MANF_RAT
ID MANF_RAT Reviewed; 179 AA.
AC P0C5H9;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Mesencephalic astrocyte-derived neurotrophic factor;
DE AltName: Full=Arginine-rich protein;
DE AltName: Full=Protein ARMET;
DE Flags: Precursor;
GN Name=Manf; Synonyms=Armet;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP PROTEIN SEQUENCE OF 45-54 AND 121-129, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=12794311; DOI=10.1385/jmn:20:2:173;
RA Petrova P., Raibekas A., Pevsner J., Vigo N., Anafi M., Moore M.K.,
RA Peaire A.E., Shridhar V., Smith D.I., Kelly J., Durocher Y.,
RA Commissiong J.W.;
RT "MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with
RT selectivity for dopaminergic neurons.";
RL J. Mol. Neurosci. 20:173-188(2003).
RN [3]
RP FUNCTION.
RX PubMed=16462600; DOI=10.1097/01.wnr.0000201504.23255.bc;
RA Zhou C., Xiao C., Commissiong J.W., Krnjevic K., Ye J.H.;
RT "Mesencephalic astrocyte-derived neurotrophic factor enhances nigral gamma-
RT aminobutyric acid release.";
RL NeuroReport 17:293-297(2006).
CC -!- FUNCTION: Selectively promotes the survival of dopaminergic neurons of
CC the ventral mid-brain (By similarity). Modulates GABAergic transmission
CC to the dopaminergic neurons of the substantia nigra (PubMed:16462600).
CC Enhances spontaneous, as well as evoked, GABAergic inhibitory
CC postsynaptic currents in dopaminergic neurons (PubMed:16462600).
CC Inhibits cell proliferation and endoplasmic reticulum (ER) stress-
CC induced cell death (By similarity). Retained in the ER/sarcoplasmic
CC reticulum (SR) through association with the endoplasmic reticulum
CC chaperone protein HSPA5 under normal conditions (By similarity). Up-
CC regulated and secreted by the ER/SR in response to ER stress and
CC hypoxia (By similarity). Following secretion by the ER/SR, directly
CC binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer
CC cell membrane of target cells (By similarity). Sulfatide binding
CC promotes its cellular uptake by endocytosis, and is required for its
CC role in alleviating ER stress and cell toxicity under hypoxic and ER
CC stress conditions (By similarity). {ECO:0000250|UniProtKB:P55145,
CC ECO:0000269|PubMed:16462600}.
CC -!- SUBUNIT: Interacts with HSPA5; the interaction is direct (By
CC similarity). Component of a complex containing at least CRELD2, MANF,
CC MATN3 and PDIA4 (By similarity). {ECO:0000250|UniProtKB:P55145,
CC ECO:0000250|UniProtKB:Q9CXI5}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P55145}.
CC Endoplasmic reticulum lumen {ECO:0000250|UniProtKB:P55145}.
CC Sarcoplasmic reticulum lumen {ECO:0000250|UniProtKB:P55145}.
CC Note=Retained in the endoplasmic reticulum (ER), and sarcoplasmic
CC reticulum (SR) under normal conditions. Up-regulated and secreted by
CC the ER/SR in response to ER stress and hypoxia.
CC {ECO:0000250|UniProtKB:P55145}.
CC -!- DOMAIN: The N-terminal region may be responsible for neurotrophic
CC activity while the C-terminal region may play a role in the ER stress
CC response. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ARMET family. {ECO:0000305}.
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DR EMBL; AABR03063460; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_006243837.1; XM_006243775.2.
DR AlphaFoldDB; P0C5H9; -.
DR SMR; P0C5H9; -.
DR BioGRID; 261211; 1.
DR IntAct; P0C5H9; 1.
DR STRING; 10116.ENSRNOP00000019107; -.
DR iPTMnet; P0C5H9; -.
DR PhosphoSitePlus; P0C5H9; -.
DR jPOST; P0C5H9; -.
DR PaxDb; P0C5H9; -.
DR PRIDE; P0C5H9; -.
DR GeneID; 315989; -.
DR UCSC; RGD:1307252; rat.
DR CTD; 7873; -.
DR RGD; 1307252; Manf.
DR VEuPathDB; HostDB:ENSRNOG00000014201; -.
DR eggNOG; KOG4154; Eukaryota.
DR HOGENOM; CLU_099080_1_0_1; -.
DR InParanoid; P0C5H9; -.
DR OMA; ECEVCVS; -.
DR OrthoDB; 1427430at2759; -.
DR PhylomeDB; P0C5H9; -.
DR TreeFam; TF314252; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR PRO; PR:P0C5H9; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000014201; Expressed in pancreas and 20 other tissues.
DR ExpressionAtlas; P0C5H9; baseline and differential.
DR Genevisible; P0C5H9; RN.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0120146; F:sulfatide binding; ISO:RGD.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IBA:GO_Central.
DR GO; GO:0031175; P:neuron projection development; IBA:GO_Central.
DR GO; GO:1905897; P:regulation of response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0002014; P:vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure; ISO:RGD.
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 Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW Growth factor; Lipid-binding; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Secreted; Signal; Stress response;
KW Unfolded protein response.
FT SIGNAL 1..21
FT /evidence="ECO:0000250"
FT CHAIN 22..179
FT /note="Mesencephalic astrocyte-derived neurotrophic factor"
FT /id="PRO_0000306859"
FT MOD_RES 73
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9CXI5"
FT DISULFID 27..114
FT /evidence="ECO:0000250"
FT DISULFID 30..103
FT /evidence="ECO:0000250"
FT DISULFID 61..72
FT /evidence="ECO:0000250"
FT DISULFID 148..151
FT /evidence="ECO:0000250"
SQ SEQUENCE 179 AA; 20388 MW; E5BCEE89063C1035 CRC64;
MWATRGLAVA LALSVLPDSR ALRPGDCEVC ISYLGRFYQD LKDRDVTFSP ATIEEELIKF
CREARGKENR LCYYIGATDD AATKIINEVS KPLAHHIPVE KICEKLKKKD SQICELKYDK
QIDLSTVDLK KLRVKELKKI LDDWGEMCKG CAEKSDYIRK INELMPKYAP KAASARTDL
