ZO3_CANLF
ID ZO3_CANLF Reviewed; 898 AA.
AC O62683;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 25-MAY-2022, entry version 127.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, INTERACTION WITH TJP1
RP AND OCLN, AND SUBCELLULAR LOCATION.
RC STRAIN=Cocker spaniel; TISSUE=Kidney;
RX PubMed=9531559; DOI=10.1083/jcb.141.1.199;
RA Haskins J., Gu L., Wittchen E.S., Hibbard J., Stevenson B.R.;
RT "ZO-3, a novel member of the MAGUK protein family found at the tight
RT junction, interacts with ZO-1 and occludin.";
RL J. Cell Biol. 141:199-208(1998).
RN [2]
RP INTERACTION WITH TJP1, AND PHOSPHORYLATION.
RX PubMed=8408213; DOI=10.1083/jcb.123.2.293;
RA Balda M.S., Gonzalez-Mariscal L., Matter K., Cereijido M., Anderson J.M.;
RT "Assembly of the tight junction: the role of diacylglycerol.";
RL J. Cell Biol. 123:293-302(1993).
RN [3]
RP INTERACTION WITH TJP1.
RX PubMed=10575001; DOI=10.1074/jbc.274.49.35179;
RA Wittchen E.S., Haskins J., Stevenson B.R.;
RT "Protein interactions at the tight junction. Actin has multiple binding
RT partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3.";
RL J. Biol. Chem. 274:35179-35185(1999).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PATJ.
RX PubMed=12021270; DOI=10.1074/jbc.m201177200;
RA Roh M.H., Liu C.-J., Laurinec S., Margolis B.;
RT "The carboxyl terminus of zona occludens-3 binds and recruits a mammalian
RT homologue of discs lost to tight junctions.";
RL J. Biol. Chem. 277:27501-27509(2002).
RN [5]
RP INDUCTION.
RX PubMed=18653465; DOI=10.1091/mbc.e08-06-0558;
RA Guillemot L., Paschoud S., Jond L., Foglia A., Citi S.;
RT "Paracingulin regulates the activity of Rac1 and RhoA GTPases by recruiting
RT Tiam1 and GEF-H1 to epithelial junctions.";
RL Mol. Biol. Cell 19:4442-4453(2008).
RN [6]
RP FUNCTION.
RX PubMed=24986862; DOI=10.1074/jbc.m114.556449;
RA Spadaro D., Tapia R., Jond L., Sudol M., Fanning A.S., Citi S.;
RT "ZO proteins redundantly regulate the transcription factor DbpA/ZONAB.";
RL J. Biol. Chem. 289:22500-22511(2014).
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:12021270). 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 (PubMed:12021270). 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 (By similarity). 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 (PubMed:24986862). 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 (By similarity). {ECO:0000250|UniProtKB:O95049,
CC ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:12021270,
CC ECO:0000269|PubMed:24986862}.
CC -!- SUBUNIT: Heterodimer with TJP1 (PubMed:9531559, PubMed:8408213,
CC PubMed:10575001). Interacts with UBN1 (By similarity). Interacts with
CC occludin OCLN and claudins (PubMed:9531559, PubMed:8408213). Interacts
CC with PATJ (PubMed:12021270). Interacts with FASLG (By similarity).
CC Interacts with CCND1 (By similarity). {ECO:0000250|UniProtKB:O95049,
CC ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:10575001,
CC ECO:0000269|PubMed:12021270, ECO:0000269|PubMed:8408213,
CC ECO:0000269|PubMed:9531559}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12021270};
CC Peripheral membrane protein {ECO:0000269|PubMed:12021270}; Cytoplasmic
CC side {ECO:0000269|PubMed:12021270}. Cell junction, tight junction
CC {ECO:0000269|PubMed:12021270, ECO:0000269|PubMed:9531559}. 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 (By similarity). {ECO:0000250|UniProtKB:O95049,
CC ECO:0000250|UniProtKB:Q9QXY1}.
CC -!- INDUCTION: Expression is up-regulated by the depletion of the
CC junctional protein paracingulin CGNL1 (PubMed:18653465).
CC {ECO:0000269|PubMed:18653465}.
CC -!- PTM: Phosphorylated (PubMed:8408213). {ECO:0000269|PubMed:8408213}.
CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
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DR EMBL; AF023617; AAC39177.1; -; mRNA.
DR RefSeq; NP_001003202.1; NM_001003202.1.
DR AlphaFoldDB; O62683; -.
DR SMR; O62683; -.
DR IntAct; O62683; 1.
DR MINT; O62683; -.
DR STRING; 9612.ENSCAFP00000028316; -.
DR PaxDb; O62683; -.
DR GeneID; 403852; -.
DR CTD; 27134; -.
DR eggNOG; KOG3580; Eukaryota.
DR InParanoid; O62683; -.
DR OrthoDB; 1175136at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005923; C:bicellular tight junction; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0070160; C:tight junction; IDA:ARUK-UCL.
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 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; Direct protein sequencing; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; SH3 domain; Tight junction.
FT CHAIN 1..898
FT /note="Tight junction protein ZO-3"
FT /id="PRO_0000094545"
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 369..435
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 464..538
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 569..750
FT /note="Guanylate kinase-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT REGION 98..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 295..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 759..898
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 316..348
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 827..846
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 867..887
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXY1"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 319
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 835
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 884
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
FT MOD_RES 885
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95049"
SQ SEQUENCE 898 AA; 98415 MW; 8091D6132DB9F15D CRC64;
MEELTIWEQH TATLCRDPRR GFGIAISGGR DRASGSVVVS DVVPGGPADG RLQTGDHVVM
VNGVSMESVT STFAIQILKT CTKLANITVK RPRKIQLPAT KAGTSGRGRQ GLEEEADCGQ
GYDGDTSSGS GRSWDKRSRR ARTGRRNQAG SRGRRSPGGN SEANGLALVS GFKRLPRQDV
HMRPVKSVLV RRTESEEFGV TLGSQIFIKH ITDSGLAARN RGLQEGDLIL QINGVSSENL
SLSDTRRLIE KSEGKLTLLV LRDRGQFLVN IPPAVSDSDS DSSFLDDISA LGSELSQAVP
SHVPPPPPHA QRSLDSDGTD SPRDSPPLRR ENSLDSRTIS EPDAPRHSSY DIYRVPSSQS
AEDRGYSPDS RVVRFHKGTT IGLRLAGGND VGIFVSGVQE GSPADGQGIQ EGDQILQVND
VPFRNLTREE AVQFLVALPP GEEVELVTQR NEDIFRKMVQ SRVGDSFYIR THFELEASPP
SGLGFTRGDV FHVLDTLCPG PGPSGARGTH WLAVRMGRDL REQERGIIPN QSRAEQLASL
ESAQRAVGAG PGASVGSSAR AEFWRLRGLR RGAKKSTQRS REDLSALTRQ GHYPPYERVV
LREASFKRPV VILGPVADIA MQKLTAEMPD QFGIADSVLR TDSPSKIIKL DTVRVIAEKN
KHALLDVTPS AVERLNYVQY YPIVVFCAPE SRAALKALRQ WLAPASRRSA RRLYAQAQKL
RKHSEHLFTA TIPLRGTSDT WYQELKAVVR EQQTRPIWTA EDQLDNSSED NLELPHRGLA
DSSADLSCDS RVNSDYETDG EGYTDGEGYT DVDEGPPAPA LARSSEPVLE EEPRSPRDHG
RASGARGAQV DRHPYHSQGR QDSMRTYGQE ALKKKFTRAR DVESSDEDGY DWGPATDL
