UniProtKB - Q9GZU1 (MCLN1_HUMAN)
Protein
Mucolipin-1
Gene
MCOLN1
Organism
Homo sapiens (Human)
Status
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, PubMed:27623384). 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 Publication11 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
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
GO - Molecular functioni
- cation channel activity Source: UniProtKB
- intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity Source: UniProtKB
- iron ion transmembrane transporter activity Source: Reactome
- ligand-gated calcium channel activity Source: UniProtKB
- lipid binding Source: UniProtKB-KW
- NAADP-sensitive calcium-release channel activity Source: GO_Central
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- autophagosome maturation Source: Ensembl
- calcium ion transmembrane transport Source: UniProtKB
- cation transport Source: UniProtKB
- cellular response to calcium ion Source: UniProtKB
- cellular response to pH Source: UniProtKB
- phagosome maturation Source: UniProtKB
- protein homotetramerization Source: UniProtKB
- transferrin transport Source: Reactome
Keywordsi
Molecular function | Ion channel |
Biological process | Adaptive immunity, Calcium transport, Immunity, Ion transport, Transport |
Ligand | Calcium, Lipid-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9GZU1 |
Reactomei | R-HSA-3295583, TRP channels R-HSA-917977, Transferrin endocytosis and recycling |
SIGNORi | Q9GZU1 |
Protein family/group databases
TCDBi | 1.A.5.3.1, the polycystin cation channel (pcc) family |
Names & Taxonomyi
Protein namesi | Recommended name: Mucolipin-11 PublicationShort name: ML1 Alternative name(s): MG-2 Mucolipidin1 Publication Transient receptor potential channel mucolipin 1 Short name: TRPML11 Publication |
Gene namesi | ORF Names:MSTP080 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:13356, MCOLN1 |
MIMi | 605248, gene |
neXtProti | NX_Q9GZU1 |
VEuPathDBi | HostDB:ENSG00000090674.15 |
Subcellular locationi
Lysosome
- Lysosome membrane 2 Publications2 Publications; Multi-pass membrane protein 1 Publication
Endosome
- Late endosome membrane 2 Publications; Multi-pass membrane protein 1 Publication
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Other locations
- Cytoplasmic vesicle membrane 1 Publication; Multi-pass membrane protein 1 Publication
- phagocytic cup By similarity
- phagosome membrane By similarity; Multi-pass membrane protein 1 Publication
Note: Delivery from the trans-Golgi to lysosomes seems to occur mainly in a direct intracellular manner without intermediate delivery to the plasma membrane (PubMed:16497227). Under normal conditions, restricted to intracellular compartments so that only a very minor proportion is present at the cell membrane (PubMed:12459486, PubMed:18794901, PubMed:28112729, PubMed:29019983).1 Publication4 Publications
Endosome
- endosome membrane Source: Reactome
- late endosome Source: UniProtKB
- late endosome membrane Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: HPA
Lysosome
- lysosomal membrane Source: UniProtKB
- lysosome Source: UniProtKB
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- phagocytic cup Source: UniProtKB-SubCell
- plasma membrane Source: GO_Central
Other locations
- cell projection Source: UniProtKB-KW
- integral component of membrane Source: UniProtKB
- intracellular membrane-bounded organelle Source: HPA
- membrane Source: GO_Central
- phagocytic vesicle membrane Source: UniProtKB-SubCell
- receptor complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 65 | Cytoplasmic1 PublicationAdd BLAST | 65 | |
Transmembranei | 66 – 86 | Helical; Name=11 PublicationAdd BLAST | 21 | |
Topological domaini | 87 – 298 | Extracellular1 PublicationAdd BLAST | 212 | |
Transmembranei | 299 – 321 | Helical; Name=21 PublicationAdd BLAST | 23 | |
Topological domaini | 322 – 350 | Cytoplasmic1 PublicationAdd BLAST | 29 | |
Transmembranei | 351 – 371 | Helical; Name=31 PublicationAdd BLAST | 21 | |
Topological domaini | 372 – 382 | Extracellular1 PublicationAdd BLAST | 11 | |
Transmembranei | 383 – 405 | Helical; Name=41 PublicationAdd BLAST | 23 | |
Topological domaini | 406 – 427 | Cytoplasmic1 PublicationAdd BLAST | 22 | |
Transmembranei | 428 – 448 | Helical; Name=51 PublicationAdd BLAST | 21 | |
Topological domaini | 449 – 456 | Extracellular1 Publication | 8 | |
Intramembranei | 457 – 477 | Pore-forming1 PublicationAdd BLAST | 21 | |
Topological domaini | 478 – 491 | Extracellular1 PublicationAdd BLAST | 14 | |
Transmembranei | 492 – 513 | Helical; Name=61 PublicationAdd BLAST | 22 | |
Topological domaini | 514 – 580 | Cytoplasmic1 PublicationAdd BLAST | 67 |
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Lysosome, MembranePathology & Biotechi
Involvement in diseasei
Mucolipidosis 4 (ML4)12 Publications
The disease is caused by variants 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 OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019369 | 106 | L → 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_019370 | 232 | T → 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_019371 | 362 | D → Y in ML4; affects channel activity; abolishes Fe(2+) permeability. 4 PublicationsCorresponds to variant dbSNP:rs121908372EnsemblClinVar. | 1 | |
Natural variantiVAR_038380 | 403 | R → C in ML4; impairs Fe(2+) permeability. 2 PublicationsCorresponds to variant dbSNP:rs121908374EnsemblClinVar. | 1 | |
Natural variantiVAR_019372 | 408 | Missing in ML4; mild psychomotor involvement; does not affect channel activity; affects channel inhibition by low pH; still localizes to late endosomes. 5 Publications | 1 | |
Natural variantiVAR_019373 | 446 | V → 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_019374 | 447 | L → P in ML4. 1 PublicationCorresponds to variant dbSNP:rs797044827EnsemblClinVar. | 1 | |
Natural variantiVAR_019375 | 465 | F → 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 15 – 16 | LL → AA: No effect on localization to lysosomes. 1 Publication | 2 | |
Mutagenesisi | 15 | L → A: Abolishes localization to lysosomes and leads to expression at the cell membrane; when associated with A-577. 2 Publications | 1 | |
Mutagenesisi | 42 – 44 | RRR → AAA: Reduces PtdIns(4,5)P2 sensitivity. 1 Publication | 3 | |
Mutagenesisi | 44 – 46 | RLK → AAA: Abolishes interaction with PDCD6 and decreases formation of aberrant endosomes upon overexpression. 1 Publication | 3 | |
Mutagenesisi | 44 | R → A: Abolishes interaction with PDCD6. 1 Publication | 1 | |
Mutagenesisi | 45 | L → A: Abolishes interaction with PDCD6. 1 Publication | 1 | |
Mutagenesisi | 47 – 49 | YFF → AAA: Abolishes interaction with PDCD6. 1 Publication | 3 | |
Mutagenesisi | 61 – 62 | RK → AA: Reduces PtdIns(3,5)P2 sensitivity. 1 Publication | 2 | |
Mutagenesisi | 109 | Y → G: Abolishes formation and extrusion of tubulo-vesicular structures and decreases lysosomal exocytosis when overexpressed. 1 Publication | 1 | |
Mutagenesisi | 110 | S → C: Modulates ion conduction; when associoated with C-112 and C-113. 1 Publication | 1 | |
Mutagenesisi | 111 | D → 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 Publication | 1 | |
Mutagenesisi | 112 | G → C: Modulates ion conduction; when associoated with C-110 and C-113. 1 Publication | 1 | |
Mutagenesisi | 113 | A → C: Modulates ion conduction; when associoated with C-110 and C-112. 1 Publication | 1 | |
Mutagenesisi | 114 | D → 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 Publication | 1 | |
Mutagenesisi | 115 | D → 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 Publication | 1 | |
Mutagenesisi | 144 | L → K: Disrupts tetrameric assembly and abolishes lysosomal localization; when associated with S-146. 1 Publication | 1 | |
Mutagenesisi | 146 | R → S: Disrupts tetrameric assembly and abolishes lysosomal localization; when associated with K-144. 1 Publication | 1 | |
Mutagenesisi | 200 | R → H: Does not prevent proteolytic cleavage but changes cleavage pattern. 1 Publication | 1 | |
Mutagenesisi | 432 | V → P: Mediates localization to the plasma membrane and strong inwardly rectifying current. 2 Publications | 1 | |
Mutagenesisi | 471 | D → A: Fails to rescue defect of lactosylceramide traffic through the late endocytic pathway in ML4 patient cells. 1 Publication | 1 | |
Mutagenesisi | 565 – 567 | CCC → AAA: Abolishes association with membranes. 1 Publication | 3 | |
Mutagenesisi | 577 – 578 | LL → AA: No effect on localization to lysosomes. 1 Publication | 2 | |
Mutagenesisi | 577 | L → A: Abolishes localization to lysosomes and leads to expression at the cell membrane; when associated with A-15. 2 Publications | 1 |
Keywords - Diseasei
Disease variant, MucolipidosisOrganism-specific databases
DisGeNETi | 57192 |
GeneReviewsi | MCOLN1 |
MalaCardsi | MCOLN1 |
MIMi | 252650, phenotype |
OpenTargetsi | ENSG00000090674 |
Orphaneti | 578, Mucolipidosis type IV |
PharmGKBi | PA30699 |
Miscellaneous databases
Pharosi | Q9GZU1, Tchem |
Chemistry databases
GuidetoPHARMACOLOGYi | 501 |
Genetic variation databases
BioMutai | MCOLN1 |
DMDMi | 50401163 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000215362 | 1 – 580 | Mucolipin-1Add BLAST | 580 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 10 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 166 ↔ 192 | Combined sources2 Publications | ||
Glycosylationi | 230 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 253 ↔ 284 | Combined sources2 Publications | ||
Modified residuei | 557 | Phosphoserine; by PAK1 Publication | 1 | |
Modified residuei | 559 | Phosphoserine; by PAK1 Publication | 1 |
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, PhosphoproteinProteomic databases
EPDi | Q9GZU1 |
jPOSTi | Q9GZU1 |
MassIVEi | Q9GZU1 |
MaxQBi | Q9GZU1 |
PaxDbi | Q9GZU1 |
PeptideAtlasi | Q9GZU1 |
PRIDEi | Q9GZU1 |
ProteomicsDBi | 80143 |
PTM databases
GlyGeni | Q9GZU1, 2 sites |
iPTMneti | Q9GZU1 |
PhosphoSitePlusi | Q9GZU1 |
SwissPalmi | Q9GZU1 |
Expressioni
Tissue specificityi
Widely expressed in adult and fetal tissues.3 Publications
Gene expression databases
Bgeei | ENSG00000090674, Expressed in right adrenal gland and 209 other tissues |
ExpressionAtlasi | Q9GZU1, baseline and differential |
Genevisiblei | Q9GZU1, HS |
Organism-specific databases
HPAi | ENSG00000090674, Low tissue specificity |
Interactioni
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 PublicationsBinary interactionsi
Hide detailsProtein-protein interaction databases
BioGRIDi | 121441, 12 interactors |
DIPi | DIP-62090N |
ELMi | Q9GZU1 |
IntActi | Q9GZU1, 7 interactors |
MINTi | Q9GZU1 |
STRINGi | 9606.ENSP00000264079 |
Miscellaneous databases
RNActi | Q9GZU1, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9GZU1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 42 – 62 | Interaction with phosphoinositides1 PublicationAdd BLAST | 21 | |
Regioni | 107 – 121 | Extracellular/lumenal pore loop1 PublicationAdd BLAST | 15 | |
Regioni | 565 – 567 | Required for palmitoylation and association with membranes1 Publication | 3 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 11 – 16 | Dileucine motif; mediates targeting to lysosomes1 Publication | 6 | |
Motifi | 469 – 474 | Selectivity filter1 Publication | 6 | |
Motifi | 573 – 578 | Dileucine internalization motif; mediates AP2 complex-dependent internalization1 Publication | 6 |
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
Sequence similaritiesi
Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN1 sub-subfamily. [View classification]Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3733, Eukaryota |
GeneTreei | ENSGT00950000183036 |
HOGENOMi | CLU_020945_1_1_1 |
InParanoidi | Q9GZU1 |
OMAi | THIQECK |
OrthoDBi | 1379516at2759 |
PhylomeDBi | Q9GZU1 |
TreeFami | TF317783 |
Family and domain databases
InterProi | View protein in InterPro IPR039031, Mucolipin IPR013122, PKD1_2_channel |
PANTHERi | PTHR12127, PTHR12127, 1 hit |
Pfami | View protein in Pfam PF08016, PKD_channel, 1 hit |
(1+)i Sequence
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
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0R1X7 | M0R1X7_HUMAN | Mucolipin-1 | MCOLN1 | 182 | Annotation score: | ||
M0QXD0 | M0QXD0_HUMAN | Mucolipin-1 | MCOLN1 | 200 | Annotation score: |
Sequence cautioni
The sequence AAQ13604 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 164 – 191 | ALCQR…MVVTD → LSASGTTTEATWTRPTTHLT LIRWWLLVN in AAG42242 (PubMed:10973263).CuratedAdd BLAST | 28 | |
Sequence conflicti | 203 | P → S in CAC08215 (PubMed:11013137).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019369 | 106 | L → 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_019370 | 232 | T → 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_036453 | 331 | V → L in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_019371 | 362 | D → Y in ML4; affects channel activity; abolishes Fe(2+) permeability. 4 PublicationsCorresponds to variant dbSNP:rs121908372EnsemblClinVar. | 1 | |
Natural variantiVAR_038380 | 403 | R → C in ML4; impairs Fe(2+) permeability. 2 PublicationsCorresponds to variant dbSNP:rs121908374EnsemblClinVar. | 1 | |
Natural variantiVAR_019372 | 408 | Missing in ML4; mild psychomotor involvement; does not affect channel activity; affects channel inhibition by low pH; still localizes to late endosomes. 5 Publications | 1 | |
Natural variantiVAR_019373 | 446 | V → 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_019374 | 447 | L → P in ML4. 1 PublicationCorresponds to variant dbSNP:rs797044827EnsemblClinVar. | 1 | |
Natural variantiVAR_019375 | 465 | F → 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: 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 , AF305572, AF305573, AF305574, AF305575, AF305576, AF305577, 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. |
CCDSi | CCDS12180.1 |
RefSeqi | NP_065394.1, NM_020533.2 |
Genome annotation databases
Ensembli | ENST00000264079; ENSP00000264079; ENSG00000090674 |
GeneIDi | 57192 |
KEGGi | hsa:57192 |
UCSCi | uc002mgo.4, human |
Similar proteinsi
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 , AF305572, AF305573, AF305574, AF305575, AF305576, AF305577, 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. |
CCDSi | CCDS12180.1 |
RefSeqi | NP_065394.1, NM_020533.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5TJA | X-ray | 2.30 | A | 84-296 | [»] | |
5TJB | X-ray | 2.40 | A | 84-296 | [»] | |
5TJC | X-ray | 2.40 | A | 84-296 | [»] | |
5WJ5 | electron microscopy | 3.70 | A/B/C/D | 1-580 | [»] | |
5WJ9 | electron microscopy | 3.49 | A/B/C/D | 1-580 | [»] | |
6E7P | electron microscopy | 3.50 | A/B/C/D | 1-580 | [»] | |
6E7Y | electron microscopy | 3.57 | A/B/C/D | 1-580 | [»] | |
6E7Z | electron microscopy | 3.73 | A/B/C/D | 1-580 | [»] | |
SMRi | Q9GZU1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121441, 12 interactors |
DIPi | DIP-62090N |
ELMi | Q9GZU1 |
IntActi | Q9GZU1, 7 interactors |
MINTi | Q9GZU1 |
STRINGi | 9606.ENSP00000264079 |
Chemistry databases
GuidetoPHARMACOLOGYi | 501 |
Protein family/group databases
TCDBi | 1.A.5.3.1, the polycystin cation channel (pcc) family |
PTM databases
GlyGeni | Q9GZU1, 2 sites |
iPTMneti | Q9GZU1 |
PhosphoSitePlusi | Q9GZU1 |
SwissPalmi | Q9GZU1 |
Genetic variation databases
BioMutai | MCOLN1 |
DMDMi | 50401163 |
Proteomic databases
EPDi | Q9GZU1 |
jPOSTi | Q9GZU1 |
MassIVEi | Q9GZU1 |
MaxQBi | Q9GZU1 |
PaxDbi | Q9GZU1 |
PeptideAtlasi | Q9GZU1 |
PRIDEi | Q9GZU1 |
ProteomicsDBi | 80143 |
Protocols and materials databases
Antibodypediai | 12053, 163 antibodies |
DNASUi | 57192 |
Genome annotation databases
Ensembli | ENST00000264079; ENSP00000264079; ENSG00000090674 |
GeneIDi | 57192 |
KEGGi | hsa:57192 |
UCSCi | uc002mgo.4, human |
Organism-specific databases
CTDi | 57192 |
DisGeNETi | 57192 |
GeneCardsi | MCOLN1 |
GeneReviewsi | MCOLN1 |
HGNCi | HGNC:13356, MCOLN1 |
HPAi | ENSG00000090674, Low tissue specificity |
MalaCardsi | MCOLN1 |
MIMi | 252650, phenotype 605248, gene |
neXtProti | NX_Q9GZU1 |
OpenTargetsi | ENSG00000090674 |
Orphaneti | 578, Mucolipidosis type IV |
PharmGKBi | PA30699 |
VEuPathDBi | HostDB:ENSG00000090674.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3733, Eukaryota |
GeneTreei | ENSGT00950000183036 |
HOGENOMi | CLU_020945_1_1_1 |
InParanoidi | Q9GZU1 |
OMAi | THIQECK |
OrthoDBi | 1379516at2759 |
PhylomeDBi | Q9GZU1 |
TreeFami | TF317783 |
Enzyme and pathway databases
PathwayCommonsi | Q9GZU1 |
Reactomei | R-HSA-3295583, TRP channels R-HSA-917977, Transferrin endocytosis and recycling |
SIGNORi | Q9GZU1 |
Miscellaneous databases
BioGRID-ORCSi | 57192, 11 hits in 879 CRISPR screens |
ChiTaRSi | MCOLN1, human |
GeneWikii | MCOLN1 |
GenomeRNAii | 57192 |
Pharosi | Q9GZU1, Tchem |
PROi | PR:Q9GZU1 |
RNActi | Q9GZU1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000090674, Expressed in right adrenal gland and 209 other tissues |
ExpressionAtlasi | Q9GZU1, baseline and differential |
Genevisiblei | Q9GZU1, HS |
Family and domain databases
InterProi | View protein in InterPro IPR039031, Mucolipin IPR013122, PKD1_2_channel |
PANTHERi | PTHR12127, PTHR12127, 1 hit |
Pfami | View protein in Pfam PF08016, PKD_channel, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MCLN1_HUMAN | |
Accessioni | Q9GZU1Primary (citable) accession number: Q9GZU1 Secondary accession number(s): D6W647 Q9H4B5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2004 |
Last sequence update: | March 1, 2001 | |
Last modified: | February 10, 2021 | |
This is version 177 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants