VAC14_RAT
ID VAC14_RAT Reviewed; 783 AA.
AC Q80W92;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Protein VAC14 homolog;
GN Name=Vac14;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=12719380; DOI=10.1093/hmg/ddg122;
RA Davy B.E., Robinson M.L.;
RT "Congenital hydrocephalus in hy3 mice is caused by a frameshift mutation in
RT Hydin, a large novel gene.";
RL Hum. Mol. Genet. 12:1163-1170(2003).
RN [2]
RP INTERACTION WITH NOS1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 781-VAL--LEU-783.
RX PubMed=17161399; DOI=10.1016/j.febslet.2006.11.061;
RA Lemaire J.F., McPherson P.S.;
RT "Binding of Vac14 to neuronal nitric oxide synthase: Characterisation of a
RT new internal PDZ-recognition motif.";
RL FEBS Lett. 580:6948-6954(2006).
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 -!- 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 (By
CC similarity). Interacts with NOS1 (PubMed:17161399).
CC {ECO:0000250|UniProtKB:Q08AM6, ECO:0000269|PubMed:17161399}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q08AM6}.
CC Microsome membrane {ECO:0000269|PubMed:17161399}. Note=Mainly
CC associated with membranes of the late endocytic pathway.
CC {ECO:0000250|UniProtKB:Q08AM6}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, lung, kidney and testis with
CC highest levels in brain and testis. {ECO:0000269|PubMed:17161399}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic brain.
CC {ECO:0000269|PubMed:17161399}.
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 -!- SIMILARITY: Belongs to the VAC14 family. {ECO:0000305}.
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DR EMBL; AY220476; AAO48767.1; -; mRNA.
DR RefSeq; NP_808791.1; NM_177930.2.
DR AlphaFoldDB; Q80W92; -.
DR BioGRID; 258827; 1.
DR IntAct; Q80W92; 4.
DR MINT; Q80W92; -.
DR STRING; 10116.ENSRNOP00000023383; -.
DR iPTMnet; Q80W92; -.
DR PhosphoSitePlus; Q80W92; -.
DR jPOST; Q80W92; -.
DR PaxDb; Q80W92; -.
DR PRIDE; Q80W92; -.
DR Ensembl; ENSRNOT00000023383; ENSRNOP00000023383; ENSRNOG00000017219.
DR GeneID; 307842; -.
DR KEGG; rno:307842; -.
DR UCSC; RGD:631410; rat.
DR CTD; 55697; -.
DR RGD; 631410; Vac14.
DR eggNOG; KOG0212; Eukaryota.
DR GeneTree; ENSGT00390000008385; -.
DR HOGENOM; CLU_007740_1_0_1; -.
DR InParanoid; Q80W92; -.
DR OMA; TYLRMQL; -.
DR OrthoDB; 306227at2759; -.
DR PhylomeDB; Q80W92; -.
DR TreeFam; TF343690; -.
DR Reactome; R-RNO-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-RNO-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-RNO-1660517; Synthesis of PIPs at the late endosome membrane.
DR PRO; PR:Q80W92; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000017219; Expressed in spleen and 19 other tissues.
DR ExpressionAtlas; Q80W92; baseline and differential.
DR Genevisible; Q80W92; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR GO; GO:0000306; C:extrinsic component of vacuolar membrane; IBA:GO_Central.
DR GO; GO:0070772; C:PAS complex; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
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 Gene3D; 1.25.10.10; -; 3.
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; Endoplasmic reticulum; Endosome; Membrane; Microsome;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..783
FT /note="Protein VAC14 homolog"
FT /id="PRO_0000300487"
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 439..476
FT /note="HEAT 5"
FT REPEAT 561..599
FT /note="HEAT 6"
FT REGION 331..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 774..778
FT /note="Mediates interaction with the PDZ domain of NOS1"
FT COMPBIAS 346..372
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 500
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q08AM6"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08AM6"
FT MOD_RES 744
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08AM6"
FT MUTAGEN 781..783
FT /note="VVL->AAA: Reduced interaction with NOS1."
FT /evidence="ECO:0000269|PubMed:17161399"
SQ SEQUENCE 783 AA; 88068 MW; 78312BE8D8A83B39 CRC64;
MNPEKDFAPL TPNIVRALND KLYEKRKVAA LEIEKLVRDF VAQNNTVQIK HVIQTLSQEF
ALSQHPHSRK GGLIGLAACS IALGKDSGLY LKELIEPVLT CFNDADSRLR YYACEALYNI
VKVARGAVLP HFNVLFDGLS KLAADPDPNV KSGSELLDRL LKDIVTESSK FDLVGFIPLL
RERIYSNNQY ARQFIISWIL VLVSVPDINL LDYLPEILDG LFQILGDNGK EIRKMCEVVL
GEFLKEIKKN PSSVKFAEMA NILVIHCQTT DDLIQLTAMC WMREFIQLAG RVMLPYSSGI
LTAVLPCLAY DDRKKSIKEV ANVCNQSLMK LVTPEDDEPD EPKSVAQKQT EPNPEDSLPK
QEGTASGGAS GPCDSSFGSG ISVFTSASTD RAPVTLHLDG IVQVLNCHLS DTTIGMMTRI
AVLKWLYHLY IKTPRKMFRH TDSLFPILLQ TLSDESDEVV LKDLEVLAEI ASSPAGQTDD
PGAPDGPDLQ VNHSELQVPT SGRANLLNPP NTKGLECSPS TPTMNSYFYK FMINLLQTFS
SERKLLEARG PFIIRQLCLL LNAENIFHSM ADILLREEDL KFASTMVHTL NTILLTSTEL
FQLRNQLKDL KTLESQNLFC CLYRSWCHNP VTTVSLCFLT QNYRHAYDLI QKFGDLEVTV
DFLTEVDKLV QLIECPIFTY LRLQLLDVKN NPYLMKALYG LLMLLPQSSA FQLLSHRLQC
VPNPELLQTE DCLKAAPKSQ KGDSPSIDYT ELLQHFEKVQ KQHLEVRHQR SGRGDHLDRR
VVL
