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Protein

PH domain leucine-rich repeat-containing protein phosphatase 1

Gene

PHLPP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity).By similarity6 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mn2+By similarityNote: Binds 2 manganese ions per subunit (By similarity). Mn2+ is inhibitory below pH 8 and activating above pH 8 (PubMed:24892992).By similarity1 Publication

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Insensitive to okadaic acid (PubMed:15808505). Deubiquitination by WDR48-USP12 complex positively regulates PHLPP1 stability (PubMed:24145035).2 Publications

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=1.5 mM for p-nitrophenyl phosphate1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi1210Manganese 1By similarity1
    Metal bindingi1210Manganese 2By similarity1
    Metal bindingi1211Manganese 1; via carbonyl oxygenBy similarity1
    Metal bindingi1374Manganese 2By similarity1
    Metal bindingi1413Manganese 2By similarity1

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    • metal ion binding Source: UniProtKB-KW
    • protein serine/threonine phosphatase activity Source: GO_Central

    GO - Biological processi

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionHydrolase, Protein phosphatase
    Biological processApoptosis
    LigandManganese, Metal-binding

    Enzyme and pathway databases

    Reactome - a knowledgebase of biological pathways and processes

    More...
    Reactomei
    R-HSA-199418 Negative regulation of the PI3K/AKT network

    SIGNOR Signaling Network Open Resource

    More...
    SIGNORi
    O60346

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    PH domain leucine-rich repeat-containing protein phosphatase 1 (EC:3.1.3.16)
    Alternative name(s):
    Pleckstrin homology domain-containing family E member 1
    Short name:
    PH domain-containing family E member 1
    Suprachiasmatic nucleus circadian oscillatory protein
    Short name:
    hSCOP
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    Name:PHLPP1
    Synonyms:KIAA0606, PHLPP, PLEKHE1, SCOP
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
    • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 18

    Organism-specific databases

    Eukaryotic Pathogen Database Resources

    More...
    EuPathDBi
    HostDB:ENSG00000081913.13

    Human Gene Nomenclature Database

    More...
    HGNCi
    HGNC:20610 PHLPP1

    Online Mendelian Inheritance in Man (OMIM)

    More...
    MIMi
    609396 gene

    neXtProt; the human protein knowledge platform

    More...
    neXtProti
    NX_O60346

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi1715 – 1717Missing : Loss of function in vivo, but does not abolishes intrinsic phosphatase activity. 1 Publication3

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    DisGeNET

    More...
    DisGeNETi
    23239

    Open Targets

    More...
    OpenTargetsi
    ENSG00000081913

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...
    PharmGKBi
    PA165429055

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...
    ChEMBLi
    CHEMBL3414405

    Polymorphism and mutation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...
    BioMutai
    PHLPP1

    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000577811 – 1717PH domain leucine-rich repeat-containing protein phosphatase 1Add BLAST1717

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1N-acetylmethionineCombined sources1
    Modified residuei317PhosphoserineCombined sources1
    Modified residuei412PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...
    EPDi
    O60346

    jPOST - Japan Proteome Standard Repository/Database

    More...
    jPOSTi
    O60346

    MaxQB - The MaxQuant DataBase

    More...
    MaxQBi
    O60346

    PaxDb, a database of protein abundance averages across all three domains of life

    More...
    PaxDbi
    O60346

    PeptideAtlas

    More...
    PeptideAtlasi
    O60346

    PRoteomics IDEntifications database

    More...
    PRIDEi
    O60346

    ProteomicsDB human proteome resource

    More...
    ProteomicsDBi
    49376

    PTM databases

    DEPOD human dephosphorylation database

    More...
    DEPODi
    O60346

    iPTMnet integrated resource for PTMs in systems biology context

    More...
    iPTMneti
    O60346

    Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

    More...
    PhosphoSitePlusi
    O60346

    <p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

    <p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

    In colorectal cancer tissue, expression is highest in the surface epithelium of normal colonic mucosa adjacent to the cancer tissue but is largely excluded from the crypt bases. Expression is lost or significantly decreased in 78% of tested tumors (at protein level). Ubiquitously expressed in non-cancerous tissues.2 Publications

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...
    Bgeei
    ENSG00000081913 Expressed in 216 organ(s), highest expression level in brain

    CleanEx database of gene expression profiles

    More...
    CleanExi
    HS_PHLPP

    ExpressionAtlas, Differential and Baseline Expression

    More...
    ExpressionAtlasi
    O60346 baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...
    Genevisiblei
    O60346 HS

    Organism-specific databases

    Human Protein Atlas

    More...
    HPAi
    HPA020200

    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats (By similarity). Interacts with AKT2, AKT3, PRKCB isoform beta-II, STK4, RPS6KB1, RAF1 (PubMed:17386267, PubMed:18162466, PubMed:19732725, PubMed:21986499, PubMed:24530606). Isoform 1 (predominantly) and isoform 2 interact with BRAP (PubMed:25820252). Interacts with FKBP5; FKBP5 acts as a scaffold for PHLPP1 and Akt (PubMed:19732725). Interacts with SCRIB; SCRIB acts as a scaffold for PHLPP1 and Akt (PubMed:21701506). Interacts with SLC9A3R1; SLC9A3R1 scaffolds a heterotrimeric complex with PTEN at the plasma membrane (PubMed:21804599). Interacts with WDR48 and USP12 (PubMed:24145035).By similarity10 Publications

    <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGrid)

    More...
    BioGridi
    116843, 50 interactors

    CORUM comprehensive resource of mammalian protein complexes

    More...
    CORUMi
    O60346

    Protein interaction database and analysis system

    More...
    IntActi
    O60346, 32 interactors

    Molecular INTeraction database

    More...
    MINTi
    O60346

    STRING: functional protein association networks

    More...
    STRINGi
    9606.ENSP00000262719

    Chemistry databases

    BindingDB database of measured binding affinities

    More...
    BindingDBi
    O60346

    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    3D structure databases

    Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

    More...
    ProteinModelPortali
    O60346

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...
    MobiDBi
    Search...

    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini536 – 636PHPROSITE-ProRule annotationAdd BLAST101
    <p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati638 – 659LRR 1Add BLAST22
    Repeati661 – 682LRR 2Add BLAST22
    Repeati692 – 712LRR 3Add BLAST21
    Repeati715 – 736LRR 4Add BLAST22
    Repeati738 – 760LRR 5Add BLAST23
    Repeati761 – 783LRR 6Add BLAST23
    Repeati784 – 804LRR 7Add BLAST21
    Repeati808 – 831LRR 8Add BLAST24
    Repeati832 – 853LRR 9Add BLAST22
    Repeati873 – 894LRR 10Add BLAST22
    Repeati895 – 916LRR 11Add BLAST22
    Repeati918 – 939LRR 12Add BLAST22
    Repeati941 – 962LRR 13Add BLAST22
    Repeati963 – 984LRR 14Add BLAST22
    Repeati987 – 1008LRR 15Add BLAST22
    Repeati1013 – 1033LRR 16Add BLAST21
    Repeati1037 – 1058LRR 17Add BLAST22
    Repeati1061 – 1082LRR 18Add BLAST22
    Repeati1084 – 1105LRR 19Add BLAST22
    Repeati1106 – 1127LRR 20Add BLAST22
    Repeati1129 – 1150LRR 21Add BLAST22
    Domaini1175 – 1422PPM-type phosphatasePROSITE-ProRule annotationAdd BLAST248

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1076 – 1205Interaction with SLC9A3R11 PublicationAdd BLAST130

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi1715 – 1717PDZ-binding; required for interaction with SLC9A3R11 Publication3

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi4 – 7Poly-Ala4
    Compositional biasi21 – 45Poly-AlaAdd BLAST25
    Compositional biasi132 – 137Poly-Ala6
    Compositional biasi138 – 144Poly-Ser7
    Compositional biasi145 – 148Poly-Ala4
    Compositional biasi254 – 257Poly-Ala4
    Compositional biasi463 – 469Poly-Pro7
    Compositional biasi1682 – 1689Poly-Gln8

    <p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

    The PH domain is required for interaction with PRKCB and its dephosphorylation.

    Keywords - Domaini

    Leucine-rich repeat, Repeat

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...
    eggNOGi
    KOG0619 Eukaryota
    COG0631 LUCA
    COG4886 LUCA

    Ensembl GeneTree

    More...
    GeneTreei
    ENSGT00940000158137

    InParanoid: Eukaryotic Ortholog Groups

    More...
    InParanoidi
    O60346

    KEGG Orthology (KO)

    More...
    KOi
    K16340

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    FTNGSRV

    Database of Orthologous Groups

    More...
    OrthoDBi
    172467at2759

    Database for complete collections of gene phylogenies

    More...
    PhylomeDBi
    O60346

    TreeFam database of animal gene trees

    More...
    TreeFami
    TF315993

    Family and domain databases

    Conserved Domains Database

    More...
    CDDi
    cd00143 PP2Cc, 1 hit

    Gene3D Structural and Functional Annotation of Protein Families

    More...
    Gene3Di
    2.30.29.30, 1 hit
    3.60.40.10, 1 hit
    3.80.10.10, 3 hits

    Integrated resource of protein families, domains and functional sites

    More...
    InterProi
    View protein in InterPro
    IPR001611 Leu-rich_rpt
    IPR003591 Leu-rich_rpt_typical-subtyp
    IPR032675 LRR_dom_sf
    IPR011993 PH-like_dom_sf
    IPR001849 PH_domain
    IPR036457 PPM-type_dom_sf
    IPR001932 PPM-type_phosphatase_dom

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF00560 LRR_1, 1 hit
    PF13516 LRR_6, 1 hit
    PF13855 LRR_8, 2 hits
    PF00169 PH, 1 hit
    PF00481 PP2C, 1 hit

    Simple Modular Architecture Research Tool; a protein domain database

    More...
    SMARTi
    View protein in SMART
    SM00369 LRR_TYP, 10 hits
    SM00332 PP2Cc, 1 hit

    Superfamily database of structural and functional annotation

    More...
    SUPFAMi
    SSF81606 SSF81606, 1 hit

    PROSITE; a protein domain and family database

    More...
    PROSITEi
    View protein in PROSITE
    PS51450 LRR, 17 hits
    PS50003 PH_DOMAIN, 1 hit
    PS51746 PPM_2, 1 hit

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

    Isoform 1 (identifier: O60346-1) [UniParc]FASTAAdd to basket
    Also known as: beta

    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
    MEPAAAATVQ RLPELGREDR ASAPAAAAAA AAAAAAAAAA LAAAAGGGRS
    60 70 80 90 100
    PEPALTPAAP SGGNGSGSGA REEAPGEAPP GPLPGRAGGA GRRRRRGAPQ
    110 120 130 140 150
    PIAGGAAPVP GAGGGANSLL LRRGRLKRNL SAAAAAASSS SSSSAAAASH
    160 170 180 190 200
    SPGAAGLPAS CSASASLCTR SLDRKTLLLK HRQTLQLQPS DRDWVRHQLQ
    210 220 230 240 250
    RGCVHVFDRH MASTYLRPVL CTLDTTAGEV AARLLQLGHK GGGVVKVLGQ
    260 270 280 290 300
    GPGAAAAREP AEPPPEAGPR LAPPEPRDSE VPPARSAPGA FGGPPRAPPA
    310 320 330 340 350
    DLPLPVGGPG GWSRRASPAP SDSSPGEPFV GGPVSSPRAP RPVVSDTESF
    360 370 380 390 400
    SLSPSAESVS DRLDPYSSGG GSSSSSEELE ADAASAPTGV PGQPRRPGHP
    410 420 430 440 450
    AQPLPLPQTA SSPQPQQKAP RAIDSPGGAV REGSCEEKAA AAVAPGGLQS
    460 470 480 490 500
    TPGRSGVTAE KAPPPPPPPT LYVQLHGETT RRLEAEEKPL QIQNDYLFQL
    510 520 530 540 550
    GFGELWRVQE EGMDSEIGCL IRFYAGKPHS TGSSERIQLS GMYNVRKGKM
    560 570 580 590 600
    QLPVNRWTRR QVILCGTCLI VSSVKDSLTG KMHVLPLIGG KVEEVKKHQH
    610 620 630 640 650
    CLAFSSSGPQ SQTYYICFDT FTEYLRWLRQ VSKVASQRIS SVDLSCCSLE
    660 670 680 690 700
    HLPANLFYSQ DLTHLNLKQN FLRQNPSLPA ARGLNELQRF TKLKSLNLSN
    710 720 730 740 750
    NHLGDFPLAV CSIPTLAELN VSCNALRSVP AAVGVMHNLQ TFLLDGNFLQ
    760 770 780 790 800
    SLPAELENMK QLSYLGLSFN EFTDIPEVLE KLTAVDKLCM SGNCVETLRL
    810 820 830 840 850
    QALRKMPHIK HVDLRLNVIR KLIADEVDFL QHVTQLDLRD NKLGDLDAMI
    860 870 880 890 900
    FNNIEVLHCE RNQLVTLDIC GYFLKALYAS SNELVQLDVY PVPNYLSYMD
    910 920 930 940 950
    VSRNRLENVP EWVCESRKLE VLDIGHNQIC ELPARLFCNS SLRKLLAGHN
    960 970 980 990 1000
    QLARLPERLE RTSVEVLDVQ HNQLLELPPN LLMKADSLRF LNASANKLES
    1010 1020 1030 1040 1050
    LPPATLSEET NSILQELYLT NNSLTDKCVP LLTGHPHLKI LHMAYNRLQS
    1060 1070 1080 1090 1100
    FPASKMAKLE ELEEIDLSGN KLKAIPTTIM NCRRMHTVIA HSNCIEVFPE
    1110 1120 1130 1140 1150
    VMQLPEIKCV DLSCNELSEV TLPENLPPKL QELDLTGNPR LVLDHKTLEL
    1160 1170 1180 1190 1200
    LNNIRCFKID QPSTGDASGA PAVWSHGYTE ASGVKNKLCV AALSVNNFCD
    1210 1220 1230 1240 1250
    NREALYGVFD GDRNVEVPYL LQCTMSDILA EELQKTKNEE EYMVNTFIVM
    1260 1270 1280 1290 1300
    QRKLGTAGQK LGGAAVLCHI KHDPVDPGGS FTLTSANVGK CQTVLCRNGK
    1310 1320 1330 1340 1350
    PLPLSRSYIM SCEEELKRIK QHKAIITEDG KVNGVTESTR ILGYTFLHPS
    1360 1370 1380 1390 1400
    VVPRPHVQSV LLTPQDEFFI LGSKGLWDSL SVEEAVEAVR NVPDALAAAK
    1410 1420 1430 1440 1450
    KLCTLAQSYG CHDSISAVVV QLSVTEDSFC CCELSAGGAV PPPSPGIFPP
    1460 1470 1480 1490 1500
    SVNMVIKDRP SDGLGVPSSS SGMASEISSE LSTSEMSSEV GSTASDEPPP
    1510 1520 1530 1540 1550
    GALSENSPAY PSEQRCMLHP ICLSNSFQRQ LSSATFSSAF SDNGLDSDDE
    1560 1570 1580 1590 1600
    EPIEGVFTNG SRVEVEVDIH CSRAKEKEKQ QHLLQVPAEA SDEGIVISAN
    1610 1620 1630 1640 1650
    EDEPGLPRKA DFSAVGTIGR RRANGSVAPQ ERSHNVIEVA TDAPLRKPGG
    1660 1670 1680 1690 1700
    YFAAPAQPDP DDQFIIPPEL EEEVKEIMKH HQEQQQQQQP PPPPQLQPQL
    1710
    PRHYQLDQLP DYYDTPL
    Length:1,717
    Mass (Da):184,672
    Last modified:June 7, 2005 - v3
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iA4AB53F334EA8AB6
    GO
    Isoform 2 (identifier: O60346-2) [UniParc]FASTAAdd to basket
    Also known as: alpha

    The sequence of this isoform differs from the canonical sequence as follows:
         1-512: Missing.

    Show »
    Length:1,205
    Mass (Da):133,565
    Checksum:iCDBECB2FDA9C7064
    GO

    <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    K7EP91K7EP91_HUMAN
    PH domain leucine-rich repeat-conta...
    PHLPP1
    197Annotation score:

    Annotation score:1 out of 5

    <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

    <p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

    The sequence AAH14927 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence AAH82244 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
    The sequence AAI26278 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence BAA91980 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti691T → A in BAA91980 (PubMed:14702039).Curated1
    Sequence conflicti1062L → F in AAH47653 (PubMed:15489334).Curated1
    Sequence conflicti1083R → S in BAA25532 (PubMed:9628581).Curated1
    Sequence conflicti1227D → V in BAA91980 (PubMed:14702039).Curated1
    Sequence conflicti1490V → M in AAH47653 (PubMed:15489334).Curated1
    Sequence conflicti1580Missing in AAH63519 (PubMed:15489334).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_0567251118S → T. Corresponds to variant dbSNP:rs9950585Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0578091 – 512Missing in isoform 2. Add BLAST512

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...
    EMBLi

    GenBank nucleotide sequence database

    More...
    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...
    DDBJi
    Links Updated
    AC015989 Genomic DNA No translation available.
    AC022046 Genomic DNA No translation available.
    AC027553 Genomic DNA No translation available.
    AB011178 mRNA Translation: BAA25532.2
    BC010706 mRNA Translation: AAH10706.1
    BC014927 mRNA Translation: AAH14927.3 Different initiation.
    BC047653 mRNA Translation: AAH47653.1
    BC063519 mRNA Translation: AAH63519.1
    BC082244 mRNA Translation: AAH82244.1 Sequence problems.
    BC126277 mRNA Translation: AAI26278.1 Different initiation.
    AK001924 mRNA Translation: BAA91980.1 Different initiation.

    The Consensus CDS (CCDS) project

    More...
    CCDSi
    CCDS45881.2 [O60346-1]

    Protein sequence database of the Protein Information Resource

    More...
    PIRi
    T00258

    NCBI Reference Sequences

    More...
    RefSeqi
    NP_919431.2, NM_194449.3 [O60346-1]

    UniGene gene-oriented nucleotide sequence clusters

    More...
    UniGenei
    Hs.465337

    Genome annotation databases

    Ensembl eukaryotic genome annotation project

    More...
    Ensembli
    ENST00000262719; ENSP00000262719; ENSG00000081913 [O60346-1]

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    23239

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    hsa:23239

    UCSC genome browser

    More...
    UCSCi
    uc021ule.2 human [O60346-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

    <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

    <p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AC015989 Genomic DNA No translation available.
    AC022046 Genomic DNA No translation available.
    AC027553 Genomic DNA No translation available.
    AB011178 mRNA Translation: BAA25532.2
    BC010706 mRNA Translation: AAH10706.1
    BC014927 mRNA Translation: AAH14927.3 Different initiation.
    BC047653 mRNA Translation: AAH47653.1
    BC063519 mRNA Translation: AAH63519.1
    BC082244 mRNA Translation: AAH82244.1 Sequence problems.
    BC126277 mRNA Translation: AAI26278.1 Different initiation.
    AK001924 mRNA Translation: BAA91980.1 Different initiation.
    CCDSiCCDS45881.2 [O60346-1]
    PIRiT00258
    RefSeqiNP_919431.2, NM_194449.3 [O60346-1]
    UniGeneiHs.465337

    3D structure databases

    ProteinModelPortaliO60346
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116843, 50 interactors
    CORUMiO60346
    IntActiO60346, 32 interactors
    MINTiO60346
    STRINGi9606.ENSP00000262719

    Chemistry databases

    BindingDBiO60346
    ChEMBLiCHEMBL3414405

    PTM databases

    DEPODiO60346
    iPTMnetiO60346
    PhosphoSitePlusiO60346

    Polymorphism and mutation databases

    BioMutaiPHLPP1

    Proteomic databases

    EPDiO60346
    jPOSTiO60346
    MaxQBiO60346
    PaxDbiO60346
    PeptideAtlasiO60346
    PRIDEiO60346
    ProteomicsDBi49376

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000262719; ENSP00000262719; ENSG00000081913 [O60346-1]
    GeneIDi23239
    KEGGihsa:23239
    UCSCiuc021ule.2 human [O60346-1]

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...
    CTDi
    23239
    DisGeNETi23239
    EuPathDBiHostDB:ENSG00000081913.13

    GeneCards: human genes, protein and diseases

    More...
    GeneCardsi
    PHLPP1

    H-Invitational Database, human transcriptome db

    More...
    H-InvDBi
    HIX0014494
    HIX0174202
    HGNCiHGNC:20610 PHLPP1
    HPAiHPA020200
    MIMi609396 gene
    neXtProtiNX_O60346
    OpenTargetsiENSG00000081913
    PharmGKBiPA165429055

    Human Unidentified Gene-Encoded large proteins database

    More...
    HUGEi
    Search...

    GenAtlas: human gene database

    More...
    GenAtlasi
    Search...

    Phylogenomic databases

    eggNOGiKOG0619 Eukaryota
    COG0631 LUCA
    COG4886 LUCA
    GeneTreeiENSGT00940000158137
    InParanoidiO60346
    KOiK16340
    OMAiFTNGSRV
    OrthoDBi172467at2759
    PhylomeDBiO60346
    TreeFamiTF315993

    Enzyme and pathway databases

    ReactomeiR-HSA-199418 Negative regulation of the PI3K/AKT network
    SIGNORiO60346

    Miscellaneous databases

    ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

    More...
    ChiTaRSi
    PHLPP1 human

    The Gene Wiki collection of pages on human genes and proteins

    More...
    GeneWikii
    PHLPP_(gene)

    Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

    More...
    GenomeRNAii
    23239

    Protein Ontology

    More...
    PROi
    PR:O60346

    The Stanford Online Universal Resource for Clones and ESTs

    More...
    SOURCEi
    Search...

    Gene expression databases

    BgeeiENSG00000081913 Expressed in 216 organ(s), highest expression level in brain
    CleanExiHS_PHLPP
    ExpressionAtlasiO60346 baseline and differential
    GenevisibleiO60346 HS

    Family and domain databases

    CDDicd00143 PP2Cc, 1 hit
    Gene3Di2.30.29.30, 1 hit
    3.60.40.10, 1 hit
    3.80.10.10, 3 hits
    InterProiView protein in InterPro
    IPR001611 Leu-rich_rpt
    IPR003591 Leu-rich_rpt_typical-subtyp
    IPR032675 LRR_dom_sf
    IPR011993 PH-like_dom_sf
    IPR001849 PH_domain
    IPR036457 PPM-type_dom_sf
    IPR001932 PPM-type_phosphatase_dom
    PfamiView protein in Pfam
    PF00560 LRR_1, 1 hit
    PF13516 LRR_6, 1 hit
    PF13855 LRR_8, 2 hits
    PF00169 PH, 1 hit
    PF00481 PP2C, 1 hit
    SMARTiView protein in SMART
    SM00369 LRR_TYP, 10 hits
    SM00332 PP2Cc, 1 hit
    SUPFAMiSSF81606 SSF81606, 1 hit
    PROSITEiView protein in PROSITE
    PS51450 LRR, 17 hits
    PS50003 PH_DOMAIN, 1 hit
    PS51746 PPM_2, 1 hit

    ProtoNet; Automatic hierarchical classification of proteins

    More...
    ProtoNeti
    Search...

    <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

    <p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiPHLP1_HUMAN
    <p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O60346
    Secondary accession number(s): A1A4F5
    , Q641Q7, Q6P4C4, Q6PJI6, Q86TN6, Q96FK2, Q9NUY1
    <p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: June 7, 2005
    Last modified: January 16, 2019
    This is version 174 of the entry and version 3 of the sequence. See complete history.
    <p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

    <p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    2. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. Human chromosome 18
      Human chromosome 18: entries, gene names and cross-references to MIM
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