LRRC38 Membrane Protein Introduction

Introduction of LRRC38

LRRC38, Leucine-rich repeat-containing protein 38 is a protein that in humans is encoded by the LRRC38 gene. The expression is found in prostate and adrenal. This gene is conserved in chimpanzee, cow, mouse, chicken, zebrafish and frog. It has been demonstrated that 198 organisms have orthologs with human gene LRRC38. The function is displayed via leucine-rich repeats domain through participating in protein-protein interactions. It’s a gamma subunit modulator of BK alpha channel.

Basic Information of LRRC38
Protein Name	Leucine-rich repeat-containing protein 38
Gene Name	LRRC38
Aliases	BK channel auxiliary gamma subunit LRRC38
Organism	Homo sapiens (Human)
UniProt ID	Q5VT99
Transmembrane Times	1
Length (aa)	294
Sequence	MRPRAPACAAAALGLCSLLLLLAPGHACPAGCACTDPHTVDCRDRGLPSVPDPFPLDVRKLLVAGNRIQRIPEDFFIFYGDLVYLDFRNNSLRSLEEGTFSGSAKLVFLDLSYNNLTQLGAGAFRSAGRLVKLSLANNNLVGVHEDAFETLESLQVLELNDNNLRSLSVAALAALPALRSLRLDGNPWLCDCDFAHLFSWIQENASKLPKGLDEIQCSLPMESRRISLRELSEASFSECRFSLSLTDLCIIIFSGVAVSIAAIISSFFLATVVQCLQRCAPNKDAEDEDEDKDD

Function of LRRC38 Membrane Protein

LRRC38 (Leucine-rich repeat-containing protein 38) is a single transmembrane protein. It’s an auxiliary subunit of the large-conductance, voltage and calcium-activated potassium channel (BK alpha channel). BK channels consist of the homotetrameric pore-forming voltage and calcium-sensing α subunits (BKα), or regulatory tissue-specific auxiliary β or γ subunits. BK channel auxiliary γ (BKγ) subunits are a group of leucine-rich repeat (LRR)-containing membrane proteins, including γ1 (LRRC26), γ2 (LRRC52), γ3 (LRRC55), and γ4 (LRRC38). LRRC38 can modulate the gating characteristics by producing a marked shift in hyperpolarizing direction and in the absence of calcium. These subunits show distinct expression in different human tissues, LRRC38 is mainly expressed in secretory glands. Also, in non-excitable cells, it’s required for conversion of BK alpha channels with the state from a high-voltage to a low-voltage activated channel type. The characteristics have been identified as negative membrane voltages and constant low levels of calcium.

Fig.1 Structural features of LRRC38 (γ4) (Li, 2015)

Application of LRRC38 Membrane Protein in Literature

Li Q., et al. Molecular basis for differential modulation of BK channel voltage-dependent gating by auxiliary γ subunits. J Gen Physiol. 2015, 145(6):543-54. PubMed ID: 26009545

This article shows the molecular basis for differential modulation of BK channel by gamma subunits, and LRRC38 is gamma-4 subunit.
Yan J and Aldrich R.W. BK potassium channel modulation by leucine-rich repeat-containing proteins. Proc Natl Acad Sci U S A. 2012, 109(20):7917-22. PubMed ID: 22547800

This article demonstrates that LRRC38 produces a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction in the absence of calcium.
Adler E.M. Of BK regulation, painful connections, and versatile neuropeptide signaling. J Gen Physiol. 2015, 145(6):457-8. PubMed ID: 26009540

This article provides comments for the article listed as reference 1, and summarizes the BK regulation, painful connections, and versatile neuropeptide signaling.
Zhang J and Yan J. Regulation of BK channels by auxiliary γ subunits. Front Physiol. 2014, 5:401. PubMed ID: 25360119

This article shows that LRRC38 can interact with BK channels to modulate the function. In non-excitable cells, it allows BK channels to an open status even at near physiological Ca²⁺ concentration and membrane voltage.

LRRC38 Preparation Options

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Reference

Li Q, et al. (2015). Molecular basis for differential modulation of BK channel voltage-dependent gating by auxiliary γ subunits. J Gen Physiol. 145(6):543-54.

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