ID SAC2_HUMAN Reviewed; 1132 AA. AC Q9Y2H2; B3KRF1; D3DRD1; Q2T9J4; Q5W135; Q5W136; Q6NVY2; Q86U97; Q9H3D9; AC Q9NT51; DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 29-APR-2008, sequence version 3. DT 27-MAR-2024, entry version 157. DE RecName: Full=Phosphatidylinositide phosphatase SAC2 {ECO:0000305}; DE EC=3.1.3.25 {ECO:0000269|PubMed:25869668, ECO:0000269|PubMed:25869669}; DE AltName: Full=Inositol polyphosphate 5-phosphatase F {ECO:0000312|HGNC:HGNC:17054}; DE AltName: Full=Sac domain-containing inositol phosphatase 2; DE AltName: Full=Sac domain-containing phosphoinositide 4-phosphatase 2 {ECO:0000305|PubMed:25869668, ECO:0000305|PubMed:25869669}; DE Short=hSAC2; GN Name=INPP5F {ECO:0000312|HGNC:HGNC:17054}; Synonyms=KIAA0966, SAC2; GN ORFNames=MSTP007, MSTP047; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, TISSUE SPECIFICITY, AND CAUTION. RX PubMed=11274189; DOI=10.1074/jbc.m101579200; RA Minagawa T., Ijuin T., Mochizuki Y., Takenawa T.; RT "Identification and characterization of a sac domain-containing RT phosphoinositide 5-phosphatase."; RL J. Biol. Chem. 276:22011-22015(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASP-997. RC TISSUE=Brain; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT RP ASP-997. RC TISSUE=Placenta, and Skin; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 274-1132 (ISOFORM 1). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 956-1132 (ISOFORM 1). RC TISSUE=Aorta; RA Liu B., Liu Y.Q., Wang X.Y., Zhao B., Sheng H., Zhao X.W., Liu S., Xu Y.Y., RA Ye J., Song L., Gao Y., Zhang C.L., Zhang J., Wei Y.J., Cao H.Q., Zhao Y., RA Liu L.S., Ding J.F., Gao R.L., Wu Q.Y., Qiang B.Q., Yuan J.G., Liew C.C., RA Zhao M.S., Hui R.T.; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [9] RP FUNCTION. RX PubMed=17322895; DOI=10.1038/nm1552; RA Trivedi C.M., Luo Y., Yin Z., Zhang M., Zhu W., Wang T., Floss T., RA Goettlicher M., Noppinger P.R., Wurst W., Ferrari V.A., Abrams C.S., RA Gruber P.J., Epstein J.A.; RT "Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta RT activity."; RL Nat. Med. 13:324-331(2007). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-907 AND SER-1103, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] RP FUNCTION, AND INTERACTION WITH STAT3. RX PubMed=25476455; DOI=10.1038/srep07330; RA Kim H.S., Li A., Ahn S., Song H., Zhang W.; RT "Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity RT and suppresses gliomas tumorigenicity."; RL Sci. Rep. 4:7330-7330(2014). RN [16] RP INTERACTION WITH INPP4A; INPP5B AND OCRL. RX PubMed=25869668; DOI=10.1083/jcb.201409064; RA Nakatsu F., Messa M., Nandez R., Czapla H., Zou Y., Strittmatter S.M., RA De Camilli P.; RT "Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic RT pathway."; RL J. Cell Biol. 209:85-95(2015). RN [17] RP TISSUE SPECIFICITY. RX PubMed=26203138; DOI=10.1523/jneurosci.1718-15.2015; RA Zou Y., Stagi M., Wang X., Yigitkanli K., Siegel C.S., Nakatsu F., RA Cafferty W.B., Strittmatter S.M.; RT "Gene-silencing screen for mammalian axon regeneration identifies Inpp5f RT (Sac2) as an endogenous suppressor of repair after spinal cord injury."; RL J. Neurosci. 35:10429-10439(2015). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 593-760, FUNCTION, SUBUNIT, RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-458. RX PubMed=25869669; DOI=10.1083/jcb.201408027; RA Hsu F., Hu F., Mao Y.; RT "Spatiotemporal control of phosphatidylinositol 4-phosphate by Sac2 RT regulates endocytic recycling."; RL J. Cell Biol. 209:97-110(2015). CC -!- FUNCTION: Inositol 4-phosphatase which mainly acts on CC phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, CC which converts phosphatidylinositol 4,5-bisphosphate to CC phosphatidylinositol, for a sequential dephosphorylation of CC phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of CC inositol, thus playing an important role in the endocytic recycling CC (PubMed:25869669). Regulator of TF:TFRC and integrins recycling CC pathway, is also involved in cell migration mechanisms CC (PubMed:25869669). Modulates AKT/GSK3B pathway by decreasing AKT and CC GSK3B phosphorylation (PubMed:17322895). Negatively regulates STAT3 CC signaling pathway through inhibition of STAT3 phosphorylation and CC translocation to the nucleus (PubMed:25476455). Functionally important CC modulator of cardiac myocyte size and of the cardiac response to stress CC (By similarity). May play a role as negative regulator of axon CC regeneration after central nervous system injuries (By similarity). CC {ECO:0000250|UniProtKB:Q8CDA1, ECO:0000269|PubMed:17322895, CC ECO:0000269|PubMed:25476455, ECO:0000269|PubMed:25869669}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a myo-inositol phosphate + H2O = myo-inositol + phosphate; CC Xref=Rhea:RHEA:24056, ChEBI:CHEBI:15377, ChEBI:CHEBI:17268, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:84139; EC=3.1.3.25; CC Evidence={ECO:0000269|PubMed:25869668, ECO:0000269|PubMed:25869669}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=14.3 uM for PtdIns(4,5)P2 (at pH 6.0) CC {ECO:0000269|PubMed:11274189}; CC -!- SUBUNIT: Homodimer (PubMed:25869669). Interacts with OCRL and RAB5A CC (PubMed:25869668). Interacts with INPP5B and INPP4A (PubMed:25869668). CC Interacts with STAT3; the interaction is independent of STAT3 'Tyr-705' CC phosphorylation status (PubMed:25476455). CC {ECO:0000250|UniProtKB:Q8CDA1, ECO:0000269|PubMed:25476455, CC ECO:0000269|PubMed:25869668, ECO:0000269|PubMed:25869669}. CC -!- SUBCELLULAR LOCATION: Membrane, clathrin-coated pit CC {ECO:0000269|PubMed:25869669}. Early endosome CC {ECO:0000269|PubMed:25869669}. Recycling endosome CC {ECO:0000269|PubMed:25869669}. Note=Also found on macropinosomes. CC {ECO:0000250|UniProtKB:Q8CDA1}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q9Y2H2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y2H2-2; Sequence=VSP_033268, VSP_033269; CC Name=3; CC IsoId=Q9Y2H2-3; Sequence=VSP_033266, VSP_033267; CC Name=4; CC IsoId=Q9Y2H2-4; Sequence=VSP_046366, VSP_046367; CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:11274189). Highly expressed in CC brain (PubMed:26203138). {ECO:0000269|PubMed:11274189, CC ECO:0000269|PubMed:26203138}. CC -!- CAUTION: INPP5F has been initially described as an inositol CC polyphosphate 5-phosphatase. {ECO:0000269|PubMed:11274189}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76810.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; AB023183; BAA76810.2; ALT_INIT; mRNA. DR EMBL; AK091448; BAG52363.1; -; mRNA. DR EMBL; AC027672; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL133461; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL158014; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49379.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49380.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49381.1; -; Genomic_DNA. DR EMBL; BC052367; AAH52367.1; -; mRNA. DR EMBL; BC067820; AAH67820.1; -; mRNA. DR EMBL; BC082755; AAH82755.1; -; mRNA. DR EMBL; BC111493; AAI11494.1; -; mRNA. DR EMBL; AL137528; CAB70792.1; -; mRNA. DR EMBL; AF113227; AAG39298.1; -; mRNA. DR EMBL; AF109361; AAQ13509.1; -; mRNA. DR CCDS; CCDS58098.1; -. [Q9Y2H2-4] DR CCDS; CCDS7616.1; -. [Q9Y2H2-1] DR CCDS; CCDS81513.1; -. [Q9Y2H2-3] DR PIR; T46372; T46372. DR RefSeq; NP_001230123.1; NM_001243194.1. [Q9Y2H2-4] DR RefSeq; NP_001230124.1; NM_001243195.1. [Q9Y2H2-3] DR RefSeq; NP_055752.1; NM_014937.3. [Q9Y2H2-1] DR PDB; 4XUU; X-ray; 2.62 A; A/B/C/D=593-760. DR PDBsum; 4XUU; -. DR AlphaFoldDB; Q9Y2H2; -. DR SMR; Q9Y2H2; -. DR BioGRID; 116543; 41. DR ELM; Q9Y2H2; -. DR IntAct; Q9Y2H2; 9. DR MINT; Q9Y2H2; -. DR STRING; 9606.ENSP00000497527; -. DR DEPOD; INPP5F; -. DR GlyCosmos; Q9Y2H2; 1 site, 1 glycan. DR GlyGen; Q9Y2H2; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y2H2; -. DR PhosphoSitePlus; Q9Y2H2; -. DR SwissPalm; Q9Y2H2; -. DR BioMuta; INPP5F; -. DR DMDM; 187611527; -. DR EPD; Q9Y2H2; -. DR jPOST; Q9Y2H2; -. DR MassIVE; Q9Y2H2; -. DR MaxQB; Q9Y2H2; -. DR PaxDb; 9606-ENSP00000354519; -. DR PeptideAtlas; Q9Y2H2; -. DR ProteomicsDB; 65795; -. DR ProteomicsDB; 85781; -. [Q9Y2H2-1] DR ProteomicsDB; 85782; -. [Q9Y2H2-2] DR ProteomicsDB; 85783; -. [Q9Y2H2-3] DR Pumba; Q9Y2H2; -. DR Antibodypedia; 32161; 121 antibodies from 19 providers. DR DNASU; 22876; -. DR Ensembl; ENST00000369081.3; ENSP00000489864.1; ENSG00000198825.15. [Q9Y2H2-3] DR Ensembl; ENST00000650409.1; ENSP00000496955.1; ENSG00000198825.15. [Q9Y2H2-4] DR Ensembl; ENST00000650623.2; ENSP00000497527.1; ENSG00000198825.15. [Q9Y2H2-1] DR GeneID; 22876; -. DR KEGG; hsa:22876; -. DR MANE-Select; ENST00000650623.2; ENSP00000497527.1; NM_014937.4; NP_055752.1. DR UCSC; uc001leo.4; human. [Q9Y2H2-1] DR AGR; HGNC:17054; -. DR CTD; 22876; -. DR DisGeNET; 22876; -. DR GeneCards; INPP5F; -. DR HGNC; HGNC:17054; INPP5F. DR HPA; ENSG00000198825; Tissue enhanced (brain). DR MIM; 609389; gene. DR neXtProt; NX_Q9Y2H2; -. DR OpenTargets; ENSG00000198825; -. DR PharmGKB; PA134927878; -. DR VEuPathDB; HostDB:ENSG00000198825; -. DR eggNOG; KOG1890; Eukaryota. DR GeneTree; ENSGT00940000155996; -. DR HOGENOM; CLU_008079_0_0_1; -. DR InParanoid; Q9Y2H2; -. DR OMA; NCCLELI; -. DR OrthoDB; 996872at2759; -. DR PhylomeDB; Q9Y2H2; -. DR TreeFam; TF313543; -. DR BioCyc; MetaCyc:HS12255-MONOMER; -. DR PathwayCommons; Q9Y2H2; -. DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane. DR SABIO-RK; Q9Y2H2; -. DR SignaLink; Q9Y2H2; -. DR BioGRID-ORCS; 22876; 19 hits in 1164 CRISPR screens. DR ChiTaRS; INPP5F; human. DR GenomeRNAi; 22876; -. DR Pharos; Q9Y2H2; Tbio. DR PRO; PR:Q9Y2H2; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q9Y2H2; Protein. DR Bgee; ENSG00000198825; Expressed in pons and 202 other cell types or tissues. DR ExpressionAtlas; Q9Y2H2; baseline and differential. DR GO; GO:0030424; C:axon; IEA:Ensembl. DR GO; GO:0045334; C:clathrin-coated endocytic vesicle; IDA:UniProtKB. DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0008934; F:inositol monophosphate 1-phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0052832; F:inositol monophosphate 3-phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0052833; F:inositol monophosphate 4-phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0034596; F:phosphatidylinositol phosphate 4-phosphatase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0034595; F:phosphatidylinositol phosphate 5-phosphatase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0043812; F:phosphatidylinositol-4-phosphate phosphatase activity; IBA:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl. DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; ISS:UniProtKB. DR GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:UniProtKB. DR GO; GO:0048681; P:negative regulation of axon regeneration; ISS:BHF-UCL. DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IDA:UniProtKB. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; TAS:Reactome. DR GO; GO:0031161; P:phosphatidylinositol catabolic process; ISS:UniProtKB. DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; ISS:UniProtKB. DR GO; GO:0001921; P:positive regulation of receptor recycling; IDA:ParkinsonsUK-UCL. DR GO; GO:2000145; P:regulation of cell motility; IMP:UniProtKB. DR GO; GO:2001135; P:regulation of endocytic recycling; IMP:UniProtKB. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR InterPro; IPR034753; hSac2. DR InterPro; IPR022158; Inositol_phosphatase. DR InterPro; IPR002013; SAC_dom. DR PANTHER; PTHR45662; PHOSPHATIDYLINOSITIDE PHOSPHATASE SAC1; 1. DR PANTHER; PTHR45662:SF8; PHOSPHATIDYLINOSITIDE PHOSPHATASE SAC2; 1. DR Pfam; PF12456; hSac2; 1. DR Pfam; PF02383; Syja_N; 1. DR PROSITE; PS51791; HSAC2; 1. DR PROSITE; PS50275; SAC; 1. DR Genevisible; Q9Y2H2; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coated pit; Endosome; Hydrolase; KW Membrane; Phosphoprotein; Reference proteome. FT CHAIN 1..1132 FT /note="Phosphatidylinositide phosphatase SAC2" FT /id="PRO_0000331621" FT DOMAIN 167..518 FT /note="SAC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00183" FT DOMAIN 593..760 FT /note="hSac2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01127" FT REGION 846..875 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 923..942 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 974..1017 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 847..875 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 827 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CDA1" FT MOD_RES 830 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CDA1" FT MOD_RES 878 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CDA1" FT MOD_RES 881 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CDA1" FT MOD_RES 907 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 910 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CDA1" FT MOD_RES 1103 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..19 FT /note="MELFQAKDHYILQQGERAL -> MCHDVIFMAWLKQQFSECT (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046366" FT VAR_SEQ 20..629 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046367" FT VAR_SEQ 206..219 FT /note="DDRFFWNKYMIQDL -> PLTARRAGFALGKK (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_033266" FT VAR_SEQ 220..1132 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_033267" FT VAR_SEQ 373..375 FT /note="VII -> QQK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_033268" FT VAR_SEQ 376..1132 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_033269" FT VARIANT 453 FT /note="I -> V (in dbSNP:rs3736822)" FT /id="VAR_042907" FT VARIANT 997 FT /note="N -> D (in dbSNP:rs3188055)" FT /evidence="ECO:0000269|PubMed:10231032, FT ECO:0000269|PubMed:15489334" FT /id="VAR_042908" FT MUTAGEN 458 FT /note="C->S: Loss of inositol 4-phosphatase activity. FT Alters TFRC distribution and delays TF recycling." FT /evidence="ECO:0000269|PubMed:25869669" FT CONFLICT 386 FT /note="I -> V (in Ref. 6; AAI11494)" FT /evidence="ECO:0000305" FT CONFLICT 654 FT /note="Y -> N (in Ref. 3; BAG52363)" FT /evidence="ECO:0000305" FT CONFLICT 1008 FT /note="P -> L (in Ref. 3; BAG52363)" FT /evidence="ECO:0000305" FT CONFLICT 1019 FT /note="S -> P (in Ref. 3; BAG52363)" FT /evidence="ECO:0000305" FT HELIX 595..610 FT /evidence="ECO:0007829|PDB:4XUU" FT STRAND 617..625 FT /evidence="ECO:0007829|PDB:4XUU" FT STRAND 639..654 FT /evidence="ECO:0007829|PDB:4XUU" FT STRAND 656..668 FT /evidence="ECO:0007829|PDB:4XUU" FT HELIX 669..671 FT /evidence="ECO:0007829|PDB:4XUU" FT STRAND 672..679 FT /evidence="ECO:0007829|PDB:4XUU" FT STRAND 683..685 FT /evidence="ECO:0007829|PDB:4XUU" FT STRAND 689..698 FT /evidence="ECO:0007829|PDB:4XUU" FT STRAND 701..710 FT /evidence="ECO:0007829|PDB:4XUU" FT HELIX 720..736 FT /evidence="ECO:0007829|PDB:4XUU" FT STRAND 743..746 FT /evidence="ECO:0007829|PDB:4XUU" SQ SEQUENCE 1132 AA; 128407 MW; 853719FC0AD455CD CRC64; MELFQAKDHY ILQQGERALW CSRRDGGLQL RPATDLLLAW NPICLGLVEG VIGKIQLHSD LPWWLILIRQ KALVGKLPGD HEVCKVTKIA VLSLSEMEPQ DLELELCKKH HFGINKPEKI IPSPDDSKFL LKTFTHIKSN VSAPNKKKVK ESKEKEKLER RLLEELLKMF MDSESFYYSL TYDLTNSVQR QSTGERDGRP LWQKVDDRFF WNKYMIQDLT EIGTPDVDFW IIPMIQGFVQ IEELVVNYTE SSDDEKSSPE TPPQESTCVD DIHPRFLVAL ISRRSRHRAG MRYKRRGVDK NGNVANYVET EQLIHVHNHT LSFVQTRGSV PVFWSQVGYR YNPRPRLDRS EKETVAYFCA HFEEQLNIYK KQVIINLVDQ AGREKIIGDA YLKQVLLFNN SHLTYVSFDF HEHCRGMKFE NVQTLTDAIY DIILDMKWCW VDEAGVICKQ EGIFRVNCMD CLDRTNVVQA AIARVVMEQQ LKKLGVMPPE QPLPVKCNRI YQIMWANNGD SISRQYAGTA ALKGDFTRTG ERKLAGVMKD GVNSANRYYL NRFKDAYRQA VIDLMQGIPV TEDLYSIFTK EKEHEALHKE NQRSHQELIS QLLQSYMKLL LPDDEKFHGG WALIDCDPSL IDATHRDVDV LLLLSNSAYY VAYYDDEVDK VNQYQRLSLE NLEKIEIGPE PTLFGKPKFS CMRLHYRYKE ASGYFHTLRA VMRNPEEDGK DTLQCIAEML QITKQAMGSD LPIIEKKLER KSSKPHEDII GIRSQNQGSL AQGKNFLMSK FSSLNQKVKQ TKSNVNIGNL RKLGNFTKPE MKVNFLKPNL KVNLWKSDSS LETMENTGVM DKVQAESDGD MSSDNDSYHS DEFLTNSKSD EDRQLANSLE SVGPIDYVLP SCGIIASAPR LGSRSQSLSS TDSSVHAPSE ITVAHGSGLG KGQESPLKKS PSAGDVHILT GFAKPMDIYC HRFVQDAQNK VTHLSETRSV SQQASQERNQ MTNQVSNETQ SESTEQTPSR PSQLDVSLSA TGPQFLSVEP AHSVASQKTP TSASSMLELE TGLHVTPSPS ESSSSRAVSP FAKIRSSMVQ VASITQAGLT HGINFAVSKV QKSPPEPEII NQVQQNELKK MFIQCQTRII QI //