UniProtKB - Q8TDD5 (MCLN3_HUMAN)
Mucolipin-3
MCOLN3
Functioni
Activity regulationi
GO - Molecular functioni
- lipid binding Source: UniProtKB-KW
- NAADP-sensitive calcium-release channel activity Source: GO_Central
GO - Biological processi
- calcium ion transmembrane transport Source: Reactome
- inner ear auditory receptor cell differentiation Source: Ensembl
- locomotory behavior Source: Ensembl
Keywordsi
Molecular function | Ion channel |
Biological process | Ion transport, Transport |
Ligand | Lipid-binding |
Enzyme and pathway databases
PathwayCommonsi | Q8TDD5 |
Reactomei | R-HSA-3295583, TRP channels |
Protein family/group databases
TCDBi | 1.A.5.3.4, the polycystin cation channel (pcc) family |
Names & Taxonomyi
Protein namesi | Recommended name: Mucolipin-31 PublicationAlternative name(s): Transient receptor potential channel mucolipin 3 Short name: TRPML31 Publication |
Gene namesi | Name:MCOLN3 |
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:13358, MCOLN3 |
MIMi | 607400, gene |
neXtProti | NX_Q8TDD5 |
VEuPathDBi | HostDB:ENSG00000055732.12 |
Subcellular locationi
Lysosome
- Lysosome membrane 1 Publication; Multi-pass membrane protein 1 Publication
Plasma membrane
- Cell membrane 2 Publications; Multi-pass membrane protein 1 Publication
Endosome
- Early endosome membrane 2 Publications; Multi-pass membrane protein 1 Publication
- Late endosome membrane 2 Publications; Multi-pass membrane protein 1 Publication
Other locations
- autophagosome membrane 1 Publication
Note: Recycles between the plasma membrane and intracellular compartments by a dynamin-dependent endocytic pathway (PubMed:19522758). Under normal conditions, only a very minor proportion is present at the cell membrane (PubMed:19522758). In the cochlea located at the base of stereocilia near the position of the ankle links (By similarity).By similarity1 Publication
Endosome
- early endosome membrane Source: UniProtKB-SubCell
- late endosome membrane Source: UniProtKB-SubCell
Lysosome
- lysosomal membrane Source: GO_Central
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- autophagosome membrane Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB-KW
- membrane Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 62 | Cytoplasmic1 PublicationAdd BLAST | 62 | |
Transmembranei | 63 – 83 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 84 – 283 | Extracellular1 PublicationAdd BLAST | 200 | |
Transmembranei | 284 – 304 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 305 – 341 | Cytoplasmic1 PublicationAdd BLAST | 37 | |
Transmembranei | 342 – 362 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 363 – 371 | Extracellular1 Publication | 9 | |
Transmembranei | 372 – 392 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 393 – 414 | Cytoplasmic1 PublicationAdd BLAST | 22 | |
Transmembranei | 415 – 435 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 436 – 443 | Extracellular1 Publication | 8 | |
Intramembranei | 444 – 464 | Pore-forming1 PublicationAdd BLAST | 21 | |
Topological domaini | 465 – 475 | Extracellular1 PublicationAdd BLAST | 11 | |
Transmembranei | 476 – 497 | Helical1 PublicationAdd BLAST | 22 | |
Topological domaini | 498 – 553 | Cytoplasmic1 PublicationAdd BLAST | 56 |
Keywords - Cellular componenti
Cell membrane, Cytoplasmic vesicle, Endosome, Lysosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 108 | D → N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-111 and N-112. 1 Publication | 1 | |
Mutagenesisi | 111 | D → N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-108 and N-112. 1 Publication | 1 | |
Mutagenesisi | 112 | D → N: Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-108 and N-111. 1 Publication | 1 | |
Mutagenesisi | 252 | H → A: Increases inhibition by lumenal H(+). Decreases inhibition by lumenal H(+); when associated with A-283. 1 Publication | 1 | |
Mutagenesisi | 273 | H → A: Increases inhibition by lumenal H(+). Decreases inhibition by lumenal H(+); when associated with A-283. 1 Publication | 1 | |
Mutagenesisi | 283 | H → 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 Publication | 1 | |
Mutagenesisi | 283 | H → R: Increases inhibition by lumenal H(+). 1 Publication | 1 | |
Mutagenesisi | 419 | A → P: Constitutive active channel; abolishes inhibition by lumenal H(+); increases the pore diameter. 2 Publications | 1 | |
Mutagenesisi | 423 | Y → A: Nearly abolishes channel activation by a synthetic agonist. 1 Publication | 1 | |
Mutagenesisi | 449 | E → A: Constitutive active channel; greatly impairs inhibition by lumenal Na(+). 1 Publication | 1 | |
Mutagenesisi | 449 | E → K: Abolishes channel activity. 1 Publication | 1 | |
Mutagenesisi | 458 – 459 | DD → KK: Enhances endocytosis. 1 Publication | 2 | |
Mutagenesisi | 458 | D → K: Nearly abolishes channel activity; inhibits starvation-induced autophagy. 1 Publication | 1 | |
Mutagenesisi | 459 | D → A: Decreases in Ca(2+) permeability and selectivity; decreases channel pore dynamic behavior. 1 Publication | 1 | |
Mutagenesisi | 497 | F → A: Nearly abolishes channel activation by a synthetic agonist. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 55283 |
OpenTargetsi | ENSG00000055732 |
PharmGKBi | PA134947324 |
Miscellaneous databases
Pharosi | Q8TDD5, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1293243 |
GuidetoPHARMACOLOGYi | 503 |
Genetic variation databases
BioMutai | MCOLN3 |
DMDMi | 50401084 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000215367 | 1 – 553 | Mucolipin-3Add BLAST | 553 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 138 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 159 ↔ 185 | By similarity | ||
Glycosylationi | 172 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 205 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 238 ↔ 269 | By similarity |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | Q8TDD5 |
MassIVEi | Q8TDD5 |
MaxQBi | Q8TDD5 |
PaxDbi | Q8TDD5 |
PeptideAtlasi | Q8TDD5 |
PRIDEi | Q8TDD5 |
ProteomicsDBi | 74270 [Q8TDD5-1] 74271 [Q8TDD5-2] |
PTM databases
GlyConnecti | 1522, 2 N-Linked glycans (1 site) |
GlyGeni | Q8TDD5, 4 sites |
iPTMneti | Q8TDD5 |
PhosphoSitePlusi | Q8TDD5 |
SwissPalmi | Q8TDD5 |
Expressioni
Gene expression databases
Bgeei | ENSG00000055732, Expressed in left adrenal gland and 175 other tissues |
ExpressionAtlasi | Q8TDD5, baseline and differential |
Genevisiblei | Q8TDD5, HS |
Organism-specific databases
HPAi | ENSG00000055732, Tissue enhanced (adrenal gland, pituitary gland) |
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 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 305 | Interaction with phosphoinositidesBy similarity | 1 |
Protein-protein interaction databases
BioGRIDi | 120571, 64 interactors |
IntActi | Q8TDD5, 40 interactors |
STRINGi | 9606.ENSP00000359621 |
Chemistry databases
BindingDBi | Q8TDD5 |
Miscellaneous databases
RNActi | Q8TDD5, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 52 – 62 | Interaction with phosphoinositidesBy similarityAdd BLAST | 11 | |
Regioni | 104 – 118 | Extracellular/lumenal pore loopBy similarityAdd BLAST | 15 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 456 – 459 | Selectivity filter1 Publication | 4 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3733, Eukaryota |
GeneTreei | ENSGT00950000183036 |
HOGENOMi | CLU_020945_1_1_1 |
InParanoidi | Q8TDD5 |
OMAi | RYMVVDQ |
OrthoDBi | 1379516at2759 |
PhylomeDBi | Q8TDD5 |
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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB1ANB7 | B1ANB7_HUMAN | Mucolipin 3, isoform CRA_d | MCOLN3 hCG_1775160 | 321 | Annotation score: | ||
S4R386 | S4R386_HUMAN | Mucolipin-3 | MCOLN3 | 141 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 9 | S → C in BAA91951 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010823 | 77 – 132 | Missing in isoform 2. 1 PublicationAdd BLAST | 56 |
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. |
CCDSi | CCDS58009.1 [Q8TDD5-2] CCDS701.1 [Q8TDD5-1] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000341115; ENSP00000342698; ENSG00000055732 [Q8TDD5-2] ENST00000370589; ENSP00000359621; ENSG00000055732 [Q8TDD5-1] |
GeneIDi | 55283 |
KEGGi | hsa:55283 |
UCSCi | uc001dkp.4, human [Q8TDD5-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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. |
CCDSi | CCDS58009.1 [Q8TDD5-2] CCDS701.1 [Q8TDD5-1] |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6AYE | electron microscopy | 4.06 | A/B/C/D | 1-553 | [»] | |
6AYF | electron microscopy | 3.62 | A/B/C/D | 1-553 | [»] | |
6AYG | electron microscopy | 4.65 | A/B/C/D | 1-553 | [»] | |
SMRi | Q8TDD5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120571, 64 interactors |
IntActi | Q8TDD5, 40 interactors |
STRINGi | 9606.ENSP00000359621 |
Chemistry databases
BindingDBi | Q8TDD5 |
ChEMBLi | CHEMBL1293243 |
GuidetoPHARMACOLOGYi | 503 |
Protein family/group databases
TCDBi | 1.A.5.3.4, the polycystin cation channel (pcc) family |
PTM databases
GlyConnecti | 1522, 2 N-Linked glycans (1 site) |
GlyGeni | Q8TDD5, 4 sites |
iPTMneti | Q8TDD5 |
PhosphoSitePlusi | Q8TDD5 |
SwissPalmi | Q8TDD5 |
Genetic variation databases
BioMutai | MCOLN3 |
DMDMi | 50401084 |
Proteomic databases
jPOSTi | Q8TDD5 |
MassIVEi | Q8TDD5 |
MaxQBi | Q8TDD5 |
PaxDbi | Q8TDD5 |
PeptideAtlasi | Q8TDD5 |
PRIDEi | Q8TDD5 |
ProteomicsDBi | 74270 [Q8TDD5-1] 74271 [Q8TDD5-2] |
Protocols and materials databases
ABCDi | Q8TDD5, 1 sequenced antibody |
Antibodypediai | 19787, 142 antibodies |
Genome annotation databases
Ensembli | ENST00000341115; ENSP00000342698; ENSG00000055732 [Q8TDD5-2] ENST00000370589; ENSP00000359621; ENSG00000055732 [Q8TDD5-1] |
GeneIDi | 55283 |
KEGGi | hsa:55283 |
UCSCi | uc001dkp.4, human [Q8TDD5-1] |
Organism-specific databases
CTDi | 55283 |
DisGeNETi | 55283 |
GeneCardsi | MCOLN3 |
HGNCi | HGNC:13358, MCOLN3 |
HPAi | ENSG00000055732, Tissue enhanced (adrenal gland, pituitary gland) |
MIMi | 607400, gene |
neXtProti | NX_Q8TDD5 |
OpenTargetsi | ENSG00000055732 |
PharmGKBi | PA134947324 |
VEuPathDBi | HostDB:ENSG00000055732.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3733, Eukaryota |
GeneTreei | ENSGT00950000183036 |
HOGENOMi | CLU_020945_1_1_1 |
InParanoidi | Q8TDD5 |
OMAi | RYMVVDQ |
OrthoDBi | 1379516at2759 |
PhylomeDBi | Q8TDD5 |
TreeFami | TF317783 |
Enzyme and pathway databases
PathwayCommonsi | Q8TDD5 |
Reactomei | R-HSA-3295583, TRP channels |
Miscellaneous databases
BioGRID-ORCSi | 55283, 11 hits in 986 CRISPR screens |
ChiTaRSi | MCOLN3, human |
GeneWikii | MCOLN3 |
GenomeRNAii | 55283 |
Pharosi | Q8TDD5, Tchem |
PROi | PR:Q8TDD5 |
RNActi | Q8TDD5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000055732, Expressed in left adrenal gland and 175 other tissues |
ExpressionAtlasi | Q8TDD5, baseline and differential |
Genevisiblei | Q8TDD5, 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 | MCLN3_HUMAN | |
Accessioni | Q8TDD5Primary (citable) accession number: Q8TDD5 Secondary accession number(s): Q5T4H5, Q5T4H6, Q9NV09 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2004 |
Last sequence update: | June 1, 2002 | |
Last modified: | April 7, 2021 | |
This is version 150 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 chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - 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