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Q8NHX9 (TPC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Two pore calcium channel protein 2
Alternative name(s):
Voltage-dependent calcium channel protein TPC2
Gene names
Name:TPCN2
Synonyms:TPC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length752 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.5

Subunit structure

Homodimer By similarity. Interacts with LRRK2. Ref.6

Subcellular location

Lysosome membrane; Multi-pass membrane protein By similarity. Note: Only the acidic lysosomal fraction is sensitive to NAADP By similarity. Ref.1 Ref.5

Tissue specificity

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

Domain

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.

Post-translational modification

N-glycosylated By similarity.

Polymorphism

Genetic variants in TPCN2 define the skin/hair/eye pigmentation variation locus 10 (SHEP10) [MIM: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.

Sequence similarities

Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 752752Two pore calcium channel protein 2
PRO_0000276856

Regions

Topological domain1 – 8484Cytoplasmic Potential
Transmembrane85 – 10521Helical; Name=S1 of repeat I; Potential
Topological domain106 – 12722Extracellular Potential
Transmembrane128 – 14821Helical; Name=S2 of repeat I; Potential
Topological domain149 – 1557Cytoplasmic Potential
Transmembrane156 – 17621Helical; Name=S3 of repeat I; Potential
Topological domain177 – 1837Extracellular Potential
Transmembrane184 – 20421Helical; Name=S4 of repeat I; Potential
Topological domain205 – 21814Cytoplasmic Potential
Transmembrane219 – 23921Helical; Name=S5 of repeat I; Potential
Topological domain240 – 25415Extracellular Potential
Intramembrane255 – 27925Helical; Pore-forming; Potential
Topological domain280 – 28910Extracellular Potential
Transmembrane290 – 31021Helical; Name=S6 of repeat I; Potential
Topological domain311 – 436126Cytoplasmic Potential
Transmembrane437 – 45923Helical; Name=S1 of repeat II; Potential
Topological domain460 – 4656Extracellular Potential
Transmembrane466 – 48621Helical; Name=S2 of repeat II; Potential
Topological domain487 – 50216Cytoplasmic Potential
Transmembrane503 – 52321Helical; Name=S3 of repeat II; Potential
Topological domain524 – 55431Extracellular Potential
Transmembrane555 – 57521Helical; Name=S4 of repeat II; Potential
Topological domain576 – 5805Cytoplasmic Potential
Transmembrane581 – 60121Helical; Name=S5 of repeat II; Potential
Topological domain602 – 63534Extracellular Potential
Intramembrane636 – 65823Helical; Pore-forming; Potential
Topological domain659 – 67315Extracellular Potential
Transmembrane674 – 69421Helical; Name=S6 of repeat II; Potential
Topological domain695 – 75258Cytoplasmic Potential
Compositional bias17 – 204Poly-Gly

Amino acid modifications

Glycosylation6111N-linked (GlcNAc...) Potential
Glycosylation6181N-linked (GlcNAc...) Potential

Natural variations

Natural variant3761K → R.
Corresponds to variant rs3750965 [ dbSNP | Ensembl ].
VAR_030492
Natural variant4841M → L Associated with SHEP10. Ref.7
Corresponds to variant rs35264875 [ dbSNP | Ensembl ].
VAR_047956
Natural variant5641L → P. Ref.1 Ref.3 Ref.4
Corresponds to variant rs2376558 [ dbSNP | Ensembl ].
VAR_030493
Natural variant7341G → E Associated with SHEP10. Ref.1 Ref.3 Ref.4 Ref.7
Corresponds to variant rs3829241 [ dbSNP | Ensembl ].
VAR_030494

Sequences

Sequence LengthMass (Da)Tools
Q8NHX9 [UniParc].

Last modified February 6, 2007. Version 2.
Checksum: 8A0794952A46C67E

FASTA75285,243
        10         20         30         40         50         60 
MAEPQAESEP LLGGARGGGG DWPAGLTTYR SIQVGPGAAA RWDLCIDQAV VFIEDAIQYR 

        70         80         90        100        110        120 
SINHRVDASS MWLYRRYYSN VCQRTLSFTI FLILFLAFIE TPSSLTSTAD VRYRAAPWEP 

       130        140        150        160        170        180 
PCGLTESVEV LCLLVFAADL SVKGYLFGWA HFQKNLWLLG YLVVLVVSLV DWTVSLSLVC 

       190        200        210        220        230        240 
HEPLRIRRLL RPFFLLQNSS MMKKTLKCIR WSLPEMASVG LLLAIHLCLF TMFGMLLFAG 

       250        260        270        280        290        300 
GKQDDGQDRE RLTYFQNLPE SLTSLLVLLT TANNPDVMIP AYSKNRAYAI FFIVFTVIGS 

       310        320        330        340        350        360 
LFLMNLLTAI IYSQFRGYLM KSLQTSLFRR RLGTRAAFEV LSSMVGEGGA FPQAVGVKPQ 

       370        380        390        400        410        420 
NLLQVLQKVQ LDSSHKQAMM EKVRSYGSVL LSAEEFQKLF NELDRSVVKE HPPRPEYQSP 

       430        440        450        460        470        480 
FLQSAQFLFG HYYFDYLGNL IALANLVSIC VFLVLDADVL PAERDDFILG ILNCVFIVYY 

       490        500        510        520        530        540 
LLEMLLKVFA LGLRGYLSYP SNVFDGLLTV VLLVLEISTL AVYRLPHPGW RPEMVGLLSL 

       550        560        570        580        590        600 
WDMTRMLNML IVFRFLRIIP SMKLMAVVAS TVLGLVQNMR AFGGILVVVY YVFAIIGINL 

       610        620        630        640        650        660 
FRGVIVALPG NSSLAPANGS APCGSFEQLE YWANNFDDFA AALVTLWNLM VVNNWQVFLD 

       670        680        690        700        710        720 
AYRRYSGPWS KIYFVLWWLV SSVIWVNLFL ALILENFLHK WDPRSHLQPL AGTPEATYQM 

       730        740        750 
TVELLFRDIL EEPGEDELTE RLSQHPHLWL CR 

« Hide

References

« Hide 'large scale' references
[1]"NAADP mobilizes calcium from acidic organelles through two-pore channels."
Calcraft P.J., Ruas M., Pan Z., Cheng X., Arredouani A., Hao X., Tang J., Rietdorf K., Teboul L., Chuang K.T., Lin P., Xiao R., Wang C., Zhu Y., Lin Y., Wyatt C.N., Parrington J., Ma J. expand/collapse author list , Evans A.M., Galione A., Zhu M.X.
Nature 459:596-600(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANTS PRO-564 AND GLU-734.
[2]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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]"Two newly identified genetic determinants of pigmentation in Europeans."
Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T., Jakobsdottir M., Steinberg S., Gudjonsson S.A., Palsson A., Thorleifsson G., Palsson S., Sigurgeirsson B., Thorisdottir K., Ragnarsson R., Benediktsdottir K.R., Aben K.K., Vermeulen S.H., Goldstein A.M. expand/collapse author list , Tucker M.A., Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U., Stefansson K.
Nat. Genet. 40:835-837(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-484 AND GLU-734, ASSOCIATION WITH SHEP10.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY029200 mRNA. Translation: AAK31802.1.
AP003071 Genomic DNA. No translation available.
BC063008 mRNA. Translation: AAH63008.1.
AL137479 mRNA. Translation: CAB70760.1.
PIRT46421.
RefSeqNP_620714.2. NM_139075.3.
UniGeneHs.131851.

3D structure databases

ProteinModelPortalQ8NHX9.
SMRQ8NHX9. Positions 68-322, 579-701.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128596. 1 interaction.
IntActQ8NHX9. 3 interactions.
STRING9606.ENSP00000294309.

Protein family/group databases

TCDB1.A.1.11.19. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteQ8NHX9.

Polymorphism databases

DMDM125991221.

Proteomic databases

PaxDbQ8NHX9.
PRIDEQ8NHX9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000294309; ENSP00000294309; ENSG00000162341.
GeneID219931.
KEGGhsa:219931.
UCSCuc001oor.2. human.

Organism-specific databases

CTD219931.
GeneCardsGC11P068816.
H-InvDBHIX0019754.
HGNCHGNC:20820. TPCN2.
HPAHPA016561.
HPA027080.
MIM612163. gene.
612267. phenotype.
neXtProtNX_Q8NHX9.
PharmGKBPA134937857.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG299468.
HOGENOMHOG000154668.
HOVERGENHBG079776.
InParanoidQ8NHX9.
KOK14077.
OMALLSLWDM.
OrthoDBEOG72ZCDF.
TreeFamTF328550.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ8NHX9.
BgeeQ8NHX9.
CleanExHS_TPCN2.
GenevestigatorQ8NHX9.

Family and domain databases

Gene3D1.20.120.350. 1 hit.
InterProIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR028798. TPC2.
[Graphical view]
PANTHERPTHR10037:SF31. PTHR10037:SF31. 1 hit.
PfamPF00520. Ion_trans. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTPCN2.
GenomeRNAi219931.
NextBio90858.
PROQ8NHX9.
SOURCESearch...

Entry information

Entry nameTPC2_HUMAN
AccessionPrimary (citable) accession number: Q8NHX9
Secondary accession number(s): Q9NT82
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: March 19, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM