MCOLN2 Membrane Protein Introduction

Introduction of MCOLN2

MCOLN2 belongs to the transient receptor potential (TRP) protein superfamily, which consists of a gated tetrameric cation channel with multiple physiological functions, particularly in sensory signaling. These proteins share a conserved structure of six transmembrane helices with different cytoplasmic oriented N- and C-terminal domains. Most TRP proteins are localized on the plasma membrane. However, the transient receptors of the potential mucolipin-like (TRPML) protein family are primarily localized in endosomes where they play a role in vesicle trafficking, autophagy and membrane fusion. The TRPML family contains three proteins, MCOLN1, MCOLN2 and MCOLN3, which can produce cation rectified inward currents. MCOLN2 is mainly expressed in immune cells.

Basic Information of MCOLN2
Protein Name	Mucolipin-2
Gene Name	MCOLN2
Aliases	Transient receptor potential channel mucolipin 2
Organism	Homo sapiens (Human)
UniProt ID	Q8IZK6
Transmembrane Times	6
Length (aa)	566
Sequence	MARQPYRFPQARIPERGSGVFRLTVRNAMAHRDSEMKEECLREDLKFYFMSPCEKYRARRQIPWKLGLQILKIVMVTTQLVRFGLSNQLVVAFKEDNTVAFKHLFLKGYSGTDEDDYSCSVYTQEDAYESIFFAINQYHQLKDITLGTLGYGENEDNRIGLKVCKQHYKKGTMFPSNETLNIDNDVELDCVQLDLQDLSKKPPDWKNSSFFRLEFYRLLQVEISFHLKGIDLQTIHSRELPDCYVFQNTIIFDNKAHSGKIKIYFDSDAKIEECKDLNIFGSTQKNAQYVLVFDAFVIVICLASLILCTRSIVLALRLRKRFLNFFLEKYKRPVCDTDQWEFINGWYVLVIISDLMTIIGSILKMEIKAKNLTNYDLCSIFLGTSTLLVWVGVIRYLGYFQAYNVLILTMQASLPKVLRFCACAGMIYLGYTFCGWIVLGPYHDKFENLNTVAECLFSLVNGDDMFATFAQIQQKSILVWLFSRLYLYSFISLFIYMILSLFIALITDSYDTIKKFQQNGFPETDLQEFLKECSSKEEYQKESSAFLSCICCRRRKRSDDHLIPIS

Function of MCOLN2 Membrane Protein

MCOLN2 is believed to be primarily localized in recirculating endosomes and plays a role in the Arf6-associated recycling pathway. MCOLN2 is expressed at low levels in most tissues and is expressed with high levels in the thymus and spleen. MCOLN2 is an interferon-stimulated gene which is shown to be induced in mouse macrophages in response to lipopolysaccharide (LPS) and chimpanzee peripheral blood mononuclear cells in response to type I IFN. The B cell transcription factor PAX5 is also found to promote MCOLN2 expression. In a mouse model, MCOLN2 knockdown resulted in impaired secretion of chemokines and reduced recruitment of peripheral macrophages following bacterial challenge. Taken together, these findings suggest a role for MCOLN2 in immunity. However, the specific role of MCOLN2 in viral infection remains unclear.

Fig.1 Illustration of the location of the K370Q mutation within MCOLN2. Transmembrane domains 1 to 6 (TM1 to TM6) in MCOLN2 are shown. (Rinkenberger, 2018)

Application of MCOLN2 Membrane Protein in Literature

Rinkenberger N., et al. Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses. Mbio. 2018, 9(1). PubMed ID: 29382735

This article finds that gated cation channel MCOLN2 regulates viral entry by enhancing the efficiency of viral transport and enhancing the endosomal system.
Schmiege P., et al. The regulatory mechanism of mammalian TRPMLs revealed by cryo-EM. Febs Journal. 2018, 285(14):2579-2585. PubMed ID: 29577631

This article describes that biophysical and electrophysiological characterization of TRPML, and reveals another natural agonist binding site in the unique domain of TRPML, possibly modulating the conformation of the S4-S5 linker.
Morelli M.B., et al. Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression. Oncotarget. 2016, 7(28):43654-43668. PubMed ID: 27248469

This article suggests that high TRPML-2 expression in glioma cells results in increased survival and proliferative signaling, and TRPML-2 plays a tumor-promoting role in glioma progression.
Cuajungco M.P., et al. The Mucolipin-2 (TRPML2) Ion Channel: a tissue-specific protein crucial to normal cell function. Pflügers Archiv-European Journal of Physiology. 2016, 468(2):177-92. PubMed ID: 26336837

This article reveals that the function of TRPML2 is still unclear, but new data suggest that it may play a key role in immune cell development and inflammatory responses.
Valadez J.A., et al. PAX5 is the transcriptional activator of mucolipin-2 (MCOLN2) gene. Gene. 2015, 555(2):194-202. PubMed ID: 25445271

This article demonstrates the role of TRPML2 in B cell development and function, further providing evidence that TRPML2 is involved in the immune system.

MCOLN2 Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-MCOLN2 antibody development services.

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

Rinkenberger N and Schoggins J W. (2018). Mucolipin-2 cation channel increases trafficking efficiency of endocytosed viruses. Mbio. 9(1).

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