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Q13488 (VPP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
V-type proton ATPase 116 kDa subunit a isoform 3

Short name=V-ATPase 116 kDa isoform a3
Alternative name(s):
Osteoclastic proton pump 116 kDa subunit
Short name=OC-116 kDa
Short name=OC116
T-cell immune regulator 1
T-cell immune response cDNA7 protein
Short name=TIRC7
Vacuolar proton translocating ATPase 116 kDa subunit a isoform 3
Gene names
Name:TCIRG1
Synonyms:ATP6N1C, ATP6V0A3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length830 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Part of the proton channel of V-ATPases By similarity. Seems to be directly involved in T-cell activation.

Subunit structure

The V-ATPase is a heteromultimeric enzyme composed of at least thirteen different subunits. It has a membrane peripheral V1 sector for ATP hydrolysis and an integral V0 for proton translocation. The V1 sector comprises subunits A-H, whereas V0 includes subunits a, d, c, c', and c''.

Subcellular location

Membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Isoform longis highly expressed in osteoclastomas. Isoform shortis highly expressed in thymus.

Involvement in disease

Osteopetrosis, autosomal recessive 1 (OPTB1) [MIM:259700]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8

Sequence similarities

Belongs to the V-ATPase 116 kDa subunit family.

Ontologies

Keywords
   Biological processHydrogen ion transport
Ion transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Osteopetrosis
   DomainTransmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP hydrolysis coupled proton transport

Inferred from electronic annotation. Source: InterPro

cellular defense response

Traceable author statement PubMed 9806637. Source: ProtInc

cellular iron ion homeostasis

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

interaction with host

Traceable author statement. Source: Reactome

phagosome maturation

Traceable author statement. Source: Reactome

positive regulation of cell proliferation

Traceable author statement PubMed 9806637. Source: ProtInc

proton transport

Traceable author statement Ref.1. Source: ProtInc

transferrin transport

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from direct assay PubMed 15800125. Source: UniProtKB

endosome membrane

Traceable author statement. Source: Reactome

integral component of plasma membrane

Traceable author statement Ref.3. Source: ProtInc

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

mitochondrion

Inferred from electronic annotation. Source: Ensembl

phagocytic vesicle membrane

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement PubMed 9806637. Source: ProtInc

vacuolar proton-transporting V-type ATPase, V0 domain

Inferred from electronic annotation. Source: InterPro

   Molecular_functionhydrogen ion transmembrane transporter activity

Inferred from electronic annotation. Source: InterPro

transporter activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: Q13488-1)

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 Short (identifier: Q13488-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-216: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 830830V-type proton ATPase 116 kDa subunit a isoform 3
PRO_0000119218

Regions

Topological domain1 – 385385Cytoplasmic Potential
Transmembrane386 – 40419Helical; Potential
Topological domain405 – 4062Vacuolar Potential
Transmembrane407 – 42317Helical; Potential
Topological domain424 – 43815Cytoplasmic Potential
Transmembrane439 – 46830Helical; Potential
Topological domain469 – 53264Vacuolar Potential
Transmembrane533 – 55220Helical; Potential
Topological domain553 – 57018Cytoplasmic Potential
Transmembrane571 – 59121Helical; Potential
Topological domain592 – 63544Vacuolar Potential
Transmembrane636 – 65520Helical; Potential
Topological domain656 – 72065Cytoplasmic Potential
Transmembrane721 – 74525Helical; Potential
Topological domain746 – 76621Vacuolar Potential
Transmembrane767 – 80741Helical; Potential
Topological domain808 – 83023Cytoplasmic Potential

Natural variations

Alternative sequence1 – 216216Missing in isoform Short.
VSP_000345
Natural variant561R → W.
Corresponds to variant rs36027301 [ dbSNP | Ensembl ].
VAR_054340
Natural variant1411A → P in OPTB1. Ref.8
VAR_020988
Natural variant1611P → L.
Corresponds to variant rs34227834 [ dbSNP | Ensembl ].
VAR_054341
Natural variant4051G → R in OPTB1. Ref.6 Ref.7 Ref.8
VAR_019569
Natural variant4441R → L in OPTB1. Ref.6
VAR_019570
Natural variant4621Missing in OPTB1. Ref.8
VAR_020989
Natural variant5171D → N in OPTB1. Ref.8
VAR_020990
Natural variant7751P → R in OPTB1. Ref.8
VAR_020991

Experimental info

Sequence conflict3771A → R in AAA97878. Ref.1
Sequence conflict6031Missing in AAA97878. Ref.1

Sequences

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

Last modified February 10, 2009. Version 3.
Checksum: 50751B41B171D9D2

FASTA83092,968
        10         20         30         40         50         60 
MGSMFRSEEV ALVQLFLPTA AAYTCVSRLG ELGLVEFRDL NASVSAFQRR FVVDVRRCEE 

        70         80         90        100        110        120 
LEKTFTFLQE EVRRAGLVLP PPKGRLPAPP PRDLLRIQEE TERLAQELRD VRGNQQALRA 

       130        140        150        160        170        180 
QLHQLQLHAA VLRQGHEPQL AAAHTDGASE RTPLLQAPGG PHQDLRVNFV AGAVEPHKAP 

       190        200        210        220        230        240 
ALERLLWRAC RGFLIASFRE LEQPLEHPVT GEPATWMTFL ISYWGEQIGQ KIRKITDCFH 

       250        260        270        280        290        300 
CHVFPFLQQE EARLGALQQL QQQSQELQEV LGETERFLSQ VLGRVLQLLP PGQVQVHKMK 

       310        320        330        340        350        360 
AVYLALNQCS VSTTHKCLIA EAWCSVRDLP ALQEALRDSS MEEGVSAVAH RIPCRDMPPT 

       370        380        390        400        410        420 
LIRTNRFTAS FQGIVDAYGV GRYQEVNPAP YTIITFPFLF AVMFGDVGHG LLMFLFALAM 

       430        440        450        460        470        480 
VLAENRPAVK AAQNEIWQTF FRGRYLLLLM GLFSIYTGFI YNECFSRATS IFPSGWSVAA 

       490        500        510        520        530        540 
MANQSGWSDA FLAQHTMLTL DPNVTGVFLG PYPFGIDPIW SLAANHLSFL NSFKMKMSVI 

       550        560        570        580        590        600 
LGVVHMAFGV VLGVFNHVHF GQRHRLLLET LPELTFLLGL FGYLVFLVIY KWLCVWAARA 

       610        620        630        640        650        660 
ASAPSILIHF INMFLFSHSP SNRLLYPRQE VVQATLVVLA LAMVPILLLG TPLHLLHRHR 

       670        680        690        700        710        720 
RRLRRRPADR QEENKAGLLD LPDASVNGWS SDEEKAGGLD DEEEAELVPS EVLMHQAIHT 

       730        740        750        760        770        780 
IEFCLGCVSN TASYLRLWAL SLAHAQLSEV LWAMVMRIGL GLGREVGVAA VVLVPIFAAF 

       790        800        810        820        830 
AVMTVAILLV MEGLSAFLHA LRLHWVEFQN KFYSGTGYKL SPFTFAATDD 

« Hide

Isoform Short [UniParc].

Checksum: B493A1F9514419FE
Show »

FASTA61468,776

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a putative novel human osteoclast-specific 116-kDa vacuolar proton pump subunit."
Li Y.P., Chen W., Stashenko P.
Biochem. Biophys. Res. Commun. 218:813-821(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
Tissue: Osteoclastoma.
[2]Utku N., Heinemann T., Bulwin C.-G., Beinke S., Beato F., Randall J., Busconi L., Delphire E., Robertson E.R., Kojima R., Volk H.D., Milford E.L., Gullans S.R.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[3]"Genomic organization of the gene coding for TIRC7, a novel membrane protein essential for T cell activation."
Heinemann T., Bulwin G.C., Randall J., Schnieders B., Sandhoff K., Volk H.D., Milford E., Gullans S.R., Utku N.
Genomics 57:398-406(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM SHORT).
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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 LONG).
Tissue: Lung and Pancreas.
[6]"The mutational spectrum of human malignant autosomal recessive osteopetrosis."
Sobacchi C., Frattini A., Orchard P., Porras O., Tezcan I., Andolina M., Babul-Hirji R., Baric I., Canham N., Chitayat D., Dupuis-Girod S., Ellis I., Etzioni A., Fasth A., Fisher A., Gerritsen B., Gulino V., Horwitz E. expand/collapse author list , Klamroth V., Lanino E., Mirolo M., Musio A., Matthijs G., Nonomaya S., Notarangelo L.D., Ochs H.D., Superti-Furga A., Valiaho J., van Hove J.L.K., Vihinen M., Vujic D., Vezzoni P., Villa A.
Hum. Mol. Genet. 10:1767-1773(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OPTB1 ARG-405 AND LEU-444.
[7]"Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis."
Scimeca J.-C., Quincey D., Parrinello H., Romatet D., Grosgeorge J., Gaudray P., Philip N., Fischer A., Carle G.F.
Hum. Mutat. 21:151-157(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT OPTB1 ARG-405.
[8]"TCIRG1-dependent recessive osteopetrosis: mutation analysis, functional identification of the splicing defects, and in vitro rescue by U1 snRNA."
Susani L., Pangrazio A., Sobacchi C., Taranta A., Mortier G., Savarirayan R., Villa A., Orchard P., Vezzoni P., Albertini A., Frattini A., Pagani F.
Hum. Mutat. 24:225-235(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OPTB1 PRO-141; ARG-405; ASN-462 DEL; ASN-517 AND ARG-775.
+Additional computationally mapped references.

Web resources

TCIRG1base

TCIRG1 mutation db

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U45285 mRNA. Translation: AAA97878.1.
AF025374 mRNA. Translation: AAC35742.1.
AF033033 Genomic DNA. Translation: AAD31081.2.
CH471076 Genomic DNA. Translation: EAW74691.1.
BC018133 mRNA. Translation: AAH18133.1.
BC032465 mRNA. Translation: AAH32465.1.
RefSeqNP_006010.2. NM_006019.3.
NP_006044.1. NM_006053.3.
XP_005273766.1. XM_005273709.1.
UniGeneHs.495985.

3D structure databases

ProteinModelPortalQ13488.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115597. 15 interactions.
IntActQ13488. 2 interactions.
STRING9606.ENSP00000265686.

PTM databases

PhosphoSiteQ13488.

Polymorphism databases

DMDM223634720.

Proteomic databases

PaxDbQ13488.
PRIDEQ13488.

Protocols and materials databases

DNASU10312.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265686; ENSP00000265686; ENSG00000110719. [Q13488-1]
ENST00000532635; ENSP00000434407; ENSG00000110719. [Q13488-2]
GeneID10312.
KEGGhsa:10312.
UCSCuc001one.3. human. [Q13488-1]

Organism-specific databases

CTD10312.
GeneCardsGC11P067806.
HGNCHGNC:11647. TCIRG1.
HPAHPA038742.
MIM259700. phenotype.
604592. gene.
neXtProtNX_Q13488.
Orphanet667. Autosomal recessive malignant osteopetrosis.
PharmGKBPA36399.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1269.
HOGENOMHOG000037059.
HOVERGENHBG014606.
InParanoidQ13488.
KOK02154.
OMAGVTHMAF.
OrthoDBEOG754HNQ.
PhylomeDBQ13488.
TreeFamTF300346.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000110719-MONOMER.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ13488.
BgeeQ13488.
CleanExHS_TCIRG1.
GenevestigatorQ13488.

Family and domain databases

InterProIPR002490. V-ATPase_116kDa_su.
IPR026028. V-type_ATPase_116kDa_su_euka.
[Graphical view]
PANTHERPTHR11629. PTHR11629. 1 hit.
PfamPF01496. V_ATPase_I. 1 hit.
[Graphical view]
PIRSFPIRSF001293. ATP6V0A1. 1 hit.
ProtoNetSearch...

Other

ChiTaRSTCIRG1. human.
GeneWikiTCIRG1.
GenomeRNAi10312.
NextBio39079.
PROQ13488.
SOURCESearch...

Entry information

Entry nameVPP3_HUMAN
AccessionPrimary (citable) accession number: Q13488
Secondary accession number(s): O75877, Q8WVC5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 10, 2009
Last modified: April 16, 2014
This is version 142 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 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