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Protein

Two pore calcium channel protein 2

Gene

TPCN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • identical protein binding Source: IntAct
  • NAADP-sensitive calcium-release channel activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • voltage-gated calcium channel activity Source: UniProtKB

GO - Biological processi

  • calcium-mediated signaling Source: ParkinsonsUK-UCL
  • cellular calcium ion homeostasis Source: UniProtKB
  • ion transmembrane transport Source: Reactome
  • lysosome organization Source: ParkinsonsUK-UCL
  • membrane depolarization during action potential Source: GO_Central
  • regulation of autophagy Source: ParkinsonsUK-UCL
  • response to vitamin D Source: Ensembl
  • smooth muscle contraction Source: UniProtKB

Keywordsi

Molecular functionCalcium channel, Ion channel, Voltage-gated channel
Biological processCalcium transport, Ion transport, Transport
LigandCalcium

Enzyme and pathway databases

ReactomeiR-HSA-2672351. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000162341.15.
HGNCiHGNC:20820. TPCN2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 84CytoplasmicSequence analysisAdd BLAST84
Transmembranei85 – 105Helical; Name=S1 of repeat ISequence analysisAdd BLAST21
Topological domaini106 – 127ExtracellularSequence analysisAdd BLAST22
Transmembranei128 – 148Helical; Name=S2 of repeat ISequence analysisAdd BLAST21
Topological domaini149 – 155CytoplasmicSequence analysis7
Transmembranei156 – 176Helical; Name=S3 of repeat ISequence analysisAdd BLAST21
Topological domaini177 – 183ExtracellularSequence analysis7
Transmembranei184 – 204Helical; Name=S4 of repeat ISequence analysisAdd BLAST21
Topological domaini205 – 218CytoplasmicSequence analysisAdd BLAST14
Transmembranei219 – 239Helical; Name=S5 of repeat ISequence analysisAdd BLAST21
Topological domaini240 – 254ExtracellularSequence analysisAdd BLAST15
Intramembranei255 – 279Helical; Pore-formingSequence analysisAdd BLAST25
Topological domaini280 – 289ExtracellularSequence analysis10
Transmembranei290 – 310Helical; Name=S6 of repeat ISequence analysisAdd BLAST21
Topological domaini311 – 436CytoplasmicSequence analysisAdd BLAST126
Transmembranei437 – 459Helical; Name=S1 of repeat IISequence analysisAdd BLAST23
Topological domaini460 – 465ExtracellularSequence analysis6
Transmembranei466 – 486Helical; Name=S2 of repeat IISequence analysisAdd BLAST21
Topological domaini487 – 502CytoplasmicSequence analysisAdd BLAST16
Transmembranei503 – 523Helical; Name=S3 of repeat IISequence analysisAdd BLAST21
Topological domaini524 – 554ExtracellularSequence analysisAdd BLAST31
Transmembranei555 – 575Helical; Name=S4 of repeat IISequence analysisAdd BLAST21
Topological domaini576 – 580CytoplasmicSequence analysis5
Transmembranei581 – 601Helical; Name=S5 of repeat IISequence analysisAdd BLAST21
Topological domaini602 – 635ExtracellularSequence analysisAdd BLAST34
Intramembranei636 – 658Helical; Pore-formingSequence analysisAdd BLAST23
Topological domaini659 – 673ExtracellularSequence analysisAdd BLAST15
Transmembranei674 – 694Helical; Name=S6 of repeat IISequence analysisAdd BLAST21
Topological domaini695 – 752CytoplasmicSequence analysisAdd BLAST58

Keywords - Cellular componenti

Lysosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi219931.
MIMi612267. phenotype.
OpenTargetsiENSG00000162341.
PharmGKBiPA134937857.

Chemistry databases

GuidetoPHARMACOLOGYi393.

Polymorphism and mutation databases

BioMutaiTPCN2.
DMDMi125991221.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002768561 – 752Two pore calcium channel protein 2Add BLAST752

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi611N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi618N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ8NHX9.
MaxQBiQ8NHX9.
PaxDbiQ8NHX9.
PeptideAtlasiQ8NHX9.
PRIDEiQ8NHX9.

PTM databases

iPTMnetiQ8NHX9.
PhosphoSitePlusiQ8NHX9.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000162341.
CleanExiHS_TPCN2.
ExpressionAtlasiQ8NHX9. baseline and differential.
GenevisibleiQ8NHX9. HS.

Organism-specific databases

HPAiHPA016561.
HPA027080.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with LRRK2 (PubMed:22012985). Interacts with HAX1 (PubMed:24188827).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi128596. 59 interactors.
IntActiQ8NHX9. 3 interactors.
STRINGi9606.ENSP00000294309.

Structurei

3D structure databases

ProteinModelPortaliQ8NHX9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi17 – 20Poly-Gly4

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

eggNOGiENOG410INF1. Eukaryota.
ENOG4111V21. LUCA.
GeneTreeiENSGT00530000063660.
HOGENOMiHOG000154668.
HOVERGENiHBG079776.
InParanoidiQ8NHX9.
KOiK14077.
OMAiSSVIWVN.
OrthoDBiEOG091G045K.
PhylomeDBiQ8NHX9.
TreeFamiTF328550.

Family and domain databases

InterProiView protein in InterPro
IPR005821. Ion_trans_dom.
IPR028798. TPC2.
PANTHERiPTHR10037:SF270. PTHR10037:SF270. 1 hit.
PfamiView protein in Pfam
PF00520. Ion_trans. 2 hits.

Sequencei

Sequence statusi: Complete.

Q8NHX9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEPQAESEP LLGGARGGGG DWPAGLTTYR SIQVGPGAAA RWDLCIDQAV
60 70 80 90 100
VFIEDAIQYR SINHRVDASS MWLYRRYYSN VCQRTLSFTI FLILFLAFIE
110 120 130 140 150
TPSSLTSTAD VRYRAAPWEP PCGLTESVEV LCLLVFAADL SVKGYLFGWA
160 170 180 190 200
HFQKNLWLLG YLVVLVVSLV DWTVSLSLVC HEPLRIRRLL RPFFLLQNSS
210 220 230 240 250
MMKKTLKCIR WSLPEMASVG LLLAIHLCLF TMFGMLLFAG GKQDDGQDRE
260 270 280 290 300
RLTYFQNLPE SLTSLLVLLT TANNPDVMIP AYSKNRAYAI FFIVFTVIGS
310 320 330 340 350
LFLMNLLTAI IYSQFRGYLM KSLQTSLFRR RLGTRAAFEV LSSMVGEGGA
360 370 380 390 400
FPQAVGVKPQ NLLQVLQKVQ LDSSHKQAMM EKVRSYGSVL LSAEEFQKLF
410 420 430 440 450
NELDRSVVKE HPPRPEYQSP FLQSAQFLFG HYYFDYLGNL IALANLVSIC
460 470 480 490 500
VFLVLDADVL PAERDDFILG ILNCVFIVYY LLEMLLKVFA LGLRGYLSYP
510 520 530 540 550
SNVFDGLLTV VLLVLEISTL AVYRLPHPGW RPEMVGLLSL WDMTRMLNML
560 570 580 590 600
IVFRFLRIIP SMKLMAVVAS TVLGLVQNMR AFGGILVVVY YVFAIIGINL
610 620 630 640 650
FRGVIVALPG NSSLAPANGS APCGSFEQLE YWANNFDDFA AALVTLWNLM
660 670 680 690 700
VVNNWQVFLD AYRRYSGPWS KIYFVLWWLV SSVIWVNLFL ALILENFLHK
710 720 730 740 750
WDPRSHLQPL AGTPEATYQM TVELLFRDIL EEPGEDELTE RLSQHPHLWL

CR
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.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030492376K → R. Corresponds to variant dbSNP:rs3750965Ensembl.1
Natural variantiVAR_047956484M → L Associated with SHEP10. 1 PublicationCorresponds to variant dbSNP:rs35264875Ensembl.1
Natural variantiVAR_030493564L → P3 PublicationsCorresponds to variant dbSNP:rs2376558Ensembl.1
Natural variantiVAR_030494734G → E Associated with SHEP10. 4 PublicationsCorresponds to variant dbSNP:rs3829241Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
UCSCiuc001oos.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTPC2_HUMAN
AccessioniPrimary (citable) accession number: Q8NHX9
Secondary accession number(s): Q9NT82
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: September 27, 2017
This is version 129 of the entry and version 2 of the sequence. See 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