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Protein

Mucolipin-2

Gene

Mcoln2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nonselective cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca2+-permeable cation channel with inwardly rectifying activity (PubMed:19763610). May activate ARF6 and be involved in the trafficking of GPI-anchored cargo proteins to the cell surface via the ARF6-regulated recycling pathway (By similarity). May play a role in immune processes. In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (PubMed:17050035). In the innate immune response, may play a role in the regulation of chemokine secretion and macrophage migration (PubMed:26432893). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events.By similarityCurated4 Publications

Enzyme regulationi

Channel activity is reduced by low extracellular/lumenal pH level.Curated1 Publication

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • chemokine (C-C motif) ligand 2 secretion Source: MGI
  • innate immune response Source: UniProtKB-KW
  • macrophage migration Source: MGI
  • neutrophil migration Source: MGI
  • positive regulation of chemokine (C-C motif) ligand 5 production Source: MGI
  • positive regulation of chemokine (C-X-C motif) ligand 2 production Source: MGI
  • positive regulation of chemokine production Source: MGI
  • positive regulation of macrophage inflammatory protein 1 alpha production Source: MGI
  • positive regulation of monocyte chemotactic protein-1 production Source: MGI
  • protein oligomerization Source: MGI

Keywordsi

Molecular functionCalcium channel, Ion channel
Biological processAdaptive immunity, Calcium transport, Immunity, Innate immunity, Ion transport, Protein transport, Transport
LigandCalcium

Enzyme and pathway databases

ReactomeiR-MMU-3295583. TRP channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Mucolipin-2
Alternative name(s):
Transient receptor potential channel mucolipin 2
Short name:
TRPML2
Gene namesi
Name:Mcoln2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1915529. Mcoln2.

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 – 65CytoplasmicBy similarityAdd BLAST65
Transmembranei66 – 86HelicalBy similarityAdd BLAST21
Topological domaini87 – 288ExtracellularBy similarityAdd BLAST202
Transmembranei289 – 309HelicalBy similarityAdd BLAST21
Topological domaini310 – 346CytoplasmicBy similarityAdd BLAST37
Transmembranei347 – 367HelicalBy similarityAdd BLAST21
Topological domaini368 – 376ExtracellularBy similarity9
Transmembranei377 – 397HelicalBy similarityAdd BLAST21
Topological domaini398 – 419CytoplasmicBy similarityAdd BLAST22
Transmembranei420 – 440HelicalBy similarityAdd BLAST21
Topological domaini441 – 448ExtracellularBy similarity8
Intramembranei449 – 469Pore-formingBy similarityAdd BLAST21
Topological domaini470 – 480ExtracellularBy similarityAdd BLAST11
Transmembranei481 – 502HelicalBy similarityAdd BLAST22
Topological domaini503 – 566CytoplasmicBy similarityAdd BLAST64

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. The secretion of specific cytokines (CCL3, CCL5 and CXCL2) by macrophages exposed to bacterial lipopolysaccharide (LPS) is decreased. Mutant mice display decreased migration of macrophages into the intraperitoneal space after injection with LPS, or after infection with E.coli O78:H11 (strain H10407).1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153661 – 566Mucolipin-2Add BLAST566

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi164 ↔ 190By similarity
Disulfide bondi243 ↔ 274By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiQ8K595.
PRIDEiQ8K595.

PTM databases

iPTMnetiQ8K595.
PhosphoSitePlusiQ8K595.

Expressioni

Tissue specificityi

Isoform 1 is widely expressed at very low levels. Isoform 2 is expressed at high levels in lymphoid tissues (thymus and spleen) and kidney, and at moderate levels in heart, lung, liver and stomach. Expressed in activated macrophages and microglia (at protein level).2 Publications

Inductioni

Up-regulated in microglia cells and macrophages by bacterial lipopolysaccharide (LPS). Up-regulated by infection with M.smegmatis.1 Publication

Gene expression databases

BgeeiENSMUSG00000011008.
CleanExiMM_MCOLN2.
ExpressionAtlasiQ8K595. baseline and differential.
GenevisibleiQ8K595. MM.

Interactioni

Subunit structurei

Forms homooligomeric complexes; probably tetrameric. Can heterooligomerize with MCOLN1; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific. Interacts with TMEM176A.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000011152.

Structurei

3D structure databases

ProteinModelPortaliQ8K595.
SMRiQ8K595.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni107 – 123Extracellular/lumenal pore loopBy similarityAdd BLAST17

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi461 – 464Selectivity 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.
InParanoidiQ8K595.
KOiK04993.
OMAiRRQIPWK.
OrthoDBiEOG091G026A.
PhylomeDBiQ8K595.
TreeFamiTF317783.

Family and domain databases

InterProiView protein in InterPro
IPR013122. PKD1_2_channel.
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

Isoform 1 (identifier: Q8K595-1) [UniParc]FASTAAdd to basket
Also known as: TRPML2lv

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
MPGDEETLDL PAWNRVPDLT WGPHHRSAMA SLDSEVREEC LREDLKFYFM
60 70 80 90 100
SPCEKYRARR QIPWKLGLQI LKIVMVTTQL VRFGLSNQLV VAFKEDNTVA
110 120 130 140 150
FKHLFLKGFS GVDEDDYSCS IYTQENTYES IFFAIKQYRH LKNISLATLG
160 170 180 190 200
YGESEDNRTG LKVCKQHYKT GAMFSSNETL NIDSDIETDC IHLDLQVLTT
210 220 230 240 250
EPEDWAQTSF FRLDFYRLVQ VDISFALKGI DLQAVHSREI PDCYLFQNTI
260 270 280 290 300
TFDNTAHSGK IKIYLNSEAN IEECKNMNIS GSTQRSTHYL LVFDVFVIMI
310 320 330 340 350
CLASLILCTR SIVLALRLRK RFLNFFLEKY KQRVCGADQW EFVNGWYVLV
360 370 380 390 400
TISDLMTIIG SILKMEIKAK KLTNYDVCSI LLGTSTLFVW VGVIRYLGYF
410 420 430 440 450
QTYNVLILTM QASLPKVLRF CACAGMIYLG YTFCGWIVLG PYHEKFENLN
460 470 480 490 500
IVAECLFSLV NGDDMFATFA QIQQKSILVW LFSRLYLYSF ISLFIYMVLS
510 520 530 540 550
LFIALITDSY HTIKKYQQHG FPETDLQKFL KESGSKDGYQ KQPSALLSCL
560
CCLRRRRSND HLILID
Length:566
Mass (Da):65,450
Last modified:October 1, 2002 - v1
Checksum:i314CEC662B3BDC07
GO
Isoform 2 (identifier: Q8K595-2) [UniParc]FASTAAdd to basket
Also known as: TRPML2sv

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.

Show »
Length:538
Mass (Da):62,269
Checksum:i9C35081FE96A628B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti558S → N in AAH29847 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0108221 – 28Missing in isoform 2. 3 PublicationsAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY083532 mRNA. Translation: AAM08925.1.
AF503575 mRNA. Translation: AAM28596.1.
AK014467 mRNA. Translation: BAB29372.1.
AK019454 mRNA. Translation: BAB31730.1.
AK150446 mRNA. Translation: BAE29568.1.
AK150547 mRNA. Translation: BAE29649.1.
AK152067 mRNA. Translation: BAE30921.1.
AK152943 mRNA. Translation: BAE31614.1.
AK159172 mRNA. Translation: BAE34872.1.
BC029847 mRNA. Translation: AAH29847.1.
CCDSiCCDS38663.1. [Q8K595-1]
CCDS38664.1. [Q8K595-2]
RefSeqiNP_001005846.1. NM_001005846.2. [Q8K595-2]
NP_080932.2. NM_026656.4. [Q8K595-1]
UniGeneiMm.116862.

Genome annotation databases

EnsembliENSMUST00000011152; ENSMUSP00000011152; ENSMUSG00000011008. [Q8K595-1]
ENSMUST00000098524; ENSMUSP00000096125; ENSMUSG00000011008. [Q8K595-2]
GeneIDi68279.
KEGGimmu:68279.
UCSCiuc008rqy.1. mouse. [Q8K595-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMCLN2_MOUSE
AccessioniPrimary (citable) accession number: Q8K595
Secondary accession number(s): Q3UCG4, Q8K2T6, Q9CQD3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: October 1, 2002
Last modified: December 20, 2017
This is version 109 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families