MCLN2_MOUSE
ID MCLN2_MOUSE Reviewed; 566 AA.
AC Q8K595; Q3UCG4; Q8K2T6; Q9CQD3;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Mucolipin-2;
DE AltName: Full=Transient receptor potential channel mucolipin 2;
DE Short=TRPML2;
GN Name=Mcoln2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J;
RX PubMed=12403827; DOI=10.1073/pnas.222425399;
RA Di Palma F., Belyantseva I.A., Kim H.J., Vogt T.F., Kachar B.,
RA Noben-Trauth K.;
RT "Mutations in Mcoln3 associated with deafness and pigmentation defects in
RT varitint-waddler (Va) mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14994-14999(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J;
RA Kennedy J.C., Falardeau J.L., Acierno J.S. Jr., Slaugenhaupt S.A.;
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17050035; DOI=10.1016/j.ejcb.2006.08.004;
RA Song Y., Dayalu R., Matthews S.A., Scharenberg A.M.;
RT "TRPML cation channels regulate the specialized lysosomal compartment of
RT vertebrate B-lymphocytes.";
RL Eur. J. Cell Biol. 85:1253-1264(2006).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19763610; DOI=10.1007/s00424-009-0716-5;
RA Samie M.A., Grimm C., Evans J.A., Curcio-Morelli C., Heller S.,
RA Slaugenhaupt S.A., Cuajungco M.P.;
RT "The tissue-specific expression of TRPML2 (MCOLN-2) gene is influenced by
RT the presence of TRPML1.";
RL Pflugers Arch. 459:79-91(2009).
RN [7]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=22753890; DOI=10.1074/jbc.m112.368876;
RA Grimm C., Joers S., Guo Z., Obukhov A.G., Heller S.;
RT "Constitutive activity of TRPML2 and TRPML3 channels versus activation by
RT low extracellular sodium and small molecules.";
RL J. Biol. Chem. 287:22701-22708(2012).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, INDUCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26432893; DOI=10.4049/jimmunol.1500163;
RA Sun L., Hua Y., Vergarajauregui S., Diab H.I., Puertollano R.;
RT "Novel role of TRPML2 in the regulation of the innate immune response.";
RL J. Immunol. 195:4922-4932(2015).
CC -!- FUNCTION: Nonselective cation channel probably playing a role in the
CC regulation of membrane trafficking events. Acts as Ca(2+)-permeable
CC cation channel with inwardly rectifying activity (PubMed:19763610). May
CC activate ARF6 and be involved in the trafficking of GPI-anchored cargo
CC proteins to the cell surface via the ARF6-regulated recycling pathway
CC (By similarity). May play a role in immune processes. In adaptive
CC immunity, TRPML2 and TRPML1 may play redundant roles in the function of
CC the specialized lysosomes of B cells (PubMed:17050035). In the innate
CC immune response, may play a role in the regulation of chemokine
CC secretion and macrophage migration (PubMed:26432893). Through a
CC possible and probably tissue-specific heteromerization with MCOLN1 may
CC be at least in part involved in many lysosome-dependent cellular
CC events. {ECO:0000250|UniProtKB:Q8IZK6, ECO:0000269|PubMed:17050035,
CC ECO:0000269|PubMed:19763610, ECO:0000269|PubMed:22753890,
CC ECO:0000269|PubMed:26432893, ECO:0000305}.
CC -!- ACTIVITY REGULATION: Channel activity is reduced by low
CC extracellular/lumenal pH level. {ECO:0000269|PubMed:22753890,
CC ECO:0000305}.
CC -!- SUBUNIT: Forms homooligomeric complexes; probably tetrameric. Can
CC heterooligomerize with MCOLN1; heteromeric assemblies have different
CC channel properties as compared to the respective homooligomers and may
CC be tissue-specific. Interacts with TMEM176A.
CC {ECO:0000250|UniProtKB:Q8IZK6}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8IZK6};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:F6RG56}. Lysosome
CC membrane {ECO:0000305|PubMed:17050035}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:F6RG56}. Recycling endosome membrane
CC {ECO:0000269|PubMed:26432893}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:F6RG56}. Note=Localizes to recycling endosomes
CC in activated macrophages and microglia. {ECO:0000269|PubMed:26432893}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=TRPML2lv;
CC IsoId=Q8K595-1; Sequence=Displayed;
CC Name=2; Synonyms=TRPML2sv;
CC IsoId=Q8K595-2; Sequence=VSP_010822;
CC -!- TISSUE SPECIFICITY: Isoform 1 is widely expressed at very low levels.
CC Isoform 2 is expressed at high levels in lymphoid tissues (thymus and
CC spleen) and kidney, and at moderate levels in heart, lung, liver and
CC stomach. Expressed in activated macrophages and microglia (at protein
CC level). {ECO:0000269|PubMed:19763610, ECO:0000269|PubMed:26432893}.
CC -!- INDUCTION: Up-regulated in microglia cells and macrophages by bacterial
CC lipopolysaccharide (LPS). Up-regulated by infection with M.smegmatis.
CC {ECO:0000269|PubMed:26432893}.
CC -!- DOMAIN: The most N-terminal extracellular/lumenal domain (referred to
CC as I-II linker or polycystin-mucolipin domain) contributes to a
CC structure with a four-fold rotational symmetry in a tetrameric
CC assembly; the structure contains a central highly electronegative pore
CC with a 14 A diameter. The pore is critical for Ca(2+) and pH
CC regulation. The protruding structure formed by the I-II linkers may
CC contain all the interaction sites with lipids and proteins in the
CC endolysosomal lumen. {ECO:0000250|UniProtKB:Q9GZU1}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. The secretion of specific
CC cytokines (CCL3, CCL5 and CXCL2) by macrophages exposed to bacterial
CC lipopolysaccharide (LPS) is decreased. Mutant mice display decreased
CC migration of macrophages into the intraperitoneal space after injection
CC with LPS, or after infection with E.coli O78:H11 (strain H10407).
CC {ECO:0000269|PubMed:26432893}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family.
CC Polycystin subfamily. MCOLN2 sub-subfamily. {ECO:0000305}.
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DR EMBL; AY083532; AAM08925.1; -; mRNA.
DR EMBL; AF503575; AAM28596.1; -; mRNA.
DR EMBL; AK014467; BAB29372.1; -; mRNA.
DR EMBL; AK019454; BAB31730.1; -; mRNA.
DR EMBL; AK150446; BAE29568.1; -; mRNA.
DR EMBL; AK150547; BAE29649.1; -; mRNA.
DR EMBL; AK152067; BAE30921.1; -; mRNA.
DR EMBL; AK152943; BAE31614.1; -; mRNA.
DR EMBL; AK159172; BAE34872.1; -; mRNA.
DR EMBL; BC029847; AAH29847.1; -; mRNA.
DR CCDS; CCDS38663.1; -. [Q8K595-1]
DR CCDS; CCDS38664.1; -. [Q8K595-2]
DR RefSeq; NP_001005846.1; NM_001005846.2. [Q8K595-2]
DR RefSeq; NP_080932.2; NM_026656.4. [Q8K595-1]
DR PDB; 7DYS; EM; 3.18 A; A/B/C/D=1-518.
DR PDBsum; 7DYS; -.
DR AlphaFoldDB; Q8K595; -.
DR SMR; Q8K595; -.
DR STRING; 10090.ENSMUSP00000011152; -.
DR iPTMnet; Q8K595; -.
DR PhosphoSitePlus; Q8K595; -.
DR PaxDb; Q8K595; -.
DR PRIDE; Q8K595; -.
DR ProteomicsDB; 292193; -. [Q8K595-1]
DR ProteomicsDB; 292194; -. [Q8K595-2]
DR Antibodypedia; 19780; 46 antibodies from 12 providers.
DR DNASU; 68279; -.
DR Ensembl; ENSMUST00000011152; ENSMUSP00000011152; ENSMUSG00000011008. [Q8K595-1]
DR Ensembl; ENSMUST00000098524; ENSMUSP00000096125; ENSMUSG00000011008. [Q8K595-2]
DR GeneID; 68279; -.
DR KEGG; mmu:68279; -.
DR UCSC; uc008rqy.1; mouse. [Q8K595-1]
DR CTD; 255231; -.
DR MGI; MGI:1915529; Mcoln2.
DR VEuPathDB; HostDB:ENSMUSG00000011008; -.
DR eggNOG; KOG3733; Eukaryota.
DR GeneTree; ENSGT00950000183036; -.
DR HOGENOM; CLU_020945_1_1_1; -.
DR InParanoid; Q8K595; -.
DR OMA; HVCDADQ; -.
DR OrthoDB; 1379516at2759; -.
DR PhylomeDB; Q8K595; -.
DR TreeFam; TF317783; -.
DR Reactome; R-MMU-3295583; TRP channels.
DR BioGRID-ORCS; 68279; 3 hits in 59 CRISPR screens.
DR PRO; PR:Q8K595; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8K595; protein.
DR Bgee; ENSMUSG00000011008; Expressed in ileal epithelium and 77 other tissues.
DR ExpressionAtlas; Q8K595; baseline and differential.
DR Genevisible; Q8K595; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0055037; C:recycling endosome; IDA:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0072345; F:NAADP-sensitive calcium-release channel activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1905517; P:macrophage migration; IMP:MGI.
DR GO; GO:1990266; P:neutrophil migration; IMP:MGI.
DR GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; IMP:MGI.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IMP:MGI.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:MGI.
DR GO; GO:0071642; P:positive regulation of macrophage inflammatory protein 1 alpha production; IMP:MGI.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IMP:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:2000341; P:regulation of chemokine (C-X-C motif) ligand 2 production; IMP:MGI.
DR InterPro; IPR039031; Mucolipin.
DR InterPro; IPR013122; PKD1_2_channel.
DR PANTHER; PTHR12127; PTHR12127; 1.
DR Pfam; PF08016; PKD_channel; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Calcium;
KW Calcium channel; Calcium transport; Cell membrane; Disulfide bond;
KW Endosome; Immunity; Innate immunity; Ion channel; Ion transport; Lysosome;
KW Membrane; Protein transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..566
FT /note="Mucolipin-2"
FT /id="PRO_0000215366"
FT TOPO_DOM 1..65
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TRANSMEM 66..86
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TOPO_DOM 87..288
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TOPO_DOM 310..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TRANSMEM 347..367
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TOPO_DOM 368..376
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TOPO_DOM 398..419
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TRANSMEM 420..440
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TOPO_DOM 441..448
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT INTRAMEM 449..469
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TOPO_DOM 470..480
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TRANSMEM 481..502
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT TOPO_DOM 503..566
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT REGION 107..123
FT /note="Extracellular/lumenal pore loop"
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT MOTIF 461..464
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT DISULFID 164..190
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT DISULFID 243..274
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12403827,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072"
FT /id="VSP_010822"
FT CONFLICT 558
FT /note="S -> N (in Ref. 4; AAH29847)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 566 AA; 65450 MW; 314CEC662B3BDC07 CRC64;
MPGDEETLDL PAWNRVPDLT WGPHHRSAMA SLDSEVREEC LREDLKFYFM SPCEKYRARR
QIPWKLGLQI LKIVMVTTQL VRFGLSNQLV VAFKEDNTVA FKHLFLKGFS GVDEDDYSCS
IYTQENTYES IFFAIKQYRH LKNISLATLG YGESEDNRTG LKVCKQHYKT GAMFSSNETL
NIDSDIETDC IHLDLQVLTT EPEDWAQTSF FRLDFYRLVQ VDISFALKGI DLQAVHSREI
PDCYLFQNTI TFDNTAHSGK IKIYLNSEAN IEECKNMNIS GSTQRSTHYL LVFDVFVIMI
CLASLILCTR SIVLALRLRK RFLNFFLEKY KQRVCGADQW EFVNGWYVLV TISDLMTIIG
SILKMEIKAK KLTNYDVCSI LLGTSTLFVW VGVIRYLGYF QTYNVLILTM QASLPKVLRF
CACAGMIYLG YTFCGWIVLG PYHEKFENLN IVAECLFSLV NGDDMFATFA QIQQKSILVW
LFSRLYLYSF ISLFIYMVLS LFIALITDSY HTIKKYQQHG FPETDLQKFL KESGSKDGYQ
KQPSALLSCL CCLRRRRSND HLILID
