MANF

Official Full Name

mesencephalic astrocyte derived neurotrophic factor

Organism

Homo sapiens

Gene ID

7873

Background

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]

Synonyms

ARP; DDDS; ARMET

Protein Sequence

MRRMWATQGLAVALALSVLPGSRALRPGDCEVCISYLGRFYQDLKDRDVTFSPATIENELIKFCREARGKENRLCYYIGATDDAATKIINEVSKPLAHHIPVEKICEKLKKKDSQICELKYDKQIDLSTVDLKKLRVKELKKILDDWGETCKGCAEKSDYIRKINELMPKYAPKAASARTDL

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Cat.No.	Product Name	Price
CSC-DC009145	Panoply™ Human MANF Knockdown Stable Cell Line	Inquiry
CSC-SC009145	Panoply™ Human MANF Over-expressing Stable Cell Line	Inquiry
CSC-RT1170	Human MANF Knockout Cell Line-HEK293T	Inquiry
CLOE-0145	Human MANF(Fc) HEK293 Cell Lysate	Inquiry
CLOE-0910	Human MANF(His) HEK293 Cell Lysate	Inquiry
CLKO-0672	MANF KO Cell Lysate-HEK293T	Inquiry

Cat.No.	Product Name	Price
AD09601Z	Human MANF adenoviral particles	Inquiry
LV17709L	human MANF (NM_006010) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH337407	shRNA set against Mouse MANF (NM_029103.3)	Inquiry
SHH337403	shRNA set against Human MANF (NM_006010.4)	Inquiry
SHH337411	shRNA set against Rat MANF (NM_001108183.1)	Inquiry
SHW010405	shRNA set against Danio rerio MANF (NM_001076629)	Inquiry

Cat.No.	Product Name	Price
RP00218	Recombinant Human MANF (C-6His)	Inquiry

Cat.No.	Product Name	Price
CDFL007331	Mouse Manf cDNA Clone(NM_029103.3)	Inquiry
CDFR007828	Rat Manf cDNA Clone(NM_001108183.1)	Inquiry
MiUTR1M-01690	MANF miRNA 3'UTR clone	Inquiry
MiUTR3H-04500	MANF miRNA 3'UTR clone	Inquiry
SKO1037	MANF Validated sgRNA vector	Inquiry
CDCB160418	Human MANF ORF clone (NM_006010.3)	Inquiry
CDCB171880	Danio rerio MANF ORF Clone (NM_001076629)	Inquiry
CDCB192740	Rabbit MANF ORF clone (XM_008260718.1)	Inquiry
CDCH388555	Human MANF ORF clone(NM_006010.4)	Inquiry
CDCL185245	Mouse MANF ORF clone(NM_029103.3)	Inquiry
CDCR374867	Rat Manf ORF Clone(NM_001108183.1)	Inquiry
CDCS418975	Human MANF ORF Clone (BC007282)	Inquiry
CDCS418976	Human MANF ORF Clone (BC113588)	Inquiry

Detailed Information

The mesencephalic astrocyte-derived ed neurotrophic factor (MANF) is a medium in which Petrova is equal to the first mid-brain type I astrocyte subcultured in vitro in 2003. A neurotrophic factor isolated to promote survival of dopaminergic neurons in vitro. It is also known as ARMET (arginine rich, mutated in early stage of tumurs) or ARP (arginine-rich protein). Another neurotrophic factor, the conserved dopamine neuro tro phic facto (CDNF), is a homologue of MANF. The homology of the two is >59%. A family of proteins that are conserved sequences of cysteine residues.

Physiological function of MANF

Studies have shown that MANF co-locates with endoplasmic reticulum and golgi membrane proteins. Brefeldin A(BFA) is used to block the protein transport between the endoplasmic reticulum and golgi, resulting in the increase of such proteins in the endoplasmic reticulum and the decrease of the amount in the culture medium. Degeneration of dopamine neuron axons, decrease of dopamine level and larvae death were observed in flies with the deletion of MANF gene, which supports that ANF is a dopamine neuron nutrient factor.

The endoplasmic reticulum is an important organelle of eukaryotic cells and is closely related to the metabolic processes of various membrane proteins, secreted proteins, phospholipids, and cholesterol. There is increasing evidence that MANF is an endoplasmic reticulum response protein, and high expression of MANF enhances cell tolerance to sugar-free status and other endoplasmic reticulum stress inducers. in vitro RNAi or in vivo knockdown of the ANF gene can cause death in cells or organisms under stress in the endoplasmic reticulum. Therefore, up-regulation of MANF may be an activation of an endogenous neuroprotective mechanism in cells under endoplasmic stress. Studies have shown that endoplasmic reticulum stress is up-regulated by the endoplasmic reticulum stress response element II. MANF may participate in unfolded protein response and improve cellular physiological state by degrading misfolded proteins, treating unfolded proteins, and regulating endoplasmic reticulum receptor activity.

Figure 1. Manf is essential for neurite extension and neuronal migration in the developing cortex. (Kuanyin, et al. 2017)

MANF and Parkinson's Disease

Studies have shown that deletion of the MANF/CDNF gene in glial cells leads to a series of pathological reactions caused by dopamine neuron loss and dopamine deficiency in animals. In the rat Parkinson's model induced by 6-hydoxy dopamine (6-OHDA), injection of M ANF/CDNF through the striatum not only protects midbrain dopamine neurons but also striatal dopaminergic nerve fibers. Moreover, it can strengthen the function of surviving neurons, repair the damaged nigrostria-striatum dopamine system, and reduce the dyskinesia in Parkinson's rats, which has the dual potential effects of prevention and treatment.

MANF and Cerebral Ischemic Injury

Neuroprotection is one of the effective methods for treating ischemic cerebrovascular. M ANF is not only found in midbrain dopamine neurons, but also abundantly expressed in the cerebral cortex and hippocampus. Cerebral ischemia causes changes in MANF expression in the hippocampus and the brain cortex. Transient or permanent cerebral ischemia can cause abnormal protein accumulation in the endoplasmic reticulum, endoplasmic reticulum stress, activate unfolded protein response, up-regulate the expression of MANF/CDNF in neurons, and enhance its immunological activity. It can reduce excessive apoptosis and necrosis of neurons in the ischemic area. MANF pretreatment can reduce the volume of infarcts in cerebral ischemia rats. It is beneficial to the recovery of behavioral function, which may be related to the reduction of glial cells in reactive hyperplasia in ischemic foci. This hypothesis is consistent with M ANF inhibition of proliferation of cultured cells in vitro.

References:

Kuanyin, T. , Danilova, T. , Domanskyi, A. , Saarma, M. , Lindahl, M. , & Airavaara, M. . (2017). Manf is essential for neurite extension and neuronal migration in the developing cortex. Eneuro, 4(5), ENEURO.0214-17.2017.
Kim, Y. , Park, S. J. , & Chen, Y. M. . (2017). Mesencephalic astrocyte-derived neurotrophic factor (manf), a new player in endoplasmic reticulum diseases: structure, biology and therapeutic roles. Translational Research, S1931524417302190.
Lindahl, M. , Saarma, M. , & Päivi Lindholm. (2017). Unconventional neurotrophic factors cdnf and manf: structure, physiological functions and therapeutic potential. Neurobiology of Disease, 97(Pt B), 90-102.

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