V-type proton ATPase subunit H (ATP6V1H)

The protein contains 483 amino acids for an estimated molecular weight of 55883 Da.

 

Subunit of the peripheral V1 complex of vacuolar ATPase. Subunit H activates the ATPase activity of the enzyme and couples ATPase activity to proton flow. Vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells, thus providing most of the energy required for transport processes in the vacuolar system (By similarity). Involved in the endocytosis mediated by clathrin-coated pits, required for the formation of endosomes. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 23%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 608861

Atpase, h+ transporting, lysosomal, 50/57-kd, v1 subunit h; atp6v1h
Nef-binding protein 1; nbp1
Vma13, s. cerevisiae, homolog of; vma13

DESCRIPTION

The vacuolar ATPase is a multisubunit enzyme that facilitates the acidification of intracellular compartments and plays a role in receptor-mediated endocytosis, intracellular trafficking, and protein degradation. ATP6V1H is a subunit of the 570-kD V1 peripheral complex responsible for hydrolysis of ATP (Geyer et al., 2002).

CLONING

Using human immunodeficiency virus (HIV)-1 Nef protein as bait in a yeast 2-hybrid screen of a B-cell cDNA library, Lu et al. (1998) cloned ATP6V1H, which they designated NBP1. The deduced 484-amino acid protein has a calculated molecular mass of 56 kD. ATP6V1H contains 7 motifs that contain tyrosine-polar-polar-hydrophobic residues and 4 dileucine motifs, mostly in its C terminus. Lu et al. (1998) stated that ATP6V1H is expressed ubiquitously as a 2.0-kb transcript. Geyer et al. (2002) characterized the ATP6V1H protein. The all-helical structure contains 8 armadillo (ARM) repeats that are also found in importins (see KPNB1; 602738). A single ARM repeat consists of about 42 residues that fold into 3 alpha helices with an almost triangular cross section. Multiple ARM repeats pack regularly side by side, forming elongated molecules with a superhelical twist.

GENE FUNCTION

Lu et al. (1998) confirmed that ATP6B1H interacts directly with HIV-1 Nef. This interaction correlated with the ability of Nef to internalize CD4 (186940), and expression of antisense ATP6V1H abrogated these effects. Geyer et al. (2002) determined that ATP6V1H binds to the C-terminal flexible loop in Nef and to the medium chain (mu-2) of the adaptor protein complex-2 (see 601024) in vitro and in vivo. The interaction sites for ATP6V1H and mu-2 were mapped to the central region of ATP6V1H, which contains 4 ARM repeats, and to the N-terminal adaptin-binding domain of mu-2. Blocking expression of ATP6V1H decreased the enhancement of virion infectivity by Nef. Geyer et al. (2002) showed that the C-terminal 350-amino acids of ATP6V1H share significant similarity with the N-terminal trunk portion of beta-adaptins (see AP1B1; 600157). They found that expression of this ATP6V1H fragment in cells blocked the internalization of transmembrane proteins, which depend upon dileucine-based sorting motifs.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the ATP6V1H gene to chromosome 8 (TMAP A003B09). ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608861 was added.