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UniProtKB - Q9GZU1 (MCLN1_HUMAN)

Entry version 173 (17 Jun 2020)
Sequence version 1 (01 Mar 2001)
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Protein

Mucolipin-1

Gene

MCOLN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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 Ca2+ 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 Ca2+ 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 Ca2+ 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 Fe2+ 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).By similarity1 Publication10 Publications
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.1 Publication

Caution

There are conflicting results relative to ion selectivity and permeation. Initially outward rectification has been reported which makes the proposed activity as lysosymal Ca2+ release channel unlikely. Inward rectification has been decribed in later studies supporting the Ca2+ release activity.Curated

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Channel activity is controlled by multiple regulatory mechanisms in different subcellular compartments. Channel function is transiently modulated by changes in Ca2+, and inhibited by a reduction of pH; pH changes modify the aggregation state of unitary channels; a negative cooperativity between extracellular/lumenal Ca2+ and H+ is suggested (PubMed:12459486, PubMed:28112729). Regulated by phosphoinositides in a compartment-specific manner: in lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) (PubMed:22733759, PubMed:29019983).4 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionIon channel
Biological processAdaptive immunity, Calcium transport, Immunity, Ion transport, Transport
LigandCalcium, Lipid-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-3295583 TRP channels
R-HSA-917977 Transferrin endocytosis and recycling

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q9GZU1

Protein family/group databases

Transport Classification Database

More...TCDBi		1.A.5.3.1 the polycystin cation channel (pcc) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Mucolipin-11 Publication
Short name:
ML1
Alternative name(s):
MG-2
Mucolipidin1 Publication
Transient receptor potential channel mucolipin 1
Short name:
TRPML11 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MCOLN1
Synonyms:ML4
ORF Names:MSTP080
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 19

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000090674.15

Human Gene Nomenclature Database

More...HGNCi		HGNC:13356 MCOLN1

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		605248 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q9GZU1

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 65Cytoplasmic1 PublicationAdd BLAST65
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei66 – 86Helical; Name=11 PublicationAdd BLAST21
Topological domaini87 – 298Extracellular1 PublicationAdd BLAST212
Transmembranei299 – 321Helical; Name=21 PublicationAdd BLAST23
Topological domaini322 – 350Cytoplasmic1 PublicationAdd BLAST29
Transmembranei351 – 371Helical; Name=31 PublicationAdd BLAST21
Topological domaini372 – 382Extracellular1 PublicationAdd BLAST11
Transmembranei383 – 405Helical; Name=41 PublicationAdd BLAST23
Topological domaini406 – 427Cytoplasmic1 PublicationAdd BLAST22
Transmembranei428 – 448Helical; Name=51 PublicationAdd BLAST21
Topological domaini449 – 456Extracellular1 Publication8
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a region that is buried within a membrane, but does not cross it.<p><a href='/help/intramem' target='_top'>More...</a></p>Intramembranei457 – 477Pore-forming1 PublicationAdd BLAST21
Topological domaini478 – 491Extracellular1 PublicationAdd BLAST14
Transmembranei492 – 513Helical; Name=61 PublicationAdd BLAST22
Topological domaini514 – 580Cytoplasmic1 PublicationAdd BLAST67

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Lysosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Mucolipidosis 4 (ML4)12 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive lysosomal storage disorder characterized by severe psychomotor retardation and ophthalmologic abnormalities, including corneal opacity, retinal degeneration and strabismus. Storage bodies of lipids and water-soluble substances are seen by electron microscopy in almost every cell type of the patients. Most patients are unable to speak or walk independently and reach a maximal developmental level of 1-2 years. All patients have constitutive achlorhydia associated with a secondary elevation of serum gastrin levels.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_019369106L → P in ML4; decreases formation and extrusion of tubulo-vesicular structures when overexpressed; disrupts tetrameric assembly; abolishes lysosomal localization. 3 PublicationsCorresponds to variant dbSNP:rs797044825EnsemblClinVar.1
Natural variantiVAR_019370232T → P in ML4; fails to localize to late endosomes; abolishes Fe(2+) permeability; disrupts tetrameric assembly; abolishes lysosomal localization. 4 PublicationsCorresponds to variant dbSNP:rs767122713EnsemblClinVar.1
Natural variantiVAR_019371362D → Y in ML4; affects channel activity; abolishes Fe(2+) permeability. 4 PublicationsCorresponds to variant dbSNP:rs121908372EnsemblClinVar.1
Natural variantiVAR_038380403R → C in ML4; impairs Fe(2+) permeability. 2 PublicationsCorresponds to variant dbSNP:rs121908374EnsemblClinVar.1
Natural variantiVAR_019372408Missing in ML4; mild psychomotor involvement; does not affect channel activity; affects channel inhibition by low pH; still localizes to late endosomes. 5 Publications1
Natural variantiVAR_019373446V → L in ML4; does not affect channel activity; affects channel inhibition by low pH; impairs Fe(2+) permeability. 3 PublicationsCorresponds to variant dbSNP:rs754097561EnsemblClinVar.1
Natural variantiVAR_019374447L → P in ML4. 1 PublicationCorresponds to variant dbSNP:rs797044827EnsemblClinVar.1
Natural variantiVAR_019375465F → L in ML4; still localizes to late endosomes; fails to rescue defect of lactosylceramide traffic through the late endocytic pathway in ML4 patient cells; minor effect on formation and extrusion of tubulo-vesicular structures when overexpressed. 4 PublicationsCorresponds to variant dbSNP:rs797044828EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi15 – 16LL → AA: No effect on localization to lysosomes. 1 Publication2
Mutagenesisi15L → A: Abolishes localization to lysosomes and leads to expression at the cell membrane; when associated with A-577. 2 Publications1
Mutagenesisi42 – 44RRR → AAA: Reduces PtdIns(4,5)P2 sensitivity. 1 Publication3
Mutagenesisi44 – 46RLK → AAA: Abolishes interaction with PDCD6 and decreases formation of aberrant endosomes upon overexpression. 1 Publication3
Mutagenesisi44R → A: Abolishes interaction with PDCD6. 1 Publication1
Mutagenesisi45L → A: Abolishes interaction with PDCD6. 1 Publication1
Mutagenesisi47 – 49YFF → AAA: Abolishes interaction with PDCD6. 1 Publication3
Mutagenesisi61 – 62RK → AA: Reduces PtdIns(3,5)P2 sensitivity. 1 Publication2
Mutagenesisi109Y → G: Abolishes formation and extrusion of tubulo-vesicular structures and decreases lysosomal exocytosis when overexpressed. 1 Publication1
Mutagenesisi110S → C: Modulates ion conduction; when associoated with C-112 and C-113. 1 Publication1
Mutagenesisi111D → Q: Modulates inhibition by Ca(2+) at different pH levels but does not abolish channel inward rectification; when associated with Q-114 and Q-115. 1 Publication1
Mutagenesisi112G → C: Modulates ion conduction; when associoated with C-110 and C-113. 1 Publication1
Mutagenesisi113A → C: Modulates ion conduction; when associoated with C-110 and C-112. 1 Publication1
Mutagenesisi114D → Q: Modulates inhibition by Ca(2+) at different pH levels but does not abolish channel inward rectification; when associated with Q-111 and Q-115. 1 Publication1
Mutagenesisi115D → Q: Modulates inhibition by Ca(2+) at different pH levels but does not abolish channel inward rectification; when associated with Q-111 and Q-114. 1 Publication1
Mutagenesisi144L → K: Disrupts tetrameric assembly and abolishes lysosomal localization; when associated with S-146. 1 Publication1
Mutagenesisi146R → S: Disrupts tetrameric assembly and abolishes lysosomal localization; when associated with K-144. 1 Publication1
Mutagenesisi200R → H: Does not prevent proteolytic cleavage but changes cleavage pattern. 1 Publication1
Mutagenesisi432V → P: Mediates localization to the plasma membrane and strong inwardly rectifying current. 2 Publications1
Mutagenesisi471D → A: Fails to rescue defect of lactosylceramide traffic through the late endocytic pathway in ML4 patient cells. 1 Publication1
Mutagenesisi565 – 567CCC → AAA: Abolishes association with membranes. 1 Publication3
Mutagenesisi577 – 578LL → AA: No effect on localization to lysosomes. 1 Publication2
Mutagenesisi577L → A: Abolishes localization to lysosomes and leads to expression at the cell membrane; when associated with A-15. 2 Publications1

Keywords - Diseasei

Disease mutation, Mucolipidosis

Organism-specific databases

DisGeNET

More...DisGeNETi		57192

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		MCOLN1

MalaCards human disease database

More...MalaCardsi		MCOLN1
MIMi252650 phenotype

Open Targets

More...OpenTargetsi		ENSG00000090674

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		578 Mucolipidosis type IV

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA30699

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q9GZU1 Tchem

Chemistry databases

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		501

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		MCOLN1

Domain mapping of disease mutations (DMDM)

More...DMDMi		50401163

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002153621 – 580Mucolipin-1Add BLAST580

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei10PhosphoserineBy similarity1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi166 ↔ 192Combined sources2 Publications
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi230N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi253 ↔ 284Combined sources2 Publications
Modified residuei557Phosphoserine; by PAK1 Publication1
Modified residuei559Phosphoserine; by PAK1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Palmitoylated; involved in association with membranes.1 Publication
Phosphorylation by PKA inhibits channel activity. Dephosphorylation increases activity.1 Publication
Proteolytically cleaved probably involving multiple lysosomal proteases including cathepsin B; inhibits lysosomal channel activity (PubMed:16257972).1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		Q9GZU1

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q9GZU1

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q9GZU1

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q9GZU1

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q9GZU1

PeptideAtlas

More...PeptideAtlasi		Q9GZU1

PRoteomics IDEntifications database

More...PRIDEi		Q9GZU1

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		80143

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q9GZU1

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q9GZU1

SwissPalm database of S-palmitoylation events

More...SwissPalmi		Q9GZU1

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed in adult and fetal tissues.3 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000090674 Expressed in right adrenal gland and 197 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q9GZU1 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q9GZU1 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000090674 Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homotetramer (PubMed:28112729, PubMed:29019983). Homooligomer (PubMed:14749347). Can heterooligomerize with MCOLN2 or MCOLN3; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific (PubMed:19885840).

Interacts with PDCD6 (PubMed:19864416).

Interacts with TMEM163 (PubMed:25130899).

Interacts with LAPTM4B (PubMed:21224396).

1 Publication6 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		121441, 10 interactors

Database of interacting proteins

More...DIPi		DIP-62090N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		Q9GZU1

Protein interaction database and analysis system

More...IntActi		Q9GZU1, 7 interactors

Molecular INTeraction database

More...MINTi		Q9GZU1

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000264079

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q9GZU1 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1580
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q9GZU1

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni42 – 62Interaction with phosphoinositides1 PublicationAdd BLAST21
Regioni107 – 121Extracellular/lumenal pore loop1 PublicationAdd BLAST15
Regioni565 – 567Required for palmitoylation and association with membranes1 Publication3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi11 – 16Dileucine motif; mediates targeting to lysosomes1 Publication6
Motifi469 – 474Selectivity filter1 Publication6
Motifi573 – 578Dileucine internalization motif; mediates AP2 complex-dependent internalization1 Publication6

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca2+ and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN1 sub-subfamily. [View classification]Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3733 Eukaryota
ENOG410Z1HH LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00950000183036

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_020945_1_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q9GZU1

KEGG Orthology (KO)

More...KOi		K04992

Identification of Orthologs from Complete Genome Data

More...OMAi		THIQECK

Database of Orthologous Groups

More...OrthoDBi		1379516at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q9GZU1

TreeFam database of animal gene trees

More...TreeFami		TF317783

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR039031 Mucolipin
IPR013122 PKD1_2_channel

The PANTHER Classification System

More...PANTHERi		PTHR12127 PTHR12127, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF08016 PKD_channel, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q9GZU1-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTAPAGPRGS ETERLLTPNP GYGTQAGPSP APPTPPEEED LRRRLKYFFM 
        60         70         80         90        100
SPCDKFRAKG RKPCKLMLQV VKILVVTVQL ILFGLSNQLA VTFREENTIA 
       110        120        130        140        150
FRHLFLLGYS DGADDTFAAY TREQLYQAIF HAVDQYLALP DVSLGRYAYV 
       160        170        180        190        200
RGGGDPWTNG SGLALCQRYY HRGHVDPAND TFDIDPMVVT DCIQVDPPER 
       210        220        230        240        250
PPPPPSDDLT LLESSSSYKN LTLKFHKLVN VTIHFRLKTI NLQSLINNEI 
       260        270        280        290        300
PDCYTFSVLI TFDNKAHSGR IPISLETQAH IQECKHPSVF QHGDNSFRLL 
       310        320        330        340        350
FDVVVILTCS LSFLLCARSL LRGFLLQNEF VGFMWRQRGR VISLWERLEF 
       360        370        380        390        400
VNGWYILLVT SDVLTISGTI MKIGIEAKNL ASYDVCSILL GTSTLLVWVG 
       410        420        430        440        450
VIRYLTFFHN YNILIATLRV ALPSVMRFCC CVAVIYLGYC FCGWIVLGPY 
       460        470        480        490        500
HVKFRSLSMV SECLFSLING DDMFVTFAAM QAQQGRSSLV WLFSQLYLYS 
       510        520        530        540        550
FISLFIYMVL SLFIALITGA YDTIKHPGGA GAEESELQAY IAQCQDSPTS 
       560        570        580
GKFRRGSGSA CSLLCCCGRD PSEEHSLLVN
Length:580
Mass (Da):65,022
Last modified:March 1, 2001 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i7E7691F58D01C804
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0QXD0M0QXD0_HUMAN
Mucolipin-1
MCOLN1
200Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
M0R1X7M0R1X7_HUMAN
Mucolipin-1
MCOLN1
182Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAQ13604 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence CAC07813 differs from that shown. Probable cloning artifact.Curated
The sequence EAW69031 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW69034 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti164 – 191ALCQR…MVVTD → LSASGTTTEATWTRPTTHLT LIRWWLLVN in AAG42242 (PubMed:10973263).CuratedAdd BLAST28
Sequence conflicti203P → S in CAC08215 (PubMed:11013137).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019369106L → P in ML4; decreases formation and extrusion of tubulo-vesicular structures when overexpressed; disrupts tetrameric assembly; abolishes lysosomal localization. 3 PublicationsCorresponds to variant dbSNP:rs797044825EnsemblClinVar.1
Natural variantiVAR_019370232T → P in ML4; fails to localize to late endosomes; abolishes Fe(2+) permeability; disrupts tetrameric assembly; abolishes lysosomal localization. 4 PublicationsCorresponds to variant dbSNP:rs767122713EnsemblClinVar.1
Natural variantiVAR_036453331V → L in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_019371362D → Y in ML4; affects channel activity; abolishes Fe(2+) permeability. 4 PublicationsCorresponds to variant dbSNP:rs121908372EnsemblClinVar.1
Natural variantiVAR_038380403R → C in ML4; impairs Fe(2+) permeability. 2 PublicationsCorresponds to variant dbSNP:rs121908374EnsemblClinVar.1
Natural variantiVAR_019372408Missing in ML4; mild psychomotor involvement; does not affect channel activity; affects channel inhibition by low pH; still localizes to late endosomes. 5 Publications1
Natural variantiVAR_019373446V → L in ML4; does not affect channel activity; affects channel inhibition by low pH; impairs Fe(2+) permeability. 3 PublicationsCorresponds to variant dbSNP:rs754097561EnsemblClinVar.1
Natural variantiVAR_019374447L → P in ML4. 1 PublicationCorresponds to variant dbSNP:rs797044827EnsemblClinVar.1
Natural variantiVAR_019375465F → L in ML4; still localizes to late endosomes; fails to rescue defect of lactosylceramide traffic through the late endocytic pathway in ML4 patient cells; minor effect on formation and extrusion of tubulo-vesicular structures when overexpressed. 4 PublicationsCorresponds to variant dbSNP:rs797044828EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AJ293659 mRNA Translation: CAC07813.1 Sequence problems.
AJ293970 mRNA Translation: CAC08215.1
AF287269 mRNA Translation: AAG00797.1
AF287270 Genomic DNA Translation: AAG00798.1
AF249319 mRNA Translation: AAG10422.1
AF305579 AF305578 Genomic DNA Translation: AAG42242.1
AK026102 mRNA Translation: BAB15360.1
CH471139 Genomic DNA Translation: EAW69031.1 Sequence problems.
CH471139 Genomic DNA Translation: EAW69034.1 Sequence problems.
BC005149 mRNA Translation: AAH05149.1
AF171088 mRNA Translation: AAQ13604.1 Different initiation.

The Consensus CDS (CCDS) project

More...CCDSi		CCDS12180.1

NCBI Reference Sequences

More...RefSeqi		NP_065394.1, NM_020533.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000264079; ENSP00000264079; ENSG00000090674

Database of genes from NCBI RefSeq genomes

More...GeneIDi		57192

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:57192

UCSC genome browser

More...UCSCi		uc002mgo.4 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ293659 mRNA Translation: CAC07813.1 Sequence problems.
AJ293970 mRNA Translation: CAC08215.1
AF287269 mRNA Translation: AAG00797.1
AF287270 Genomic DNA Translation: AAG00798.1
AF249319 mRNA Translation: AAG10422.1
AF305579 AF305578 Genomic DNA Translation: AAG42242.1
AK026102 mRNA Translation: BAB15360.1
CH471139 Genomic DNA Translation: EAW69031.1 Sequence problems.
CH471139 Genomic DNA Translation: EAW69034.1 Sequence problems.
BC005149 mRNA Translation: AAH05149.1
AF171088 mRNA Translation: AAQ13604.1 Different initiation.
CCDSiCCDS12180.1
RefSeqiNP_065394.1, NM_020533.2

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5TJAX-ray2.30A84-296[»]
5TJBX-ray2.40A84-296[»]
5TJCX-ray2.40A84-296[»]
5WJ5electron microscopy3.70A/B/C/D1-580[»]
5WJ9electron microscopy3.49A/B/C/D1-580[»]
6E7Pelectron microscopy3.50A/B/C/D1-580[»]
6E7Yelectron microscopy3.57A/B/C/D1-580[»]
6E7Zelectron microscopy3.73A/B/C/D1-580[»]
SMRiQ9GZU1
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi121441, 10 interactors
DIPiDIP-62090N
ELMiQ9GZU1
IntActiQ9GZU1, 7 interactors
MINTiQ9GZU1
STRINGi9606.ENSP00000264079

Chemistry databases

GuidetoPHARMACOLOGYi501

Protein family/group databases

TCDBi1.A.5.3.1 the polycystin cation channel (pcc) family

PTM databases

iPTMnetiQ9GZU1
PhosphoSitePlusiQ9GZU1
SwissPalmiQ9GZU1

Polymorphism and mutation databases

BioMutaiMCOLN1
DMDMi50401163

Proteomic databases

EPDiQ9GZU1
jPOSTiQ9GZU1
MassIVEiQ9GZU1
MaxQBiQ9GZU1
PaxDbiQ9GZU1
PeptideAtlasiQ9GZU1
PRIDEiQ9GZU1
ProteomicsDBi80143

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		12053 161 antibodies

The DNASU plasmid repository

More...DNASUi		57192

Genome annotation databases

EnsembliENST00000264079; ENSP00000264079; ENSG00000090674
GeneIDi57192
KEGGihsa:57192
UCSCiuc002mgo.4 human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		57192
DisGeNETi57192
EuPathDBiHostDB:ENSG00000090674.15

GeneCards: human genes, protein and diseases

More...GeneCardsi		MCOLN1
GeneReviewsiMCOLN1
HGNCiHGNC:13356 MCOLN1
HPAiENSG00000090674 Low tissue specificity
MalaCardsiMCOLN1
MIMi252650 phenotype
605248 gene
neXtProtiNX_Q9GZU1
OpenTargetsiENSG00000090674
Orphaneti578 Mucolipidosis type IV
PharmGKBiPA30699

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3733 Eukaryota
ENOG410Z1HH LUCA
GeneTreeiENSGT00950000183036
HOGENOMiCLU_020945_1_1_1
InParanoidiQ9GZU1
KOiK04992
OMAiTHIQECK
OrthoDBi1379516at2759
PhylomeDBiQ9GZU1
TreeFamiTF317783

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels
R-HSA-917977 Transferrin endocytosis and recycling
SIGNORiQ9GZU1

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		57192 10 hits in 794 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		MCOLN1 human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		MCOLN1

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		57192
PharosiQ9GZU1 Tchem

Protein Ontology

More...PROi		PR:Q9GZU1
RNActiQ9GZU1 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000090674 Expressed in right adrenal gland and 197 other tissues
ExpressionAtlasiQ9GZU1 baseline and differential
GenevisibleiQ9GZU1 HS

Family and domain databases

InterProiView protein in InterPro
IPR039031 Mucolipin
IPR013122 PKD1_2_channel
PANTHERiPTHR12127 PTHR12127, 1 hit
PfamiView protein in Pfam
PF08016 PKD_channel, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiMCLN1_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9GZU1
Secondary accession number(s): D6W647
, Q7Z4F7, Q9H292, Q9H4B3, Q9H4B5
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: March 1, 2001
Last modified: June 17, 2020
This is version 173 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
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