TCIRG1

Protein identityUniProt · HPA

UniProt accession

Q13488

Gene

TCIRG1

Ensembl

ENSG00000110719

Chromosome

11

Canonical length

830 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

This gene encodes a subunit of a large protein complex known as a vacuolar H+-ATPase (V-ATPase). The protein complex acts as a pump to move protons across the membrane. This movement of protons helps regulate the pH of cells and their surrounding environment. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. V-ATPase is comprised of a cytosolic V1 domain and a transmembrane V0 domain. Alternative splicing results in multiple transcript variants. Mutations in this gene are associated with infantile malignant osteopetrosis. [provided by RefSeq, May 2017]

Canonical amino-acid sequenceUniProt

830 residues, UniProt reviewed canonical sequence.

>Q13488|TCIRG1
     1  MGSMFRSEEV ALVQLFLPTA AAYTCVSRLG ELGLVEFRDL NASVSAFQRR FVVDVRRCEE
    61  LEKTFTFLQE EVRRAGLVLP PPKGRLPAPP PRDLLRIQEE TERLAQELRD VRGNQQALRA
   121  QLHQLQLHAA VLRQGHEPQL AAAHTDGASE RTPLLQAPGG PHQDLRVNFV AGAVEPHKAP
   181  ALERLLWRAC RGFLIASFRE LEQPLEHPVT GEPATWMTFL ISYWGEQIGQ KIRKITDCFH
   241  CHVFPFLQQE EARLGALQQL QQQSQELQEV LGETERFLSQ VLGRVLQLLP PGQVQVHKMK
   301  AVYLALNQCS VSTTHKCLIA EAWCSVRDLP ALQEALRDSS MEEGVSAVAH RIPCRDMPPT
   361  LIRTNRFTAS FQGIVDAYGV GRYQEVNPAP YTIITFPFLF AVMFGDVGHG LLMFLFALAM
   421  VLAENRPAVK AAQNEIWQTF FRGRYLLLLM GLFSIYTGFI YNECFSRATS IFPSGWSVAA
   481  MANQSGWSDA FLAQHTMLTL DPNVTGVFLG PYPFGIDPIW SLAANHLSFL NSFKMKMSVI
   541  LGVVHMAFGV VLGVFNHVHF GQRHRLLLET LPELTFLLGL FGYLVFLVIY KWLCVWAARA
   601  ASAPSILIHF INMFLFSHSP SNRLLYPRQE VVQATLVVLA LAMVPILLLG TPLHLLHRHR
   661  RRLRRRPADR QEENKAGLLD LPDASVNGWS SDEEKAGGLD DEEEAELVPS EVLMHQAIHT
   721  IEFCLGCVSN TASYLRLWAL SLAHAQLSEV LWAMVMRIGL GLGREVGVAA VVLVPIFAAF
   781  AVMTVAILLV MEGLSAFLHA LRLHWVEFQN KFYSGTGYKL SPFTFAATDD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TCIRG1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

8

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

278 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TCIRG1.

Disease | AllUniProt

Conditions TCIRG1 is implicated in, by any mechanism.

• Osteopetrosis, autosomal recessive 1 (OPTB1) MIM:259700

Disease | GeneticClinVar

279 pathogenic / likely-pathogenic of 1,784 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive osteopetrosis 1
• Osteopetrosis
• TCIRG1-related disorder
• Autosomal recessive osteopetrosis
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.87

gnomAD pLI

0

gnomAD missense Z

0.63

DepMap mean gene effect

-0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• autophagosome assembly
• B cell differentiation
• bone resorption
• cellular defense response
• cellular response to cytokine stimulus
• enamel mineralization
• establishment of cell polarity
• establishment of vesicle localization
• gene expression
• hematopoietic stem cell homeostasis
• immunoglobulin mediated immune response
• inflammatory response
• intracellular calcium ion homeostasis
• lysosomal lumen acidification
• macroautophagy
• memory T cell activation
• optic nerve development
• ossification
• osteoclast differentiation
• osteoclast proliferation
• pH reduction
• phagosome acidification
• positive regulation of cell population proliferation
• protein catabolic process in the vacuole
• proton transmembrane transport
• regulation of gene expression
• regulation of insulin secretion
• regulation of osteoblast differentiation
• regulation of proton transport
• retina development in camera-type eye
• ruffle organization
• T cell differentiation
• T cell homeostasis
• T-helper 1 cell activation
• tooth eruption
• vacuolar acidification
• dentin mineralization
• response to silver ion

Molecular functions

• ATPase binding
• proton-transporting ATPase activity, rotational mechanism

Cellular components

• apical plasma membrane
• endosome membrane
• ficolin-1-rich granule membrane
• late endosome
• lysosomal membrane
• nucleus
• phagocytic vesicle membrane
• plasma membrane
• proton-transporting V-type ATPase complex
• vacuolar proton-transporting V-type ATPase complex
• vacuolar proton-transporting V-type ATPase, V0 domain

Protein domainsUniProt · Pfam · InterPro

• V-type ATPase, V0 complex, 116kDa subunit family
• ATPase, V0 complex, subunit 116kDa, eukaryotic
• V-type ATPase 116kDa subunit family

KeywordsUniProt

• Hydrogen ion transport
• Ion transport
• Membrane
• Osteopetrosis
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of TCIRG1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATP6AP2
• ATP6V0A2
• ATP6V1D