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TRPML1

Family: Transient Receptor Potential channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Ion Selectivity and Conductance
Tissue Distribution
Physiological Functions
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 580 19p13.3-p13.2 MCOLN1 mucolipin 1 1,9
Mouse 6 1 580 8 A1.1 Mcoln1 mucolipin 1 3
Rat 6 1 580 12p12 Mcoln1 mucolipin 1
Previous and Unofficial Names
MCOLN1
Mucolipin1
ML1
ML4
MLIV
MST080
MSTP080
TRPM-L1
LOC288371
Mcoln1_predicted
mucolipin 1
mucolipin 1 (predicted)
mucolipin-1
mucolipidin
2210015I05Rik
Database Links
Ensembl ENSG00000090674 (Hs), ENSMUSG00000004567 (Mm), ENSRNOG00000000975 (Rn)
Entrez Gene 57192 (Hs), 94178 (Mm), 288371 (Rn)
GeneCards MCOLN1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Mcoln1 (Mm)
HomoloGene 10744 (Hs)
Human Protein Reference Database 05582 (Hs)
InterPro Q9GZU1 (Hs), Q99J21 (Mm)
KEGG Gene hsa:57192 (Hs), mmu:94178 (Mm), rno:288371 (Rn)
OMIM 605248 (Hs)
Orphanet Gene ORPHA123175 (Hs)
PharmGKB Gene PA30699 (Hs)
PhosphoSitePlus Q9GZU1 (Hs), Q99J21 (Mm)
Protein Ontology (PRO) PRO:000010252 (Hs)
RefSeq Nucleotide NM_020533 (Hs), NM_053177 (Mm), NM_001105903 (Rn)
RefSeq Protein NP_065394 (Hs), NP_444407 (Mm), NP_001099373 (Rn)
TreeFam ENSG00000090674 (Hs), ENSMUSG00000004567 (Mm), ENSRNOG00000000975 (Rn)
UniGene Hs. 631858 (Hs)
UniProt Q9GZU1 (Hs), Q99J21 (Mm)
Wikipedia TRPML1
Transient Receptor Potential channels
Search for 3D structures on the PDB
Search by keyword: Transient Receptor Potential channels TRPML1 Search by accession number: Q9GZU1, Q99J21
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [84.3 - 92.4 pS] > Na+ [80.8 - 82.6 pS] > Ba2+ [44.6 pS] > Sr2+ [37.2 pS] > Ca2+ [32.5 - 34.4 pS]
References:  5,7
Ion Selectivity and Conductance Comments
The plasma membrane-localized and constitutively active mutant (V432P) is inwardly rectifying and permeant to the monovalent cations Na+, K+, Cs+ as well as the divalent cations Ca2+ and Mg2+ [4,10] but does not conduct protons [10]. This mutation is unlikely to affect selectivity and is currently accepted as representing the wild type TRPML1 permeation properties. The wild type protein appears to span intracellular membranes (lysosomal/endosomal) and has not been characterised in situ.
Voltage Dependence
Not Determined
Activators (Human)
TRPML1Va: Constitutively active, current potentiated by extracellular acidification (equivalent to intralysosomal acidification)
Activators
Not Determined
Pore Blockers
Not Determined
Tissue Distribution
Brain, skeletal muscle, colon, thymus, liver, lung, leukocytes
Species:  Human
Technique:  Northern Blot
References:  1
Functional Assays
Not Determined
Physiological Functions
An involvement in membrane sorting and/or the late steps of endocytosis is suggested by defects in transport along the lysosomal pathway in Mucolipidosis Type IV patients.
Species:  Human
Tissue:  Fibroblasts
References:  2,6
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0001406 abnormal gait PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0005209 abnormal gastric mucosa morphology PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0003632 abnormal nervous system morphology PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0001330 abnormal optic nerve morphology PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0003731 abnormal retinal outer nuclear layer morphology PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0008843 absent subcutaneous adipose tissue PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0001262 decreased body weight PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0000774 decreased brain size PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0004819 decreased skeletal muscle mass PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0002795 dilated cardiomyopathy PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0001270 distended abdomen PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0000539 distended urinary bladder PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0000755 hindlimb paralysis PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0001505 hunched posture PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0004731 increased circulating gastrin level PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0005202 lethargy PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0001513 limb grasping PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0002083 premature death PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0001326 retinal degeneration PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0001407 short stride length PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0008511 thin retinal inner nuclear layer PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0008513 thin retinal inner plexiform layer PMID: 17924347 
Mcoln1tm1Sasl Mcoln1tm1Sasl/Mcoln1tm1Sasl
involves: 129S6/SvEvTac * C57BL/6		 MGI:1890498  MP:0000746 weakness PMID: 17924347 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Mucolipidosis IV
OMIM:  252650
Orphanet:  578
Role:  Probably affects lysosomal function.
References:  1,9
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human A5534G (genomic seq.) 8
Missense Human F465L 8
Missense Human 454-469del 8
Missense Human V446L 8
Missense Human F408del 8
Missense None D362Y 8
Missense Human R322L 8
Missense Human T232P 8
Missense Human R172X 8
Missense Human R102X 8
Truncation Human del 511-6499 (genomic seq) 8
Truncation Human 1569insGCCCTGCTGCG (mRNA) 8
Truncation Human 1334-1335insT (mRNA) 8
Truncation Human 598-599delCC (mRNA) 8

REFERENCES

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1. Bargal, R; Avidan, N; Ben-Asher, E; Olender, Z; Zeigler, M; Frumkin, A; Raas-Rothschild, A; Glusman, G; Lancet, D; Bach, G. (2000) Identification of the gene causing mucolipidosis type IV. Nat. Genet., 26 (1): 118-23. [PMID:10973263]

2. Bargal, R; Bach, G. (1997) Mucolipidosis type IV: abnormal transport of lipids to lysosomes. J. Inherit. Metab. Dis., 20 (5): 625-32. [PMID:9323557]

3. Falardeau, JL; Kennedy, JC; Acierno, JS; Sun, M; Stahl, S; Goldin, E; Slaugenhaupt, SA. (2002) Cloning and characterization of the mouse Mcoln1 gene reveals an alternatively spliced transcript not seen in humans. BMC Genomics, 3 (1): 3. [PMID:11897010]

4. Grimm, C; Cuajungco, MP; van Aken, AF; Schnee, M; Jörs, S; Kros, CJ; Ricci, AJ; Heller, S. (2007) A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse. Proc. Natl. Acad. Sci. U.S.A., 104 (49): 19583-8. [PMID:18048323]

5. LaPlante, JM; Falardeau, J; Sun, M; Kanazirska, M; Brown, EM; Slaugenhaupt, SA; Vassilev, PM. (2002) Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway. FEBS Lett., 532 (1-2): 183-7. [PMID:12459486]

6. LaPlante, JM; Sun, M; Falardeau, J; Dai, D; Brown, EM; Slaugenhaupt, SA; Vassilev, PM. (2006) Lysosomal exocytosis is impaired in mucolipidosis type IV. Mol. Genet. Metab., 89 (4): 339-48. [PMID:16914343]

7. LaPlante, JM; Ye, CP; Quinn, SJ; Goldin, E; Brown, EM; Slaugenhaupt, SA; Vassilev, PM. (2004) Functional links between mucolipin-1 and Ca2+-dependent membrane trafficking in mucolipidosis IV. Biochem. Biophys. Res. Commun., 322 (4): 1384-91. [PMID:15336987]

8. Slaugenhaupt, SA. (2002) The molecular basis of mucolipidosis type IV. Curr. Mol. Med., 2 (5): 445-50. [PMID:12125810]

9. Sun, M; Goldin, E; Stahl, S; Falardeau, JL; Kennedy, JC; Acierno, JS; Bove, C; Kaneski, CR; Nagle, J; Bromley, MC; Colman, M; Schiffmann, R; Slaugenhaupt, SA. (2000) Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel. Hum. Mol. Genet., 9 (17): 2471-8. [PMID:11030752]

10. Xu, H; Delling, M; Li, L; Dong, X; Clapham, DE. (2007) Activating mutation in a mucolipin transient receptor potential channel leads to melanocyte loss in varitint-waddler mice. Proc. Natl. Acad. Sci. U.S.A., 104 (46): 18321-6. [PMID:17989217]

To cite this database page, please use the following:

David E. Clapham, Bernd Nilius, Grzegorz Owsianik.
Transient Receptor Potential channels: TRPML1. Last modified on 07/11/2011. Accessed on 26/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=501.


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