LOCUS       NM_153259               3044 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens mucolipin TRP cation channel 2 (MCOLN2), transcript
            variant 1, mRNA.
ACCESSION   NM_153259 XM_371263
VERSION     NM_153259.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3044)
  AUTHORS   Santoni,G., Amantini,C., Nabissi,M., Arcella,A., Maggi,F.,
            Santoni,M. and Morelli,M.B.
  TITLE     Functional In Vitro Assessment of VEGFA/NOTCH2 Signaling Pathway
            and pRB Proteasomal Degradation and the Clinical Relevance of
            Mucolipin TRPML2 Overexpression in Glioblastoma Patients
  JOURNAL   Int J Mol Sci 23 (2), 688 (2022)
   PUBMED   35054871
  REMARK    GeneRIF: Functional In Vitro Assessment of VEGFA/NOTCH2 Signaling
            Pathway and pRB Proteasomal Degradation and the Clinical Relevance
            of Mucolipin TRPML2 Overexpression in Glioblastoma Patients.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3044)
  AUTHORS   Yu,H., Xie,M., Meng,Z., Lo,C.Y., Chan,F.L., Jiang,L., Meng,X. and
            Yao,X.
  TITLE     Endolysosomal ion channel MCOLN2 (Mucolipin-2) promotes prostate
            cancer progression via IL-1beta/NF-kappaB pathway
  JOURNAL   Br J Cancer 125 (10), 1420-1431 (2021)
   PUBMED   34548638
  REMARK    GeneRIF: Endolysosomal ion channel MCOLN2 (Mucolipin-2) promotes
            prostate cancer progression via IL-1beta/NF-kappaB pathway.
REFERENCE   3  (bases 1 to 3044)
  AUTHORS   Viet,K.K., Wagner,A., Schwickert,K., Hellwig,N., Brennich,M.,
            Bader,N., Schirmeister,T., Morgner,N., Schindelin,H. and
            Hellmich,U.A.
  TITLE     Structure of the Human TRPML2 Ion Channel Extracytosolic/Lumenal
            Domain
  JOURNAL   Structure 27 (8), 1246-1257 (2019)
   PUBMED   31178222
  REMARK    GeneRIF: The acidic TRPML2 extracytosolic/lumenal domain (ELD)
            pre-pore loop exhibits a pH-dependent Ca2+ interaction, suggesting
            a mechanism for channel activity regulation in the endolysosomal
            system.
REFERENCE   4  (bases 1 to 3044)
  AUTHORS   Rinkenberger,N. and Schoggins,J.W.
  TITLE     Mucolipin-2 Cation Channel Increases Trafficking Efficiency of
            Endocytosed Viruses
  JOURNAL   mBio 9 (1), e02314-17 (2018)
   PUBMED   29382735
  REMARK    GeneRIF: The authors show that MCOLN2 specifically promotes viral
            vesicular trafficking and subsequent escape from endosomal
            compartments. This mechanism requires channel activity, occurs
            independently of antiviral signaling, and broadly applies to
            enveloped RNA viruses that require transport to late endosomes for
            infection, including influenza A virus, yellow fever virus, and
            Zika virus.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3044)
  AUTHORS   Morelli,M.B., Nabissi,M., Amantini,C., Tomassoni,D., Rossi,F.,
            Cardinali,C., Santoni,M., Arcella,A., Oliva,M.A., Santoni,A.,
            Polidori,C., Mariani,M.P. and Santoni,G.
  TITLE     Overexpression of transient receptor potential mucolipin-2 ion
            channels in gliomas: role in tumor growth and progression
  JOURNAL   Oncotarget 7 (28), 43654-43668 (2016)
   PUBMED   27248469
  REMARK    GeneRIF: High TRPML-2 expression in glioma cells resulted in
            increased survival and proliferation signaling, suggesting a
            pro-tumorigenic role played by TRPML-2 in glioma progression.
REFERENCE   6  (bases 1 to 3044)
  AUTHORS   Samie,M.A., Grimm,C., Evans,J.A., Curcio-Morelli,C., Heller,S.,
            Slaugenhaupt,S.A. and Cuajungco,M.P.
  TITLE     The tissue-specific expression of TRPML2 (MCOLN-2) gene is
            influenced by the presence of TRPML1
  JOURNAL   Pflugers Arch 459 (1), 79-91 (2009)
   PUBMED   19763610
  REMARK    GeneRIF: TRPML1 appears to play a novel role in the tissue-specific
            transcriptional regulation of TRPML2.
REFERENCE   7  (bases 1 to 3044)
  AUTHORS   Karacsonyi,C., Miguel,A.S. and Puertollano,R.
  TITLE     Mucolipin-2 localizes to the Arf6-associated pathway and regulates
            recycling of GPI-APs
  JOURNAL   Traffic 8 (10), 1404-1414 (2007)
   PUBMED   17662026
  REMARK    GeneRIF: MCOLN2 traffics through the ADP-ribosylation factor 6
            (Arf6)-associated pathway, colocalizing with major
            histocompatibility protein class I and CD59 in long recycling
            endosomes.
REFERENCE   8  (bases 1 to 3044)
  AUTHORS   Venkatachalam,K., Hofmann,T. and Montell,C.
  TITLE     Lysosomal localization of TRPML3 depends on TRPML2 and the
            mucolipidosis-associated protein TRPML1
  JOURNAL   J Biol Chem 281 (25), 17517-17527 (2006)
   PUBMED   16606612
  REMARK    GeneRIF: there is a hierarchy controlling the subcellular
            distributions of the TRPMLs such that TRPML1 and TRPML2 dictate the
            localization of TRPML3 and not vice versa
REFERENCE   9  (bases 1 to 3044)
  AUTHORS   Clapham,D.E., Julius,D., Montell,C. and Schultz,G.
  TITLE     International Union of Pharmacology. XLIX. Nomenclature and
            structure-function relationships of transient receptor potential
            channels
  JOURNAL   Pharmacol Rev 57 (4), 427-450 (2005)
   PUBMED   16382100
  REMARK    Review article
REFERENCE   10 (bases 1 to 3044)
  AUTHORS   Di Palma,F., Belyantseva,I.A., Kim,H.J., Vogt,T.F., Kachar,B. and
            Noben-Trauth,K.
  TITLE     Mutations in Mcoln3 associated with deafness and pigmentation
            defects in varitint-waddler (Va) mice
  JOURNAL   Proc Natl Acad Sci U S A 99 (23), 14994-14999 (2002)
   PUBMED   12403827
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DR007194.1, AL358789.22,
            BC104891.1, AK094010.1, AL139150.12, AA664369.1 and BF512441.1.
            
            On Nov 22, 2018 this sequence version replaced NM_153259.3.
            
            Summary: Mucolipins constitute a family of cation channel proteins
            with homology to the transient receptor potential superfamily. In
            mammals, the mucolipin family includes 3 members, MCOLN1 (MIM
            605248), MCOLN2, and MCOLN3 (MIM 607400), that exhibit a common
            6-membrane-spanning topology. Homologs of mammalian mucolipins
            exist in Drosophila and C. elegans. Mutations in the human MCOLN1
            gene cause mucolipodosis IV (MIM 262650) (Karacsonyi et al., 2007
            [PubMed 17662026]).[supplied by OMIM, Sep 2009].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC104893.1, DRR138524.906254.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000370608.8/ ENSP00000359640.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-46                DR007194.1         26-71
            47-47               AL358789.22        20194-20194         c
            48-215              DR007194.1         73-240
            216-1998            BC104891.1         43-1825
            1999-2410           AK094010.1         1683-2094
            2411-2411           AL139150.12        81090-81090         c
            2412-2719           AK094010.1         2096-2403
            2720-2825           AA664369.1         220-325             c
            2826-3044           BF512441.1         17-235              c
FEATURES             Location/Qualifiers
     source          1..3044
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p22.3"
     gene            1..3044
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /note="mucolipin TRP cation channel 2"
                     /db_xref="GeneID:255231"
                     /db_xref="HGNC:HGNC:13357"
                     /db_xref="MIM:607399"
     exon            1..318
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     CDS             242..1942
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /note="isoform 1 is encoded by transcript variant 1;
                     transient receptor potential channel mucolipin 2"
                     /codon_start=1
                     /product="mucolipin-2 isoform 1"
                     /protein_id="NP_694991.2"
                     /db_xref="CCDS:CCDS30762.1"
                     /db_xref="GeneID:255231"
                     /db_xref="HGNC:HGNC:13357"
                     /db_xref="MIM:607399"
                     /translation="MARQPYRFPQARIPERGSGVFRLTVRNAMAHRDSEMKEECLRED
                     LKFYFMSPCEKYRARRQIPWKLGLQILKIVMVTTQLVRFGLSNQLVVAFKEDNTVAFK
                     HLFLKGYSGTDEDDYSCSVYTQEDAYESIFFAINQYHQLKDITLGTLGYGENEDNRIG
                     LKVCKQHYKKGTMFPSNETLNIDNDVELDCVQLDLQDLSKKPPDWKNSSFFRLEFYRL
                     LQVEISFHLKGIDLQTIHSRELPDCYVFQNTIIFDNKAHSGKIKIYFDSDAKIEECKD
                     LNIFGSTQKNAQYVLVFDAFVIVICLASLILCTRSIVLALRLRKRFLNFFLEKYKRPV
                     CDTDQWEFINGWYVLVIISDLMTIIGSILKMEIKAKNLTNYDLCSIFLGTSTLLVWVG
                     VIRYLGYFQAYNVLILTMQASLPKVLRFCACAGMIYLGYTFCGWIVLGPYHDKFENLN
                     TVAECLFSLVNGDDMFATFAQIQQKSILVWLFSRLYLYSFISLFIYMILSLFIALITD
                     SYDTIKKFQQNGFPETDLQEFLKECSSKEEYQKESSAFLSCICCRRRKRSDDHLIPIS
                     "
     exon            319..478
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            479..652
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            653..806
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            807..891
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            892..988
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            989..1088
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            1089..1201
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            1202..1351
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            1352..1453
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            1454..1576
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            1577..1783
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            1784..1905
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     exon            1906..3044
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3021..3026
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /note="hexamer: AATAAA"
     polyA_site      3044
                     /gene="MCOLN2"
                     /gene_synonym="TRP-ML2; TRPML2"
                     /note="major polyA site"
ORIGIN      
        1 acacagagcc gcctttcagc cgcccgagaa ctgcccgccg cactccacga ctgcggcgcc
       61 tgctctcggg ccggggtctg cgcgcaccac gcggccggca gaaagggtaa gagaagggaa
      121 ccccgctttg cagggctcca acttcggcgg acgcgttacg gcgagggcga aatgagtcgg
      181 ccgtgaacgg tgtttcctgt tccgaatccc gagagccctg gaaagttttg aaggaggagg
      241 catggcccgg cagccttatc gttttcccca ggcaaggatt ccggagagag gatcaggtgt
      301 tttcaggtta accgtcagaa atgcaatggc acatcgtgat tctgagatga aagaagaatg
      361 tctaagggaa gacctgaagt tttacttcat gagcccttgt gaaaaatacc gagccagacg
      421 ccagattccg tggaaactgg gtttgcagat tttgaagata gtcatggtca ccacacagct
      481 tgttcgtttt ggtttaagta accagctggt ggttgctttc aaagaagata acactgttgc
      541 ttttaagcac ttgtttttga aaggatattc tggtacagat gaagatgact acagctgcag
      601 tgtatatact caagaggatg cctatgagag catctttttt gctattaatc agtatcatca
      661 gctaaaggac attaccctgg ggacccttgg ttatggagaa aatgaagaca atagaattgg
      721 cttaaaagtc tgtaagcagc attacaagaa agggaccatg tttccttcta atgagacact
      781 gaatattgac aacgacgttg agctcgattg tgttcaatta gaccttcagg acctctccaa
      841 gaagcctccg gactggaaga actcatcatt cttcagactg gaattttatc ggctcttaca
      901 ggttgaaatc tcctttcatc ttaaaggcat tgacctacag acaattcatt cccgtgagtt
      961 accagactgt tatgtctttc agaatacgat tatctttgac aataaagctc acagtggcaa
     1021 aatcaaaatc tattttgaca gtgatgccaa aattgaagaa tgtaaagact tgaacatatt
     1081 tggatctact cagaaaaatg ctcagtatgt cctggtgttt gatgcatttg tcattgtgat
     1141 ttgcttggca tctcttattc tgtgtacaag atccattgtt cttgctctaa ggttacggaa
     1201 gagatttcta aatttcttcc tggagaagta caagcggcct gtgtgtgaca ccgaccagtg
     1261 ggagttcatc aacggctggt atgtcctggt gattatcagc gacctaatga caatcattgg
     1321 ctccatatta aaaatggaaa tcaaagcaaa gaatctcaca aactatgatc tctgcagcat
     1381 ttttcttgga acctctacgc tcttggtttg ggttggagtc atcagatacc tgggttattt
     1441 ccaggcatat aatgtgctga ttttaacaat gcaggcctca ctgccaaaag ttcttcggtt
     1501 ttgtgcttgt gctggtatga tttatctggg ttacacattc tgtggctgga ttgtcttagg
     1561 accataccat gacaagtttg aaaatctgaa cacagttgct gagtgtctgt tttctctggt
     1621 caacggtgat gacatgtttg caacctttgc ccaaatccag cagaagagca tcttggtgtg
     1681 gctgttcagt cgtctgtatt tatattcctt catcagcctt tttatatata tgattctcag
     1741 tctttttatt gcacttatta cagattctta tgacaccatt aagaaattcc aacagaatgg
     1801 gtttcctgaa acggatttgc aggaattcct gaaggaatgc agtagcaaag aagagtatca
     1861 gaaagagtcc tcagccttcc tgtcctgcat ctgctgtcgg aggaggaaaa gaagtgatga
     1921 tcacttgata cctattagct aaagttctgc taaagatgat taaagttcag gcatccttat
     1981 ccagcggctg agcagaggaa ccccaaatga cttggacaag cagttccaaa atgactctct
     2041 tatttaattg tggagtggga aagaggactc acagttagcc agctgaccat gactgaagtt
     2101 ccagctttac tttttataaa cttgaatgat aaagaataga ccatgggcta ctactgggca
     2161 ttagtgcaat ataacagcga taataaaatt ctctattagt ctgttaattt atgacatgat
     2221 ctcggaatgg aaaaagatca tttcagagtg tgcgaaataa tagtctttaa ccatgtaatt
     2281 aaatatgtgt gtttattgtc aaataaggat ttgttttaaa ggtgattctt gggtttgaag
     2341 acatttgtta attcatggtc tgtacagaaa tgaagctggt tgcaatacca atctagagag
     2401 tccaagctgg tgaactatta agctgtttaa agatcaccct tggcctggca cagtggttca
     2461 cacctgtaat cccagcactt tgggaggcct aggcaggcag actgagctca ggagcttgag
     2521 accagcctgg gcaacatggc aaaaacccac ctctacaaaa agtacaaaaa ttagtcgggc
     2581 gtgatggcag gcatctgtag tcccagctac ttgggaagct gaagtgggag gatcacctga
     2641 gctctggagg tggaggctgc catgagccat gatcgtgcca ctacactcca gcctgggtga
     2701 cagagtgaga tcctgtctca aaaaaaaaaa aaaatcaccc ttaaatcaac aaaaagacct
     2761 catgctcatg cagtggacat ttcttggcct gttttcctgt gggttttctt cagcatgata
     2821 tgaagcaact gttggcatag ccagtgggat aaataagaaa tggaatcatt tggctgcctc
     2881 gtcacttgtg ctaatggtca gttgtacaca catgacatgt ggaagtgacc tgtagcagcg
     2941 gtcactcatt ttaacaattg aactctgctg ggttgggtat ttacctttgt ctagaaaaga
     3001 aatatgatat attttctcta aataaattta ttttcatcat tcca
//
