MANF
entrez
7873
canonical
uniprot
P55145
canonical
ensembl
ENSG00000145050
resolver
ensp
ENSP00000432799
resolver
enst
ENST00000528157
resolver
genesymbol
MANF
resolver
genesymbol_syn
ARMET
resolver
genesymbol_syn
ARP
resolver
hgnc
HGNC:15461
resolver
uniprot
A8K878
resolver
uniprot
Q14CX4
resolver
uniprot
Q86U67
resolver
uniprot
Q96IS4
resolver
uniprot_entry
A8K878_HUMAN
resolver
uniprot_entry
MANF_HUMAN
resolver
uniprot_sec
Q14CX4
resolver
uniprot_sec
Q86U67
resolver
uniprot_sec
Q96IS4
resolver
amino_acid_sequence
MRRMWATQGLAVALALSVLPGSRALRPGDCEVCISYLGRFYQDLKDRDVTFSPATIENELIKFCREARGKENRLCYYIGATDDAATKIINEVSKPLAHHIPVEKICEKLKKKDSQICELKYDKQIDLSTVDLKKLRVKELKKILDDWGETCKGCAEKSDYIRKINELMPKYAPKAASARTDL
uniprot
proteins
disease_involvement
DISEASE: Diabetes, deafness, developmental delay, and short stature syndrome (DDDS) [MIM:620651]: An autosomal recessive, multisystem disorder characterized by childhood-onset non-autoimmune diabetes mellitus, short stature, bilateral sensorineural deafness, developmental delay, mildly impaired intellectual development, and microcephaly. {ECO:0000269|PubMed:26077850, ECO:0000269|PubMed:33500254}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:P0C5H9, ECO:0000250|UniProtKB:Q9CXI5, ECO:0000269|PubMed:12794311, ECO:0000269|PubMed:18561914, ECO:0000269|PubMed:22637475, ECO:0000269|PubMed:29497057, ECO:0000269|PubMed:36739529}.
uniprot
proteins
mass_dalton
20700
uniprot
proteins
mutagenesis
MUTAGEN 112; /note="K->L: Reduced sulfatide binding and uptake by target cells. Reduces cytoprotective effect of the wild-type protein. Attenuates stress granule formation in response to endoplasmic reticulum stress."; /evidence="ECO:0000269|PubMed:29497057"; MUTAGEN 179..182; /note="Missing: Two-fold increase in secretion."; /evidence="ECO:0000269|PubMed:22637475"; MUTAGEN 179; /note="R->K: 14-fold decrease in secretion."; /evidence="ECO:0000269|PubMed:22637475
uniprot
proteins
post_translational_modification
PTM: May contain sialic acid residues.
uniprot
proteins
protein_family
ARMET family
uniprot
proteins
pubmed
12665801
uniprot
proteins
pubmed
12794311
uniprot
proteins
pubmed
15144186
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
18561914
uniprot
proteins
pubmed
19258449
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22637475
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26077850
uniprot
proteins
pubmed
29497057
uniprot
proteins
pubmed
33500254
uniprot
proteins
pubmed
36739529
uniprot
proteins
pubmed
8649854
uniprot
proteins
pubmed
8971156
uniprot
proteins
pubmed
9174057
uniprot
proteins
sequence_length
182
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12794311, ECO:0000269|PubMed:18561914, ECO:0000269|PubMed:22637475, ECO:0000269|PubMed:29497057}. Endoplasmic reticulum lumen {ECO:0000305|PubMed:29497057}. Sarcoplasmic reticulum lumen {ECO:0000269|PubMed:22637475}. Note=Retained in the endoplasmic reticulum (ER), and sarcoplasmic reticulum (SR) under normal conditions (PubMed:22637475). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PubMed:22637475, PubMed:29497057). {ECO:0000269|PubMed:22637475, ECO:0000269|PubMed:29497057}.
uniprot
proteins