Manf
entrez
74840
canonical
uniprot
Q9CXI5
canonical
ensembl
ENSMUSG00000032575
resolver
ensp
ENSMUSP00000124562
resolver
enst
ENSMUST00000159283
resolver
genesymbol
Manf
resolver
genesymbol_syn
Armet
resolver
uniprot
Q3TMX5
resolver
uniprot_entry
MANF_MOUSE
resolver
uniprot_sec
Q3TMX5
resolver
amino_acid_sequence
MWATRGLAVALALSVLPDSRALRPGDCEVCISYLGRFYQDLKDRDVTFSPATIEEELIKFCREARGKENRLCYYIGATDDAATKIINEVSKPLAHHIPVEKICEKLKKKDSQICELKYDKQIDLSTVDLKKLRVKELKKILDDWGEMCKGCAEKSDYIRKINELMPKYAPKAASARTDL
uniprot
proteins
function
FUNCTION: Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra. Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons. Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death. Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions. Stabilizes HSPA5/BiP in its substrate-bound ADP state, which facilitates HSPA5/BiP incorporation into chaperone-client complexes during endoplasmic reticulum stress, its interaction with HSPA5/BiP inhibits ATP binding to HSPA5/BiP and subsequent nucleotide exchange (PubMed:30710085). As a result acts as a repressor of the unfolded protein response (UPR) pathway (PubMed:30710085). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia. Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells. Sulfatide binding promotes its cellular uptake by endocytosis, and is required for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions. Essential for embryonic lung development (PubMed:30543055). Required for the correct postnatal temporal and structural development of splenic white pulp (PubMed:38159526). Required for the repair-associated myeloid response in skeletal muscle, acts as a regulator of phenotypic transition towards prorepair macrophages in response to muscle injury and as a result limits excessive proinflammatory signaling (PubMed:37118549). Represses RELA expression and therefore NF-kB signaling in the myocardium, as a result limits macrophage infiltration of injured tissue and M1 macrophage differentiation in response to myocardial injury (PubMed:33939070). Required for endochondral ossification in long bones and the skull during postnatal development (PubMed:30543055). {ECO:0000250|UniProtKB:P0C5H9, ECO:0000250|UniProtKB:P55145, ECO:0000269|PubMed:30543055, ECO:0000269|PubMed:30710085, ECO:0000269|PubMed:33939070, ECO:0000269|PubMed:37118549, ECO:0000269|PubMed:38159526}.
uniprot
proteins
mass_dalton
20388
uniprot
proteins
mutagenesis
MUTAGEN 133; /note="R->E: Abolishes inhibition of HSPA5 ATP nucleotide exchange."; /evidence="ECO:0000269|PubMed:30710085"; MUTAGEN 153; /note="E->A: Abolishes inhibition of HSPA5 ATP nucleotide exchange."; /evidence="ECO:0000269|PubMed:30710085
uniprot
proteins
protein_family
ARMET family
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17507765
uniprot
proteins
pubmed
18034455
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20214902
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23956175
uniprot
proteins
pubmed
30543055
uniprot
proteins
pubmed
30710085
uniprot
proteins
pubmed
33939070
uniprot
proteins
pubmed
36739529
uniprot
proteins
pubmed
37118549
uniprot
proteins
pubmed
38159526
uniprot
proteins
sequence_length
179
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17507765, ECO:0000269|PubMed:23956175, ECO:0000269|PubMed:30710085}. Endoplasmic reticulum lumen {ECO:0000269|PubMed:23956175, ECO:0000269|PubMed:36739529}. Sarcoplasmic reticulum lumen {ECO:0000250|UniProtKB:P55145}. Note=Retained in the endoplasmic reticulum (ER), and sarcoplasmic reticulum (SR) under normal conditions. Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia. {ECO:0000250|UniProtKB:P55145}.
uniprot
proteins