MCOLN2 mucolipin TRP cation channel 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MCOLN2provided by HGNC
Official Full Name: mucolipin TRP cation channel 2provided by HGNC
Primary source: HGNC:HGNC:13357
See related: Ensembl:ENSG00000153898 MIM:607399; AllianceGenome:HGNC:13357
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TRPML2; TRP-ML2
Summary: Mucolipins constitute a family of cation channel proteins with homology to the transient receptor potential superfamily. In mammals, the mucolipin family includes 3 members, MCOLN1 (MIM 605248), MCOLN2, and MCOLN3 (MIM 607400), that exhibit a common 6-membrane-spanning topology. Homologs of mammalian mucolipins exist in Drosophila and C. elegans. Mutations in the human MCOLN1 gene cause mucolipodosis IV (MIM 262650) (Karacsonyi et al., 2007 [PubMed 17662026]).[supplied by OMIM, Sep 2009]
Expression: Broad expression in lymph node (RPKM 3.6), spleen (RPKM 2.0) and 14 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p22.3

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (84925583..84997113, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (84766210..84837786, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (85391266..85462796, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Functional In Vitro Assessment of VEGFA/NOTCH2 Signaling Pathway and pRB Proteasomal Degradation and the Clinical Relevance of Mucolipin TRPML2 Overexpression in Glioblastoma Patients.
Title: Functional In Vitro Assessment of VEGFA/NOTCH2 Signaling Pathway and pRB Proteasomal Degradation and the Clinical Relevance of Mucolipin TRPML2 Overexpression in Glioblastoma Patients.
Endolysosomal ion channel MCOLN2 (Mucolipin-2) promotes prostate cancer progression via IL-1beta/NF-kappaB pathway.
Title: Endolysosomal ion channel MCOLN2 (Mucolipin-2) promotes prostate cancer progression via IL-1β/NF-κB pathway.
The acidic TRPML2 extracytosolic/lumenal domain (ELD) pre-pore loop exhibits a pH-dependent Ca2+ interaction, suggesting a mechanism for channel activity regulation in the endolysosomal system.
Title: Structure of the Human TRPML2 Ion Channel Extracytosolic/Lumenal Domain.
The authors show that MCOLN2 specifically promotes viral vesicular trafficking and subsequent escape from endosomal compartments. This mechanism requires channel activity, occurs independently of antiviral signaling, and broadly applies to enveloped RNA viruses that require transport to late endosomes for infection, including influenza A virus, yellow fever virus, and Zika virus.
Title: Mucolipin-2 Cation Channel Increases Trafficking Efficiency of Endocytosed Viruses.
High TRPML-2 expression in glioma cells resulted in increased survival and proliferation signaling, suggesting a pro-tumorigenic role played by TRPML-2 in glioma progression.
Title: Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression.
MCOLN2 is transcriptionally activated by PAX5 and has roles in B cell development and function
Title: PAX5 is the transcriptional activator of mucolipin-2 (MCOLN2) gene.
TRPML2 is activated by lowering the extracellular sodium concentration as well as by a subset of small chemical compounds that were previously identified as activators of TRPML3.
Title: Constitutive activity of TRPML2 and TRPML3 channels versus activation by low extracellular sodium and small molecules.
TRPML 1, 2 and 3 assemblies regulated cell viability and starvation-induced autophagy.
Title: Heteromultimeric TRPML channel assemblies play a crucial role in the regulation of cell viability models and starvation-induced autophagy.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
constitutively active h-TRPML2 leads to cell death by causing Ca(2+) overload
Title: Constitutive activity of the human TRPML2 channel induces cell degeneration.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-78598 (e-PCR)
- UniSTS:101703

RH103324 (e-PCR)
- UniSTS:97655

NoName (e-PCR)
- UniSTS:490164

NoName (e-PCR)
- UniSTS:481486

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables NAADP-sensitive calcium-release channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium channel activity	TAS Traceable Author Statement more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables iron ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in calcium ion transmembrane transport	TAS Traceable Author Statement more info
involved_in calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in iron ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in macrophage migration	IEA Inferred from Electronic Annotation more info
involved_in neutrophil migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of chemokine (C-C motif) ligand 5 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of chemokine (C-X-C motif) ligand 2 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of macrophage inflammatory protein 1 alpha production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of monocyte chemotactic protein-1 production	IEA Inferred from Electronic Annotation more info
involved_in protein transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
NOT is_active_in lysosomal membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
NOT is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in recycling endosome membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: mucolipin-2

Names: mucolipin 2; transient receptor potential channel mucolipin 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001330647.2 → NP_001317576.1 mucolipin-2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AL139150, AL358789

Consensus CDS

CCDS81347.1

UniProtKB/Swiss-Prot

Q8IZK6
NM_153259.4 → NP_694991.2 mucolipin-2 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AA664369, AK094010, AL139150, AL358789, BC104891, BF512441, DR007194

Consensus CDS

CCDS30762.1

UniProtKB/Swiss-Prot

A6NI99, Q2M3I6, Q5TAG5, Q8IZK6, Q8N9R3

Related

ENSP00000359640.3, ENST00000370608.8

Conserved Domains (1) summary

cl27887
Location:388 → 513

PKD_channel; Polycystin cation channel

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

84925583..84997113 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005270719.4 → XP_005270776.1 mucolipin-2 isoform X1

UniProtKB/Swiss-Prot

Q8IZK6

Related

ENSP00000284027.5, ENST00000284027.5

Conserved Domains (1) summary

pfam08016
Location:360 → 485

PKD_channel; Polycystin cation channel
XM_011541188.4 → XP_011539490.1 mucolipin-2 isoform X1

UniProtKB/Swiss-Prot

Q8IZK6

Conserved Domains (1) summary

pfam08016
Location:360 → 485

PKD_channel; Polycystin cation channel
XM_011541187.3 → XP_011539489.1 mucolipin-2 isoform X1

UniProtKB/Swiss-Prot

Q8IZK6

Conserved Domains (1) summary

pfam08016
Location:360 → 485

PKD_channel; Polycystin cation channel
XM_047416964.1 → XP_047272920.1 mucolipin-2 isoform X3
XM_047416962.1 → XP_047272918.1 mucolipin-2 isoform X2
XM_047416968.1 → XP_047272924.1 mucolipin-2 isoform X4