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UniProtKB - Q8IZK6 (MCLN2_HUMAN)

Protein

Mucolipin-2

Gene

MCOLN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity regulationi

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

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000153898.12
HGNCiHGNC:13357 MCOLN2
MIMi607399 gene
neXtProtiNX_Q8IZK6

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

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
ProteomicsDBi71363
71364 [Q8IZK6-2]

PTM databases

iPTMnetiQ8IZK6
PhosphoSitePlusiQ8IZK6

Expressioni

Gene expression databases

BgeeiENSG00000153898 Expressed in 132 organ(s), highest expression level in tibia
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-specific (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

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

Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN2 sub-subfamily. [View classification]Curated

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
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 1 potential isoform that is computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G5EA24G5EA24_HUMAN
Mucolipin 2, isoform CRA_a
MCOLN2 hCG_2039430
249Annotation score:

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 12, 2018
This is version 126 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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