Overview
| Uniprot ID | P55145 |
| Protein Name | Mesencephalic astrocyte-derived neurotrophic factor |
| Gene Name | MANF |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 120 |
DSQICELKYDKQIDL |
| 123 |
ICELKYDKQIDLSTV |
| 157 |
TCKGCAEKSDYIRKI |
Function
Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (PubMed:12794311). Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (By similarity). Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (By similarity). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death (PubMed:18561914, PubMed:22637475, PubMed:29497057, PubMed:36739529). Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (PubMed:22637475). 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 (By similarity). As a result acts as a repressor of the unfolded protein response (UPR) pathway (By similarity). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PubMed:22637475). Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (PubMed:29497057). 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 (PubMed:29497057). Essential for embryonic lung development (By similarity). Required for the correct postnatal temporal and structural development of splenic white pulp (By similarity). 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 (By similarity). 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 (By similarity). Required for endochondral ossification in long bones and the skull during postnatal development (By similarity)
Protein Sequence
10
MRRMWATQGL
20
AVALALSVLP
30
GSRALRPGDC
40
EVCISYLGRF
50
YQDLKDRDVT
60
FSPATIENEL
70
IKFCREARGK
80
ENRLCYYIGA
90
TDDAATKIIN
100
EVSKPLAHHI
110
PVEKICEKLK
120
KKDSQICELK
130
YDKQIDLSTV
140
DLKKLRVKEL
150
KKILDDWGET
160
CKGCAEKSDY
170
IRKINELMPK
180
YAPKAASART
DL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005783 |
endoplasmic reticulum |
| Cellular Component |
GO:0005788 |
endoplasmic reticulum lumen |
| Cellular Component |
GO:0005576 |
extracellular region |
| Cellular Component |
GO:0005615 |
extracellular space |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0033018 |
sarcoplasmic reticulum lumen |
| Molecular Function |
GO:0008083 |
growth factor activity |
| Molecular Function |
GO:0003723 |
RNA binding |
| Molecular Function |
GO:0120146 |
sulfatide binding |
| Biological Process |
GO:0036500 |
ATF6-mediated unfolded protein response |
| Biological Process |
GO:0071542 |
dopaminergic neuron differentiation |
| Biological Process |
GO:0031175 |
neuron projection development |
| Biological Process |
GO:1905897 |
regulation of response to endoplasmic reticulum stress |
Reference
[1] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.