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Q16821

- PPR3A_HUMAN

UniProt

Q16821 - PPR3A_HUMAN

Protein

Protein phosphatase 1 regulatory subunit 3A

Gene

PPP1R3A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 108 (01 Oct 2014)
      Sequence version 3 (15 Jun 2010)
      Previous versions | rss
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    Functioni

    Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase By similarity.By similarity

    GO - Biological processi

    1. glycogen metabolic process Source: UniProtKB-KW

    Keywords - Biological processi

    Carbohydrate metabolism, Glycogen metabolism

    Protein family/group databases

    CAZyiCBM21. Carbohydrate-Binding Module Family 21.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein phosphatase 1 regulatory subunit 3A
    Alternative name(s):
    Protein phosphatase 1 glycogen-associated regulatory subunit
    Protein phosphatase type-1 glycogen targeting subunit
    Short name:
    RG1
    Gene namesi
    Name:PPP1R3A
    Synonyms:PP1G
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:9291. PPP1R3A.

    Subcellular locationi

    Membrane By similarity; Single-pass membrane protein By similarity

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti931 – 9311A → E in NIDDM. 1 Publication
    Corresponds to variant rs35449651 [ dbSNP | Ensembl ].
    VAR_019699

    Keywords - Diseasei

    Diabetes mellitus, Disease mutation

    Organism-specific databases

    MIMi125853. phenotype.
    PharmGKBiPA33651.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11221122Protein phosphatase 1 regulatory subunit 3APRO_0000071500Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei38 – 381Phosphoserine; by GSK3By similarity
    Modified residuei42 – 421Phosphoserine; by GSK3By similarity
    Modified residuei46 – 461Phosphoserine; by PKA and ISPKBy similarity
    Modified residuei65 – 651Phosphoserine; by PKABy similarity

    Post-translational modificationi

    Phosphorylation at Ser-46 by ISPK stimulates the dephosphorylation of glycogen synthase and phosphorylase kinase.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ16821.
    PRIDEiQ16821.

    PTM databases

    PhosphoSiteiQ16821.

    Expressioni

    Tissue specificityi

    Skeletal muscle and heart.1 Publication

    Gene expression databases

    BgeeiQ16821.
    CleanExiHS_PPP1R3A.
    GenevestigatoriQ16821.

    Interactioni

    Subunit structurei

    Interacts with PPP1CC catalytic subunit of PP1, and associates with glycogen.By similarity

    Protein-protein interaction databases

    BioGridi111499. 2 interactions.
    IntActiQ16821. 1 interaction.
    STRINGi9606.ENSP00000284601.

    Structurei

    3D structure databases

    ProteinModelPortaliQ16821.
    SMRiQ16821. Positions 110-230.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1078 – 109821HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini122 – 230109CBM21PROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi62 – 654PP1-binding motif

    Domaini

    The CBM21 domain is known to be involved in the localization to glycogen and is characteristic of some regulatory subunit of phosphatase complexes.

    Sequence similaritiesi

    Contains 1 CBM21 (carbohydrate binding type-21) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG288354.
    HOVERGENiHBG053657.
    InParanoidiQ16821.
    KOiK07189.
    OMAiAFDPHEG.
    OrthoDBiEOG769ZKR.
    PhylomeDBiQ16821.
    TreeFamiTF105537.

    Family and domain databases

    InterProiIPR005036. CBM_21.
    [Graphical view]
    PfamiPF03370. CBM_21. 1 hit.
    [Graphical view]
    PROSITEiPS51159. CBM21. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q16821-1) [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

    MEPSEVPSQI SKDNFLEVPN LSDSLCEDEE VTFQPGFSPQ PSRRGSDSSE     50
    DIYLDTPSSG TRRVSFADSF GFNLVSVKEF DCWELPSAST TFDLGTDIFH 100
    TEEYVLAPLF DLPSSKEDLM QQLQIQKAIL ESTESLLGST SIKGIIRVLN 150
    VSFEKLVYVR MSLDDWQTHY DILAEYVPNS CDGETDQFSF KIVLVPPYQK 200
    DGSKVEFCIR YETSVGTFWS NNNGTNYTFI CQKKEQEPEP VKPWKEVPNR 250
    QIKGCLKVKS SKEESSVTSE ENNFENPKNT DTYIPTIICS HEDKEDLEAS 300
    NRNVKDVNRE HDEHNEKELE LMINQHLIRT RSTASRDERN TFSTDPVNFP 350
    NKAEGLEKKQ IHGEICTDLF QRSLSPSSSA ESSVKGDFYC NEKYSSGDDC 400
    THQPSEETTS NMGEIKPSLG DTSSDELVQL HTGSKEVLDD NANPAHGNGT 450
    VQIPCPSSDQ LMAGNLNKKH EGGAKNIEVK DLGCLRRDFH SDTSACLKES 500
    TEEGSSKEDY YGNGKDDEEQ RIYLGVNEKQ RKNFQTILHD QERKMGNPKI 550
    SVAGIGASNR DLATLLSEHT AIPTRAITAD VSHSPRTNLS WEEAVLTPEH 600
    HHLTSEGSAL GGITGQVCSS RTGNVLRNDY LFQVEEKSGG INSEDQDNSP 650
    QHKQSWNVLE SQGKSRENKT NITEHIKGQT DCEDVWGKRD NTRSLKATTE 700
    ELFTCQETVC CELSSLADHG ITEKAEAGTA YIIKTTSEST PESMSAREKA 750
    IIAKLPQETA RSDRPIEVKE TAFDPHEGRN DDSHYTLCQR DTVGVIYDND 800
    FEKESRLGIC NVRVDEMEKE ETMSMYNPRK THDREKCGTG NITSVEESSW 850
    VITEYQKATS KLDLQLGMLP TDKTVFSENR DLRQVQELSK KTDSDAIVHS 900
    AFNSDTNRAP QNSSPFSKHH TEISVSTNEQ AIAVENAVTT MASQPISTKS 950
    ENICNSTREI QGIEKHPYPE SKPEEVSRSS GIVTSGSRKE RCIGQIFQTE 1000
    EYSVEKSLGP MILINKPLEN MEEARHENEG LVSSGQSLYT SGEKESDSSA 1050
    STSLPVEESQ AQGNESLFSK YTNSKIPYFL LFLIFLITVY HYDLMIGLTF 1100
    YVLSLSWLSW EEGRQKESVK KK 1122
    Length:1,122
    Mass (Da):125,767
    Last modified:June 15, 2010 - v3
    Checksum:iFACB2CEA7C00E75B
    GO
    Isoform 2 (identifier: Q16821-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         60-74: GTRRVSFADSFGFNL → ERTRAGACKTMERSS
         75-1122: Missing.

    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Show »
    Length:74
    Mass (Da):8,187
    Checksum:i16A09845C8C8273A
    GO

    Sequence cautioni

    The sequence AAS07492.1 differs from that shown. Reason: Erroneous gene model prediction.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti45 – 451G → S.
    Corresponds to variant rs8192687 [ dbSNP | Ensembl ].
    VAR_027929
    Natural varianti231 – 2311C → Y.
    Corresponds to variant rs7801819 [ dbSNP | Ensembl ].
    VAR_027930
    Natural varianti451 – 4511V → M.4 Publications
    Corresponds to variant rs2974942 [ dbSNP | Ensembl ].
    VAR_027931
    Natural varianti476 – 4761N → K.4 Publications
    Corresponds to variant rs2974944 [ dbSNP | Ensembl ].
    VAR_027932
    Natural varianti554 – 5541G → A in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036287
    Natural varianti627 – 6271R → K.
    Corresponds to variant rs35067467 [ dbSNP | Ensembl ].
    VAR_057128
    Natural varianti748 – 7481E → K.
    Corresponds to variant rs4304271 [ dbSNP | Ensembl ].
    VAR_027933
    Natural varianti882 – 8821L → H.4 Publications
    Corresponds to variant rs2974938 [ dbSNP | Ensembl ].
    VAR_027934
    Natural varianti883 – 8831R → S.1 Publication
    Corresponds to variant rs1800000 [ dbSNP | Ensembl ].
    VAR_019697
    Natural varianti905 – 9051D → Y Common polymorphism; can be associated with insulin resistance. 2 Publications
    Corresponds to variant rs1799999 [ dbSNP | Ensembl ].
    VAR_019698
    Natural varianti931 – 9311A → E in NIDDM. 1 Publication
    Corresponds to variant rs35449651 [ dbSNP | Ensembl ].
    VAR_019699

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei60 – 7415GTRRV…FGFNL → ERTRAGACKTMERSS in isoform 2. 1 PublicationVSP_011585Add
    BLAST
    Alternative sequencei75 – 11221048Missing in isoform 2. 1 PublicationVSP_011586Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF024578, AF024576, AF024577 Genomic DNA. Translation: AAB94596.1.
    AF024579 mRNA. Translation: AAB94597.1.
    AC092465 Genomic DNA. Translation: AAS07492.1. Sequence problems.
    AC093598 Genomic DNA. Translation: AAP22361.1.
    CH236947 Genomic DNA. Translation: EAL24370.1.
    BC126451 mRNA. Translation: AAI26452.1.
    BC126453 mRNA. Translation: AAI26454.1.
    X78578 mRNA. Translation: CAA55316.1.
    CCDSiCCDS5759.1. [Q16821-1]
    PIRiI38127.
    RefSeqiNP_002702.2. NM_002711.3. [Q16821-1]
    UniGeneiHs.458309.

    Genome annotation databases

    EnsembliENST00000284601; ENSP00000284601; ENSG00000154415. [Q16821-1]
    ENST00000284602; ENSP00000284602; ENSG00000154415. [Q16821-2]
    GeneIDi5506.
    KEGGihsa:5506.
    UCSCiuc010ljy.1. human. [Q16821-1]

    Polymorphism databases

    DMDMi298286906.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF024578 , AF024576 , AF024577 Genomic DNA. Translation: AAB94596.1 .
    AF024579 mRNA. Translation: AAB94597.1 .
    AC092465 Genomic DNA. Translation: AAS07492.1 . Sequence problems.
    AC093598 Genomic DNA. Translation: AAP22361.1 .
    CH236947 Genomic DNA. Translation: EAL24370.1 .
    BC126451 mRNA. Translation: AAI26452.1 .
    BC126453 mRNA. Translation: AAI26454.1 .
    X78578 mRNA. Translation: CAA55316.1 .
    CCDSi CCDS5759.1. [Q16821-1 ]
    PIRi I38127.
    RefSeqi NP_002702.2. NM_002711.3. [Q16821-1 ]
    UniGenei Hs.458309.

    3D structure databases

    ProteinModelPortali Q16821.
    SMRi Q16821. Positions 110-230.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111499. 2 interactions.
    IntActi Q16821. 1 interaction.
    STRINGi 9606.ENSP00000284601.

    Protein family/group databases

    CAZyi CBM21. Carbohydrate-Binding Module Family 21.

    PTM databases

    PhosphoSitei Q16821.

    Polymorphism databases

    DMDMi 298286906.

    Proteomic databases

    PaxDbi Q16821.
    PRIDEi Q16821.

    Protocols and materials databases

    DNASUi 5506.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000284601 ; ENSP00000284601 ; ENSG00000154415 . [Q16821-1 ]
    ENST00000284602 ; ENSP00000284602 ; ENSG00000154415 . [Q16821-2 ]
    GeneIDi 5506.
    KEGGi hsa:5506.
    UCSCi uc010ljy.1. human. [Q16821-1 ]

    Organism-specific databases

    CTDi 5506.
    GeneCardsi GC07M113516.
    H-InvDB HIX0033522.
    HGNCi HGNC:9291. PPP1R3A.
    MIMi 125853. phenotype.
    600917. gene.
    neXtProti NX_Q16821.
    PharmGKBi PA33651.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG288354.
    HOVERGENi HBG053657.
    InParanoidi Q16821.
    KOi K07189.
    OMAi AFDPHEG.
    OrthoDBi EOG769ZKR.
    PhylomeDBi Q16821.
    TreeFami TF105537.

    Miscellaneous databases

    GeneWikii PPP1R3A.
    GenomeRNAii 5506.
    NextBioi 21300.
    PROi Q16821.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q16821.
    CleanExi HS_PPP1R3A.
    Genevestigatori Q16821.

    Family and domain databases

    InterProi IPR005036. CBM_21.
    [Graphical view ]
    Pfami PF03370. CBM_21. 1 hit.
    [Graphical view ]
    PROSITEi PS51159. CBM21. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A common variant in PPP1R3 associated with insulin resistance and type 2 diabetes."
      Xia J., Scherer S.W., Cohen P.T.W., Majer M., Xi T., Norman R.A., Knowler W.C., Bogardus C., Prochazka M.
      Diabetes 47:1519-1524(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, VARIANTS MET-451; LYS-476; HIS-882; SER-883 AND TYR-905.
      Tissue: Skeletal muscle.
    2. "The DNA sequence of human chromosome 7."
      Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
      , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
      Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Human chromosome 7: DNA sequence and biology."
      Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
      , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
      Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS MET-451; LYS-476 AND HIS-882.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS MET-451; LYS-476 AND HIS-882.
    5. "Sequence of the human glycogen-associated regulatory subunit of type I protein phosphatase and analysis of its coding region and mRNA level in muscle from patients with non-insulin-dependent diabetes."
      Chen Y.H., Hansen L., Chen M.X., Bjorbaek C., Vestergaard H., Hansen T., Cohen P.T.W., Pederson O.
      Diabetes 43:1234-1241(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-1122 (ISOFORM 1), VARIANTS MET-451; LYS-476 AND HIS-882, VARIANT NIDDM GLU-931.
      Tissue: Skeletal muscle.
    6. "A widespread amino acid polymorphism at codon 905 of the glycogen-associated regulatory subunit of protein phosphatase-1 is associated with insulin resistance and hypersecretion of insulin."
      Hansen L., Hansen T., Vestergaard H., Bjorbaek C., Echwald S.M., Clausen J.O., Chen Y.H., Chen M.X., Cohen P.T.W., Pedersen O.
      Hum. Mol. Genet. 4:1313-1320(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TYR-905.
    7. Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-554.

    Entry informationi

    Entry nameiPPR3A_HUMAN
    AccessioniPrimary (citable) accession number: Q16821
    Secondary accession number(s): A0AVQ2
    , A4D0T6, O43476, Q75LN8, Q7KYM8, Q86UI6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 13, 2004
    Last sequence update: June 15, 2010
    Last modified: October 1, 2014
    This is version 108 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 7
      Human chromosome 7: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3