Search Results

Overview

Uniprot IDP0C5H9
Protein NameMesencephalic astrocyte-derived neurotrophic factor
Gene NameManf
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
120 ICELKYDKQIDLSTV
154 MCKGCAEKSDYIRKI
42 GRFYQDLKDRDVTFS
91 KIINEVSKPLAHHIP

Function

Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (By similarity). Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (PubMed:16462600). Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (PubMed:16462600). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death (By similarity). Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (By similarity). 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 (By similarity). Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (By similarity). 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 (By similarity). 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 MWATRGLAVA 20 LALSVLPDSR 30 ALRPGDCEVC 40 ISYLGRFYQD 50 LKDRDVTFSP 60 ATIEEELIKF 70 CREARGKENR 80 LCYYIGATDD 90 AATKIINEVS 100 KPLAHHIPVE 110 KICEKLKKKD 120 SQICELKYDK 130 QIDLSTVDLK 140 KLRVKELKKI 150 LDDWGEMCKG 160 CAEKSDYIRK 170 INELMPKYAP KAASARTDL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0005788 endoplasmic reticulum lumen
Cellular Component GO:0005615 extracellular space
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0033018 sarcoplasmic reticulum lumen
Molecular Function GO:0008083 growth factor activity
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
Biological Process GO:0002014 vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.