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Protein

Mucolipin-3

Gene

Mcoln3

Organism
Mus musculus (Mouse)
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:17989217). 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 (By similarity). 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 (PubMed:18801844). Involved in the regulation of autophagy. Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca2+ for the fusion process (PubMed:24269818). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events. Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (By similarity).By similarity3 Publications

Activity regulationi

Inhibited by lumenal H+ and Na+. The channel pore shows dynamic behavior and undergoes spontaneous, Ca2+-dependent modulation when conducting Ca2+.By similarity

GO - Molecular functioni

GO - Biological processi

  • inner ear auditory receptor cell differentiation Source: MGI
  • locomotory behavior Source: MGI

Keywordsi

Molecular functionIon channel
Biological processIon transport, Transport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-MMU-3295583 TRP channels

Protein family/group databases

TCDBi1.A.5.3.2 the polycystin cation channel (pcc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Mucolipin-3
Alternative name(s):
Transient receptor potential channel mucolipin 3
Short name:
TRPML3
Gene namesi
Name:Mcoln3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1890500 Mcoln3

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 – 62CytoplasmicBy similarityAdd BLAST62
Transmembranei63 – 83HelicalBy similarityAdd BLAST21
Topological domaini84 – 283ExtracellularBy similarityAdd BLAST200
Transmembranei284 – 304HelicalBy similarityAdd BLAST21
Topological domaini305 – 341CytoplasmicBy similarityAdd BLAST37
Transmembranei342 – 362HelicalBy similarityAdd BLAST21
Topological domaini363 – 371ExtracellularBy similarity9
Transmembranei372 – 392HelicalBy similarityAdd BLAST21
Topological domaini393 – 414CytoplasmicBy similarityAdd BLAST22
Transmembranei415 – 435HelicalBy similarityAdd BLAST21
Topological domaini436 – 443ExtracellularBy similarity8
Intramembranei444 – 464Pore-formingBy similarityAdd BLAST21
Topological domaini465 – 475ExtracellularBy similarityAdd BLAST11
Transmembranei476 – 497HelicalBy similarityAdd BLAST22
Topological domaini498 – 553CytoplasmicBy similarityAdd BLAST56

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Defects in Mcoln3 are the cause of the varitin-waddler (Va) phenotype. Classical Va mice exhibit early-onset hearing loss, vestibular defects, pigmentation abnormalities and perinatal lethality. The phenotype varitin-waddler Jackcon (Va-J), which arose in a cross segregating for Va, is similar but less severe.2 Publications

Disruption phenotypei

No severe auditory and vestibular phenotype; does not lead to circling behavior, balance impairment or hearing loss.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi458 – 459DD → KK: Abolishes channel activity. 1 Publication2

Keywords - Diseasei

Disease mutation

Chemistry databases

GuidetoPHARMACOLOGYi503

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153681 – 553Mucolipin-3Add BLAST553

Amino acid modifications

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

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ8R4F0
PaxDbiQ8R4F0
PRIDEiQ8R4F0

PTM databases

iPTMnetiQ8R4F0
PhosphoSitePlusiQ8R4F0

Expressioni

Tissue specificityi

Expressed in the cochlea; particularly in the inner and outer hair cells (at protein level).2 Publications

Gene expression databases

BgeeiENSMUSG00000036853 Expressed in 118 organ(s), highest expression level in small intestine
CleanExiMM_MCOLN3
ExpressionAtlasiQ8R4F0 baseline and differential
GenevisibleiQ8R4F0 MM

Interactioni

Subunit structurei

Homotetramer. Can heterooligomerize with MCOLN1; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific. May heterooligomerize with TRPV5 to form a functional distinct ion channel (By similarity). Interacts with GABARAPL2 (PubMed:24269818).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei305Interaction with phosphoinositidesBy similarity1

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000038801

Structurei

3D structure databases

ProteinModelPortaliQ8R4F0
SMRiQ8R4F0
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 filterBy similarity4

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
InParanoidiQ8R4F0
KOiK04994
OMAiHEEENRC
OrthoDBiEOG091G026A
PhylomeDBiQ8R4F0
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q8R4F0-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MANPEVLVSS CRARQDESPC TFHPSSSPSE QLLLEDQMRR KLKFFFMNPC
60 70 80 90 100
EKFWARGRKP WKLAIQILKI AMVTIQLVLF GLSNQMVVAF KEENTIAFKH
110 120 130 140 150
LFLKGYMDRM DDTYAVYTQS EVYDQIIFAV TQYLQLQNIS VGNHAYENKG
160 170 180 190 200
TKQSAMAICQ HFYRQGTICP GNDTFDIDPE VETECFLVEP DEASHLGTPG
210 220 230 240 250
ENKLNLSLDF HRLLTVELQF KLKAINLQTV RHQELPDCYD FTLTITFDNK
260 270 280 290 300
AHSGRIKISL DNDISIKECK DWHVSGSIQK NTHYMMIFDA FVILTCLASL
310 320 330 340 350
VLCARSVIRG LQLQQEFVNF FLLHYKKEVS ASDQMEFING WYIMIIISDI
360 370 380 390 400
LTIVGSVLKM EIQAKSLTSY DVCSILLGTS TMLVWLGVIR YLGFFAKYNL
410 420 430 440 450
LILTLQAALP NVMRFCCCAA MIYLGYCFCG WIVLGPYHEK FRSLNRVSEC
460 470 480 490 500
LFSLINGDDM FSTFAKMQQK SYLVWLFSRV YLYSFISLFI YMILSLFIAL
510 520 530 540 550
ITDTYETIKH YQQDGFPETE LRKFIAECKD LPNSGKYRLE DDPPGSLLCC

CKK
Length:553
Mass (Da):63,748
Last modified:June 1, 2002 - v1
Checksum:i8E257B05D96DF536
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3YZE2D3YZE2_MOUSE
Mucolipin-3
Mcoln3
96Annotation score:

Sequence cautioni

The sequence BAC27146 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC28123 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC28916 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti193A → D in BAC27146 (PubMed:16141072).Curated1
Sequence conflicti467M → K in BAC27146 (PubMed:16141072).Curated1
Sequence conflicti543P → A in BAC28916 (PubMed:16141072).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti362I → T in Va-J. 1 Publication1
Natural varianti419A → P in Va and Va-J; constitutive active cation channel localized to plasma membrane. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY083531 mRNA Translation: AAM08924.1
AF475086 mRNA Translation: AAL84623.1
AK030819 mRNA Translation: BAC27146.1 Different initiation.
AK033008 mRNA Translation: BAC28123.1 Different initiation.
AK035029 mRNA Translation: BAC28916.1 Different initiation.
CCDSiCCDS17900.1
RefSeqiNP_598921.1, NM_134160.1
XP_006501144.1, XM_006501081.2
XP_006501145.1, XM_006501082.3
XP_006501146.1, XM_006501083.3
XP_006501147.1, XM_006501084.3
UniGeneiMm.114683

Genome annotation databases

EnsembliENSMUST00000039450; ENSMUSP00000038801; ENSMUSG00000036853
GeneIDi171166
KEGGimmu:171166
UCSCiuc008rqx.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY083531 mRNA Translation: AAM08924.1
AF475086 mRNA Translation: AAL84623.1
AK030819 mRNA Translation: BAC27146.1 Different initiation.
AK033008 mRNA Translation: BAC28123.1 Different initiation.
AK035029 mRNA Translation: BAC28916.1 Different initiation.
CCDSiCCDS17900.1
RefSeqiNP_598921.1, NM_134160.1
XP_006501144.1, XM_006501081.2
XP_006501145.1, XM_006501082.3
XP_006501146.1, XM_006501083.3
XP_006501147.1, XM_006501084.3
UniGeneiMm.114683

3D structure databases

ProteinModelPortaliQ8R4F0
SMRiQ8R4F0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000038801

Chemistry databases

GuidetoPHARMACOLOGYi503

Protein family/group databases

TCDBi1.A.5.3.2 the polycystin cation channel (pcc) family

PTM databases

iPTMnetiQ8R4F0
PhosphoSitePlusiQ8R4F0

Proteomic databases

MaxQBiQ8R4F0
PaxDbiQ8R4F0
PRIDEiQ8R4F0

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000039450; ENSMUSP00000038801; ENSMUSG00000036853
GeneIDi171166
KEGGimmu:171166
UCSCiuc008rqx.1 mouse

Organism-specific databases

CTDi55283
MGIiMGI:1890500 Mcoln3

Phylogenomic databases

eggNOGiKOG3733 Eukaryota
ENOG410Z1HH LUCA
GeneTreeiENSGT00390000017126
HOGENOMiHOG000232158
HOVERGENiHBG052430
InParanoidiQ8R4F0
KOiK04994
OMAiHEEENRC
OrthoDBiEOG091G026A
PhylomeDBiQ8R4F0
TreeFamiTF317783

Enzyme and pathway databases

ReactomeiR-MMU-3295583 TRP channels

Miscellaneous databases

PROiPR:Q8R4F0
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036853 Expressed in 118 organ(s), highest expression level in small intestine
CleanExiMM_MCOLN3
ExpressionAtlasiQ8R4F0 baseline and differential
GenevisibleiQ8R4F0 MM

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_MOUSE
AccessioniPrimary (citable) accession number: Q8R4F0
Secondary accession number(s): Q8BS73, Q8BSG1, Q8CDB2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: June 1, 2002
Last modified: September 12, 2018
This is version 119 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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