ZO3_MOUSE
ID ZO3_MOUSE Reviewed; 905 AA.
AC Q9QXY1;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 152.
DE RecName: Full=Tight junction protein ZO-3;
DE AltName: Full=Tight junction protein 3;
DE AltName: Full=Zona occludens protein 3;
DE AltName: Full=Zonula occludens protein 3;
GN Name=Tjp3; Synonyms=Zo3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CLAUDINS, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=BALB/cJ;
RX PubMed=10601346; DOI=10.1083/jcb.147.6.1351;
RA Itoh M., Furuse M., Morita K., Kubota K., Saitou M., Tsukita S.;
RT "Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and
RT ZO-3, with the COOH termini of claudins.";
RL J. Cell Biol. 147:1351-1363(1999).
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14622136; DOI=10.1046/j.1365-2443.2003.00681.x;
RA Inoko A., Itoh M., Tamura A., Matsuda M., Furuse M., Tsukita S.;
RT "Expression and distribution of ZO-3, a tight junction MAGUK protein, in
RT mouse tissues.";
RL Genes Cells 8:837-845(2003).
RN [3]
RP FUNCTION.
RX PubMed=17000770; DOI=10.1128/mcb.01811-05;
RA Adachi M., Inoko A., Hata M., Furuse K., Umeda K., Itoh M., Tsukita S.;
RT "Normal establishment of epithelial tight junctions in mice and cultured
RT cells lacking expression of ZO-3, a tight-junction MAGUK protein.";
RL Mol. Cell. Biol. 26:9003-9015(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156; SER-157; SER-161;
RP SER-343; SER-891 AND SER-892, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP FUNCTION.
RX PubMed=18172007; DOI=10.1128/mcb.00891-07;
RA Xu J., Kausalya P.J., Phua D.C., Ali S.M., Hossain Z., Hunziker W.;
RT "Early embryonic lethality of mice lacking ZO-2, but not ZO-3, reveals
RT critical and nonredundant roles for individual zonula occludens proteins in
RT mammalian development.";
RL Mol. Cell. Biol. 28:1669-1678(2008).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=19538286; DOI=10.1111/j.1749-6632.2009.04056.x;
RA Tsukita S., Katsuno T., Yamazaki Y., Umeda K., Tamura A., Tsukita S.;
RT "Roles of ZO-1 and ZO-2 in establishment of the belt-like adherens and
RT tight junctions with paracellular permselective barrier function.";
RL Ann. N. Y. Acad. Sci. 1165:44-52(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156; SER-157; SER-161;
RP SER-311; SER-343; SER-891 AND SER-892, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CCND1.
RX PubMed=21411630; DOI=10.1091/mbc.e10-08-0677;
RA Capaldo C.T., Koch S., Kwon M., Laur O., Parkos C.A., Nusrat A.;
RT "Tight function zonula occludens-3 regulates cyclin D1-dependent cell
RT proliferation.";
RL Mol. Biol. Cell 22:1677-1685(2011).
CC -!- FUNCTION: Tjp1, Tjp2, and Tjp3 are closely related scaffolding proteins
CC that link tight junction (TJ) transmembrane proteins such as claudins,
CC junctional adhesion molecules, and occludin to the actin cytoskeleton
CC (PubMed:17000770). The tight junction acts to limit movement of
CC substances through the paracellular space and as a boundary between the
CC compositionally distinct apical and basolateral plasma membrane domains
CC of epithelial and endothelial cells. Binds and recruits PatJ to tight
CC junctions where it connects and stabilizes apical and lateral
CC components of tight junctions (By similarity). Promotes cell-cycle
CC progression through the sequestration of cyclin D1 (Ccnd1) at tight
CC junctions during mitosis which prevents Ccnd1 degradation during M-
CC phase and enables S-phase transition (PubMed:21411630). With Tjp1 and
CC Tjp2, participates in the junctional retention and stability of the
CC transcription factor DbpA, but is not involved in its shuttling to the
CC nucleus (By similarity). Contrary to Tjp2, Tjp3 is dispensable for
CC individual viability, embryonic development, epithelial
CC differentiation, and the establishment of TJs, at least in the
CC laboratory environment (PubMed:17000770, PubMed:18172007).
CC {ECO:0000250|UniProtKB:O62683, ECO:0000250|UniProtKB:O95049,
CC ECO:0000269|PubMed:17000770, ECO:0000269|PubMed:18172007,
CC ECO:0000269|PubMed:21411630}.
CC -!- SUBUNIT: Interacts with occludin OCLN, claudins and TPJ1 (By
CC similarity). Interacts with PATJ (By similarity). Interacts with UBN1
CC (By similarity). Interacts with FASLG (By similarity). Interacts with
CC CCND1 (PubMed:21411630). {ECO:0000250|UniProtKB:O62683,
CC ECO:0000269|PubMed:21411630}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21411630};
CC Peripheral membrane protein {ECO:0000269|PubMed:21411630}; Cytoplasmic
CC side {ECO:0000269|PubMed:21411630}. Cell junction, tight junction
CC {ECO:0000269|PubMed:10601346, ECO:0000269|PubMed:14622136,
CC ECO:0000269|PubMed:19538286, ECO:0000269|PubMed:21411630}. Nucleus
CC {ECO:0000250|UniProtKB:O95049}. Note=Exhibits predominant nuclear
CC expression in proliferating cells but is exclusively junctionally
CC expressed after confluence is reached (By similarity). Shows an
CC epithelial-specific tight junction localization in a Tjp1/Tjp2-
CC dependent fashion (PubMed:21411630). {ECO:0000250|UniProtKB:O95049,
CC ECO:0000269|PubMed:21411630}.
CC -!- TISSUE SPECIFICITY: Is concentrated in various types of epithelium, in
CC tissues such as the lung, liver and kidney, but not in endothelium or
CC at cadherin-based cell-cell adhesion sites (PubMed:14622136).
CC {ECO:0000269|PubMed:14622136}.
CC -!- PTM: Phosphorylated (By similarity). {ECO:0000250|UniProtKB:O62683}.
CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
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DR EMBL; AF157006; AAF24175.1; -; mRNA.
DR AlphaFoldDB; Q9QXY1; -.
DR SMR; Q9QXY1; -.
DR MINT; Q9QXY1; -.
DR STRING; 10090.ENSMUSP00000036438; -.
DR iPTMnet; Q9QXY1; -.
DR PhosphoSitePlus; Q9QXY1; -.
DR jPOST; Q9QXY1; -.
DR MaxQB; Q9QXY1; -.
DR PaxDb; Q9QXY1; -.
DR PRIDE; Q9QXY1; -.
DR ProteomicsDB; 275313; -.
DR MGI; MGI:1351650; Tjp3.
DR eggNOG; KOG3580; Eukaryota.
DR InParanoid; Q9QXY1; -.
DR PhylomeDB; Q9QXY1; -.
DR ChiTaRS; Tjp3; mouse.
DR PRO; PR:Q9QXY1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9QXY1; protein.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0005923; C:bicellular tight junction; IDA:MGI.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; IDA:ARUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0045216; P:cell-cell junction organization; IBA:GO_Central.
DR GO; GO:0090557; P:establishment of endothelial intestinal barrier; IBA:GO_Central.
DR GO; GO:1905605; P:positive regulation of blood-brain barrier permeability; IBA:GO_Central.
DR GO; GO:0150105; P:protein localization to cell-cell junction; IBA:GO_Central.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IGI:MGI.
DR Gene3D; 2.30.42.10; -; 3.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR008145; GK/Ca_channel_bsu.
DR InterPro; IPR008144; Guanylate_kin-like_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR005417; ZO.
DR InterPro; IPR005420; ZO-3.
DR PANTHER; PTHR13865:SF11; PTHR13865:SF11; 1.
DR Pfam; PF00625; Guanylate_kin; 1.
DR Pfam; PF00595; PDZ; 3.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR01597; ZONOCCLUDNS.
DR PRINTS; PR01600; ZONOCCLUDNS3.
DR SMART; SM00072; GuKc; 1.
DR SMART; SM00228; PDZ; 3.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF50156; SSF50156; 3.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1.
DR PROSITE; PS50106; PDZ; 3.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain; Tight junction.
FT CHAIN 1..905
FT /note="Tight junction protein ZO-3"
FT /id="PRO_0000094547"
FT DOMAIN 11..93
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 187..264
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 368..434
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 464..541
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 573..754
FT /note="Guanylate kinase-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT REGION 92..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..367
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 773..818
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 850..905
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 794..818
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 857..894
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 317
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 584
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 891
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 892
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
SQ SEQUENCE 905 AA; 99324 MW; B787BA1592661FEE CRC64;
MEELTIWEQH TATLYKDPRR GFGIAVSGGH DRASGSVVVS DVVPGSPAEG RLRTGDHIVM
VNGVSVENVT SAFAIQILKT CTKTANVTVK RPRRVQLPAT KASPASGHQL SDQEEADHGR
GYEGDSSSGS GRSWGERSRR SRAGRRGRVG SHGRRSSGGG SEANGLDLVS GYKRLPKQDV
LMRPLKSVLV KRRNSEEFGV KLGSQIFIKH ITESGLAARN HGLQEGDLIL QINGVSSANL
SLSDTRRLIE KSEGELTLLV LRDSGQFLVN IPPAVSDSDS SLMEDISDLT SELSQAPPSH
VPPPPLKGQR SPEDSQTDSP VETPQPRRRE RSVNSRAIAE PESPGESRYD IYRVPSRQSL
EDRGYSPDTR VVSFPKGASI GLRLAGGNDV GIFVSGVQAG SPADGQGIQE GDEILQVNGM
PFRNLTREEA VQFLLGLPPG EDMELVTQSK TGHSLRRWSQ SRVGDSFYIR THFELEPSPP
YGLGFTRGDV FHVVDTLYPG SGPGHGHSSH GGLWLAARMG RDLREQERGV IPNQSRAEQL
ASLEAAQRAA GVGPGASVGS NPRAEFWRLR SLRRGTKKAS TQRSREDLSA LTRQGHYPPY
ERVVLREASF KRPVVILGPV ADIAMKKLTT EMPEEFEIAE SMSRTDSPSK IIKLDTVRVI
AERDKHALLD VTPSAIERLN YVQYYPIVIF CAPESRPALK ALREWLAPAS RRSSRRLYAQ
AQKLQKHSGH LFTATIPLHG TSDSWYQEVK AVIQQQQARP IWTAEDQLNS SSEDLDLTGH
GLAASSGDLS CDSRTNSDYE DTDGEGAYTD REGGPQDVDE EVAPTALARS SEPVWVDDHQ
GLMGHGTTIT DKWETQADSH YTQDQRRQDS MRTYKHEALR KKFTRARDVE SSDDEGYDWG
PATDL
