Q08AM6 · VAC14_HUMAN
- ProteinProtein VAC14 homolog
- GeneVAC14
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids782 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Scaffold protein component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Pentamerizes into a star-shaped structure and nucleates the assembly of the complex. The pentamer binds a single copy each of PIKFYVE and FIG4 and coordinates both PIKfyve kinase activity and FIG4 phosphatase activity, being required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 5-phosphate (PtdIns5P) (PubMed:33098764).
Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes
Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | early endosome membrane | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | endosome membrane | |
Cellular Component | Golgi membrane | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | late endosome membrane | |
Cellular Component | PAS complex | |
Cellular Component | presynaptic endosome | |
Molecular Function | identical protein binding | |
Molecular Function | signaling receptor activity | |
Biological Process | phosphatidylinositol biosynthetic process | |
Biological Process | regulation of postsynaptic neurotransmitter receptor internalization | |
Biological Process | signal transduction |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein VAC14 homolog
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ08AM6
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Mainly associated with membranes of the late endocytic pathway.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Striatonigral degeneration, childhood-onset (SNDC)
- Note
- DescriptionAn autosomal recessive neurological disorder characterized by sudden childhood onset of developmental regression. Affected children develop impaired movements with dystonia, progressively become non-ambulatory and non-verbal, and exhibit striatal abnormalities on MRI.
- See alsoMIM:617054
Natural variants in SNDC
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_077031 | 424 | W>L | in SNDC; dbSNP:rs762388639 | |
VAR_077032 | 582 | A>S | in SNDC; dbSNP:rs749094914 | |
VAR_077033 | 583 | S>L | in SNDC; dbSNP:rs879255645 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_077031 | 424 | in SNDC; dbSNP:rs762388639 | |||
Sequence: W → L | ||||||
Natural variant | VAR_077032 | 582 | in SNDC; dbSNP:rs749094914 | |||
Sequence: A → S | ||||||
Natural variant | VAR_077033 | 583 | in SNDC; dbSNP:rs879255645 | |||
Sequence: S → L | ||||||
Mutagenesis | 773 | Reduces interaction with NOS1. | ||||
Sequence: G → A | ||||||
Mutagenesis | 774 | Reduces interaction with NOS1. | ||||
Sequence: D → A | ||||||
Mutagenesis | 776 | Reduces interaction with NOS1. | ||||
Sequence: L → A | ||||||
Mutagenesis | 777 | Abolishes interaction with NOS1. | ||||
Sequence: D → A | ||||||
Mutagenesis | 780-782 | Reduces interaction with NOS1. | ||||
Sequence: VVL → AAA | ||||||
Mutagenesis | 782 | Reduces interaction with NOS1. | ||||
Sequence: L → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 753 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000300485 | 1-782 | UniProt | Protein VAC14 homolog | |||
Sequence: MNPEKDFAPLTPNIVRALNDKLYEKRKVAALEIEKLVREFVAQNNTVQIKHVIQTLSQEFALSQHPHSRKGGLIGLAACSIALGKDSGLYLKELIEPVLTCFNDADSRLRYYACEALYNIVKVARGAVLPHFNVLFDGLSKLAADPDPNVKSGSELLDRLLKDIVTESNKFDLVSFIPLLRERIYSNNQYARQFIISWILVLESVPDINLLDYLPEILDGLFQILGDNGKEIRKMCEVVLGEFLKEIKKNPSSVKFAEMANILVIHCQTTDDLIQLTAMCWMREFIQLAGRVMLPYSSGILTAVLPCLAYDDRKKSIKEVANVCNQSLMKLVTPEDDELDELRPGQRQAEPTPDDALPKQEGTASGGPDGSCDSSFSSGISVFTAASTERAPVTLHLDGIVQVLNCHLSDTAIGMMTRIAVLKWLYHLYIKTPRKMFRHTDSLFPILLQTLSDESDEVILKDLEVLAEIASSPAGQTDDPGPLDGPDLQASHSELQVPTPGRAGLLNTSGTKGLECSPSTPTMNSYFYKFMINLLKRFSSERKLLEVRGPFIIRQLCLLLNAENIFHSMADILLREEDLKFASTMVHALNTILLTSTELFQLRNQLKDLKTLESQNLFCCLYRSWCHNPVTTVSLCFLTQNYRHAYDLIQKFGDLEVTVDFLAEVDKLVQLIECPIFTYLRLQLLDVKNNPYLIKALYGLLMLLPQSSAFQLLSHRLQCVPNPELLQTEDSLKAAPKSQKADSPSIDYAELLQHFEKVQNKHLEVRHQRSGRGDHLDRRVVL | |||||||
Modified residue | 11 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 11 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 491 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 499 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 508 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 509 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 517 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 517 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 743 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 743 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Forms pentamers (PubMed:18950639, PubMed:33098764).
Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities (PubMed:17556371, PubMed:18950639, PubMed:33098764).
Interacts with NOS1 (PubMed:17161399).
Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities (PubMed:17556371, PubMed:18950639, PubMed:33098764).
Interacts with NOS1 (PubMed:17161399).
(Microbial infection) Interacts with HTLV-1 Tax.
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 5-42 | HEAT 1 | ||||
Sequence: KDFAPLTPNIVRALNDKLYEKRKVAALEIEKLVREFVA | ||||||
Repeat | 89-126 | HEAT 2 | ||||
Sequence: LYLKELIEPVLTCFNDADSRLRYYACEALYNIVKVARG | ||||||
Repeat | 171-208 | HEAT 3 | ||||
Sequence: FDLVSFIPLLRERIYSNNQYARQFIISWILVLESVPDI | ||||||
Repeat | 212-249 | HEAT 4 | ||||
Sequence: DYLPEILDGLFQILGDNGKEIRKMCEVVLGEFLKEIKK | ||||||
Region | 335-372 | Disordered | ||||
Sequence: EDDELDELRPGQRQAEPTPDDALPKQEGTASGGPDGSC | ||||||
Repeat | 438-475 | HEAT 5 | ||||
Sequence: RHTDSLFPILLQTLSDESDEVILKDLEVLAEIASSPAG | ||||||
Region | 471-517 | Disordered | ||||
Sequence: SSPAGQTDDPGPLDGPDLQASHSELQVPTPGRAGLLNTSGTKGLECS | ||||||
Compositional bias | 492-517 | Polar residues | ||||
Sequence: HSELQVPTPGRAGLLNTSGTKGLECS | ||||||
Repeat | 560-598 | HEAT 6 | ||||
Sequence: LNAENIFHSMADILLREEDLKFASTMVHALNTILLTSTE | ||||||
Region | 773-777 | Mediates interaction with the PDZ domain of NOS1 | ||||
Sequence: GDHLD |
Domain
The C-terminal domain (residues 523-782) mediates pentameric interactions and is necessary for the formation and maintenance of the PI(3,5)P2 regulatory complex.
Sequence similarities
Belongs to the VAC14 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q08AM6-1
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.
- Name1
- Length782
- Mass (Da)87,973
- Last updated2006-10-31 v1
- ChecksumB39AC1F4D619570F
Q08AM6-2
- Name2
- Differences from canonical
- 1-568: Missing
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H3BUU8 | H3BUU8_HUMAN | VAC14 | 201 | ||
H3BQD9 | H3BQD9_HUMAN | VAC14 | 260 | ||
H3BN23 | H3BN23_HUMAN | VAC14 | 40 | ||
J3QLC3 | J3QLC3_HUMAN | VAC14 | 17 | ||
A0A087WT26 | A0A087WT26_HUMAN | VAC14 | 185 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_056097 | 1-568 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 257 | in Ref. 4; AAB03813 | ||||
Sequence: A → P | ||||||
Sequence conflict | 263 | in Ref. 4; AAB03813 | ||||
Sequence: L → P | ||||||
Sequence conflict | 352 | in Ref. 5; CAG33624 | ||||
Sequence: T → A | ||||||
Compositional bias | 492-517 | Polar residues | ||||
Sequence: HSELQVPTPGRAGLLNTSGTKGLECS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK025479 EMBL· GenBank· DDBJ | BAB15145.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK056433 EMBL· GenBank· DDBJ | BAG51707.1 EMBL· GenBank· DDBJ | mRNA | ||
AK093941 EMBL· GenBank· DDBJ | BAG52790.1 EMBL· GenBank· DDBJ | mRNA | ||
AC020763 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC027281 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC000536 EMBL· GenBank· DDBJ | AAH00536.2 EMBL· GenBank· DDBJ | mRNA | ||
BC007214 EMBL· GenBank· DDBJ | AAH07214.2 EMBL· GenBank· DDBJ | mRNA | ||
BC125108 EMBL· GenBank· DDBJ | AAI25109.1 EMBL· GenBank· DDBJ | mRNA | ||
BC125109 EMBL· GenBank· DDBJ | AAI25110.1 EMBL· GenBank· DDBJ | mRNA | ||
U25801 EMBL· GenBank· DDBJ | AAB03813.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
CR457343 EMBL· GenBank· DDBJ | CAG33624.1 EMBL· GenBank· DDBJ | mRNA |