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Protein

Tight junction protein ZO-3

Gene

TJP3

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

Functioni

TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:16129888). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates to the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity).By similarity2 Publications

Names & Taxonomyi

Protein namesi
Recommended name:
Tight junction protein ZO-3
Alternative name(s):
Tight junction protein 3
Zona occludens protein 3
Zonula occludens protein 3
Gene namesi
Name:TJP3
Synonyms:ZO3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105289.14
HGNCiHGNC:11829 TJP3
MIMi612689 gene
neXtProtiNX_O95049

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 junction, Cell membrane, Membrane, Nucleus, Tight junction

Pathology & Biotechi

Organism-specific databases

DisGeNETi27134
OpenTargetsiENSG00000105289
PharmGKBiPA36534

Polymorphism and mutation databases

BioMutaiTJP3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000945461 – 919Tight junction protein ZO-3Add BLAST919

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei112PhosphoserineCombined sources1
Modified residuei136PhosphoserineCombined sources1
Modified residuei164PhosphoserineCombined sources1
Modified residuei169PhosphoserineBy similarity1
Modified residuei203PhosphoserineCombined sources1
Modified residuei319PhosphoserineCombined sources1
Modified residuei325PhosphothreonineCombined sources1
Modified residuei327PhosphoserineCombined sources1
Modified residuei371PhosphoserineCombined sources1
Modified residuei591PhosphoserineCombined sources1
Modified residuei856PhosphoserineCombined sources1
Modified residuei905PhosphoserineCombined sources1
Modified residuei906PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO95049
MaxQBiO95049
PaxDbiO95049
PeptideAtlasiO95049
PRIDEiO95049
ProteomicsDBi50630
50632 [O95049-3]

PTM databases

GlyConnecti1809
iPTMnetiO95049
PhosphoSitePlusiO95049

Expressioni

Inductioni

Exhibits enhanced expression in matured epithelial layers (PubMed:23608536). Apical leptin, Staphylococcus aureus alpha-toxin and Pseudomonas aeruginosa acyl-homoserine lactone 3O-C12-HSl lower expression levels, altering junctional integrity in intestinal cells (PubMed:20434232, PubMed:22354024, PubMed:24314862).4 Publications

Gene expression databases

BgeeiENSG00000105289 Expressed in 123 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_TJP3
ExpressionAtlasiO95049 baseline and differential
GenevisibleiO95049 HS

Organism-specific databases

HPAiCAB013244
HPA046863
HPA053337

Interactioni

Subunit structurei

Interacts with occludin OCLN, claudins and TPJ1 (By similarity). Interacts with PATJ (By similarity). Interacts with UBN1 (PubMed:20434232). Interacts with FASLG (PubMed:19807924). Interacts with CCND1 (PubMed:21411630).By similarity3 Publications

Protein-protein interaction databases

BioGridi118025, 7 interactors
IntActiO95049, 5 interactors
MINTiO95049
STRINGi9606.ENSP00000262968

Structurei

Secondary structure

1919
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95049
SMRiO95049
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95049

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 93PDZ 1PROSITE-ProRule annotationAdd BLAST83
Domaini195 – 272PDZ 2PROSITE-ProRule annotationAdd BLAST78
Domaini380 – 446PDZ 3PROSITE-ProRule annotationAdd BLAST67
Domaini475 – 549SH3PROSITE-ProRule annotationAdd BLAST75
Domaini580 – 761Guanylate kinase-likePROSITE-ProRule annotationAdd BLAST182

Sequence similaritiesi

Belongs to the MAGUK family.Curated

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiENOG410IQ5J Eukaryota
ENOG410XS08 LUCA
GeneTreeiENSGT00760000118866
HOGENOMiHOG000230923
HOVERGENiHBG017627
InParanoidiO95049
KOiK06097
OMAiIVVFCAP
OrthoDBiEOG091G0AJZ
TreeFamiTF315606

Family and domain databases

InterProiView protein in InterPro
IPR008145 GK/Ca_channel_bsu
IPR008144 Guanylate_kin-like_dom
IPR027417 P-loop_NTPase
IPR001478 PDZ
IPR036034 PDZ_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR005417 ZO
IPR005420 ZO-3
PANTHERiPTHR13865:SF11 PTHR13865:SF11, 1 hit
PfamiView protein in Pfam
PF00625 Guanylate_kin, 1 hit
PF00595 PDZ, 3 hits
PF07653 SH3_2, 1 hit
PRINTSiPR01597 ZONOCCLUDNS
PR01600 ZONOCCLUDNS3
SMARTiView protein in SMART
SM00072 GuKc, 1 hit
SM00228 PDZ, 3 hits
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF50156 SSF50156, 3 hits
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50052 GUANYLATE_KINASE_2, 1 hit
PS50106 PDZ, 3 hits
PS50002 SH3, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 5 (identifier: O95049-1) [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
MEELTIWEQH TATLSKDPRR GFGIAISGGR DRPGGSMVVS DVVPGGPAEG
60 70 80 90 100
RLQTGDHIVM VNGVSMENAT SAFAIQILKT CTKMANITVK RPRRIHLPAT
110 120 130 140 150
KASPSSPGRQ DSDEDDGPQR VEEVDQGRGY DGDSSSGSGR SWDERSRRPR
160 170 180 190 200
PGRRGRAGSH GRRSPGGGSE ANGLALVSGF KRLPRQDVQM KPVKSVLVKR
210 220 230 240 250
RDSEEFGVKL GSQIFIKHIT DSGLAARHRG LQEGDLILQI NGVSSQNLSL
260 270 280 290 300
NDTRRLIEKS EGKLSLLVLR DRGQFLVNIP PAVSDSDSSP LEDISDLASE
310 320 330 340 350
LSQAPPSHIP PPPRHAQRSP EASQTDSPVE SPRLRRESSV DSRTISEPDE
360 370 380 390 400
QRSELPRESS YDIYRVPSSQ SMEDRGYSPD TRVVRFLKGK SIGLRLAGGN
410 420 430 440 450
DVGIFVSGVQ AGSPADGQGI QEGDQILQVN DVPFQNLTRE EAVQFLLGLP
460 470 480 490 500
PGEEMELVTQ RKQDIFWKMV QSRVGDSFYI RTHFELEPSP PSGLGFTRGD
510 520 530 540 550
VFHVLDTLHP GPGQSHARGG HWLAVRMGRD LREQERGIIP NQSRAEQLAS
560 570 580 590 600
LEAAQRAVGV GPGSSAGSNA RAEFWRLRGL RRGAKKTTQR SREDLSALTR
610 620 630 640 650
QGRYPPYERV VLREASFKRP VVILGPVADI AMQKLTAEMP DQFEIAETVS
660 670 680 690 700
RTDSPSKIIK LDTVRVIAEK DKHALLDVTP SAIERLNYVQ YYPIVVFFIP
710 720 730 740 750
ESRPALKALR QWLAPASRRS TRRLYAQAQK LRKHSSHLFT ATIPLNGTSD
760 770 780 790 800
TWYQELKAII REQQTRPIWT AEDQLDGSLE DNLDLPHHGL ADSSADLSCD
810 820 830 840 850
SRVNSDYETD GEGGAYTDGE GYTDGEGGPY TDVDDEPPAP ALARSSEPVQ
860 870 880 890 900
ADESQSPRDR GRISAHQGAQ VDSRHPQGQW RQDSMRTYER EALKKKFMRV
910
HDAESSDEDG YDWGPATDL
Length:919
Mass (Da):101,397
Last modified:March 19, 2014 - v3
Checksum:iD36EB684E7E4A6C8
GO
Isoform 3 (identifier: O95049-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MNLCGLMPIFPAPLDQVADM

Note: No experimental confirmation available.
Show »
Length:938
Mass (Da):103,424
Checksum:i603411581EB7FA85
GO
Isoform 4 (identifier: O95049-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAVRFQVADM

Show »
Length:928
Mass (Da):102,415
Checksum:iB418537346F205CF
GO
Isoform 6 (identifier: O95049-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Show »
Length:883
Mass (Da):97,488
Checksum:i511564BFC624B3A8
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7ESC0K7ESC0_HUMAN
Tight junction protein ZO-3
TJP3
123Annotation score:
K7EJ86K7EJ86_HUMAN
Tight junction protein ZO-3
TJP3
59Annotation score:

Sequence cautioni

The sequence AAC72274 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW69293 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19R → H in AAI08907 (PubMed:15489334).Curated1
Sequence conflicti96H → L in BAG52285 (PubMed:14702039).Curated1
Sequence conflicti449L → P in BAG54652 (PubMed:14702039).Curated1
Sequence conflicti802R → H in BAG52285 (PubMed:14702039).Curated1
Sequence conflicti901H → R in BAG52285 (PubMed:14702039).Curated1
Sequence conflicti917T → M in BAG65278 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_056114898M → T1 PublicationCorresponds to variant dbSNP:rs1046268Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0538441 – 36Missing in isoform 6. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_0402381M → MNLCGLMPIFPAPLDQVADM in isoform 3. 1 Publication1
Alternative sequenceiVSP_0470221M → MAVRFQVADM in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK091118 mRNA Translation: BAG52285.1
AK128237 mRNA Translation: BAG54652.1
AK304462 mRNA Translation: BAG65278.1
AC005954 Genomic DNA Translation: AAC72274.1 Sequence problems.
AC006125 Genomic DNA No translation available.
CH471139 Genomic DNA Translation: EAW69293.1 Sequence problems.
BC108906 mRNA Translation: AAI08907.1
CCDSiCCDS32873.2 [O95049-1]
CCDS59332.1 [O95049-4]
RefSeqiNP_001254489.1, NM_001267560.1 [O95049-1]
NP_001254490.1, NM_001267561.1 [O95049-4]
UniGeneiHs.25527

Genome annotation databases

EnsembliENST00000539908; ENSP00000439991; ENSG00000105289 [O95049-5]
ENST00000541714; ENSP00000439278; ENSG00000105289 [O95049-1]
ENST00000587686; ENSP00000467864; ENSG00000105289 [O95049-3]
ENST00000589378; ENSP00000465419; ENSG00000105289 [O95049-4]
GeneIDi27134
KEGGihsa:27134
UCSCiuc010xhs.4 human [O95049-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK091118 mRNA Translation: BAG52285.1
AK128237 mRNA Translation: BAG54652.1
AK304462 mRNA Translation: BAG65278.1
AC005954 Genomic DNA Translation: AAC72274.1 Sequence problems.
AC006125 Genomic DNA No translation available.
CH471139 Genomic DNA Translation: EAW69293.1 Sequence problems.
BC108906 mRNA Translation: AAI08907.1
CCDSiCCDS32873.2 [O95049-1]
CCDS59332.1 [O95049-4]
RefSeqiNP_001254489.1, NM_001267560.1 [O95049-1]
NP_001254490.1, NM_001267561.1 [O95049-4]
UniGeneiHs.25527

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KFVX-ray2.80A475-775[»]
ProteinModelPortaliO95049
SMRiO95049
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118025, 7 interactors
IntActiO95049, 5 interactors
MINTiO95049
STRINGi9606.ENSP00000262968

PTM databases

GlyConnecti1809
iPTMnetiO95049
PhosphoSitePlusiO95049

Polymorphism and mutation databases

BioMutaiTJP3

Proteomic databases

EPDiO95049
MaxQBiO95049
PaxDbiO95049
PeptideAtlasiO95049
PRIDEiO95049
ProteomicsDBi50630
50632 [O95049-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000539908; ENSP00000439991; ENSG00000105289 [O95049-5]
ENST00000541714; ENSP00000439278; ENSG00000105289 [O95049-1]
ENST00000587686; ENSP00000467864; ENSG00000105289 [O95049-3]
ENST00000589378; ENSP00000465419; ENSG00000105289 [O95049-4]
GeneIDi27134
KEGGihsa:27134
UCSCiuc010xhs.4 human [O95049-1]

Organism-specific databases

CTDi27134
DisGeNETi27134
EuPathDBiHostDB:ENSG00000105289.14
GeneCardsiTJP3
H-InvDBiHIX0014645
HGNCiHGNC:11829 TJP3
HPAiCAB013244
HPA046863
HPA053337
MIMi612689 gene
neXtProtiNX_O95049
OpenTargetsiENSG00000105289
PharmGKBiPA36534
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQ5J Eukaryota
ENOG410XS08 LUCA
GeneTreeiENSGT00760000118866
HOGENOMiHOG000230923
HOVERGENiHBG017627
InParanoidiO95049
KOiK06097
OMAiIVVFCAP
OrthoDBiEOG091G0AJZ
TreeFamiTF315606

Miscellaneous databases

ChiTaRSiTJP3 human
EvolutionaryTraceiO95049
GeneWikiiTJP3
GenomeRNAii27134
PROiPR:O95049
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105289 Expressed in 123 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_TJP3
ExpressionAtlasiO95049 baseline and differential
GenevisibleiO95049 HS

Family and domain databases

InterProiView protein in InterPro
IPR008145 GK/Ca_channel_bsu
IPR008144 Guanylate_kin-like_dom
IPR027417 P-loop_NTPase
IPR001478 PDZ
IPR036034 PDZ_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR005417 ZO
IPR005420 ZO-3
PANTHERiPTHR13865:SF11 PTHR13865:SF11, 1 hit
PfamiView protein in Pfam
PF00625 Guanylate_kin, 1 hit
PF00595 PDZ, 3 hits
PF07653 SH3_2, 1 hit
PRINTSiPR01597 ZONOCCLUDNS
PR01600 ZONOCCLUDNS3
SMARTiView protein in SMART
SM00072 GuKc, 1 hit
SM00228 PDZ, 3 hits
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF50156 SSF50156, 3 hits
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50052 GUANYLATE_KINASE_2, 1 hit
PS50106 PDZ, 3 hits
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiZO3_HUMAN
AccessioniPrimary (citable) accession number: O95049
Secondary accession number(s): A6NFP3
, B3KR73, B3KXZ0, B4E2W6, F5H2X0, F5H4S9, K7EK22, Q32N01
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: March 19, 2014
Last modified: November 7, 2018
This is version 164 of the entry and version 3 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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