Tchem MCOLN1 Mucolipin-1

Protein Summary

Description

Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis. Proposed to play a major role in Ca(2+) release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy (PubMed:11013137, PubMed:12459486, PubMed:15336987, PubMed:14749347, PubMed:29019983). Required for efficient uptake of large particles in macrophages in which Ca(2+) release from the lysosomes triggers lysosomal exocytosis. May also play a role in phagosome-lysosome fusion (By similarity). Involved in lactosylceramide trafficking indicative for a role in the regulation of late endocytic membrane fusion/fission events (PubMed:16978393). By mediating lysosomal Ca(2+) release is involved in regulation of mTORC1 signaling and in mTOR/TFEB-dependent lysosomal adaptation to environmental cues such as nutrient levels (PubMed:27787197, PubMed:25733853). Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy (PubMed:27357649). Functions as a Fe(2+) permeable channel in late endosomes and lysosomes (PubMed:18794901). Proposed to play a role in zinc homeostasis probably implicating its association with TMEM163 (PubMed:25130899) In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (By similarity). May contribute to cellular lipase activity within the late endosomal pathway or at the cell surface which may be involved in processes of membrane reshaping and vesiculation, especially the growth of tubular structures. However, it is not known, whether it conveys the enzymatic activity directly, or merely facilitates the activity of an associated phospholipase. This gene encodes a memberof the transient receptor potential (TRP) cation channel gene family. The transmembrane protein localizes to intracellular vesicular membranes including lysosomes, and functions in the late endocytic pathway and in the regulation of lysosomal exocytosis. The channel is permeable to Ca(2+), Fe(2+), Na(+), K(+), and H(+), and is modulated by changes in Ca(2+) concentration. Mutations in this gene result in mucolipidosis type IV. [provided by RefSeq, Oct 2009]

Uniprot Accession IDs

• Q9GZU1
• D6W647
• Q7Z4F7
• Q9H292
• Q9H4B3
• Q9H4B5
• ML1

Gene Name

• MCOLN1

Ensembl ID

• ENST00000264079
• ENSP00000264079
• ENSG00000090674

Symbol

• ML4
• ML1
• ML4
• MG-2
• MLIV
• MST080
• TRPML1
• MSTP080
• TRP-ML1
• TRPM-L1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor perturbation	0.84
molecular function	0.81
cellular component	0.8
transcription factor binding site profile	0.78
tissue sample	0.67

Protein Classes

PANTHER Classes

Protein / Transporter / Ion Channel / Mucolipin-1

DTO Classes

Protein / Ion Channel / Transient Receptor Potential Calcium Channel (Trp-cc) Family / Polycystin Subfamily / Mcoln1 Sub-subfamily / Mucolipin-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 271.07   (req: < 5)

Gene RIFs: 54   (req: <= 3)

Antibodies: 152   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 271.07   (req: >= 5)

Gene RIFs: 54   (req: > 3)

Antibodies: 152   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 15

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 5

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (5)

Explore Active Ligands

1 – 5 of 5

phosphatidyl (3,5) inositol bisphosphate

MCOLN1Tchem IC

pEC50 : 7.32

SF-22

MCOLN1Tchem IC

-log(-) : 6.3

SF-51

MCOLN1Tchem IC

pEC50 : 5.84

MK6-83

MCOLN1Tchem IC

-log(-) : 7

ML SA1

MCOLN1Tchem IC

-log(-) : 7.3

Protein-Protein Interactions (87)

Explore Interacting Targets

1 – 10 of 87

• See Interactions on String-DB

MCOLN3

Tchem

Family:  IC

Novelty:  0.03209262

p_int:  0.999999167

p_ni:  7.87e-7

p_wrong:  4.6e-8

Score:  0.22

Data Source:  BioPlex,STRINGDB

CSGALNACT2

Tbio

Family:  Enzyme

Novelty:  0.0770692

p_int:  0.999998962

p_ni:  0.000001001

p_wrong:  3.7e-8

Score:  0.161

Data Source:  BioPlex,STRINGDB

CCR6

Tchem

Family:  GPCR

Novelty:  0.00257933

p_int:  0.999996525

p_ni:  0.000003341

p_wrong:  1.34e-7

Data Source:  BioPlex

TPST2

Tbio

Family:  Enzyme

Novelty:  0.02551048

p_int:  0.999980798

p_ni:  0.000016168

p_wrong:  0.000003034

Data Source:  BioPlex

MCOLN2

Tchem

Family:  IC

Novelty:  0.05195244

p_int:  0.999472318

p_ni:  0.00003276

p_wrong:  0.000494922

Data Source:  BioPlex

LY6D

Tbio

Novelty:  0.07032941

p_int:  0.996870405

p_ni:  0.000010111

p_wrong:  0.003119484

Data Source:  BioPlex

CLEC2B

Tbio

Novelty:  0.06581244

p_int:  0.92648181

p_ni:  0.000146068

p_wrong:  0.073372122

Data Source:  BioPlex

TPCN2

Tchem

Family:  IC

Novelty:  0.01351129

Score:  0.783

Data Source:  STRINGDB

TRPM1

Tchem

Family:  IC

Novelty:  0.00822899

Score:  0.77

Data Source:  STRINGDB

NEU3

Tchem

Family:  Enzyme

Novelty:  0.00746819

Score:  0.75

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (10)

Reactome (6)

KEGG (1)

WikiPathways (3)

Ion channel transport (R-HSA-983712)

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Items per page:

5

1 – 5 of 6

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Ion channel transport	179 targets	R-HSA-983712
Reactome	Iron uptake and transport	59 targets	R-HSA-917937
Reactome	Stimuli-sensing channels	102 targets	R-HSA-2672351
Reactome	TRP channels	25 targets	R-HSA-3295583
Reactome	Transferrin endocytosis and recycling	31 targets	R-HSA-917977

Name	Explore in Pharos	Explore in Source
Ion channel transport	179 targets	R-HSA-983712
Iron uptake and transport	59 targets	R-HSA-917937
Stimuli-sensing channels	102 targets	R-HSA-2672351
TRP channels	25 targets	R-HSA-3295583
Transferrin endocytosis and recycling	31 targets	R-HSA-917977

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (28)

Functions (7)

Components (13)

Processes (8)

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10

1 – 7 of 7

GO Term	Evidence	Assigned by
ligand-gated calcium channel activity	Inferred from Direct Assay (IDA)	UniProtKB
NAADP-sensitive calcium-release channel activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
calcium channel activity	Traceable Author Statement (TAS)	Reactome
iron ion transmembrane transporter activity	Traceable Author Statement (TAS)	Reactome
cation channel activity	Non-traceable Author Statement (NAS)	UniProtKB
lipid binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (4)

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5

1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
electrocardiography	EFO_0004327	1	1	20		58.4
mean platelet volume	EFO_0004584	1	1	1		53.7
left ventricular structural measurement	EFO_0008205	3	1	3		49.5
opioid overdose severity measurement	EFO_0010140	1	1	1		31.4

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
electrocardiography	EFO_0004327	20		58.4
mean platelet volume	EFO_0004584	1		53.7
left ventricular structural measurement	EFO_0008205	3		49.5
opioid overdose severity measurement	EFO_0010140	1		31.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Adaptive immunity
Calcium
Calcium transport
Cell membrane
Cell projection
Complete proteome
Cytoplasmic vesicle
Disease mutation
Disulfide bond

GWAS Trait Find Similar Targets

No Header	No Header
electrocardiography
left ventricular structural measurement
mean platelet volume
opioid overdose severity measurement

MGI Phenotype Find Similar Targets

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adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	mucolipin 1	VGNC:2317	455656
Macaque	mucolipin 1		703775
Mouse	mucolipin 1	MGI:1890498	94178
Rat	mucolipin 1	RGD:1308953	288371
Dog	mucolipin 1	VGNC:43090	611517

Species	Name	OMA	EggNOG	Inparanoid
Chimp	mucolipin 1
Macaque	mucolipin 1
Mouse	mucolipin 1
Rat	mucolipin 1
Dog	mucolipin 1

Publication Statistics

PubMed Score 271.07

PubMed score by year

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PubTator Score 172.11

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Patents

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Related Publications

Text Mined References (77)

GeneRif Annotations (54)

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PMID	Year	Title