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Protein

Mucolipin-2

Gene

MCOLN2

Organism
Homo sapiens (Human)
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:19940139, PubMed:19885840). May activate ARF6 and be involved in the trafficking of GPI-anchored cargo proteins to the cell surface via the ARF6-regulated recycling pathway (PubMed:17662026). 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 (By similarity). In the innate immune response, may play a role in the regulation of chemokine secretion and macrophage migration (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).By similarityCurated3 Publications

Enzyme regulationi

Channel activity is reduced by low extracellular/lumenal pH level (PubMed:19940139).Curated1 Publication

GO - Molecular functioni

GO - Biological processi

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-HSA-3295583. TRP channels.

Protein family/group databases

TCDBi1.A.5.3.3. the polycystin cation channel (pcc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Mucolipin-2
Alternative name(s):
Transient receptor potential channel mucolipin 2
Short name:
TRPML2
Gene namesi
Name:MCOLN2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000153898.12.
HGNCiHGNC:13357. 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 – 65CytoplasmicCuratedAdd BLAST65
Transmembranei66 – 86HelicalBy similarityCuratedAdd BLAST21
Topological domaini87 – 288ExtracellularCuratedAdd BLAST202
Transmembranei289 – 309HelicalSequence analysisAdd BLAST21
Topological domaini310 – 341CytoplasmicCuratedAdd BLAST32
Transmembranei342 – 362HelicalSequence analysisAdd BLAST21
Topological domaini363 – 379ExtracellularCuratedAdd BLAST17
Transmembranei380 – 400HelicalSequence analysisAdd BLAST21
Topological domaini401 – 419CytoplasmicCuratedAdd BLAST19
Transmembranei420 – 440HelicalSequence analysisAdd BLAST21
Topological domaini441 – 485ExtracellularCuratedAdd BLAST45
Transmembranei486 – 506HelicalSequence analysisAdd BLAST21
Topological domaini507 – 566CytoplasmicCuratedAdd BLAST60

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi424A → P: Constitutive active Ca(2+) permeable and inward rectifying channel. 1 Publication1
Mutagenesisi457F → L: Does not effect current amplitude; possible effect on regulation. 1 Publication1
Mutagenesisi463 – 464DD → KK: Blocks channel activity. Decreases recycling of internalized CD59 to the cell surface. 2 Publications2

Organism-specific databases

DisGeNETi255231.
OpenTargetsiENSG00000153898.
PharmGKBiPA134913691.

Polymorphism and mutation databases

BioMutaiMCOLN2.
DMDMi212276802.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002153651 – 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

PaxDbiQ8IZK6.
PeptideAtlasiQ8IZK6.
PRIDEiQ8IZK6.

PTM databases

PhosphoSitePlusiQ8IZK6.

Expressioni

Gene expression databases

BgeeiENSG00000153898.
CleanExiHS_MCOLN2.
ExpressionAtlasiQ8IZK6. baseline and differential.
GenevisibleiQ8IZK6. HS.

Organism-specific databases

HPAiHPA019114.
HPA048999.

Interactioni

Subunit structurei

Forms homooligomeric complexes; probably tetrameric (By similarity). Can heterooligomerize with MCOLN1; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specifc (PubMed:19885840). Interacts with TMEM176A (PubMed:25130899).By similarity2 Publications

Protein-protein interaction databases

BioGridi129087. 25 interactors.
STRINGi9606.ENSP00000359640.

Structurei

3D structure databases

ProteinModelPortaliQ8IZK6.
SMRiQ8IZK6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

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.
InParanoidiQ8IZK6.
KOiK04993.
OMAiRRQIPWK.
OrthoDBiEOG091G026A.
PhylomeDBiQ8IZK6.
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: Q8IZK6-1) [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
MARQPYRFPQ ARIPERGSGV FRLTVRNAMA HRDSEMKEEC LREDLKFYFM
60 70 80 90 100
SPCEKYRARR QIPWKLGLQI LKIVMVTTQL VRFGLSNQLV VAFKEDNTVA
110 120 130 140 150
FKHLFLKGYS GTDEDDYSCS VYTQEDAYES IFFAINQYHQ LKDITLGTLG
160 170 180 190 200
YGENEDNRIG LKVCKQHYKK GTMFPSNETL NIDNDVELDC VQLDLQDLSK
210 220 230 240 250
KPPDWKNSSF FRLEFYRLLQ VEISFHLKGI DLQTIHSREL PDCYVFQNTI
260 270 280 290 300
IFDNKAHSGK IKIYFDSDAK IEECKDLNIF GSTQKNAQYV LVFDAFVIVI
310 320 330 340 350
CLASLILCTR SIVLALRLRK RFLNFFLEKY KRPVCDTDQW EFINGWYVLV
360 370 380 390 400
IISDLMTIIG SILKMEIKAK NLTNYDLCSI FLGTSTLLVW VGVIRYLGYF
410 420 430 440 450
QAYNVLILTM QASLPKVLRF CACAGMIYLG YTFCGWIVLG PYHDKFENLN
460 470 480 490 500
TVAECLFSLV NGDDMFATFA QIQQKSILVW LFSRLYLYSF ISLFIYMILS
510 520 530 540 550
LFIALITDSY DTIKKFQQNG FPETDLQEFL KECSSKEEYQ KESSAFLSCI
560
CCRRRKRSDD HLIPIS
Note: No experimental confirmation available.
Length:566
Mass (Da):65,942
Last modified:July 22, 2008 - v2
Checksum:i6F017BA416624E63
GO
Isoform 2 (identifier: Q8IZK6-2) [UniParc]FASTAAdd to basket

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

Show »
Length:538
Mass (Da):62,685
Checksum:i1BCCB92F8D6C83C4
GO

Sequence cautioni

The sequence BAC04267 differs from that shown. Reason: Erroneous termination at position 64. Translated as Trp.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052394365M → V. Corresponds to variant dbSNP:rs17117841Ensembl.1
Natural variantiVAR_052395370K → Q. Corresponds to variant dbSNP:rs6704203Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0346421 – 28Missing in isoform 2. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY083533 mRNA. Translation: AAM08926.1.
AL139150 Genomic DNA. No translation available.
CH471097 Genomic DNA. Translation: EAW73221.1.
BC104891 mRNA. Translation: AAI04892.1.
BC104893 mRNA. Translation: AAI04894.1.
AK094010 mRNA. Translation: BAC04267.1. Sequence problems.
CCDSiCCDS30762.1. [Q8IZK6-1]
CCDS81347.1. [Q8IZK6-2]
RefSeqiNP_001317576.1. NM_001330647.1. [Q8IZK6-2]
NP_694991.2. NM_153259.3. [Q8IZK6-1]
XP_005270776.1. XM_005270719.3. [Q8IZK6-2]
XP_011539489.1. XM_011541187.2. [Q8IZK6-2]
XP_011539490.1. XM_011541188.2. [Q8IZK6-2]
UniGeneiHs.591446.

Genome annotation databases

EnsembliENST00000284027; ENSP00000284027; ENSG00000153898. [Q8IZK6-2]
ENST00000370608; ENSP00000359640; ENSG00000153898. [Q8IZK6-1]
GeneIDi255231.
KEGGihsa:255231.
UCSCiuc001dkm.4. human. [Q8IZK6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMCLN2_HUMAN
AccessioniPrimary (citable) accession number: Q8IZK6
Secondary accession number(s): A6NI99
, Q2M3I6, Q5TAG5, Q8N9R3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 22, 2008
Last modified: September 27, 2017
This is version 119 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families