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Protein

Phosphatidylinositide phosphatase SAC2

Gene

INPP5F

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a sequential dephosphorylation of phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of inositol, thus playing an important role in the endocytic recycling (PubMed:25869669). Regulator of TF:TFRC and integrins recycling pathway, is also involved in cell migration mechanisms (PubMed:25869669). Modulates AKT/GSK3B pathway by decreasing AKT and GSK3B phosphorylation (PubMed:17322895). Negatively regulates STAT3 signaling pathway through inhibition of STAT3 phosphorylation and translocation to the nucleus (PubMed:25476455). Functionally important modulator of cardiac myocyte size and of the cardiac response to stress (By similarity). May play a role as negative regulator of axon regeneration after central nervous system injuries (By similarity).By similarity3 Publications

Catalytic activityi

Myo-inositol phosphate + H2O = myo-inositol + phosphate.2 Publications

Kineticsi

  1. KM=14.3 µM for PtdIns(4,5)P2 (at pH 6.0)1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Enzyme and pathway databases

    BioCyciMetaCyc:HS12255-MONOMER.
    ZFISH:HS12255-MONOMER.
    ReactomeiR-HSA-1660516. Synthesis of PIPs at the early endosome membrane.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositide phosphatase SAC2Curated (EC:3.1.3.252 Publications)
    Alternative name(s):
    Inositol polyphosphate 5-phosphatase FImported
    Sac domain-containing inositol phosphatase 2
    Sac domain-containing phosphoinositide 4-phosphatase 22 Publications
    Short name:
    hSAC2
    Gene namesi
    Name:INPP5FImported
    Synonyms:KIAA0966, SAC2
    ORF Names:MSTP007, MSTP047
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:17054. INPP5F.

    Subcellular locationi

    • Membraneclathrin-coated pit 1 Publication
    • Early endosome 1 Publication
    • Recycling endosome 1 Publication

    • Note: Also found on macropinosomes.By similarity

    GO - Cellular componenti

    • axon Source: Ensembl
    • clathrin-coated endocytic vesicle Source: UniProtKB
    • clathrin-coated pit Source: UniProtKB-SubCell
    • dendrite Source: Ensembl
    • early endosome Source: UniProtKB
    • early endosome membrane Source: Reactome
    • neuronal cell body Source: Ensembl
    • recycling endosome Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Coated pit, Endosome, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi458C → S: Loss of inositol 4-phosphatase activity. Alters TFRC distribution and delays TF recycling. 1 Publication1

    Organism-specific databases

    DisGeNETi22876.
    OpenTargetsiENSG00000198825.
    PharmGKBiPA134927878.

    Polymorphism and mutation databases

    BioMutaiINPP5F.
    DMDMi187611527.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003316211 – 1132Phosphatidylinositide phosphatase SAC2Add BLAST1132

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei827PhosphoserineBy similarity1
    Modified residuei830PhosphoserineBy similarity1
    Modified residuei878PhosphoserineBy similarity1
    Modified residuei881PhosphoserineBy similarity1
    Modified residuei907PhosphoserineCombined sources1
    Modified residuei910PhosphoserineBy similarity1
    Modified residuei1103PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ9Y2H2.
    PaxDbiQ9Y2H2.
    PeptideAtlasiQ9Y2H2.
    PRIDEiQ9Y2H2.

    PTM databases

    DEPODiQ9Y2H2.
    iPTMnetiQ9Y2H2.
    PhosphoSitePlusiQ9Y2H2.
    SwissPalmiQ9Y2H2.

    Expressioni

    Tissue specificityi

    Ubiquitous (PubMed:11274189). Highly expressed in brain (PubMed:26203138).2 Publications

    Gene expression databases

    BgeeiENSG00000198825.
    CleanExiHS_INPP5F.
    ExpressionAtlasiQ9Y2H2. baseline and differential.
    GenevisibleiQ9Y2H2. HS.

    Organism-specific databases

    HPAiHPA035297.
    HPA042605.

    Interactioni

    Subunit structurei

    Homodimer (PubMed:25869669). Interacts with OCRL and RAB5A (PubMed:25869668). Interacts with INPP5B and INPP4A (PubMed:25869668). Interacts with STAT3; the interaction is independent of STAT3 'TYR-705' phosphorylation status (PubMed:25476455).By similarity3 Publications

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi116543. 1 interactor.
    IntActiQ9Y2H2. 1 interactor.
    STRINGi9606.ENSP00000354519.

    Structurei

    Secondary structure

    11132
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi595 – 610Combined sources16
    Beta strandi617 – 625Combined sources9
    Beta strandi639 – 654Combined sources16
    Beta strandi656 – 668Combined sources13
    Helixi669 – 671Combined sources3
    Beta strandi672 – 679Combined sources8
    Beta strandi683 – 685Combined sources3
    Beta strandi689 – 698Combined sources10
    Beta strandi701 – 710Combined sources10
    Helixi720 – 736Combined sources17
    Beta strandi743 – 746Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4XUUX-ray2.62A/B/C/D593-760[»]
    ProteinModelPortaliQ9Y2H2.
    SMRiQ9Y2H2.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini167 – 518SACPROSITE-ProRule annotationAdd BLAST352
    Domaini593 – 760hSac2PROSITE-ProRule annotationAdd BLAST168

    Sequence similaritiesi

    Contains 1 hSac2 domain.PROSITE-ProRule annotation
    Contains 1 SAC domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG1890. Eukaryota.
    COG5329. LUCA.
    GeneTreeiENSGT00530000063393.
    HOGENOMiHOG000139946.
    HOVERGENiHBG095361.
    InParanoidiQ9Y2H2.
    OMAiENTGVMD.
    OrthoDBiEOG091G059J.
    PhylomeDBiQ9Y2H2.
    TreeFamiTF313543.

    Family and domain databases

    InterProiIPR022158. Inositol_phosphatase.
    IPR002013. SAC_dom.
    [Graphical view]
    PfamiPF12456. hSac2. 1 hit.
    PF02383. Syja_N. 1 hit.
    [Graphical view]
    PROSITEiPS51791. HSAC2. 1 hit.
    PS50275. SAC. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9Y2H2-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MELFQAKDHY ILQQGERALW CSRRDGGLQL RPATDLLLAW NPICLGLVEG
    60 70 80 90 100
    VIGKIQLHSD LPWWLILIRQ KALVGKLPGD HEVCKVTKIA VLSLSEMEPQ
    110 120 130 140 150
    DLELELCKKH HFGINKPEKI IPSPDDSKFL LKTFTHIKSN VSAPNKKKVK
    160 170 180 190 200
    ESKEKEKLER RLLEELLKMF MDSESFYYSL TYDLTNSVQR QSTGERDGRP
    210 220 230 240 250
    LWQKVDDRFF WNKYMIQDLT EIGTPDVDFW IIPMIQGFVQ IEELVVNYTE
    260 270 280 290 300
    SSDDEKSSPE TPPQESTCVD DIHPRFLVAL ISRRSRHRAG MRYKRRGVDK
    310 320 330 340 350
    NGNVANYVET EQLIHVHNHT LSFVQTRGSV PVFWSQVGYR YNPRPRLDRS
    360 370 380 390 400
    EKETVAYFCA HFEEQLNIYK KQVIINLVDQ AGREKIIGDA YLKQVLLFNN
    410 420 430 440 450
    SHLTYVSFDF HEHCRGMKFE NVQTLTDAIY DIILDMKWCW VDEAGVICKQ
    460 470 480 490 500
    EGIFRVNCMD CLDRTNVVQA AIARVVMEQQ LKKLGVMPPE QPLPVKCNRI
    510 520 530 540 550
    YQIMWANNGD SISRQYAGTA ALKGDFTRTG ERKLAGVMKD GVNSANRYYL
    560 570 580 590 600
    NRFKDAYRQA VIDLMQGIPV TEDLYSIFTK EKEHEALHKE NQRSHQELIS
    610 620 630 640 650
    QLLQSYMKLL LPDDEKFHGG WALIDCDPSL IDATHRDVDV LLLLSNSAYY
    660 670 680 690 700
    VAYYDDEVDK VNQYQRLSLE NLEKIEIGPE PTLFGKPKFS CMRLHYRYKE
    710 720 730 740 750
    ASGYFHTLRA VMRNPEEDGK DTLQCIAEML QITKQAMGSD LPIIEKKLER
    760 770 780 790 800
    KSSKPHEDII GIRSQNQGSL AQGKNFLMSK FSSLNQKVKQ TKSNVNIGNL
    810 820 830 840 850
    RKLGNFTKPE MKVNFLKPNL KVNLWKSDSS LETMENTGVM DKVQAESDGD
    860 870 880 890 900
    MSSDNDSYHS DEFLTNSKSD EDRQLANSLE SVGPIDYVLP SCGIIASAPR
    910 920 930 940 950
    LGSRSQSLSS TDSSVHAPSE ITVAHGSGLG KGQESPLKKS PSAGDVHILT
    960 970 980 990 1000
    GFAKPMDIYC HRFVQDAQNK VTHLSETRSV SQQASQERNQ MTNQVSNETQ
    1010 1020 1030 1040 1050
    SESTEQTPSR PSQLDVSLSA TGPQFLSVEP AHSVASQKTP TSASSMLELE
    1060 1070 1080 1090 1100
    TGLHVTPSPS ESSSSRAVSP FAKIRSSMVQ VASITQAGLT HGINFAVSKV
    1110 1120 1130
    QKSPPEPEII NQVQQNELKK MFIQCQTRII QI
    Length:1,132
    Mass (Da):128,407
    Last modified:April 29, 2008 - v3
    Checksum:i853719FC0AD455CD
    GO
    Isoform 2 (identifier: Q9Y2H2-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         373-375: VII → QQK
         376-1132: Missing.

    Show »
    Length:375
    Mass (Da):43,817
    Checksum:iE9A76393F10C6CC3
    GO
    Isoform 3 (identifier: Q9Y2H2-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         206-219: DDRFFWNKYMIQDL → PLTARRAGFALGKK
         220-1132: Missing.

    Show »
    Length:219
    Mass (Da):25,174
    Checksum:i8AAA498682414245
    GO
    Isoform 4 (identifier: Q9Y2H2-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-19: MELFQAKDHYILQQGERAL → MCHDVIFMAWLKQQFSECT
         20-629: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:522
    Mass (Da):57,800
    Checksum:i8A15030B00C8E9A1
    GO

    Sequence cautioni

    The sequence BAA76810 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti386I → V in AAI11494 (PubMed:15489334).Curated1
    Sequence conflicti654Y → N in BAG52363 (PubMed:14702039).Curated1
    Sequence conflicti1008P → L in BAG52363 (PubMed:14702039).Curated1
    Sequence conflicti1019S → P in BAG52363 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_042907453I → V.Corresponds to variant rs3736822dbSNPEnsembl.1
    Natural variantiVAR_042908997N → D.2 PublicationsCorresponds to variant rs3188055dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0463661 – 19MELFQ…GERAL → MCHDVIFMAWLKQQFSECT in isoform 4. 1 PublicationAdd BLAST19
    Alternative sequenceiVSP_04636720 – 629Missing in isoform 4. 1 PublicationAdd BLAST610
    Alternative sequenceiVSP_033266206 – 219DDRFF…MIQDL → PLTARRAGFALGKK in isoform 3. 1 PublicationAdd BLAST14
    Alternative sequenceiVSP_033267220 – 1132Missing in isoform 3. 1 PublicationAdd BLAST913
    Alternative sequenceiVSP_033268373 – 375VII → QQK in isoform 2. 1 Publication3
    Alternative sequenceiVSP_033269376 – 1132Missing in isoform 2. 1 PublicationAdd BLAST757

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB023183 mRNA. Translation: BAA76810.2. Different initiation.
    AK091448 mRNA. Translation: BAG52363.1.
    AC027672 Genomic DNA. No translation available.
    AL133461, AL158014 Genomic DNA. Translation: CAH72974.1.
    AL158014, AL133461 Genomic DNA. Translation: CAI16957.1.
    CH471066 Genomic DNA. Translation: EAW49379.1.
    CH471066 Genomic DNA. Translation: EAW49380.1.
    CH471066 Genomic DNA. Translation: EAW49381.1.
    BC052367 mRNA. Translation: AAH52367.1.
    BC067820 mRNA. Translation: AAH67820.1.
    BC082755 mRNA. Translation: AAH82755.1.
    BC111493 mRNA. Translation: AAI11494.1.
    AL137528 mRNA. Translation: CAB70792.1.
    AF113227 mRNA. Translation: AAG39298.1.
    AF109361 mRNA. Translation: AAQ13509.1.
    CCDSiCCDS58098.1. [Q9Y2H2-4]
    CCDS7616.1. [Q9Y2H2-1]
    CCDS81513.1. [Q9Y2H2-3]
    PIRiT46372.
    RefSeqiNP_001230123.1. NM_001243194.1. [Q9Y2H2-4]
    NP_001230124.1. NM_001243195.1. [Q9Y2H2-3]
    NP_055752.1. NM_014937.3. [Q9Y2H2-1]
    UniGeneiHs.369755.

    Genome annotation databases

    EnsembliENST00000361976; ENSP00000354519; ENSG00000198825. [Q9Y2H2-1]
    ENST00000369080; ENSP00000358076; ENSG00000198825. [Q9Y2H2-4]
    ENST00000369081; ENSP00000489864; ENSG00000198825. [Q9Y2H2-3]
    GeneIDi22876.
    KEGGihsa:22876.
    UCSCiuc001leo.4. human. [Q9Y2H2-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB023183 mRNA. Translation: BAA76810.2. Different initiation.
    AK091448 mRNA. Translation: BAG52363.1.
    AC027672 Genomic DNA. No translation available.
    AL133461, AL158014 Genomic DNA. Translation: CAH72974.1.
    AL158014, AL133461 Genomic DNA. Translation: CAI16957.1.
    CH471066 Genomic DNA. Translation: EAW49379.1.
    CH471066 Genomic DNA. Translation: EAW49380.1.
    CH471066 Genomic DNA. Translation: EAW49381.1.
    BC052367 mRNA. Translation: AAH52367.1.
    BC067820 mRNA. Translation: AAH67820.1.
    BC082755 mRNA. Translation: AAH82755.1.
    BC111493 mRNA. Translation: AAI11494.1.
    AL137528 mRNA. Translation: CAB70792.1.
    AF113227 mRNA. Translation: AAG39298.1.
    AF109361 mRNA. Translation: AAQ13509.1.
    CCDSiCCDS58098.1. [Q9Y2H2-4]
    CCDS7616.1. [Q9Y2H2-1]
    CCDS81513.1. [Q9Y2H2-3]
    PIRiT46372.
    RefSeqiNP_001230123.1. NM_001243194.1. [Q9Y2H2-4]
    NP_001230124.1. NM_001243195.1. [Q9Y2H2-3]
    NP_055752.1. NM_014937.3. [Q9Y2H2-1]
    UniGeneiHs.369755.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4XUUX-ray2.62A/B/C/D593-760[»]
    ProteinModelPortaliQ9Y2H2.
    SMRiQ9Y2H2.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116543. 1 interactor.
    IntActiQ9Y2H2. 1 interactor.
    STRINGi9606.ENSP00000354519.

    PTM databases

    DEPODiQ9Y2H2.
    iPTMnetiQ9Y2H2.
    PhosphoSitePlusiQ9Y2H2.
    SwissPalmiQ9Y2H2.

    Polymorphism and mutation databases

    BioMutaiINPP5F.
    DMDMi187611527.

    Proteomic databases

    EPDiQ9Y2H2.
    PaxDbiQ9Y2H2.
    PeptideAtlasiQ9Y2H2.
    PRIDEiQ9Y2H2.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000361976; ENSP00000354519; ENSG00000198825. [Q9Y2H2-1]
    ENST00000369080; ENSP00000358076; ENSG00000198825. [Q9Y2H2-4]
    ENST00000369081; ENSP00000489864; ENSG00000198825. [Q9Y2H2-3]
    GeneIDi22876.
    KEGGihsa:22876.
    UCSCiuc001leo.4. human. [Q9Y2H2-1]

    Organism-specific databases

    CTDi22876.
    DisGeNETi22876.
    GeneCardsiINPP5F.
    HGNCiHGNC:17054. INPP5F.
    HPAiHPA035297.
    HPA042605.
    MIMi609389. gene.
    neXtProtiNX_Q9Y2H2.
    OpenTargetsiENSG00000198825.
    PharmGKBiPA134927878.
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1890. Eukaryota.
    COG5329. LUCA.
    GeneTreeiENSGT00530000063393.
    HOGENOMiHOG000139946.
    HOVERGENiHBG095361.
    InParanoidiQ9Y2H2.
    OMAiENTGVMD.
    OrthoDBiEOG091G059J.
    PhylomeDBiQ9Y2H2.
    TreeFamiTF313543.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS12255-MONOMER.
    ZFISH:HS12255-MONOMER.
    ReactomeiR-HSA-1660516. Synthesis of PIPs at the early endosome membrane.

    Miscellaneous databases

    ChiTaRSiINPP5F. human.
    GenomeRNAii22876.
    PROiQ9Y2H2.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000198825.
    CleanExiHS_INPP5F.
    ExpressionAtlasiQ9Y2H2. baseline and differential.
    GenevisibleiQ9Y2H2. HS.

    Family and domain databases

    InterProiIPR022158. Inositol_phosphatase.
    IPR002013. SAC_dom.
    [Graphical view]
    PfamiPF12456. hSac2. 1 hit.
    PF02383. Syja_N. 1 hit.
    [Graphical view]
    PROSITEiPS51791. HSAC2. 1 hit.
    PS50275. SAC. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSAC2_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y2H2
    Secondary accession number(s): B3KRF1
    , D3DRD1, Q2T9J4, Q5W135, Q5W136, Q6NVY2, Q86U97, Q9H3D9, Q9NT51
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 29, 2008
    Last sequence update: April 29, 2008
    Last modified: November 2, 2016
    This is version 117 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Caution

    INPP5F has been initially described as an inositol polyphosphate 5-phosphatase.1 Publication

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.