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Q8NHX9

- TPC2_HUMAN

UniProt

Q8NHX9 - TPC2_HUMAN

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Protein
Two pore calcium channel protein 2
Gene
TPCN2, TPC2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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

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
Complete GO annotation...

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; Multi-pass membrane protein By similarity
Note: Only the acidic lysosomal fraction is sensitive to NAADP By similarity.2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8484Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei85 – 10521Helical; Name=S1 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini106 – 12722Extracellular Reviewed prediction
Add
BLAST
Transmembranei128 – 14821Helical; Name=S2 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini149 – 1557Cytoplasmic Reviewed prediction
Transmembranei156 – 17621Helical; Name=S3 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini177 – 1837Extracellular Reviewed prediction
Transmembranei184 – 20421Helical; Name=S4 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini205 – 21814Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei219 – 23921Helical; Name=S5 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini240 – 25415Extracellular Reviewed prediction
Add
BLAST
Intramembranei255 – 27925Helical; Pore-forming; Reviewed prediction
Add
BLAST
Topological domaini280 – 28910Extracellular Reviewed prediction
Transmembranei290 – 31021Helical; Name=S6 of repeat I; Reviewed prediction
Add
BLAST
Topological domaini311 – 436126Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei437 – 45923Helical; Name=S1 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini460 – 4656Extracellular Reviewed prediction
Transmembranei466 – 48621Helical; Name=S2 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini487 – 50216Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei503 – 52321Helical; Name=S3 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini524 – 55431Extracellular Reviewed prediction
Add
BLAST
Transmembranei555 – 57521Helical; Name=S4 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini576 – 5805Cytoplasmic Reviewed prediction
Transmembranei581 – 60121Helical; Name=S5 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini602 – 63534Extracellular Reviewed prediction
Add
BLAST
Intramembranei636 – 65823Helical; Pore-forming; Reviewed prediction
Add
BLAST
Topological domaini659 – 67315Extracellular Reviewed prediction
Add
BLAST
Transmembranei674 – 69421Helical; Name=S6 of repeat II; Reviewed prediction
Add
BLAST
Topological domaini695 – 75258Cytoplasmic Reviewed prediction
Add
BLAST

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
Complete GO annotation...

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 2
PRO_0000276856Add
BLAST

Amino acid modifications

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

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 LRRK2.1 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.

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.

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...

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 101 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

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