MANF_MOUSE
ID MANF_MOUSE Reviewed; 179 AA.
AC Q9CXI5;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 117.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=17507765; DOI=10.1247/csf.07001;
RA Mizobuchi N., Hoseki J., Kubota H., Toyokuni S., Nozaki J., Naitoh M.,
RA Koizumi A., Nagata K.;
RT "ARMET is a soluble ER protein induced by the unfolded protein response via
RT ERSE-II element.";
RL Cell Struct. Funct. 32:41-50(2007).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-73, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP STRUCTURE BY NMR OF 22-179, AND DISULFIDE BONDS.
RX PubMed=20214902; DOI=10.1016/j.febslet.2010.03.008;
RA Hoseki J., Sasakawa H., Yamaguchi Y., Maeda M., Kubota H., Kato K.,
RA Nagata K.;
RT "Solution structure and dynamics of mouse ARMET.";
RL FEBS Lett. 584:1536-1542(2010).
RN [6]
RP IDENTIFICATION IN COMPLEX WITH CRELD2; MATN3 AND PDIA4, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=23956175; DOI=10.1093/hmg/ddt383;
RA Hartley C.L., Edwards S., Mullan L., Bell P.A., Fresquet M.,
RA Boot-Handford R.P., Briggs M.D.;
RT "Armet/Manf and Creld2 are components of a specialized ER stress response
RT provoked by inappropriate formation of disulphide bonds: implications for
RT genetic skeletal diseases.";
RL Hum. Mol. Genet. 22:5262-5275(2013).
CC -!- FUNCTION: Selectively promotes the survival of dopaminergic neurons of
CC the ventral mid-brain. Modulates GABAergic transmission to the
CC dopaminergic neurons of the substantia nigra. Enhances spontaneous, as
CC well as evoked, GABAergic inhibitory postsynaptic currents in
CC dopaminergic neurons. Inhibits cell proliferation and endoplasmic
CC reticulum (ER) stress-induced cell death. Retained in the
CC ER/sarcoplasmic reticulum (SR) through association with the endoplasmic
CC reticulum chaperone protein HSPA5 under normal conditions. Up-regulated
CC and secreted by the ER/SR in response to ER stress and hypoxia.
CC Following secretion by the ER/SR, directly binds to 3-O-
CC sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane
CC of target cells. Sulfatide binding promotes its cellular uptake by
CC endocytosis, and is required for its role in alleviating ER stress and
CC cell toxicity under hypoxic and ER stress conditions.
CC {ECO:0000250|UniProtKB:P0C5H9, ECO:0000250|UniProtKB:P55145}.
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 (PubMed:23956175). {ECO:0000250|UniProtKB:P55145,
CC ECO:0000269|PubMed:23956175}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17507765,
CC ECO:0000269|PubMed:23956175}. Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:23956175}. Sarcoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:P55145}. Note=Retained in the endoplasmic
CC reticulum (ER), and sarcoplasmic reticulum (SR) under normal
CC conditions. Up-regulated and secreted by the ER/SR in response to ER
CC stress and hypoxia. {ECO:0000250|UniProtKB:P55145}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in pancreatic islets and
CC spermatocytes (at protein level). Expressed in chondrocytes (at protein
CC level) (PubMed:23956175). {ECO:0000269|PubMed:17507765,
CC ECO:0000269|PubMed:23956175}.
CC -!- DEVELOPMENTAL STAGE: Expressed from birth.
CC {ECO:0000269|PubMed:23956175}.
CC -!- INDUCTION: By endoplasmic reticulum (ER) stress.
CC {ECO:0000269|PubMed:17507765}.
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; AK014338; BAB29281.1; -; mRNA.
DR PDB; 2RQY; NMR; -; A=22-179.
DR PDB; 6H9U; X-ray; 1.57 A; B=126-169.
DR PDB; 6HA7; X-ray; 2.49 A; C/D=22-179.
DR PDBsum; 2RQY; -.
DR PDBsum; 6H9U; -.
DR PDBsum; 6HA7; -.
DR AlphaFoldDB; Q9CXI5; -.
DR SMR; Q9CXI5; -.
DR STRING; 10090.ENSMUSP00000124562; -.
DR iPTMnet; Q9CXI5; -.
DR PhosphoSitePlus; Q9CXI5; -.
DR EPD; Q9CXI5; -.
DR jPOST; Q9CXI5; -.
DR MaxQB; Q9CXI5; -.
DR PaxDb; Q9CXI5; -.
DR PeptideAtlas; Q9CXI5; -.
DR PRIDE; Q9CXI5; -.
DR ProteomicsDB; 292015; -.
DR TopDownProteomics; Q9CXI5; -.
DR MGI; MGI:1922090; Manf.
DR eggNOG; KOG4154; Eukaryota.
DR InParanoid; Q9CXI5; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR ChiTaRS; Manf; mouse.
DR EvolutionaryTrace; Q9CXI5; -.
DR PRO; PR:Q9CXI5; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9CXI5; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
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:MGI.
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:MGI.
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; IDA:MGI.
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; Disulfide bond; Endoplasmic reticulum; Growth factor;
KW Lipid-binding; Phosphoprotein; Reference proteome; Sarcoplasmic reticulum;
KW Secreted; Signal; Stress response; 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_0000002306"
FT MOD_RES 73
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT DISULFID 27..114
FT /evidence="ECO:0000269|PubMed:20214902"
FT DISULFID 30..103
FT /evidence="ECO:0000269|PubMed:20214902"
FT DISULFID 61..72
FT /evidence="ECO:0000269|PubMed:20214902"
FT DISULFID 148..151
FT /evidence="ECO:0000269|PubMed:20214902"
FT TURN 24..27
FT /evidence="ECO:0007829|PDB:6HA7"
FT HELIX 28..43
FT /evidence="ECO:0007829|PDB:6HA7"
FT HELIX 50..62
FT /evidence="ECO:0007829|PDB:6HA7"
FT HELIX 67..74
FT /evidence="ECO:0007829|PDB:6HA7"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:2RQY"
FT HELIX 87..94
FT /evidence="ECO:0007829|PDB:6HA7"
FT HELIX 99..109
FT /evidence="ECO:0007829|PDB:6HA7"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:6HA7"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:6HA7"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:6HA7"
FT HELIX 134..143
FT /evidence="ECO:0007829|PDB:6H9U"
FT HELIX 154..164
FT /evidence="ECO:0007829|PDB:6H9U"
FT HELIX 165..168
FT /evidence="ECO:0007829|PDB:2RQY"
FT HELIX 170..175
FT /evidence="ECO:0007829|PDB:6HA7"
SQ SEQUENCE 179 AA; 20374 MW; E5BCEE8C033C1530 CRC64;
MWATRGLAVA LALSVLPDSR ALRPGDCEVC ISYLGRFYQD LKDRDVTFSP ATIEEELIKF
CREARGKENR LCYYIGATDD AATKIINEVS KPLAHHIPVE KICEKLKKKD SQICELKYDN
QIDLSTVDLK KLRVKELKKI LDDWGEMCKG CAEKSDYIRK INELMPKYAP KAASARTDL
