Vesicle-associated membrane protein 8 (VAMP8)

The protein contains 100 amino acids for an estimated molecular weight of 11438 Da.

 

SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t-SNARE complex (PubMed:23217709, PubMed:25686604). Also required for dense-granule secretion in platelets (PubMed:12130530). Plays also a role in regulated enzyme secretion in pancreatic acinar cells (By similarity). Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells (By similarity). Involved in the homotypic fusion of early and late endosomes (By similarity). Participates also in the activation of type I interferon antiviral response through a TRIM6-dependent mechanism (PubMed:31694946). (updated: Oct. 7, 2020)

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, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.

Topcons

Interpro domains
Total structural coverage: 97%
Model score: 129
MODL_MODELLER-9.18

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The reference OMIM entry for this protein is 603177

Vesicle-associated membrane protein 8; vamp8
Endobrevin
Synaptobrevin-like, endosome-associated

DESCRIPTION

Synaptobrevins/VAMPs, syntaxins (e.g., 186590), and the 25-kD synaptosomal-associated protein SNAP25 (600322) are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. Bock and Scheller (1997) reviewed the 'SNARE (SNAP receptor) hypothesis' of vesicular trafficking.

CLONING

By searching sequence databases with the sequences of VAMP family members, Wong et al. (1998) and Bock and Scheller (1997) identified mammalian ESTs encoding VAMP8, or endobrevin, a protein with sequence similarity to synaptobrevins. Wong et al. (1998) reported that the predicted 100-amino acid human protein shares approximately 32%, 33%, and 31% sequence identity with VAMP1 (185880), VAMP2 (185881), and cellubrevin (VAMP3; 603657), respectively. Endobrevin migrates as a 15-kD protein on Western blots of mammalian cell extracts. Membrane fractionation, immunofluorescence, and electron microscopy studies demonstrated that endobrevin is associated with the perinuclear vesicular structures of the early endocytic compartment. Advani et al. (1998) cloned Vamp8 from an embryonic mouse cDNA library. The deduced 101-amino acid protein contains an amphipathic helix that may participate in coiled-coil interactions and a C-terminal hydrophobic domain predicted to serve as a membrane anchor. Northern blot analysis of mouse tissues revealed abundant expression in kidney, intermediate expression in heart and spleen, and lower expression in brain, thymus, and liver. Transfection of Vamp8 into normal rat kidney cells resulted in broadly distributed puncta throughout the cell with a juxtanuclear enrichment.

GENE FUNCTION

Using in vitro binding assays, Wong et al. (1998) found that endobrevin interacts specifically with the soluble NSF (601633)-attachment protein (NAPA; 603215), most likely through an endobrevin-containing SNARE complex. Low et al. (2003) found that 2 members of the SNARE membrane fusion machinery, syntaxin-2 (EPIM; 132350) and Vamp8, localized to the midbody during cytokinesis in rat and canine kidney cell lines. Inhibition of syntaxin-2 and Vamp8 function by overexpression of nonmembrane-anchored mutants caused failure of cytokinesis leading to the formation of binucleated cells. Time-lapse microscopy showed that only midbody abscission and not further upstream events, such as furrowing, were affected. Using RT-PCR, immunoblot analysis, and immunofluorescence microscopy, Sander et al. (2008) demonstrated that human intestinal mast cells (MCs) expressed SNAP23 (602534), STX1B (601485), STX2, STX3 (STX3A; 600876), STX4 (STX4A; 186591), and STX6 (603944), but not SNAP25. MCs also expressed VAMP3, VAMP7 (300053), and VAMP8, but, in contrast with rodent MCs, they expressed only low levels of VAMP2. VAMP7 and VAMP8 translocated to the plasma membrane and interacted with SNAP23 and STX4 upon activation. Inhibition of STX4, SNAP23, VAMP7, or VAMP8, but not VAMP2 or VAMP3, resulted in markedly reduced high-affinity IgE receptor-mediated histamine release. Sander et al. (2008) concluded that human MCs express a specific pattern of SNAREs and that VAMP7 and VAMP8, but not VAMP2, are required for rapid degranulation.

MAPPING

By radiation hybrid analysis, Bui et al. (1998) mapped the VAMP8 gene to human chromosome 2p12-p11.2 and to a region of conserved synteny on mouse chromosome 6.

ANIMAL MODEL

Wang et al. (2004) found that Vamp8-null ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

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

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603177 was added.