MANF Human Active Protein

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 promotes cell proliferation. The protein was initially thought to be longer at the N-terminus and to contain an arginine-rich region but transcribed evidence indicates a smaller open reading frame that does not encode the arginine tract. The presence of polymorphisms in the arginine-rich region, including a specific mutation that changes the previously numbered codon 50 from ATG 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 not tumor-related. [provided by RefSeq, Jun 2010]

Function: 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

By similarity. Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death. Ref.6 Ref.8

Subcellular location: Secreted Ref.6 Ref.8.

Induction: By endoplasmic reticulum stress. Ref.8

Domain: The N-terminal region may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response. Ref.10

Post-translational modification: May contain sialic acid residues.

Sequence similarities: Belongs to the ARMET family.

Caution: Was originally (Ref.1, Ref.11 and Ref.12) thought to be much longer and included an arginine-rich region thought to be the target of cancer-causing mutations. All these mutations are in what is now thought to be the 5'-UTR of the mRNA.It is uncertain whether Met-1 or Met-4 is the initiator.

Sequence caution: The sequence AAB08753.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence AAI13589.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence AAI13591.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.