SAC1_RAT
ID SAC1_RAT Reviewed; 587 AA.
AC Q9ES21;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Phosphatidylinositol-3-phosphatase SAC1;
DE EC=3.1.3.64 {ECO:0000269|PubMed:10887188};
DE AltName: Full=Phosphatidylinositol-4-phosphate phosphatase {ECO:0000303|PubMed:10887188};
DE AltName: Full=Suppressor of actin mutations 1-like protein;
GN Name=Sacm1l; Synonyms=Sac1 {ECO:0000303|PubMed:10887188};
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], FUNCTION, CATALYTIC ACTIVITY, TOPOLOGY,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-391 AND ALA-442, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=10887188; DOI=10.1074/jbc.m003923200;
RA Nemoto Y., Kearns B.G., Wenk M.R., Chen H., Mori K., Alb J.G. Jr.,
RA De Camilli P., Bankaitis V.A.;
RT "Functional characterization of a mammalian Sac1 and mutants exhibiting
RT substrate-specific defects in phosphoinositide phosphatase activity.";
RL J. Biol. Chem. 275:34293-34305(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=27044890; DOI=10.1083/jcb.201508106;
RA Dickson E.J., Jensen J.B., Vivas O., Kruse M., Traynor-Kaplan A.E.,
RA Hille B.;
RT "Dynamic formation of ER-PM junctions presents a lipid phosphatase to
RT regulate phosphoinositides.";
RL J. Cell Biol. 213:33-48(2016).
CC -!- FUNCTION: Phosphoinositide phosphatase which catalyzes the hydrolysis
CC of phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol
CC 3-phosphate (PtdIns(3)P) and has low activity towards
CC phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:10887188,
CC PubMed:27044890). Shows a very robust PtdIns(4)P phosphatase activity
CC when it binds PtdIns(4)P in a 'cis' configuration in the cellular
CC environment, with much less activity seen when it binds PtdIns(4)P in
CC 'trans' configuration (By similarity). PtdIns(4)P phosphatase activity
CC (when it binds PtdIns(4)P in 'trans' configuration) is enhanced in the
CC presence of PLEKHA3 (By similarity). {ECO:0000250|UniProtKB:Q9NTJ5,
CC ECO:0000269|PubMed:10887188, ECO:0000269|PubMed:27044890}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-
CC phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol) + phosphate; Xref=Rhea:RHEA:12316, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57880, ChEBI:CHEBI:58088; EC=3.1.3.64;
CC Evidence={ECO:0000269|PubMed:10887188};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12317;
CC Evidence={ECO:0000305|PubMed:10887188};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-
CC phosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol) + phosphate; Xref=Rhea:RHEA:55652, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57880, ChEBI:CHEBI:58178;
CC Evidence={ECO:0000269|PubMed:10887188, ECO:0000269|PubMed:27044890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55653;
CC Evidence={ECO:0000305|PubMed:10887188};
CC -!- SUBUNIT: Interacts with TMEM39A (By similarity). Interacts with SEC23A
CC and SEC24A; this interaction is reduced in the absence of TMEM39A (By
CC similarity). Interacts with PLEKHA3 and VAPA and/or VAPB to form a
CC ternary complex (By similarity). {ECO:0000250|UniProtKB:Q9NTJ5}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10887188}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9NTJ5};
CC Multi-pass membrane protein {ECO:0000255}. Note=Trafficking between the
CC ER and Golgi is regulated by nutrient status and by TMEM39A (By
CC similarity). Localizes to endoplasmic reticulum-plasma membrane contact
CC sites (EPCS) in the presence of phosphatidylinositol-4,5-bisphosphate
CC (PubMed:27044890). {ECO:0000250|UniProtKB:Q9NTJ5,
CC ECO:0000269|PubMed:27044890}.
CC -!- TISSUE SPECIFICITY: Detected in spleen, lung, liver, skeletal muscle,
CC kidney, testis and in cerebellar Purkinje cells (at protein level).
CC Ubiquitous. Highly expressed in brain, spleen, liver and kidney.
CC {ECO:0000269|PubMed:10887188}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF251186; AAG29810.1; -; mRNA.
DR RefSeq; NP_446250.1; NM_053798.2.
DR AlphaFoldDB; Q9ES21; -.
DR SMR; Q9ES21; -.
DR BioGRID; 250459; 1.
DR IntAct; Q9ES21; 1.
DR STRING; 10116.ENSRNOP00000007223; -.
DR iPTMnet; Q9ES21; -.
DR PhosphoSitePlus; Q9ES21; -.
DR jPOST; Q9ES21; -.
DR PaxDb; Q9ES21; -.
DR PRIDE; Q9ES21; -.
DR GeneID; 116482; -.
DR KEGG; rno:116482; -.
DR UCSC; RGD:69223; rat.
DR CTD; 22908; -.
DR RGD; 69223; Sacm1l.
DR VEuPathDB; HostDB:ENSRNOG00000005149; -.
DR eggNOG; KOG1889; Eukaryota.
DR HOGENOM; CLU_003016_7_4_1; -.
DR InParanoid; Q9ES21; -.
DR OMA; FRDINVH; -.
DR OrthoDB; 359616at2759; -.
DR PhylomeDB; Q9ES21; -.
DR TreeFam; TF313543; -.
DR Reactome; R-RNO-1483248; Synthesis of PIPs at the ER membrane.
DR Reactome; R-RNO-1660514; Synthesis of PIPs at the Golgi membrane.
DR PRO; PR:Q9ES21; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000005149; Expressed in cerebellum and 20 other tissues.
DR Genevisible; Q9ES21; RN.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0140268; C:endoplasmic reticulum-plasma membrane contact site; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:RGD.
DR GO; GO:0016791; F:phosphatase activity; IMP:UniProtKB.
DR GO; GO:0034593; F:phosphatidylinositol bisphosphate phosphatase activity; IDA:RGD.
DR GO; GO:0004438; F:phosphatidylinositol-3-phosphatase activity; IDA:RGD.
DR GO; GO:0043812; F:phosphatidylinositol-4-phosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:RGD.
DR InterPro; IPR002013; SAC_dom.
DR Pfam; PF02383; Syja_N; 1.
DR PROSITE; PS50275; SAC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Endoplasmic reticulum; Golgi apparatus; Hydrolase;
KW Lipid metabolism; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..587
FT /note="Phosphatidylinositol-3-phosphatase SAC1"
FT /id="PRO_0000317174"
FT TOPO_DOM 1..520
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10887188"
FT TRANSMEM 521..541
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 542..548
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:10887188"
FT TRANSMEM 549..569
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 570..587
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:10887188"
FT DOMAIN 122..451
FT /note="SAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00183"
FT REGION 452..587
FT /note="Essential for phosphatidylinositol-4-phosphate
FT phosphatase activity"
FT /evidence="ECO:0000250|UniProtKB:Q9NTJ5"
FT MOD_RES 456
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NTJ5"
FT MUTAGEN 391
FT /note="D->N: Reduces phosphatase activity towards
FT PtdIns(4)P, but not towards PtdIns(3)P or PtdIns(3,5)P2."
FT /evidence="ECO:0000269|PubMed:10887188"
FT MUTAGEN 442
FT /note="A->V: Reduces phosphatase activity towards
FT PtdIns(4)P, but not towards PtdIns(3)P or PtdIns(3,5)P2."
FT /evidence="ECO:0000269|PubMed:10887188"
SQ SEQUENCE 587 AA; 67039 MW; 77C29FFB08F54FF8 CRC64;
MAATAYEHLK LHITPEKFYV EACDDGADDV LIIDRVSTEV TLAVKKDVPP SAVTRPIYGI
MGTIHLVAGN YLVVITKKMK VGEFFNHVIW KATDFDVLSY KKTMLHLTDI QLQDNKTFLA
MLNHVLSTDG FYFSTTYDLT HTLQRLSNTS PEFQEMSLLE RADQRFVWNG HLLRELSAQP
EVHRFALPVL HGFITMHSCS INGKYFDWIL ISRRSCFRAG VRYYVRGIDS EGHAANFVET
EQIVHYSGNR ASFVQTRGSI PVFWSQRPNL KYKPDPQINK VANHMDGFQR HFDSQVIIYG
KQVIINLVNH KGSEKPLEQT FAKMVSSLGS GMIRYIAFDF HKECKNMRWD RLSILLDQVA
EMQDELSYFL VDSAGKVVTN QEGVFRSNCM DCLDRTNVIQ SLLARRSLQA QLQRLGVLHV
GQKLEEQDEF EKIYKNAWAD NANACAKQYA GTGALKTDFT RTGKRTQLGL VMDGFNSLLR
YYKNNFSDGF RQDSIDLFLG NYSVDELDSH SPLSVPRDWK FLALPIIMVV AFSMCIICLL
MAGDTWTETL AYVLFWGVAS IGTFFIILYN GKDFVDAPRL VQKEKID
