Two pore calcium channel protein 2 - Homo sapiens (Human)

Contribute

Send feedback

Read comments (?) or add your own

Q8NHX9 (TPC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 86. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Two pore calcium channel protein 2

Alternative name(s):
Voltage-dependent calcium channel protein TPC2

Gene names

Name:	TPCN2
Synonyms:	TPC2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	752 AA.
Sequence status	Complete.
Protein existence	Evidence 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]

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Lysosome Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Calcium channel Ion channel Voltage-gated channel
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular calcium ion homeostasis Inferred from direct assay Ref.1. Source: UniProtKB release of sequestered calcium ion into cytosol Inferred from electronic annotation. Source: Compara smooth muscle contraction Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	endosome membrane Inferred from direct assay Ref.5. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lysosomal membrane Inferred from direct assay Ref.1 Ref.5. Source: UniProtKB
Molecular_function	NAADP-sensitive calcium-release channel activity Inferred from direct assay Ref.1 Ref.5. Source: UniProtKB voltage-gated calcium channel activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		4	EBI-5239949,EBI-5239949
TPCN1	Q9ULQ1	9	EBI-5239949,EBI-5239895

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 752

752

Two pore calcium channel protein 2

PRO_0000276856

Regions

Topological domain

1 – 84

Cytoplasmic Potential

Transmembrane

85 – 105

Helical; Name=S1 of repeat I; Potential

Topological domain

106 – 127

Extracellular Potential

Transmembrane

128 – 148

Helical; Name=S2 of repeat I; Potential

Topological domain

149 – 155

Cytoplasmic Potential

Transmembrane

156 – 176

Helical; Name=S3 of repeat I; Potential

Topological domain

177 – 183

Extracellular Potential

Transmembrane

184 – 204

Helical; Name=S4 of repeat I; Potential

Topological domain

205 – 218

Cytoplasmic Potential

Transmembrane

219 – 239

Helical; Name=S5 of repeat I; Potential

Topological domain

240 – 254

Extracellular Potential

Intramembrane

255 – 279

Helical; Pore-forming; Potential

Topological domain

280 – 289

Extracellular Potential

Transmembrane

290 – 310

Helical; Name=S6 of repeat I; Potential

Topological domain

311 – 436

126

Cytoplasmic Potential

Transmembrane

437 – 459

Helical; Name=S1 of repeat II; Potential

Topological domain

460 – 465

Extracellular Potential

Transmembrane

466 – 486

Helical; Name=S2 of repeat II; Potential

Topological domain

487 – 502

Cytoplasmic Potential

Transmembrane

503 – 523

Helical; Name=S3 of repeat II; Potential

Topological domain

524 – 554

Extracellular Potential

Transmembrane

555 – 575

Helical; Name=S4 of repeat II; Potential

Topological domain

576 – 580

Cytoplasmic Potential

Transmembrane

581 – 601

Helical; Name=S5 of repeat II; Potential

Topological domain

602 – 635

Extracellular Potential

Intramembrane

636 – 658

Helical; Pore-forming; Potential

Topological domain

659 – 673

Extracellular Potential

Transmembrane

674 – 694

Helical; Name=S6 of repeat II; Potential

Topological domain

695 – 752

Cytoplasmic Potential

Compositional bias

17 – 20

Poly-Gly

Amino acid modifications

Glycosylation

611

N-linked (GlcNAc...) Potential

Glycosylation

618

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

376

K → R.
Corresponds to variant rs3750965 [ dbSNP | Ensembl ].

VAR_030492

Natural variant

484

M → L Associated with SHEP10. Ref.7
Corresponds to variant rs35264875 [ dbSNP | Ensembl ].

VAR_047956

Natural variant

564

L → P. Ref.1 Ref.3 Ref.4
Corresponds to variant rs2376558 [ dbSNP | Ensembl ].

VAR_030493

Natural variant

734

G → E Associated with SHEP10. Ref.1 Ref.3 Ref.4 Ref.7
Corresponds to variant rs3829241 [ dbSNP | Ensembl ].

VAR_030494

Sequences

Sequence

Length

Mass (Da)

Tools

Q8NHX9 [UniParc].

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

FASTA

752

85,243

        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' referencesShow '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. , 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. 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. 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.
IPI	IPI00169371.
PIR	T46421.
RefSeq	NP_620714.2. NM_139075.3.
UniGene	Hs.131851.
3D structure databases
ProteinModelPortal	Q8NHX9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8NHX9. 1 interaction.
STRING	9606.ENSP00000294309.
PTM databases
PhosphoSite	Q8NHX9.
Polymorphism databases
DMDM	125991221.
Proteomic databases
PaxDb	Q8NHX9.
PRIDE	Q8NHX9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000294309; ENSP00000294309; ENSG00000162341.
GeneID	219931.
KEGG	hsa:219931.
UCSC	uc001oos.2. human.
Organism-specific databases
CTD	219931.
GeneCards	GC11P068816.
H-InvDB	HIX0019754.
HGNC	HGNC:20820. TPCN2.
HPA	HPA027080.
MIM	612163. gene. 612267. phenotype.
neXtProt	NX_Q8NHX9.
PharmGKB	PA134937857.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG299468.
HOGENOM	HOG000154668.
HOVERGEN	HBG079776.
InParanoid	Q8NHX9.
KO	K14077.
OMA	LLSLWDM.
OrthoDB	EOG4XWFXH.
Gene expression databases
ArrayExpress	Q8NHX9.
Bgee	Q8NHX9.
CleanEx	HS_TPCN2.
Genevestigator	Q8NHX9.
Family and domain databases
InterPro	IPR005821. Ion_trans_dom. [Graphical view]
Pfam	PF00520. Ion_trans. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	219931.
NextBio	90858.
SOURCE	Search...

Entry information

Entry name

TPC2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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

Human chromosome 11

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents