MANF_BOVIN
ID MANF_BOVIN Reviewed; 179 AA.
AC P80513; A6QPB9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 116.
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, ARP;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 22-60.
RC TISSUE=Kidney;
RX PubMed=8660651; DOI=10.1006/abbi.1996.0248;
RA Galat A., Gerbod M.C., Bouet F., Riviere S.;
RT "Proteins and their amino acid compositions: uniqueness, variability, and
RT applications.";
RL Arch. Biochem. Biophys. 330:229-237(1996).
RN [3]
RP PROTEIN SEQUENCE OF 22-31.
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).
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 (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; BC149246; AAI49247.1; -; mRNA.
DR PIR; S69268; S69268.
DR RefSeq; NP_001094681.1; NM_001101211.2.
DR AlphaFoldDB; P80513; -.
DR SMR; P80513; -.
DR STRING; 9913.ENSBTAP00000042500; -.
DR PaxDb; P80513; -.
DR PeptideAtlas; P80513; -.
DR PRIDE; P80513; -.
DR Ensembl; ENSBTAT00000045083; ENSBTAP00000042500; ENSBTAG00000031797.
DR GeneID; 540432; -.
DR KEGG; bta:540432; -.
DR CTD; 7873; -.
DR VEuPathDB; HostDB:ENSBTAG00000031797; -.
DR VGNC; VGNC:31171; MANF.
DR eggNOG; KOG4154; Eukaryota.
DR GeneTree; ENSGT00390000007160; -.
DR HOGENOM; CLU_099080_1_0_1; -.
DR InParanoid; P80513; -.
DR OMA; ECEVCVS; -.
DR OrthoDB; 1427430at2759; -.
DR TreeFam; TF314252; -.
DR Reactome; R-BTA-114608; Platelet degranulation.
DR Proteomes; UP000009136; Chromosome 22.
DR Bgee; ENSBTAG00000031797; Expressed in spermatocyte and 106 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
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:0000269|PubMed:17507765,
FT ECO:0000269|PubMed:8660651"
FT CHAIN 22..179
FT /note="Mesencephalic astrocyte-derived neurotrophic factor"
FT /id="PRO_0000221218"
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"
FT CONFLICT 27
FT /note="C -> T (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 179 AA; 20357 MW; 183F89FE5560A7FC CRC64;
MWATHGLAVA LALSVLPASR ALRQGDCEVC ISYLGRFYQD LKDRDVTFSP ASIEKELIKF
CREARGKENR LCYYIGATED AATKIINEVS KPLSHHIPVE KICEKLKKKD SQICELKYDK
QIDLSTVDLK KLRVKELKKI LDDWGETCKG CAEKSDYIRK INELMPKYAP KAASSRTDL
