VAC14_MOUSE
ID VAC14_MOUSE Reviewed; 782 AA.
AC Q80WQ2; Q3TAX7; Q8C8K8;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Protein VAC14 homolog;
GN Name=Vac14; Synonyms=D8Wsu151e;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Limb;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=17956977; DOI=10.1073/pnas.0702275104;
RA Zhang Y., Zolov S.N., Chow C.Y., Slutsky S.G., Richardson S.C., Piper R.C.,
RA Yang B., Nau J.J., Westrick R.J., Morrison S.J., Meisler M.H.,
RA Weisman L.S.;
RT "Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol
RT 3,5-bisphosphate, results in neurodegeneration in mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:17518-17523(2007).
RN [4]
RP IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, FUNCTION, SUBCELLULAR
RP LOCATION, AND VARIANT INGLS ARG-156.
RX PubMed=19037259; DOI=10.1038/emboj.2008.248;
RA Jin N., Chow C.Y., Liu L., Zolov S.N., Bronson R., Davisson M.,
RA Petersen J.L., Zhang Y., Park S., Duex J.E., Goldowitz D., Meisler M.H.,
RA Weisman L.S.;
RT "VAC14 nucleates a protein complex essential for the acute interconversion
RT of PI3P and PI(3,5)P(2) in yeast and mouse.";
RL EMBO J. 27:3221-3234(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Scaffold protein component of the PI(3,5)P2 regulatory
CC complex which regulates both the synthesis and turnover of
CC phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Pentamerizes
CC into a star-shaped structure and nucleates the assembly of the complex.
CC The pentamer binds a single copy each of PIKFYVE and FIG4 and
CC coordinates both PIKfyve kinase activity and FIG4 phosphatase activity,
CC being required to maintain normal levels of phosphatidylinositol 3-
CC phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate
CC (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier
CC vesicles (ECV) / multivesicular bodies (MVB) transport intermediates
CC from early endosomes. {ECO:0000250|UniProtKB:Q08AM6,
CC ECO:0000269|PubMed:17956977, ECO:0000269|PubMed:19037259}.
CC -!- SUBUNIT: Forms pentamers. Component of the PI(3,5)P2 regulatory
CC complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14.
CC VAC14 nucleates the assembly of the complex and serves as a scaffold by
CC pentamerizing into a star-shaped structure, which can bind a single
CC copy each of PIKFYVE and FIG4 and coordinates their activities.
CC Interacts with NOS1. {ECO:0000250|UniProtKB:Q08AM6}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:19037259}.
CC Microsome membrane {ECO:0000250|UniProtKB:Q80W92}. Note=Mainly
CC associated with membranes of the late endocytic pathway.
CC {ECO:0000250|UniProtKB:Q08AM6}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:17956977}.
CC -!- DOMAIN: The C-terminal domain (residues 523-782) mediates pentameric
CC interactions and is necessary for the formation and maintenance of the
CC PI(3,5)P2 regulatory complex. {ECO:0000250|UniProtKB:Q08AM6}.
CC -!- DISEASE: Note=Defects in Vac14 are the cause of the infantile gliosis
CC phenotype (ingls). Mice exhibit reduced body size and diluted
CC pigmentation that can be recognized as early as postnatal day 3 (P3).
CC By P14, the mice exhibit a tremor and impaired motor function. Maximal
CC survival of the mice is for 3 weeks. Small areas with the appearance of
CC spongiform degeneration are visible in several brain regions, including
CC the thalamus, brain stem and cerebellar nucleus.
CC {ECO:0000269|PubMed:19037259}.
CC -!- DISRUPTION PHENOTYPE: Mice die perinatally and exhibit profound
CC degeneration in certain regions of the central and peripheral nervous
CC systems. Selected regions in the brain are affected, especially the
CC medulla, the pons and the midbrain and increased cell death occurs in
CC these areas. Affected neurons contain large vacuoles.
CC {ECO:0000269|PubMed:17956977}.
CC -!- SIMILARITY: Belongs to the VAC14 family. {ECO:0000305}.
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DR EMBL; AK046826; BAC32886.1; -; mRNA.
DR EMBL; AK171577; BAE42537.1; -; mRNA.
DR EMBL; BC052199; AAH52199.1; -; mRNA.
DR CCDS; CCDS22663.1; -.
DR RefSeq; NP_666328.2; NM_146216.2.
DR AlphaFoldDB; Q80WQ2; -.
DR BioGRID; 231569; 6.
DR IntAct; Q80WQ2; 6.
DR MINT; Q80WQ2; -.
DR STRING; 10090.ENSMUSP00000034190; -.
DR ChEMBL; CHEMBL2176841; -.
DR iPTMnet; Q80WQ2; -.
DR PhosphoSitePlus; Q80WQ2; -.
DR SwissPalm; Q80WQ2; -.
DR EPD; Q80WQ2; -.
DR jPOST; Q80WQ2; -.
DR MaxQB; Q80WQ2; -.
DR PaxDb; Q80WQ2; -.
DR PeptideAtlas; Q80WQ2; -.
DR PRIDE; Q80WQ2; -.
DR ProteomicsDB; 300208; -.
DR Antibodypedia; 16467; 106 antibodies from 22 providers.
DR DNASU; 234729; -.
DR Ensembl; ENSMUST00000034190; ENSMUSP00000034190; ENSMUSG00000010936.
DR GeneID; 234729; -.
DR KEGG; mmu:234729; -.
DR UCSC; uc009nkv.2; mouse.
DR CTD; 55697; -.
DR MGI; MGI:2157980; Vac14.
DR VEuPathDB; HostDB:ENSMUSG00000010936; -.
DR eggNOG; KOG0212; Eukaryota.
DR GeneTree; ENSGT00390000008385; -.
DR HOGENOM; CLU_007740_1_0_1; -.
DR InParanoid; Q80WQ2; -.
DR OMA; TYLRMQL; -.
DR OrthoDB; 306227at2759; -.
DR PhylomeDB; Q80WQ2; -.
DR TreeFam; TF343690; -.
DR Reactome; R-MMU-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-MMU-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-MMU-1660517; Synthesis of PIPs at the late endosome membrane.
DR BioGRID-ORCS; 234729; 15 hits in 77 CRISPR screens.
DR PRO; PR:Q80WQ2; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q80WQ2; protein.
DR Bgee; ENSMUSG00000010936; Expressed in animal zygote and 218 other tissues.
DR ExpressionAtlas; Q80WQ2; baseline and differential.
DR Genevisible; Q80WQ2; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0000306; C:extrinsic component of vacuolar membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0070772; C:PAS complex; IBA:GO_Central.
DR GO; GO:0005774; C:vacuolar membrane; ISA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019209; F:kinase activator activity; ISA:MGI.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0006970; P:response to osmotic stress; ISA:MGI.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR026825; Vac14.
DR InterPro; IPR021841; VAC14_Fig4p-bd.
DR PANTHER; PTHR16023; PTHR16023; 1.
DR Pfam; PF11916; Vac14_Fig4_bd; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Acetylation; Disease variant; Endoplasmic reticulum; Endosome; Membrane;
KW Microsome; Neurodegeneration; Neuropathy; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..782
FT /note="Protein VAC14 homolog"
FT /id="PRO_0000300486"
FT REPEAT 5..42
FT /note="HEAT 1"
FT REPEAT 89..126
FT /note="HEAT 2"
FT REPEAT 171..208
FT /note="HEAT 3"
FT REPEAT 212..249
FT /note="HEAT 4"
FT REPEAT 438..475
FT /note="HEAT 5"
FT REPEAT 560..598
FT /note="HEAT 6"
FT REGION 331..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 773..777
FT /note="Mediates interaction with the PDZ domain of NOS1"
FT /evidence="ECO:0000250"
FT COMPBIAS 346..360
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..519
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q08AM6"
FT MOD_RES 11
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08AM6"
FT MOD_RES 499
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08AM6"
FT MOD_RES 517
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08AM6"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08AM6"
FT VARIANT 156
FT /note="L -> R (in ingls; loss of interaction with Pikfyve
FT but not with Fig4)"
FT /evidence="ECO:0000269|PubMed:19037259"
FT CONFLICT 41
FT /note="V -> A (in Ref. 1; BAC32886)"
FT /evidence="ECO:0000305"
FT CONFLICT 614
FT /note="S -> R (in Ref. 1; BAE42537)"
FT /evidence="ECO:0000305"
FT CONFLICT 758
FT /note="V -> A (in Ref. 1; BAE42537)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 782 AA; 88048 MW; 5545622BDE5D8F09 CRC64;
MNPEKDFAPL TPNIVRALND KLYEKRKVAA LEIEKLVRDF VAQNNTMQIK HVIQTLSQEF
ALSQHPHSRK GGLIGLAACS IALGKDSGLY LKELIEPVLT CFNDADSRLR YYACEALYNI
VKVARGAVLP HFNVLFDGLS KLAADPDPNV KSGSELLDRL LKDIVTESSK FDLVSFIPLL
RERIYSNNQY ARQFIISWIL VLVSVPDINL LDYLPEILDG LFQILGDNGK EIRKMCEVVL
GEFLKEIKKN PSSVKFAEMA NILVIHCQTT DDLIQLTAMC WMREFIQLAG RVMLPYSSGI
LTAVLPCLAY DDRKKSIKEV ANVCNQSLMK LVTPEDDEPD EPKSVAQKQT EPNPEDSLPK
QEGTASGGPG SCDSSFGSGI NVFTSANTDR APVTLHLDGI VQVLNCHLSD TTIGMMTRIA
VLKWLYHLYI KTPRKMFRHT DSLFPILLQT LSDESDEVVL KDLEVLAEIA SSPAGQTDDP
GAPDGPDLRV NHSELQVPTS GRANLLNPPS TKGLEGSPST PTMNSYFYKF MINLLQTFSS
ERKLLEARGP FIIRQLCLLL NAENIFHSMA DILLREEDLK FASTMVHTLN TILLTSTELF
QLRNQLKDLQ TPESQNLFCC LYRSWCHNPV TTVSLCFLTQ NYRHAYDLIQ KFGDLEVTVD
FLTEVDKLVQ LIECPIFTYL RLQLLDVKNN PYLIKALYGL LMLLPQSSAF QLLSHRLQCV
PNPELLQTED CLKAAPKSQK GDSPSIDYTE LLQHFEKVQK QHLEVRHQRS GRGDHLDRRV
IL
