MANF

Protein identityUniProt · HPA

UniProt accession

P55145

Gene

MANF

Ensembl

ENSG00000145050

Chromosome

3

Canonical length

182 aa

Protein class

Plasma proteins, Predicted secreted proteins

Subcellular location

Endoplasmic reticulum

Secretome location

Secreted to blood

OverviewNCBI Gene

The protein encoded by this gene is localized in the endoplasmic reticulum (ER) and golgi, and is also secreted. Reducing expression of this gene increases susceptibility to ER stress-induced death and results in cell proliferation. Activity of this protein is important in promoting the survival of dopaminergic neurons. The presence of polymorphisms in the N-terminal arginine-rich region, including a specific mutation that changes an ATG start codon to AGG, have been reported in a variety of solid tumors; however, these polymorphisms were later shown to exist in normal tissues and are thus no longer thought to be tumor-related. [provided by RefSeq, Apr 2014]

Canonical amino-acid sequenceUniProt

182 residues, UniProt reviewed canonical sequence.

>P55145|MANF
     1  MRRMWATQGL AVALALSVLP GSRALRPGDC EVCISYLGRF YQDLKDRDVT FSPATIENEL
    61  IKFCREARGK ENRLCYYIGA TDDAATKIIN EVSKPLAHHI PVEKICEKLK KKDSQICELK
   121  YDKQIDLSTV DLKKLRVKEL KKILDDWGET CKGCAEKSDY IRKINELMPK YAPKAASART
   181  DL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MANF can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

160 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MANF.

Disease | AllUniProt

Conditions MANF is implicated in, by any mechanism.

• Diabetes, deafness, developmental delay, and short stature syndrome (DDDS) MIM:620651

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 42 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Diabetes, deafness, developmental delay, and short stature syndrome
• Cerebro-costo-mandibular syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.47

gnomAD pLI

0

gnomAD missense Z

0.67

DepMap mean gene effect

-0.34

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ATF6-mediated unfolded protein response
• dopaminergic neuron differentiation
• neuron projection development
• regulation of response to endoplasmic reticulum stress
• vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure

Molecular functions

• growth factor activity
• RNA binding
• sulfatide binding

Cellular components

• cytosol
• endoplasmic reticulum
• endoplasmic reticulum lumen
• extracellular region
• extracellular space
• nucleus
• sarcoplasmic reticulum lumen

Protein domainsUniProt · Pfam · InterPro

• ARMET, C-terminal
• SAP domain superfamily
• ARMET, N-terminal
• ARMET-like
• ARMET, C-terminal
• ARMET, N-terminal

KeywordsUniProt

• Deafness
• Diabetes mellitus
• Disulfide bond
• Dwarfism
• Endoplasmic reticulum
• Glycoprotein
• Growth factor
• Lipid-binding
• Phosphoprotein
• Sarcoplasmic reticulum
• Secreted
• Sialic acid
• Signal
• Stress response
• Unfolded protein response

InteractionsUniProt · HPA

Protein binding partners of MANF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HSPA5