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Q8NHX9

- TPC2_HUMAN

UniProt

Q8NHX9 - TPC2_HUMAN

Protein

Two pore calcium channel protein 2

Gene

TPCN2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 2 (06 Feb 2007)
      Previous versions | rss
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    Functioni

    Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca2+ channels (VDCC) across the lysosomal membrane. May be involved in smooth muscle contraction.2 Publications

    GO - Molecular functioni

    1. identical protein binding Source: IntAct
    2. NAADP-sensitive calcium-release channel activity Source: UniProtKB
    3. protein binding Source: IntAct
    4. protein kinase binding Source: UniProtKB
    5. voltage-gated calcium channel activity Source: UniProtKB

    GO - Biological processi

    1. calcium ion transport Source: RefGenome
    2. cellular calcium ion homeostasis Source: UniProtKB
    3. ion transmembrane transport Source: RefGenome
    4. membrane depolarization during action potential Source: RefGenome
    5. release of sequestered calcium ion into cytosol Source: Ensembl
    6. smooth muscle contraction Source: UniProtKB
    7. transmembrane transport Source: Reactome

    Keywords - Molecular functioni

    Calcium channel, Ion channel, Voltage-gated channel

    Keywords - Biological processi

    Calcium transport, Ion transport, Transport

    Keywords - Ligandi

    Calcium

    Enzyme and pathway databases

    ReactomeiREACT_160189. Stimuli-sensing channels.

    Protein family/group databases

    TCDBi1.A.1.11.19. the voltage-gated ion channel (vic) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Two pore calcium channel protein 2
    Alternative name(s):
    Voltage-dependent calcium channel protein TPC2
    Gene namesi
    Name:TPCN2
    Synonyms:TPC2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:20820. TPCN2.

    Subcellular locationi

    Lysosome membrane By similarity; Multi-pass membrane protein By similarity
    Note: Only the acidic lysosomal fraction is sensitive to NAADP.By similarity

    GO - Cellular componenti

    1. endosome membrane Source: UniProtKB
    2. integral component of membrane Source: UniProtKB-KW
    3. lysosomal membrane Source: UniProtKB
    4. plasma membrane Source: RefGenome

    Keywords - Cellular componenti

    Lysosome, Membrane

    Pathology & Biotechi

    Organism-specific databases

    MIMi612267. phenotype.
    PharmGKBiPA134937857.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 752752Two pore calcium channel protein 2PRO_0000276856Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi611 – 6111N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi618 – 6181N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiQ8NHX9.
    PaxDbiQ8NHX9.
    PRIDEiQ8NHX9.

    PTM databases

    PhosphoSiteiQ8NHX9.

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed at high level in liver and kidney.1 Publication

    Gene expression databases

    ArrayExpressiQ8NHX9.
    BgeeiQ8NHX9.
    CleanExiHS_TPCN2.
    GenevestigatoriQ8NHX9.

    Organism-specific databases

    HPAiHPA016561.
    HPA027080.

    Interactioni

    Subunit structurei

    Homodimer By similarity. Interacts with LRRK2.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself4EBI-5239949,EBI-5239949
    HAX1O001654EBI-5239949,EBI-357001
    MTORP423452EBI-5239949,EBI-359260
    TPCN1Q9ULQ19EBI-5239949,EBI-5239895

    Protein-protein interaction databases

    BioGridi128596. 1 interaction.
    IntActiQ8NHX9. 3 interactions.
    STRINGi9606.ENSP00000294309.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8NHX9.
    SMRiQ8NHX9. Positions 254-316, 424-565.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 8484CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini106 – 12722ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini149 – 1557CytoplasmicSequence Analysis
    Topological domaini177 – 1837ExtracellularSequence Analysis
    Topological domaini205 – 21814CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini240 – 25415ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini280 – 28910ExtracellularSequence Analysis
    Topological domaini311 – 436126CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini460 – 4656ExtracellularSequence Analysis
    Topological domaini487 – 50216CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini524 – 55431ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini576 – 5805CytoplasmicSequence Analysis
    Topological domaini602 – 63534ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini659 – 67315ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini695 – 75258CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei255 – 27925Helical; Pore-formingSequence AnalysisAdd
    BLAST
    Intramembranei636 – 65823Helical; Pore-formingSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei85 – 10521Helical; Name=S1 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei128 – 14821Helical; Name=S2 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei156 – 17621Helical; Name=S3 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei184 – 20421Helical; Name=S4 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei219 – 23921Helical; Name=S5 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei290 – 31021Helical; Name=S6 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei437 – 45923Helical; Name=S1 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei466 – 48621Helical; Name=S2 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei503 – 52321Helical; Name=S3 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei555 – 57521Helical; Name=S4 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei581 – 60121Helical; Name=S5 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei674 – 69421Helical; Name=S6 of repeat IISequence AnalysisAdd
    BLAST

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi17 – 204Poly-Gly

    Domaini

    Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position By similarity.By similarity

    Sequence similaritiesi

    Keywords - Domaini

    Repeat, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG299468.
    HOGENOMiHOG000154668.
    HOVERGENiHBG079776.
    InParanoidiQ8NHX9.
    KOiK14077.
    OMAiSSVIWVN.
    OrthoDBiEOG72ZCDF.
    PhylomeDBiQ8NHX9.
    TreeFamiTF328550.

    Family and domain databases

    Gene3Di1.20.120.350. 1 hit.
    InterProiIPR027359. Channel_four-helix_dom.
    IPR005821. Ion_trans_dom.
    IPR028798. TPC2.
    [Graphical view]
    PANTHERiPTHR10037:SF175. PTHR10037:SF175. 1 hit.
    PfamiPF00520. Ion_trans. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q8NHX9-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAEPQAESEP LLGGARGGGG DWPAGLTTYR SIQVGPGAAA RWDLCIDQAV    50
    VFIEDAIQYR SINHRVDASS MWLYRRYYSN VCQRTLSFTI FLILFLAFIE 100
    TPSSLTSTAD VRYRAAPWEP PCGLTESVEV LCLLVFAADL SVKGYLFGWA 150
    HFQKNLWLLG YLVVLVVSLV DWTVSLSLVC HEPLRIRRLL RPFFLLQNSS 200
    MMKKTLKCIR WSLPEMASVG LLLAIHLCLF TMFGMLLFAG GKQDDGQDRE 250
    RLTYFQNLPE SLTSLLVLLT TANNPDVMIP AYSKNRAYAI FFIVFTVIGS 300
    LFLMNLLTAI IYSQFRGYLM KSLQTSLFRR RLGTRAAFEV LSSMVGEGGA 350
    FPQAVGVKPQ NLLQVLQKVQ LDSSHKQAMM EKVRSYGSVL LSAEEFQKLF 400
    NELDRSVVKE HPPRPEYQSP FLQSAQFLFG HYYFDYLGNL IALANLVSIC 450
    VFLVLDADVL PAERDDFILG ILNCVFIVYY LLEMLLKVFA LGLRGYLSYP 500
    SNVFDGLLTV VLLVLEISTL AVYRLPHPGW RPEMVGLLSL WDMTRMLNML 550
    IVFRFLRIIP SMKLMAVVAS TVLGLVQNMR AFGGILVVVY YVFAIIGINL 600
    FRGVIVALPG NSSLAPANGS APCGSFEQLE YWANNFDDFA AALVTLWNLM 650
    VVNNWQVFLD AYRRYSGPWS KIYFVLWWLV SSVIWVNLFL ALILENFLHK 700
    WDPRSHLQPL AGTPEATYQM TVELLFRDIL EEPGEDELTE RLSQHPHLWL 750
    CR 752
    Length:752
    Mass (Da):85,243
    Last modified:February 6, 2007 - v2
    Checksum:i8A0794952A46C67E
    GO

    Polymorphismi

    Genetic variants in TPCN2 define the skin/hair/eye pigmentation variation locus 10 (SHEP10) [MIMi:612267]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti376 – 3761K → R.
    Corresponds to variant rs3750965 [ dbSNP | Ensembl ].
    VAR_030492
    Natural varianti484 – 4841M → L Associated with SHEP10. 1 Publication
    Corresponds to variant rs35264875 [ dbSNP | Ensembl ].
    VAR_047956
    Natural varianti564 – 5641L → P.3 Publications
    Corresponds to variant rs2376558 [ dbSNP | Ensembl ].
    VAR_030493
    Natural varianti734 – 7341G → E Associated with SHEP10. 4 Publications
    Corresponds to variant rs3829241 [ dbSNP | Ensembl ].
    VAR_030494

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY029200 mRNA. Translation: AAK31802.1.
    AP003071 Genomic DNA. No translation available.
    BC063008 mRNA. Translation: AAH63008.1.
    AL137479 mRNA. Translation: CAB70760.1.
    CCDSiCCDS8189.1.
    PIRiT46421.
    RefSeqiNP_620714.2. NM_139075.3.
    UniGeneiHs.131851.

    Genome annotation databases

    EnsembliENST00000294309; ENSP00000294309; ENSG00000162341.
    GeneIDi219931.
    KEGGihsa:219931.
    UCSCiuc001oor.2. human.

    Polymorphism databases

    DMDMi125991221.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY029200 mRNA. Translation: AAK31802.1 .
    AP003071 Genomic DNA. No translation available.
    BC063008 mRNA. Translation: AAH63008.1 .
    AL137479 mRNA. Translation: CAB70760.1 .
    CCDSi CCDS8189.1.
    PIRi T46421.
    RefSeqi NP_620714.2. NM_139075.3.
    UniGenei Hs.131851.

    3D structure databases

    ProteinModelPortali Q8NHX9.
    SMRi Q8NHX9. Positions 254-316, 424-565.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 128596. 1 interaction.
    IntActi Q8NHX9. 3 interactions.
    STRINGi 9606.ENSP00000294309.

    Protein family/group databases

    TCDBi 1.A.1.11.19. the voltage-gated ion channel (vic) superfamily.

    PTM databases

    PhosphoSitei Q8NHX9.

    Polymorphism databases

    DMDMi 125991221.

    Proteomic databases

    MaxQBi Q8NHX9.
    PaxDbi Q8NHX9.
    PRIDEi Q8NHX9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000294309 ; ENSP00000294309 ; ENSG00000162341 .
    GeneIDi 219931.
    KEGGi hsa:219931.
    UCSCi uc001oor.2. human.

    Organism-specific databases

    CTDi 219931.
    GeneCardsi GC11P068816.
    H-InvDB HIX0019754.
    HGNCi HGNC:20820. TPCN2.
    HPAi HPA016561.
    HPA027080.
    MIMi 612163. gene.
    612267. phenotype.
    neXtProti NX_Q8NHX9.
    PharmGKBi PA134937857.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG299468.
    HOGENOMi HOG000154668.
    HOVERGENi HBG079776.
    InParanoidi Q8NHX9.
    KOi K14077.
    OMAi SSVIWVN.
    OrthoDBi EOG72ZCDF.
    PhylomeDBi Q8NHX9.
    TreeFami TF328550.

    Enzyme and pathway databases

    Reactomei REACT_160189. Stimuli-sensing channels.

    Miscellaneous databases

    GeneWikii TPCN2.
    GenomeRNAii 219931.
    NextBioi 90858.
    PROi Q8NHX9.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8NHX9.
    Bgeei Q8NHX9.
    CleanExi HS_TPCN2.
    Genevestigatori Q8NHX9.

    Family and domain databases

    Gene3Di 1.20.120.350. 1 hit.
    InterProi IPR027359. Channel_four-helix_dom.
    IPR005821. Ion_trans_dom.
    IPR028798. TPC2.
    [Graphical view ]
    PANTHERi PTHR10037:SF175. PTHR10037:SF175. 1 hit.
    Pfami PF00520. Ion_trans. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS PRO-564 AND GLU-734.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS PRO-564 AND GLU-734.
      Tissue: Blood.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 382-752, VARIANTS PRO-564 AND GLU-734.
      Tissue: Testis.
    5. "Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling."
      Brailoiu E., Churamani D., Cai X., Schrlau M.G., Brailoiu G.C., Gao X., Hooper R., Boulware M.J., Dun N.J., Marchant J.S., Patel S.
      J. Cell Biol. 186:201-209(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    6. "Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
      Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
      Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LRRK2.
    7. Cited for: VARIANTS LEU-484 AND GLU-734, ASSOCIATION WITH SHEP10.

    Entry informationi

    Entry nameiTPC2_HUMAN
    AccessioniPrimary (citable) accession number: Q8NHX9
    Secondary accession number(s): Q9NT82
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 6, 2007
    Last sequence update: February 6, 2007
    Last modified: October 1, 2014
    This is version 102 of the entry and version 2 of the sequence. [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 11
      Human chromosome 11: 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

    External Data

    Dasty 3