1. Home
  2. Targets
  3. receptor
  4. Protein VAC14 homolog

Tbio Protein VAC14 homolog

The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Acts as a positive activator of PIKfyve kinase activity. Also required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.

The content of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. VAC14 is a component of a trimolecular complex that tightly regulates the level of PtdIns(3,5)P2. Other components of this complex are the PtdIns(3,5)P2-synthesizing enzyme PIKFYVE (MIM 609414) and the PtdIns(3,5)P2 phosphatase FIG4 (MIM 609390). VAC14 functions as an activator of PIKFYVE (Sbrissa et al., 2007 [PubMed 17556371]).[supplied by OMIM, Feb 2010]

 Comments

Property Summary

NCBI Gene PubMed Count 16
PubMed Score 18.77
PubTator Score 21.52

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Disease Target Count P-value
diabetes mellitus 1663 2.9e-03
Disease Target Count Z-score Confidence
Neurodegenerative disease 383 0.0 4.0
Disease Target Count Z-score Confidence
Neuropathy 210 3.462 1.7

Expression

  Differential Expression (1)

Disease log2 FC p
diabetes mellitus -1.100 2.9e-03

Synonym

Accession Q08AM6 B3KPJ5 B3KSM8 Q13174 Q6IA12 Q7L4Y1 Q9BW96 Q9H6V6
Symbols TRX
SNDC
TAX1BP2
ArPIKfyve

Gene

VAC14

PANTHER Protein Class (1)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (11)

See all...

 GO Function (1)

 GO Component (6)

 GO Process (4)

 Compartment GO Term (36)

See all...

 MGI Phenotype (8)

 HCA RNA Cell Line (56)

See all...

Pathway (13)

See all...

Protein-protein Interaction (20)

ATP2B4   ATP2B2   ME1   PIKFYVE   ERGIC3   FIG4   ZMPSTE24   MTCH2   SLMAP   LNPK   ERGIC2   QKI   MPZL1   DHODH   MAVS   VAMP3   PRAF2   CLCN7   SLC26A6   RAB21  

Gene RIF (8)

PMID Text
24578385 Rab7 GAP TBC1D15 with Vac14.
20630877 a novel regulatory mechanism whereby ArPIKfyve enhances Sac3 abundance by attenuating Sac3 proteasome-dependent degradation and suggest that a failure of this mechanism could be the primary molecular defect in the pathogenesis of CMT4J.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
19840946 PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase activity and endocytic membrane homeostasis
18950639 The authors data indicate that the PAS complex is organized to provide optimal PIKfyve functionality and is maintained via ArPIKfyve homomeric and heteromeric interactions.
17556371 demonstrate a coupling between the machinery for PtdIns(3,5)P2 synthesis and turnover achieved through a physical assembly of PIKfyve, ArPIKfyve, and Sac3.
17161399 describe a novel interaction between the PDZ domain of nitric oxide synthase and Vac14
15542851 the PIKfyve-associated hVac14 protein has a major role in activating PIKfyve and thereby regulating PtdIns(3,5)P(2) synthesis and endomembrane homeostasis in mammalian cells

AA Sequence 

MNPEKDFAPLTPNIVRALNDKLYEKRKVAALEIEKLVREFVAQNNTVQIKHVIQTLSQEFALSQHPHSRK      1 - 70
GGLIGLAACSIALGKDSGLYLKELIEPVLTCFNDADSRLRYYACEALYNIVKVARGAVLPHFNVLFDGLS     71 - 140
KLAADPDPNVKSGSELLDRLLKDIVTESNKFDLVSFIPLLRERIYSNNQYARQFIISWILVLESVPDINL    141 - 210
LDYLPEILDGLFQILGDNGKEIRKMCEVVLGEFLKEIKKNPSSVKFAEMANILVIHCQTTDDLIQLTAMC    211 - 280
WMREFIQLAGRVMLPYSSGILTAVLPCLAYDDRKKSIKEVANVCNQSLMKLVTPEDDELDELRPGQRQAE    281 - 350
PTPDDALPKQEGTASGGPDGSCDSSFSSGISVFTAASTERAPVTLHLDGIVQVLNCHLSDTAIGMMTRIA    351 - 420
VLKWLYHLYIKTPRKMFRHTDSLFPILLQTLSDESDEVILKDLEVLAEIASSPAGQTDDPGPLDGPDLQA    421 - 490
SHSELQVPTPGRAGLLNTSGTKGLECSPSTPTMNSYFYKFMINLLKRFSSERKLLEVRGPFIIRQLCLLL    491 - 560
NAENIFHSMADILLREEDLKFASTMVHALNTILLTSTELFQLRNQLKDLKTLESQNLFCCLYRSWCHNPV    561 - 630
TTVSLCFLTQNYRHAYDLIQKFGDLEVTVDFLAEVDKLVQLIECPIFTYLRLQLLDVKNNPYLIKALYGL    631 - 700
LMLLPQSSAFQLLSHRLQCVPNPELLQTEDSLKAAPKSQKADSPSIDYAELLQHFEKVQNKHLEVRHQRS    701 - 770
GRGDHLDRRVVL                                                              771 - 782
//

Text Mined References (26)

PMID Year Title
25416956 2014 A proteome-scale map of the human interactome network.
24578385 2014 The Vac14-interaction network is linked to regulators of the endolysosomal and autophagic pathway.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
21269460 2011 Initial characterization of the human central proteome.
20630877 2010 ArPIKfyve regulates Sac3 protein abundance and turnover: disruption of the mechanism by Sac3I41T mutation causing Charcot-Marie-Tooth 4J disorder.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19840946 2009 PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase activity and endocytic membrane homeostasis.
19369195 2009 Large-scale proteomics analysis of the human kinome.
19037259 2008 VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse.
18950639 2008 ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
17956977 2007 Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice.
17556371 2007 Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex.
17353931 2007 Large-scale mapping of human protein-protein interactions by mass spectrometry.
17161399 2006 Binding of Vac14 to neuronal nitric oxide synthase: Characterisation of a new internal PDZ-recognition motif.
15616553 2004 The sequence and analysis of duplication-rich human chromosome 16.
15542851 2004 A mammalian ortholog of Saccharomyces cerevisiae Vac14 that associates with and up-regulates PIKfyve phosphoinositide 5-kinase activity.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12719380 2003 Congenital hydrocephalus in hy3 mice is caused by a frameshift mutation in Hydin, a large novel gene.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
8611628 1996 Isolation of a cDNA clone, TRX encoding a human T-cell lymphotrophic virus type-I Tax1 binding protein.