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ARMET_DROME
ID   ARMET_DROME             Reviewed;         173 AA.
AC   Q9XZ63; Q9VEW4;
DT   24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2001, sequence version 2.
DT   03-AUG-2022, entry version 137.
DE   RecName: Full=Mesencephalic astrocyte-derived neurotrophic factor homolog;
DE            Short=DmMANF;
DE   AltName: Full=MANF/CDNF-like protein;
DE   Flags: Precursor;
GN   Name=Manf; Synonyms=ARP-like; ORFNames=CG7013;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Oregon-R;
RX   PubMed=10597048;
RA   Goo J.H., Ahn Y., Park O.K., Park W.J.;
RT   "Selection of Drosophila genes encoding secreted and membrane proteins.";
RL   Mol. Cells 9:564-568(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Embryo;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP   AND DISRUPTION PHENOTYPE.
RX   PubMed=19164766; DOI=10.1073/pnas.0810996106;
RA   Palgi M., Lindstrom R., Peranen J., Piepponen T.P., Saarma M., Heino T.I.;
RT   "Evidence that DmMANF is an invertebrate neurotrophic factor supporting
RT   dopaminergic neurons.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:2429-2434(2009).
CC   -!- FUNCTION: Required during the maturation of the embryonic nervous
CC       system for maintenance of neuronal and cuticular connectivity.
CC       Essential for maintenance of dopaminergic neurons and dopamine levels.
CC       {ECO:0000269|PubMed:19164766}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19164766}.
CC   -!- TISSUE SPECIFICITY: In stage 12, expression is seen in the stomodeum
CC       and the salivary gland primordia, and weakly in the mesoderm. From
CC       stage 13 onward, expression is in Garland cells, the outer wall of the
CC       proventriculus and salivary glands. Punctuate expression is also in the
CC       ventral nerve cord (VNC), specifically in eagle (eg)-positive cell body
CC       glia. Epidermal expression is seen at stage 15.
CC       {ECO:0000269|PubMed:19164766}.
CC   -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically through
CC       all developmental stages. {ECO:0000269|PubMed:19164766}.
CC   -!- DISRUPTION PHENOTYPE: Total loss of dopaminergic neurites and drastic
CC       reduction in dopamine levels followed by degeneration of axonal bundles
CC       in the embryonic central nervous system and subsequent nonapoptotic
CC       cell death. Also exhibits cuticular defects.
CC       {ECO:0000269|PubMed:19164766}.
CC   -!- SIMILARITY: Belongs to the ARMET family. {ECO:0000305}.
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DR   EMBL; AF132912; AAD32615.1; -; mRNA.
DR   EMBL; AE014297; AAF55303.1; -; Genomic_DNA.
DR   EMBL; AY061080; AAL28628.1; -; mRNA.
DR   RefSeq; NP_477445.1; NM_058097.6.
DR   AlphaFoldDB; Q9XZ63; -.
DR   SMR; Q9XZ63; -.
DR   BioGRID; 67028; 4.
DR   DIP; DIP-21713N; -.
DR   IntAct; Q9XZ63; 1.
DR   STRING; 7227.FBpp0082735; -.
DR   PaxDb; Q9XZ63; -.
DR   PRIDE; Q9XZ63; -.
DR   DNASU; 41983; -.
DR   EnsemblMetazoa; FBtr0083283; FBpp0082735; FBgn0027095.
DR   GeneID; 41983; -.
DR   KEGG; dme:Dmel_CG7013; -.
DR   UCSC; CG7013-RA; d. melanogaster.
DR   CTD; 7873; -.
DR   FlyBase; FBgn0027095; Manf.
DR   VEuPathDB; VectorBase:FBgn0027095; -.
DR   eggNOG; KOG4154; Eukaryota.
DR   GeneTree; ENSGT00390000007160; -.
DR   HOGENOM; CLU_099080_1_0_1; -.
DR   InParanoid; Q9XZ63; -.
DR   OMA; ECEVCVS; -.
DR   OrthoDB; 1427430at2759; -.
DR   PhylomeDB; Q9XZ63; -.
DR   Reactome; R-DME-114608; Platelet degranulation.
DR   BioGRID-ORCS; 41983; 0 hits in 3 CRISPR screens.
DR   ChiTaRS; Manf; fly.
DR   GenomeRNAi; 41983; -.
DR   PRO; PR:Q9XZ63; -.
DR   Proteomes; UP000000803; Chromosome 3R.
DR   Bgee; FBgn0027095; Expressed in male reproductive gland and 44 other tissues.
DR   Genevisible; Q9XZ63; DM.
DR   GO; GO:0012505; C:endomembrane system; HDA:FlyBase.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:FlyBase.
DR   GO; GO:0005576; C:extracellular region; IDA:FlyBase.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0042417; P:dopamine metabolic process; IMP:FlyBase.
DR   GO; GO:0071542; P:dopaminergic neuron differentiation; IBA:GO_Central.
DR   GO; GO:0070050; P:neuron cellular homeostasis; IMP:FlyBase.
DR   GO; GO:0031175; P:neuron projection development; IMP:FlyBase.
DR   GO; GO:0001963; P:synaptic transmission, dopaminergic; IMP:UniProtKB.
DR   Gene3D; 1.10.720.30; -; 1.
DR   InterPro; IPR045333; ARMET-like.
DR   InterPro; IPR019345; ARMET_C.
DR   InterPro; IPR045332; ARMET_N.
DR   InterPro; IPR018247; EF_Hand_1_Ca_BS.
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   2: Evidence at transcript level;
KW   Developmental protein; Disulfide bond; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..173
FT                   /note="Mesencephalic astrocyte-derived neurotrophic factor
FT                   homolog"
FT                   /id="PRO_0000002308"
FT   DISULFID        28..114
FT                   /evidence="ECO:0000250"
FT   DISULFID        31..103
FT                   /evidence="ECO:0000250"
FT   DISULFID        61..72
FT                   /evidence="ECO:0000250"
FT   DISULFID        148..151
FT                   /evidence="ECO:0000250"
FT   CONFLICT        74
FT                   /note="Missing (in Ref. 1; AAD32615)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   173 AA;  20136 MW;  E734A191F51F15D2 CRC64;
     MKTWYMVVVI GFLATLAQTS LALKEEDCEV CVKTVRRFAD SLDDSTKKDY KQIETAFKKF
     CKAQKNKEHR FCYYLGGLEE SATGILNELS KPLSWSMPAE KICEKLKKKD AQICDLRYEK
     QIDLNSVDLK KLKVRDLKKI LNDWDESCDG CLEKGDFIKR IEELKPKYSR SEL
 
 
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