;
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 [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., 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 [2]
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 (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 project:
RT 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., Leppaenen V.-M.,
RA Andressoo J.-O., Lindahl M., Janhunen S., Kalkkinen N., Timmusk T.,
RA 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., Saarma M.,
RA Leppanen V.-M., Goldman A.;
RT "The structure of the conserved neurotrophic factors MANF and CDNF explains
RT 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 neurons.
CC When administered after 6-OHDA-lesioning, restores the dopaminergic
CC function and prevents the degeneration of dopaminergic neurons in
CC substantia nigra (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17611540,
CC ECO:0000269|PubMed:18561914}.
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 -!- TISSUE SPECIFICITY: Widely expressed in neuronal and non-neuronal
CC tissues. In the brain, highest levels in the optic nerve and corpus
CC callosum. {ECO:0000269|PubMed:17611540}.
CC -!- INDUCTION: Not induced by endoplasmic reticulum stress.
CC {ECO:0000269|PubMed:18561914}.
CC -!- SIMILARITY: Belongs to the ARMET family. {ECO:0000305}.
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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 CCDS; CCDS31148.1; -. [Q49AH0-1]
DR RefSeq; NP_001025125.2; NM_001029954.2. [Q49AH0-1]
DR PDB; 2LPN; NMR; -; A=27-131.
DR PDB; 2W50; X-ray; 1.60 A; A/B=32-133.
DR PDB; 4BIT; NMR; -; A=27-187.
DR PDBsum; 2LPN; -.
DR PDBsum; 2W50; -.
DR PDBsum; 4BIT; -.
DR AlphaFoldDB; Q49AH0; -.
DR BMRB; Q49AH0; -.
DR SMR; Q49AH0; -.
DR BioGRID; 137570; 5.
DR IntAct; Q49AH0; 1.
DR STRING; 9606.ENSP00000419395; -.
DR iPTMnet; Q49AH0; -.
DR PhosphoSitePlus; Q49AH0; -.
DR BioMuta; CDNF; -.
DR DMDM; 143955278; -.
DR jPOST; Q49AH0; -.
DR MassIVE; Q49AH0; -.
DR PaxDb; Q49AH0; -.
DR PeptideAtlas; Q49AH0; -.
DR PRIDE; Q49AH0; -.
DR ProteomicsDB; 62043; -. [Q49AH0-1]
DR ProteomicsDB; 62044; -. [Q49AH0-2]
DR Antibodypedia; 24933; 296 antibodies from 32 providers.
DR DNASU; 441549; -.
DR Ensembl; ENST00000378442.5; ENSP00000367703.1; ENSG00000185267.10. [Q49AH0-2]
DR Ensembl; ENST00000465530.2; ENSP00000419395.1; ENSG00000185267.10. [Q49AH0-1]
DR GeneID; 441549; -.
DR KEGG; hsa:441549; -.
DR MANE-Select; ENST00000465530.2; ENSP00000419395.1; NM_001029954.3; NP_001025125.2.
DR UCSC; uc001inb.2; human. [Q49AH0-1]
DR CTD; 441549; -.
DR DisGeNET; 441549; -.
DR GeneCards; CDNF; -.
DR HGNC; HGNC:24913; CDNF.
DR HPA; ENSG00000185267; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 611233; gene.
DR neXtProt; NX_Q49AH0; -.
DR OpenTargets; ENSG00000185267; -.
DR PharmGKB; PA165548325; -.
DR VEuPathDB; HostDB:ENSG00000185267; -.
DR eggNOG; KOG4154; Eukaryota.
DR GeneTree; ENSGT00390000007160; -.
DR HOGENOM; CLU_2624470_0_0_1; -.
DR InParanoid; Q49AH0; -.
DR OMA; ARPMSVH; -.
DR OrthoDB; 1427430at2759; -.
DR PhylomeDB; Q49AH0; -.
DR TreeFam; TF314252; -.
DR PathwayCommons; Q49AH0; -.
DR SignaLink; Q49AH0; -.
DR BioGRID-ORCS; 441549; 5 hits in 1029 CRISPR screens.
DR EvolutionaryTrace; Q49AH0; -.
DR GeneWiki; Cerebral_dopamine_neurotrophic_factor; -.
DR GenomeRNAi; 441549; -.
DR Pharos; Q49AH0; Tbio.
DR PRO; PR:Q49AH0; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q49AH0; protein.
DR Bgee; ENSG00000185267; Expressed in hindlimb stylopod muscle and 107 other tissues.
DR Genevisible; Q49AH0; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IBA:GO_Central.
DR GO; GO:0031175; P:neuron projection development; IBA:GO_Central.
DR Gene3D; 1.10.720.30; -; 1.
DR InterPro; IPR045333; ARMET-like.
DR InterPro; IPR019345; ARMET_C.
DR InterPro; IPR045332; ARMET_N.
DR InterPro; IPR036361; SAP_dom_sf.
DR PANTHER; PTHR12990; PTHR12990; 1.
DR Pfam; PF10208; ARMET_C; 1.
DR Pfam; PF20145; ARMET_N; 1.
DR SUPFAM; SSF68906; SSF68906; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disulfide bond; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..187
FT /note="Cerebral dopamine neurotrophic factor"
FT /id="PRO_0000281137"
FT DISULFID 37..124
FT /evidence="ECO:0000269|PubMed:19258449"
FT DISULFID 40..113
FT /evidence="ECO:0000269|PubMed:19258449"
FT DISULFID 71..82
FT /evidence="ECO:0000269|PubMed:19258449"
FT VAR_SEQ 1..102
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023986"
FT HELIX 38..53
FT /evidence="ECO:0007829|PDB:2W50"
FT HELIX 60..71
FT /evidence="ECO:0007829|PDB:2W50"
FT HELIX 76..84
FT /evidence="ECO:0007829|PDB:2W50"
FT HELIX 93..103
FT /evidence="ECO:0007829|PDB:2W50"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:2W50"
FT HELIX 109..117
FT /evidence="ECO:0007829|PDB:2W50"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:2W50"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:4BIT"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:4BIT"
FT HELIX 144..153
FT /evidence="ECO:0007829|PDB:4BIT"
FT HELIX 164..178
FT /evidence="ECO:0007829|PDB:4BIT"
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
