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Protein

Mucolipin-3

Gene

MCOLN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Nonselective ligand-gated cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca2+-permeable cation channel with inwardly rectifying activity (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840, PubMed:29106414). Mediates release of Ca2+ from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (PubMed:21245134). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (By similarity). Involved in the regulation of autophagy (PubMed:19522758). Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca2+ for the fusion process (By similarity). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events (PubMed:19885840). Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (PubMed:23469151).By similarityCurated8 Publications

Activity regulationi

Inhibited by lumenal H+ and Na+ (PubMed:18369318, PubMed:29106414). The channel pore shows dynamic behavior and undergoes spontaneous, Ca2+-dependent modulation when conducting Ca2+ (PubMed:20378547).3 Publications

GO - Molecular functioni

  • calcium channel activity Source: Reactome
  • lipid binding Source: UniProtKB-KW
  • NAADP-sensitive calcium-release channel activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionIon channel
Biological processIon transport, Transport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels

Protein family/group databases

TCDBi1.A.5.3.4 the polycystin cation channel (pcc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Mucolipin-31 Publication
Alternative name(s):
Transient receptor potential channel mucolipin 3
Short name:
TRPML31 Publication
Gene namesi
Name:MCOLN3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000055732.12
HGNCiHGNC:13358 MCOLN3
MIMi607400 gene
neXtProtiNX_Q8TDD5

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; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 62Cytoplasmic1 PublicationAdd BLAST62
Transmembranei63 – 83Helical1 PublicationAdd BLAST21
Topological domaini84 – 283Extracellular1 PublicationAdd BLAST200
Transmembranei284 – 304Helical1 PublicationAdd BLAST21
Topological domaini305 – 341Cytoplasmic1 PublicationAdd BLAST37
Transmembranei342 – 362Helical1 PublicationAdd BLAST21
Topological domaini363 – 371Extracellular1 Publication9
Transmembranei372 – 392Helical1 PublicationAdd BLAST21
Topological domaini393 – 414Cytoplasmic1 PublicationAdd BLAST22
Transmembranei415 – 435Helical1 PublicationAdd BLAST21
Topological domaini436 – 443Extracellular1 Publication8
Intramembranei444 – 464Pore-forming1 PublicationAdd BLAST21
Topological domaini465 – 475Extracellular1 PublicationAdd BLAST11
Transmembranei476 – 497Helical1 PublicationAdd BLAST22
Topological domaini498 – 553Cytoplasmic1 PublicationAdd BLAST56

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi108D → N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-111 and N-112. 1 Publication1
Mutagenesisi111D → N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-108 and N-112. 1 Publication1
Mutagenesisi112D → N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-108 and N-111. 1 Publication1
Mutagenesisi252H → A: Increases inhibition by lumenal H(+). Decreases inhibition by lumenal H(+); when associated with A-283. 1 Publication1
Mutagenesisi273H → A: Increases inhibition by lumenal H(+). Decreases inhibition by lumenal H(+); when associated with A-283. 1 Publication1
Mutagenesisi283H → A: Constitutive active channel; abolishes inhibition by lumenal H(+); retains the Ca(2+)-dependent inactivation of the Ca(2+) current. Decreases inhibition by lumenal H(+); when associated with A-252. Decreases inhibition by lumenal H(+); when associated with A-273. 1 Publication1
Mutagenesisi283H → R: Increases inhibition by lumenal H(+). 1 Publication1
Mutagenesisi419A → P: Constitutive active channel; abolishes inhibition by lumenal H(+); increases the pore diameter. 2 Publications1
Mutagenesisi423Y → A: Nearly abolishes channel activation by a synthetic agonist. 1 Publication1
Mutagenesisi449E → A: Constitutive active channel; greatly impairs inhibition by lumenal Na(+). 1 Publication1
Mutagenesisi449E → K: Abolishes channel activity. 1 Publication1
Mutagenesisi458 – 459DD → KK: Enhances endocytosis. 1 Publication2
Mutagenesisi458D → K: Nearly abolishes channel activity; inhibits starvation-induced autophagy. 1 Publication1
Mutagenesisi459D → A: Decreases in Ca(2+) permeability and selectivity; decreases channel pore dynamic behavior. 1 Publication1
Mutagenesisi497F → A: Nearly abolishes channel activation by a synthetic agonist. 1 Publication1

Organism-specific databases

DisGeNETi55283
OpenTargetsiENSG00000055732
PharmGKBiPA134947324

Chemistry databases

ChEMBLiCHEMBL1293243
GuidetoPHARMACOLOGYi503

Polymorphism and mutation databases

BioMutaiMCOLN3
DMDMi50401084

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153671 – 553Mucolipin-3Add BLAST553

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi138N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi159 ↔ 185By similarity
Glycosylationi172N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi205N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi238 ↔ 269By similarity

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ8TDD5
PaxDbiQ8TDD5
PeptideAtlasiQ8TDD5
PRIDEiQ8TDD5
ProteomicsDBi74270
74271 [Q8TDD5-2]

PTM databases

GlyConnecti1522
iPTMnetiQ8TDD5
PhosphoSitePlusiQ8TDD5
SwissPalmiQ8TDD5

Expressioni

Gene expression databases

BgeeiENSG00000055732 Expressed in 160 organ(s), highest expression level in left adrenal gland
CleanExiHS_MCOLN3
ExpressionAtlasiQ8TDD5 baseline and differential
GenevisibleiQ8TDD5 HS

Organism-specific databases

HPAiHPA018106
HPA062137

Interactioni

Subunit structurei

Homotetramer (PubMed:29106414). Can heterooligomerize with MCOLN1; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific (PubMed:19885840). May heterooligomerize with TRPV5 to form a functional distinct ion channel (PubMed:23469151). Interacts with GABARAPL2 (By similarity).By similarity1 Publication2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei305Interaction with phosphoinositidesBy similarity1

Protein-protein interaction databases

BioGridi120571, 60 interactors
IntActiQ8TDD5, 1 interactor
STRINGi9606.ENSP00000304843

Chemistry databases

BindingDBiQ8TDD5

Structurei

3D structure databases

ProteinModelPortaliQ8TDD5
SMRiQ8TDD5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni52 – 62Interaction with phosphoinositidesBy similarityAdd BLAST11
Regioni104 – 118Extracellular/lumenal pore loopBy similarityAdd BLAST15

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi456 – 459Selectivity filter1 Publication4

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.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3733 Eukaryota
ENOG410Z1HH LUCA
GeneTreeiENSGT00390000017126
HOGENOMiHOG000232158
HOVERGENiHBG052430
InParanoidiQ8TDD5
KOiK04994
OMAiQHTSPSE
OrthoDBiEOG091G026A
PhylomeDBiQ8TDD5
TreeFamiTF317783

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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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

Isoform 1 (identifier: Q8TDD5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MADPEVVVSS CSSHEEENRC NFNQQTSPSE ELLLEDQMRR KLKFFFMNPC
60 70 80 90 100
EKFWARGRKP WKLAIQILKI AMVTIQLVLF GLSNQMVVAF KEENTIAFKH
110 120 130 140 150
LFLKGYMDRM DDTYAVYTQS DVYDQLIFAV NQYLQLYNVS VGNHAYENKG
160 170 180 190 200
TKQSAMAICQ HFYKRGNIYP GNDTFDIDPE IETECFFVEP DEPFHIGTPA
210 220 230 240 250
ENKLNLTLDF HRLLTVELQF KLKAINLQTV RHQELPDCYD FTLTITFDNK
260 270 280 290 300
AHSGRIKISL DNDISIRECK DWHVSGSIQK NTHYMMIFDA FVILTCLVSL
310 320 330 340 350
ILCIRSVIRG LQLQQEFVNF FLLHYKKEVS VSDQMEFVNG WYIMIIISDI
360 370 380 390 400
LTIIGSILKM EIQAKSLTSY DVCSILLGTS TMLVWLGVIR YLGFFAKYNL
410 420 430 440 450
LILTLQAALP NVIRFCCCAA MIYLGYCFCG WIVLGPYHDK FRSLNMVSEC
460 470 480 490 500
LFSLINGDDM FATFAKMQQK SYLVWLFSRI YLYSFISLFI YMILSLFIAL
510 520 530 540 550
ITDTYETIKQ YQQDGFPETE LRTFISECKD LPNSGKYRLE DDPPVSLFCC

CKK
Length:553
Mass (Da):64,248
Last modified:June 1, 2002 - v1
Checksum:i2E63DA196379F9E3
GO
Isoform 2 (identifier: Q8TDD5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     77-132: Missing.

Show »
Length:497
Mass (Da):57,723
Checksum:iB014DF953C034761
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B1ANB7B1ANB7_HUMAN
Mucolipin 3, isoform CRA_d
MCOLN3 hCG_1775160
321Annotation score:
S4R386S4R386_HUMAN
Mucolipin-3
MCOLN3
141Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9S → C in BAA91951 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01082377 – 132Missing in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF475085 mRNA Translation: AAL84622.1
AK001868 mRNA Translation: BAA91951.1
AL358789 Genomic DNA No translation available.
CCDSiCCDS58009.1 [Q8TDD5-2]
CCDS701.1 [Q8TDD5-1]
RefSeqiNP_001240622.1, NM_001253693.1 [Q8TDD5-2]
NP_060768.8, NM_018298.10 [Q8TDD5-1]
XP_005271060.1, XM_005271003.1 [Q8TDD5-1]
XP_006710813.1, XM_006710750.1 [Q8TDD5-1]
UniGeneiHs.535239

Genome annotation databases

EnsembliENST00000341115; ENSP00000342698; ENSG00000055732 [Q8TDD5-2]
ENST00000370589; ENSP00000359621; ENSG00000055732 [Q8TDD5-1]
GeneIDi55283
KEGGihsa:55283
UCSCiuc001dkp.4 human [Q8TDD5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF475085 mRNA Translation: AAL84622.1
AK001868 mRNA Translation: BAA91951.1
AL358789 Genomic DNA No translation available.
CCDSiCCDS58009.1 [Q8TDD5-2]
CCDS701.1 [Q8TDD5-1]
RefSeqiNP_001240622.1, NM_001253693.1 [Q8TDD5-2]
NP_060768.8, NM_018298.10 [Q8TDD5-1]
XP_005271060.1, XM_005271003.1 [Q8TDD5-1]
XP_006710813.1, XM_006710750.1 [Q8TDD5-1]
UniGeneiHs.535239

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6AYEelectron microscopy4.06A/B/C/D1-553[»]
6AYFelectron microscopy3.62A/B/C/D1-553[»]
6AYGelectron microscopy4.65A/B/C/D1-553[»]
ProteinModelPortaliQ8TDD5
SMRiQ8TDD5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120571, 60 interactors
IntActiQ8TDD5, 1 interactor
STRINGi9606.ENSP00000304843

Chemistry databases

BindingDBiQ8TDD5
ChEMBLiCHEMBL1293243
GuidetoPHARMACOLOGYi503

Protein family/group databases

TCDBi1.A.5.3.4 the polycystin cation channel (pcc) family

PTM databases

GlyConnecti1522
iPTMnetiQ8TDD5
PhosphoSitePlusiQ8TDD5
SwissPalmiQ8TDD5

Polymorphism and mutation databases

BioMutaiMCOLN3
DMDMi50401084

Proteomic databases

MaxQBiQ8TDD5
PaxDbiQ8TDD5
PeptideAtlasiQ8TDD5
PRIDEiQ8TDD5
ProteomicsDBi74270
74271 [Q8TDD5-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000341115; ENSP00000342698; ENSG00000055732 [Q8TDD5-2]
ENST00000370589; ENSP00000359621; ENSG00000055732 [Q8TDD5-1]
GeneIDi55283
KEGGihsa:55283
UCSCiuc001dkp.4 human [Q8TDD5-1]

Organism-specific databases

CTDi55283
DisGeNETi55283
EuPathDBiHostDB:ENSG00000055732.12
GeneCardsiMCOLN3
HGNCiHGNC:13358 MCOLN3
HPAiHPA018106
HPA062137
MIMi607400 gene
neXtProtiNX_Q8TDD5
OpenTargetsiENSG00000055732
PharmGKBiPA134947324
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3733 Eukaryota
ENOG410Z1HH LUCA
GeneTreeiENSGT00390000017126
HOGENOMiHOG000232158
HOVERGENiHBG052430
InParanoidiQ8TDD5
KOiK04994
OMAiQHTSPSE
OrthoDBiEOG091G026A
PhylomeDBiQ8TDD5
TreeFamiTF317783

Enzyme and pathway databases

ReactomeiR-HSA-3295583 TRP channels

Miscellaneous databases

GeneWikiiMCOLN3
GenomeRNAii55283
PROiPR:Q8TDD5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000055732 Expressed in 160 organ(s), highest expression level in left adrenal gland
CleanExiHS_MCOLN3
ExpressionAtlasiQ8TDD5 baseline and differential
GenevisibleiQ8TDD5 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
ProtoNetiSearch...

Entry informationi

Entry nameiMCLN3_HUMAN
AccessioniPrimary (citable) accession number: Q8TDD5
Secondary accession number(s): Q5T4H5, Q5T4H6, Q9NV09
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: June 1, 2002
Last modified: November 7, 2018
This is version 134 of the entry and version 1 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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