Q13488 (VPP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	830 AA.
Sequence status	Complete.
Protein existence	Evidence 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 an 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 long is highly expressed in osteoclastomas. Isoform short is highly expressed in thymus.
Involvement in disease	Defects in TCIRG1 are the cause of osteopetrosis autosomal recessive type 1 (OPTB1) [MIM:259700]; also called autosomal recessive Albers-Schonberg disease or infantile malignant osteopetrosis. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder 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. The features of OPTB1 are macrocephaly, progressive deafness and blindness, hepatosplenomegaly, and severe anemia beginning in early infancy or in fetal life. Deafness and blindness are generally thought to represent effects of pressure on nerves. Ref.6 Ref.7 Ref.8
Sequence similarities	Belongs to the V-ATPase 116 kDa subunit family.

Ontologies

Keywords
Biological process	Hydrogen ion transport Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Osteopetrosis
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	ATP hydrolysis coupled proton transport Inferred from electronic annotation. Source: InterPro cellular defense response Traceable author statement. Source: ProtInc cellular iron ion homeostasis Traceable author statement. Source: Reactome insulin receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of cell proliferation Traceable author statement. Source: ProtInc transferrin transport Traceable author statement. Source: Reactome
Cellular component	apical plasma membrane Inferred from direct assay. Source: UniProtKB endosome membrane Traceable author statement. Source: Reactome integral to plasma membrane Traceable author statement. Source: ProtInc proton-transporting two-sector ATPase complex, proton-transporting domain Inferred from electronic annotation. Source: InterPro
Molecular function	hydrogen ion transmembrane transporter activity Inferred from electronic annotation. Source: InterPro
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 830	830	V-type proton ATPase 116 kDa subunit a isoform 3		PRO_0000119218
Regions
	Topological domain	1 – 385	385	Cytoplasmic Potential
	Transmembrane	386 – 404	19	Helical; Potential
	Topological domain	405 – 406	2	Vacuolar Potential
	Transmembrane	407 – 423	17	Helical; Potential
	Topological domain	424 – 438	15	Cytoplasmic Potential
	Transmembrane	439 – 468	30	Helical; Potential
	Topological domain	469 – 532	64	Vacuolar Potential
	Transmembrane	533 – 552	20	Helical; Potential
	Topological domain	553 – 570	18	Cytoplasmic Potential
	Transmembrane	571 – 591	21	Helical; Potential
	Topological domain	592 – 635	44	Vacuolar Potential
	Transmembrane	636 – 655	20	Helical; Potential
	Topological domain	656 – 720	65	Cytoplasmic Potential
	Transmembrane	721 – 745	25	Helical; Potential
	Topological domain	746 – 766	21	Vacuolar Potential
	Transmembrane	767 – 807	41	Helical; Potential
	Topological domain	808 – 830	23	Cytoplasmic Potential
Natural variations
	Alternative sequence	1 – 216	216	Missing in isoform Short.		VSP_000345
	Natural variant	56	1	R → W. Corresponds to variant rs36027301 [ dbSNP | Ensembl ].		VAR_054340
	Natural variant	141	1	A → P in OPTB1. Ref.8		VAR_020988
	Natural variant	161	1	P → L. Corresponds to variant rs34227834 [ dbSNP | Ensembl ].		VAR_054341
	Natural variant	405	1	G → R in OPTB1. Ref.6 Ref.7 Ref.8		VAR_019569
	Natural variant	444	1	R → L in OPTB1. Ref.6		VAR_019570
	Natural variant	462	1	Missing in OPTB1.		VAR_020989
	Natural variant	517	1	D → N in OPTB1. Ref.8		VAR_020990
	Natural variant	775	1	P → R in OPTB1. Ref.8		VAR_020991
Experimental info
	Sequence conflict	377	1	A → R in AAA97878. Ref.1
	Sequence conflict	603	1	Missing in AAA97878. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified February 10, 2009. Version 3. Checksum: 50751B41B171D9D2	FASTA	830	92,968
	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
	Isoform Short [UniParc]. Checksum: B493A1F9514419FE	FASTA	614	68,776
	10 20 30 40 50 60 MTFLISYWGE QIGQKIRKIT DCFHCHVFPF LQQEEARLGA LQQLQQQSQE LQEVLGETER 70 80 90 100 110 120 FLSQVLGRVL QLLPPGQVQV HKMKAVYLAL NQCSVSTTHK CLIAEAWCSV RDLPALQEAL 130 140 150 160 170 180 RDSSMEEGVS AVAHRIPCRD MPPTLIRTNR FTASFQGIVD AYGVGRYQEV NPAPYTIITF 190 200 210 220 230 240 PFLFAVMFGD VGHGLLMFLF ALAMVLAENR PAVKAAQNEI WQTFFRGRYL LLLMGLFSIY 250 260 270 280 290 300 TGFIYNECFS RATSIFPSGW SVAAMANQSG WSDAFLAQHT MLTLDPNVTG VFLGPYPFGI 310 320 330 340 350 360 DPIWSLAANH LSFLNSFKMK MSVILGVVHM AFGVVLGVFN HVHFGQRHRL LLETLPELTF 370 380 390 400 410 420 LLGLFGYLVF LVIYKWLCVW AARAASAPSI LIHFINMFLF SHSPSNRLLY PRQEVVQATL 430 440 450 460 470 480 VVLALAMVPI LLLGTPLHLL HRHRRRLRRR PADRQEENKA GLLDLPDASV NGWSSDEEKA 490 500 510 520 530 540 GGLDDEEEAE LVPSEVLMHQ AIHTIEFCLG CVSNTASYLR LWALSLAHAQ LSEVLWAMVM 550 560 570 580 590 600 RIGLGLGREV GVAAVVLVPI FAAFAVMTVA ILLVMEGLSA FLHALRLHWV EFQNKFYSGT 610 GYKLSPFTFA ATDD

References

	« Hide 'large scale' referencesShow '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: 8579597] [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: 10329006] [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. , 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: 15489334] [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. , 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: 11532986] [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: 12552563] [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: 15300850] [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.
IPI	IPI00219663. IPI00299719.
RefSeq	NP_006010.2. NM_006019.3. NP_006044.1. NM_006053.3.
UniGene	Hs.495985.
3D structure databases
ProteinModelPortal	Q13488.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13488. 2 interactions.
STRING	Q13488.
PTM databases
PhosphoSite	Q13488.
Polymorphism databases
DMDM	223634720.
Proteomic databases
PRIDE	Q13488.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265686; ENSP00000265686; ENSG00000110719.
GeneID	10312.
KEGG	hsa:10312.
UCSC	uc001one.1. human.
Organism-specific databases
CTD	10312.
GeneCards	GC11P067806.
H-InvDB	HIX0201672.
HGNC	HGNC:11647. TCIRG1.
HPA	HPA038742.
MIM	259700. phenotype. 604592. gene.
neXtProt	NX_Q13488.
Orphanet	667. Autosomal recessive malignant osteopetrosis.
PharmGKB	PA36399.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17301.
HOGENOM	HBG629705.
HOVERGEN	HBG014606.
InParanoid	Q13488.
OMA	VRGNQQA.
OrthoDB	EOG4PG60B.
PhylomeDB	Q13488.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q13488.
Bgee	Q13488.
CleanEx	HS_TCIRG1.
Genevestigator	Q13488.
GermOnline	ENSG00000110719. Homo sapiens.
Family and domain databases
InterPro	IPR002490. ATPase_V0/A0-cplx_116kDa_su. [Graphical view]
KO	K02154.
PANTHER	PTHR11629. ATPase_V0/A0_116. 1 hit.
Pfam	PF01496. V_ATPase_I. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	39079.
SOURCE	Search...

Entry information

Entry name

VPP3_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 119 of the entry and version 3 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.