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Protein

Mesencephalic astrocyte-derived neurotrophic factor

Gene

Manf

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGrowth factor
Biological processStress response, Unfolded protein response
LigandLipid-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Mesencephalic astrocyte-derived neurotrophic factor
Alternative name(s):
Arginine-rich protein
Protein ARMET
Gene namesi
Name:Manf
Synonyms:Armet
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1922090 Manf

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Sarcoplasmic reticulum, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21By similarityAdd BLAST21
ChainiPRO_000000230622 – 179Mesencephalic astrocyte-derived neurotrophic factorAdd BLAST158

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 1141 Publication
Disulfide bondi30 ↔ 1031 Publication
Disulfide bondi61 ↔ 721 Publication
Modified residuei73PhosphotyrosineCombined sources1
Disulfide bondi148 ↔ 1511 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiQ9CXI5
MaxQBiQ9CXI5
PaxDbiQ9CXI5
PeptideAtlasiQ9CXI5
PRIDEiQ9CXI5
TopDownProteomicsiQ9CXI5

PTM databases

iPTMnetiQ9CXI5
PhosphoSitePlusiQ9CXI5

Expressioni

Tissue specificityi

Strongly expressed in pancreatic islets and spermatocytes (at protein level).1 Publication

Inductioni

By endoplasmic reticulum (ER) stress.1 Publication

Gene expression databases

CleanExiMM_ARMET

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9CXI5, 5 interactors
MINTiQ9CXI5
STRINGi10090.ENSMUSP00000124562

Structurei

Secondary structure

1179
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9CXI5
SMRiQ9CXI5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9CXI5

Family & Domainsi

Domaini

The N-terminal region may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response.By similarity

Sequence similaritiesi

Belongs to the ARMET family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4154 Eukaryota
ENOG4111QMZ LUCA
HOGENOMiHOG000264245
InParanoidiQ9CXI5

Family and domain databases

Gene3Di1.10.720.30, 1 hit
InterProiView protein in InterPro
IPR019345 Armet_prot
IPR036361 SAP_dom_sf
PANTHERiPTHR12990 PTHR12990, 1 hit
PfamiView protein in Pfam
PF10208 Armet, 1 hit
SUPFAMiSSF68906 SSF68906, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

Q9CXI5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MWATRGLAVA LALSVLPDSR ALRPGDCEVC ISYLGRFYQD LKDRDVTFSP
60 70 80 90 100
ATIEEELIKF CREARGKENR LCYYIGATDD AATKIINEVS KPLAHHIPVE
110 120 130 140 150
KICEKLKKKD SQICELKYDN QIDLSTVDLK KLRVKELKKI LDDWGEMCKG
160 170
CAEKSDYIRK INELMPKYAP KAASARTDL
Length:179
Mass (Da):20,374
Last modified:June 1, 2001 - v1
Checksum:iE5BCEE8C033C1530
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q3TMX5Q3TMX5_MOUSE
Arginine-rich, mutated in early sta...
Manf Armet, mCG_19507
179Annotation score:
Q80ZP8Q80ZP8_MOUSE
Armet protein
Manf Armet
165Annotation score:
F6T4L3F6T4L3_MOUSE
Mesencephalic astrocyte-derived neu...
Manf
128Annotation score:
F7C1S6F7C1S6_MOUSE
Mesencephalic astrocyte-derived neu...
Manf
52Annotation score:
F6USD5F6USD5_MOUSE
Mesencephalic astrocyte-derived neu...
Manf
121Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK014338 mRNA Translation: BAB29281.1
UniGeneiMm.29778
Mm.471819

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK014338 mRNA Translation: BAB29281.1
UniGeneiMm.29778
Mm.471819

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RQYNMR-A22-179[»]
ProteinModelPortaliQ9CXI5
SMRiQ9CXI5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9CXI5, 5 interactors
MINTiQ9CXI5
STRINGi10090.ENSMUSP00000124562

PTM databases

iPTMnetiQ9CXI5
PhosphoSitePlusiQ9CXI5

Proteomic databases

EPDiQ9CXI5
MaxQBiQ9CXI5
PaxDbiQ9CXI5
PeptideAtlasiQ9CXI5
PRIDEiQ9CXI5
TopDownProteomicsiQ9CXI5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1922090 Manf

Phylogenomic databases

eggNOGiKOG4154 Eukaryota
ENOG4111QMZ LUCA
HOGENOMiHOG000264245
InParanoidiQ9CXI5

Miscellaneous databases

EvolutionaryTraceiQ9CXI5
PROiPR:Q9CXI5
SOURCEiSearch...

Gene expression databases

CleanExiMM_ARMET

Family and domain databases

Gene3Di1.10.720.30, 1 hit
InterProiView protein in InterPro
IPR019345 Armet_prot
IPR036361 SAP_dom_sf
PANTHERiPTHR12990 PTHR12990, 1 hit
PfamiView protein in Pfam
PF10208 Armet, 1 hit
SUPFAMiSSF68906 SSF68906, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMANF_MOUSE
AccessioniPrimary (citable) accession number: Q9CXI5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: June 1, 2001
Last modified: November 7, 2018
This is version 102 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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