Vacuolar protein sorting-associated protein 37A (VPS37A)

The protein contains 397 amino acids for an estimated molecular weight of 44314 Da.

 

Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation. (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.

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.

Interpro domains
Total structural coverage: 20%
Model score: 0

(right-click above to access to more options from the contextual menu)

VariantDescription
dbSNP:rs17502618
dbSNP:rs17687375
SPG53

The reference OMIM entry for this protein is 609927

Vacuolar protein sorting 37, yeast, homolog of, a; vps37a
Hepatocellular carcinoma-related protein 1; hcrp1

DESCRIPTION

The VPS37A gene encodes a subunit of the endosomal sorting complex required for transport I (ESCRT-I) complex and also may play a role in ubiquitination (summary by Zivony-Elboum et al., 2012).

CLONING

By positional cloning in the region of chromosome 8p21-p21 in which deletions are frequently found in hepatocellular carcinoma (HCC), Xu et al. (2003) identified a novel cDNA, which they designated HCRP1, from a human liver cDNA library. HCRP1 encodes a deduced 397-amino acid protein. Northern blot analysis showed ubiquitous expression of an approximately 2-kb HCRP1 transcript, with most abundant expression in liver. Western blot analysis showed reduced HCRP1 expression in 6 of 8 HCC tissues, but higher expression levels of HCRP1 in adjacent normal tissues in all 8 cases. Transient transfection of GFP-HCRP1 fusion constructs showed that HCRP1 is localized throughout the cell, but predominantly in the nucleus. By database analysis with the sequence of the yeast endosomal sorting complex protein Vps37/Srn2 sequence as query, Bache et al. (2004) identified HCRP1, which they designated VPS37A. The yeast and human proteins share 22% sequence identity in the C terminus, and both contain a modifier of rudimentary [mod(r)] domain. By searching a database for sequences homologous to yeast Vps37, Stuchell et al. (2004) identified VPS37A. VPS37A has an N-terminal ubiquitin E2 variant (UEV) domain and a C-terminal mod(r) domain, and both of these domains contain a coiled-coil region. Zivony-Elboum et al. (2012) found expression of the VPS37 gene in several human tissues, including heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas, with lower levels of expression in the brain and skeletal muscle.

GENE FUNCTION

Using a series of transfection experiments into HCC cell lines, Xu et al. (2003) showed that overexpression of HCRP1 inhibits both anchorage-dependent and anchorage-independent cell growth. Conversely, reduction of HCRP1 expression by short hairpin RNA enhanced cell growth and increased invasive ability in HCC cell lines. Using immunofluorescence microscopy, Bache et al. (2004) demonstrated colocalization of HCRP1 and VPS28 (601387) on LAMP1 (153330)-positive endosomes. Immunoprecipitation experiments demonstrated strong interaction of HCRP1 with TSG101 (601387) and VPS28, which are components of the endosomal sorting complex required for transport I (ESCRT-I), and weak interaction with HRS (604375), an upstream regulator of the ESCRT-I complex. Pull-down assays demonstrated that the interaction between HCRP1 and TSG101 occurs through the mod(r) domain. By size exclusion chromatography, HCRP1 cofractionated with TSG101 and VPS28. Depletion of TSG101 by siRNA treatment resulted in reduction in HCRP1 levels in HeLa cells. Whereas siRNA-mediated depletion of HCRP1 had no effect on either TSG101 or VPS28 levels, it strongly retarded EGF receptor (131550) degradation.

MAPPING

Xu et al. (2003) identified the VPS37A gene within the region of frequent loss of heterozygosity in HCC on chromosome 8p23-p21.

MOLECULAR GENETICS

In 9 affected members of 2 consanguineous Arab Moslem families with early-onset autosomal recessive spastic paraplegia-53 (SPG53; 614898), Zivony-Elboum et al. (2012) identified a homozygous mutation in the VPS37A gene (K382N; 609927.0001). The mutation was found by linkage analysis followed by candidate gene sequencing. Although the mutant pro ... More on the omim web site

Subscribe to this protein entry history

May 13, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

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

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

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609927 was added.

Feb. 25, 2016: Protein entry updated
Automatic update: model status changed

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed