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Q9ULQ1 (TPC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Two pore calcium channel protein 1
Alternative name(s):
Voltage-dependent calcium channel protein TPC1
Gene names
Name:TPCN1
Synonyms:KIAA1169, TPC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length816 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 and endosomal membrane. Ref.7

Subunit structure

Dimer Potential.

Subcellular location

Lysosome membrane; Multi-pass membrane protein. Endosome membrane; Multi-pass membrane protein Ref.7.

Tissue specificity

Highest expression found in the heart and kidney, and lowest expression found in the spleen. Ref.2

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.

Sequence similarities

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

Sequence caution

The sequence AK057414 differs from that shown. Reason: Frameshift at position 273.

The sequence BAA86483.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Transport
   Cellular componentEndosome
Lysosome
Membrane
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
Repeat
Transmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionCalcium channel
Ion channel
Voltage-gated channel
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium ion transport

Inferred from Biological aspect of Ancestor. Source: RefGenome

ion transmembrane transport

Inferred from Biological aspect of Ancestor. Source: RefGenome

membrane depolarization during action potential

Inferred from Biological aspect of Ancestor. Source: RefGenome

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentendosome membrane

Inferred from direct assay Ref.7. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lysosomal membrane

Inferred from direct assay Ref.7. Source: UniProtKB

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionNAADP-sensitive calcium-release channel activity

Inferred from direct assay Ref.7. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 21903581. Source: IntAct

protein binding

Inferred from physical interaction PubMed 21903581PubMed 24188827. Source: IntAct

voltage-gated calcium channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9ULQ1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9ULQ1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-366: Missing.
     569-618: SLGLTLLIFY...WRNHTVGNRT → RYCQPPPWPA...PDGAPRSLES
     619-816: Missing.
Isoform 3 (identifier: Q9ULQ1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MESCYIAQAGLELLGSSSSPTLTSQSAEITEDASNGGVSEQHPWPSGFERELKPETISSPGYHILRATGEENM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 816816Two pore calcium channel protein 1
PRO_0000276853

Regions

Topological domain1 – 112112Cytoplasmic Potential
Transmembrane113 – 13321Helical; Name=S1 of repeat I; Potential
Topological domain1341Extracellular Potential
Transmembrane135 – 15521Helical; Name=S2 of repeat I; Potential
Topological domain156 – 17722Cytoplasmic Potential
Transmembrane178 – 19821Helical; Name=S3 of repeat I; Potential
Topological domain199 – 2002Extracellular Potential
Transmembrane201 – 22020Helical; Name=S4 of repeat I; Potential
Topological domain221 – 23414Cytoplasmic Potential
Transmembrane235 – 25521Helical; Name=S5 of repeat I; Potential
Topological domain256 – 2627Extracellular Potential
Intramembrane263 – 28624Helical; Pore-forming; Potential
Topological domain287 – 2948Extracellular Potential
Transmembrane295 – 31521Helical; Name=S6 of repeat I; Potential
Topological domain316 – 444129Cytoplasmic Potential
Transmembrane445 – 46521Helical; Name=S1 of repeat II; Potential
Topological domain466 – 47914Extracellular Potential
Transmembrane480 – 50021Helical; Name=S2 of repeat II; Potential
Topological domain501 – 5033Cytoplasmic Potential
Transmembrane504 – 52623Helical; Name=S3 of repeat II; Potential
Topological domain527 – 5348Extracellular Potential
Transmembrane535 – 54915Helical; Name=S4 of repeat II; Potential
Topological domain550 – 57324Cytoplasmic Potential
Transmembrane574 – 59421Helical; Name=S5 of repeat II; Potential
Topological domain595 – 62935Extracellular Potential
Intramembrane630 – 65324Helical; Pore-forming; Potential
Topological domain654 – 67017Extracellular Potential
Transmembrane671 – 69121Helical; Name=S6 of repeat II; Potential
Topological domain692 – 816125Cytoplasmic Potential
Coiled coil769 – 79628 Potential

Amino acid modifications

Glycosylation5991N-linked (GlcNAc...) Potential
Glycosylation6111N-linked (GlcNAc...) Potential
Glycosylation6161N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 366366Missing in isoform 2.
VSP_023003
Alternative sequence11M → MESCYIAQAGLELLGSSSSP TLTSQSAEITEDASNGGVSE QHPWPSGFERELKPETISSP GYHILRATGEENM in isoform 3.
VSP_041346
Alternative sequence569 – 61850SLGLT…VGNRT → RYCQPPPWPAGPGAVWQCPV GAGAEWQSGERSSTKDCNRG PDGAPRSLES in isoform 2.
VSP_023004
Alternative sequence619 – 816198Missing in isoform 2.
VSP_023005

Experimental info

Mutagenesis2731L → P: Loss of NAADP-mediated cytoplasmic calcium release. Ref.7
Sequence conflict6211E → G in AK057414. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 6, 2007. Version 3.
Checksum: D6D26BFAF33E1463

FASTA81694,147
        10         20         30         40         50         60 
MAVSLDDDVP LILTLDEGGS APLAPSNGLG QEELPSKNGG SYAIHDSQAP SLSSGGESSP 

        70         80         90        100        110        120 
SSPAHNWEMN YQEAAIYLQE GENNDKFFTH PKDAKALAAY LFAHNHLFYL MELATALLLL 

       130        140        150        160        170        180 
LLSLCEAPAV PALRLGIYVH ATLELFALMV VVFELCMKLR WLGLHTFIRH KRTMVKTSVL 

       190        200        210        220        230        240 
VVQFVEAIVV LVRQMSHVRV TRALRCIFLV DCRYCGGVRR NLRQIFQSLP PFMDILLLLL 

       250        260        270        280        290        300 
FFMIIFAILG FYLFSPNPSD PYFSTLENSI VSLFVLLTTA NFPDVMMPSY SRNPWSCVFF 

       310        320        330        340        350        360 
IVYLSIELYF IMNLLLAVVF DTFNDIEKRK FKSLLLHKRT AIQHAYRLLI SQRRPAGISY 

       370        380        390        400        410        420 
RQFEGLMRFY KPRMSARERY LTFKALNQNN TPLLSLKDFY DIYEVAALKW KAKKNREHWF 

       430        440        450        460        470        480 
DELPRTALLI FKGINILVKS KAFQYFMYLV VAVNGVWILV ETFMLKGGNF FSKHVPWSYL 

       490        500        510        520        530        540 
VFLTIYGVEL FLKVAGLGPV EYLSSGWNLF DFSVTVFAFL GLLALALNME PFYFIVVLRP 

       550        560        570        580        590        600 
LQLLRLFKLK ERYRNVLDTM FELLPRMASL GLTLLIFYYS FAIVGMEFFC GIVFPNCCNT 

       610        620        630        640        650        660 
STVADAYRWR NHTVGNRTVV EEGYYYLNNF DNILNSFVTL FELTVVNNWY IIMEGVTSQT 

       670        680        690        700        710        720 
SHWSRLYFMT FYIVTMVVMT IIVAFILEAF VFRMNYSRKN QDSEVDGGIT LEKEISKEEL 

       730        740        750        760        770        780 
VAVLELYREA RGASSDVTRL LETLSQMERY QQHSMVFLGR RSRTKSDLSL KMYQEEIQEW 

       790        800        810 
YEEHAREQEQ QRQLSSSAAP AAQQPPGSRQ RSQTVT 

« Hide

Isoform 2 [UniParc].

Checksum: BDD06287A468FA93
Show »

FASTA25229,136
Isoform 3 [UniParc].

Checksum: D3267C511D4C6BC4
Show »

FASTA888101,796

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] (ISOFORM 1).
[2]"Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain."
Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.
DNA Res. 6:329-336(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Brain.
[3]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Tissue: Placenta.
[5]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1).
Tissue: Brain.
[7]"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, MUTAGENESIS OF LEU-273, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY083666 mRNA. Translation: AAM01199.1.
AB032995 mRNA. Translation: BAA86483.2. Different initiation.
AK057414 mRNA. No translation available.
AK075071 mRNA. Translation: BAC11385.1.
AC010178 Genomic DNA. No translation available.
AC089999 Genomic DNA. No translation available.
AC127004 Genomic DNA. No translation available.
BC136795 mRNA. Translation: AAI36796.1.
BC136796 mRNA. Translation: AAI36797.1.
BC150203 mRNA. Translation: AAI50204.1.
BC152423 mRNA. Translation: AAI52424.1.
CCDSCCDS31908.1. [Q9ULQ1-1]
CCDS44985.1. [Q9ULQ1-3]
RefSeqNP_001137291.1. NM_001143819.1. [Q9ULQ1-3]
NP_060371.2. NM_017901.4. [Q9ULQ1-1]
UniGeneHs.524763.

3D structure databases

ProteinModelPortalQ9ULQ1.
SMRQ9ULQ1. Positions 198-321, 434-689.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9ULQ1. 3 interactions.
STRING9606.ENSP00000376350.

PTM databases

PhosphoSiteQ9ULQ1.

Polymorphism databases

DMDM125991219.

Proteomic databases

MaxQBQ9ULQ1.
PaxDbQ9ULQ1.
PRIDEQ9ULQ1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335509; ENSP00000335300; ENSG00000186815. [Q9ULQ1-1]
ENST00000541517; ENSP00000438125; ENSG00000186815. [Q9ULQ1-3]
ENST00000550785; ENSP00000448083; ENSG00000186815. [Q9ULQ1-3]
GeneID53373.
KEGGhsa:53373.
UCSCuc001tuw.3. human. [Q9ULQ1-1]
uc001tux.3. human. [Q9ULQ1-3]

Organism-specific databases

CTD53373.
GeneCardsGC12P113660.
HGNCHGNC:18182. TPCN1.
HPAHPA039757.
MIM609666. gene.
neXtProtNX_Q9ULQ1.
PharmGKBPA134922711.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG280094.
HOGENOMHOG000006773.
HOVERGENHBG080605.
InParanoidQ9ULQ1.
KOK16896.
OMAWLGFHTF.
OrthoDBEOG7W41B7.
PhylomeDBQ9ULQ1.
TreeFamTF328550.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ9ULQ1.
BgeeQ9ULQ1.
CleanExHS_TPCN1.
GenevestigatorQ9ULQ1.

Family and domain databases

Gene3D1.20.120.350. 1 hit.
InterProIPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR028801. TPC1.
[Graphical view]
PANTHERPTHR10037:SF201. PTHR10037:SF201. 1 hit.
PfamPF00520. Ion_trans. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTPCN1. human.
GeneWikiTPCN1.
GenomeRNAi53373.
NextBio56034.
PROQ9ULQ1.
SOURCESearch...

Entry information

Entry nameTPC1_HUMAN
AccessionPrimary (citable) accession number: Q9ULQ1
Secondary accession number(s): A7E258, Q86XS9, Q8NC20
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: July 9, 2014
This is version 103 of the entry and version 3 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 chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM