O95049 (ZO3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tight junction protein ZO-3

Alternative name(s):
Tight junction protein 3
Zona occludens protein 3
Zonula occludens protein 3

Gene names

Name:	TJP3
Synonyms:	ZO3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	933 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Subunit structure	Interacts with occludin, claudins and ZO-1. Interacts with INADL By similarity. Interacts with UBN1. Interacts with FASLG. Ref.5 Ref.6
Subcellular location	Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cell junction › tight junction By similarity.
Sequence similarities	Belongs to the MAGUK family. Contains 1 guanylate kinase-like domain. Contains 3 PDZ (DHR) domains. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Membrane Tight junction
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of G1/S transition of mitotic cell cycle Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.6. Source: UniProtKB tight junction Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95049-1)

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.

Isoform 2 (identifier: O95049-2)

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

Note: No experimental confirmation available.

Isoform 3 (identifier: O95049-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MNLCGLMPIFPAPLDQVADM
     293-306: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 933

933

Tight junction protein ZO-3

PRO_0000094546

Regions

Domain

11 – 93

83

PDZ 1

Domain

195 – 272

78

PDZ 2

Domain

394 – 460

67

PDZ 3

Domain

489 – 563

75

SH3

Domain

594 – 775

182

Guanylate kinase-like

Amino acid modifications

Modified residue

112

1

Phosphoserine By similarity

Modified residue

159

1

Phosphoserine By similarity

Modified residue

164

1

Phosphoserine Ref.4 Ref.7 Ref.8 Ref.9

Modified residue

169

1

Phosphoserine By similarity

Modified residue

203

1

Phosphoserine By similarity

Modified residue

579

1

Phosphoserine By similarity

Modified residue

605

1

Phosphoserine By similarity

Modified residue

919

1

Phosphoserine Ref.4 Ref.8

Modified residue

920

1

Phosphoserine Ref.4 Ref.8

Natural variations

Alternative sequence

1

1

M → MNLCGLMPIFPAPLDQVADM in isoform 2 and isoform 3.

VSP_040238

Alternative sequence

293 – 306

14

Missing in isoform 3.

VSP_040239

Natural variant

912

1

M → T. Ref.3
Corresponds to variant rs1046268 [ dbSNP | Ensembl ].

VAR_056114

Experimental info

Sequence conflict

19

1

R → H in AAI08907. Ref.3

Secondary structure

1

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933

Helix Strand Turn

Details...

Beta strand

492 – 496

5

Beta strand

504 – 507

4

Beta strand

515 – 520

6

Beta strand

536 – 541

6

Beta strand

547 – 553

7

Helix

556 – 569

14

Helix

610 – 616

7

Beta strand

620 – 628

9

Beta strand

635 – 639

5

Helix

642 – 652

11

Turn

654 – 656

3

Beta strand

657 – 659

3

Helix

675 – 683

9

Beta strand

687 – 690

4

Helix

694 – 702

9

Beta strand

708 – 715

8

Helix

717 – 727

11

Helix

735 – 749

15

Helix

750 – 752

3

Beta strand

754 – 759

6

Beta strand

761 – 763

3

Helix

765 – 777

13

Beta strand

780 – 785

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: 680298CFD0615B47	FASTA	933	102,800
	10 20 30 40 50 60 MEELTIWEQH TATLSKDPRR GFGIAISGGR DRPGGSMVVS DVVPGGPAEG RLQTGDHIVM 70 80 90 100 110 120 VNGVSMENAT SAFAIQILKT CTKMANITVK RPRRIHLPAT KASPSSPGRQ DSDEDDGPQR 130 140 150 160 170 180 VEEVDQGRGY DGDSSSGSGR SWDERSRRPR PGRRGRAGSH GRRSPGGGSE ANGLALVSGF 190 200 210 220 230 240 KRLPRQDVQM KPVKSVLVKR RDSEEFGVKL GSQIFIKHIT DSGLAARHRG LQEGDLILQI 250 260 270 280 290 300 NGVSSQNLSL NDTRRLIEKS EGKLSLLVLR DRGQFLVNIP PAVSDSDSSP LEEGVTMADE 310 320 330 340 350 360 MSSPPADISD LASELSQAPP SHIPPPPRHA QRSPEASQTD SPVESPRLRR ESSVDSRTIS 370 380 390 400 410 420 EPDEQRSELP RESSYDIYRV PSSQSMEDRG YSPDTRVVRF LKGKSIGLRL AGGNDVGIFV 430 440 450 460 470 480 SGVQAGSPAD GQGIQEGDQI LQVNDVPFQN LTREEAVQFL LGLPPGEEME LVTQRKQDIF 490 500 510 520 530 540 WKMVQSRVGD SFYIRTHFEL EPSPPSGLGF TRGDVFHVLD TLHPGPGQSH ARGGHWLAVR 550 560 570 580 590 600 MGRDLREQER GIIPNQSRAE QLASLEAAQR AVGVGPGSSA GSNARAEFWR LRGLRRGAKK 610 620 630 640 650 660 TTQRSREDLS ALTRQGRYPP YERVVLREAS FKRPVVILGP VADIAMQKLT AEMPDQFEIA 670 680 690 700 710 720 ETVSRTDSPS KIIKLDTVRV IAEKDKHALL DVTPSAIERL NYVQYYPIVV FFIPESRPAL 730 740 750 760 770 780 KALRQWLAPA SRRSTRRLYA QAQKLRKHSS HLFTATIPLN GTSDTWYQEL KAIIREQQTR 790 800 810 820 830 840 PIWTAEDQLD GSLEDNLDLP HHGLADSSAD LSCDSRVNSD YETDGEGGAY TDGEGYTDGE 850 860 870 880 890 900 GGPYTDVDDE PPAPALARSS EPVQADESQS PRDRGRISAH QGAQVDSRHP QGQWRQDSMR 910 920 930 TYEREALKKK FMRVHDAESS DEDGYDWGPA TDL
	Isoform 2 [UniParc]. Checksum: 6611F0D4451295EE	FASTA	952	104,828
	10 20 30 40 50 60 MNLCGLMPIF PAPLDQVADM EELTIWEQHT ATLSKDPRRG FGIAISGGRD RPGGSMVVSD 70 80 90 100 110 120 VVPGGPAEGR LQTGDHIVMV NGVSMENATS AFAIQILKTC TKMANITVKR PRRIHLPATK 130 140 150 160 170 180 ASPSSPGRQD SDEDDGPQRV EEVDQGRGYD GDSSSGSGRS WDERSRRPRP GRRGRAGSHG 190 200 210 220 230 240 RRSPGGGSEA NGLALVSGFK RLPRQDVQMK PVKSVLVKRR DSEEFGVKLG SQIFIKHITD 250 260 270 280 290 300 SGLAARHRGL QEGDLILQIN GVSSQNLSLN DTRRLIEKSE GKLSLLVLRD RGQFLVNIPP 310 320 330 340 350 360 AVSDSDSSPL EEGVTMADEM SSPPADISDL ASELSQAPPS HIPPPPRHAQ RSPEASQTDS 370 380 390 400 410 420 PVESPRLRRE SSVDSRTISE PDEQRSELPR ESSYDIYRVP SSQSMEDRGY SPDTRVVRFL 430 440 450 460 470 480 KGKSIGLRLA GGNDVGIFVS GVQAGSPADG QGIQEGDQIL QVNDVPFQNL TREEAVQFLL 490 500 510 520 530 540 GLPPGEEMEL VTQRKQDIFW KMVQSRVGDS FYIRTHFELE PSPPSGLGFT RGDVFHVLDT 550 560 570 580 590 600 LHPGPGQSHA RGGHWLAVRM GRDLREQERG IIPNQSRAEQ LASLEAAQRA VGVGPGSSAG 610 620 630 640 650 660 SNARAEFWRL RGLRRGAKKT TQRSREDLSA LTRQGRYPPY ERVVLREASF KRPVVILGPV 670 680 690 700 710 720 ADIAMQKLTA EMPDQFEIAE TVSRTDSPSK IIKLDTVRVI AEKDKHALLD VTPSAIERLN 730 740 750 760 770 780 YVQYYPIVVF FIPESRPALK ALRQWLAPAS RRSTRRLYAQ AQKLRKHSSH LFTATIPLNG 790 800 810 820 830 840 TSDTWYQELK AIIREQQTRP IWTAEDQLDG SLEDNLDLPH HGLADSSADL SCDSRVNSDY 850 860 870 880 890 900 ETDGEGGAYT DGEGYTDGEG GPYTDVDDEP PAPALARSSE PVQADESQSP RDRGRISAHQ 910 920 930 940 950 GAQVDSRHPQ GQWRQDSMRT YEREALKKKF MRVHDAESSD EDGYDWGPAT DL
	Isoform 3 [UniParc]. Checksum: 603411581EB7FA85	FASTA	938	103,424
	10 20 30 40 50 60 MNLCGLMPIF PAPLDQVADM EELTIWEQHT ATLSKDPRRG FGIAISGGRD RPGGSMVVSD 70 80 90 100 110 120 VVPGGPAEGR LQTGDHIVMV NGVSMENATS AFAIQILKTC TKMANITVKR PRRIHLPATK 130 140 150 160 170 180 ASPSSPGRQD SDEDDGPQRV EEVDQGRGYD GDSSSGSGRS WDERSRRPRP GRRGRAGSHG 190 200 210 220 230 240 RRSPGGGSEA NGLALVSGFK RLPRQDVQMK PVKSVLVKRR DSEEFGVKLG SQIFIKHITD 250 260 270 280 290 300 SGLAARHRGL QEGDLILQIN GVSSQNLSLN DTRRLIEKSE GKLSLLVLRD RGQFLVNIPP 310 320 330 340 350 360 AVSDSDSSPL EDISDLASEL SQAPPSHIPP PPRHAQRSPE ASQTDSPVES PRLRRESSVD 370 380 390 400 410 420 SRTISEPDEQ RSELPRESSY DIYRVPSSQS MEDRGYSPDT RVVRFLKGKS IGLRLAGGND 430 440 450 460 470 480 VGIFVSGVQA GSPADGQGIQ EGDQILQVND VPFQNLTREE AVQFLLGLPP GEEMELVTQR 490 500 510 520 530 540 KQDIFWKMVQ SRVGDSFYIR THFELEPSPP SGLGFTRGDV FHVLDTLHPG PGQSHARGGH 550 560 570 580 590 600 WLAVRMGRDL REQERGIIPN QSRAEQLASL EAAQRAVGVG PGSSAGSNAR AEFWRLRGLR 610 620 630 640 650 660 RGAKKTTQRS REDLSALTRQ GRYPPYERVV LREASFKRPV VILGPVADIA MQKLTAEMPD 670 680 690 700 710 720 QFEIAETVSR TDSPSKIIKL DTVRVIAEKD KHALLDVTPS AIERLNYVQY YPIVVFFIPE 730 740 750 760 770 780 SRPALKALRQ WLAPASRRST RRLYAQAQKL RKHSSHLFTA TIPLNGTSDT WYQELKAIIR 790 800 810 820 830 840 EQQTRPIWTA EDQLDGSLED NLDLPHHGLA DSSADLSCDS RVNSDYETDG EGGAYTDGEG 850 860 870 880 890 900 YTDGEGGPYT DVDDEPPAPA LARSSEPVQA DESQSPRDRG RISAHQGAQV DSRHPQGQWR 910 920 930 QDSMRTYERE ALKKKFMRVH DAESSDEDGY DWGPATDL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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 3), VARIANT THR-912.
[4]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164; SER-919 AND SER-920, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[5]	"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening." Voss M., Lettau M., Janssen O. BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FASLG.
[6]	"Characterization of the ubinuclein protein as a new member of the nuclear and adhesion complex components (NACos)." Aho S., Lupo J., Coly P.-A., Sabine A., Castellazzi M., Morand P., Sergeant A., Manet E., Boyer V., Gruffat H. Biol. Cell 101:319-334(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBN1.
[7]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[8]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164; SER-919 AND SER-920, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, MASS SPECTROMETRY.
[10]	"Crystal structure of the SH3-kinase fragment of tight junction protein 3 (TJP3) in apo-form." Structural genomics consortium (SGC) Submitted (NOV-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 489-789.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AC005954 Genomic DNA. Translation: AAC72274.1.
AC006125 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69293.1.
BC108906 mRNA. Translation: AAI08907.1.

IPI

IPI00744036.
IPI00792295.
IPI00973106.

UniGene

Hs.25527.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3KFV	X-ray	2.80	A	489-789	[»]

ProteinModelPortal

O95049.

ModBase

Search...

Protein-protein interaction databases

IntAct

O95049. 2 interactions.

MINT

MINT-210473.

STRING

9606.ENSP00000262968.

PTM databases

PhosphoSite

O95049.

Proteomic databases

PaxDb

O95049.

PRIDE

O95049.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262968; ENSP00000262968; ENSG00000105289.
ENST00000382008; ENSP00000371438; ENSG00000105289.
ENST00000587686; ENSP00000467864; ENSG00000105289.

UCSC

uc010xhu.2. human.
uc010xhv.2. human.

Organism-specific databases

GeneCards

GC19P003659.

H-InvDB

HIX0014645.

HGNC

HGNC:11829. TJP3.

HPA

CAB013244.

MIM

612689. gene.

neXtProt

NX_O95049.

PharmGKB

PA36534.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG239704.

HOGENOM

HOG000230923.

HOVERGEN

HBG017627.

InParanoid

O95049.

OMA

EQERGII.

OrthoDB

EOG4VMFDT.

PhylomeDB

O95049.

Gene expression databases

ArrayExpress

O95049.

Bgee

O95049.

CleanEx

HS_TJP3.

Genevestigator

O95049.

GermOnline

ENSG00000105289. Homo sapiens.

Family and domain databases

InterPro

IPR008144. Guanylate_kin.
IPR008145. Guanylate_kin/L-typ_Ca_channel.
IPR001478. PDZ.
IPR011511. SH3_2.
IPR001452. SH3_domain.
IPR005417. ZonOcculdens.
IPR005420. ZonOcculS3.
[Graphical view]

PANTHER

PTHR13865:SF11. PTHR13865:SF11. 1 hit.

Pfam

PF00625. Guanylate_kin. 1 hit.
PF00595. PDZ. 3 hits.
PF07653. SH3_2. 1 hit.
[Graphical view]

PRINTS

PR01597. ZONOCCLUDNS.
PR01600. ZONOCCLUDNS3.

SMART

SM00072. GuKc. 1 hit.
SM00228. PDZ. 3 hits.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50156. PDZ. 3 hits.
SSF50044. SH3. 1 hit.

PROSITE

PS00856. GUANYLATE_KINASE_1. False negative.
PS50052. GUANYLATE_KINASE_2. 1 hit.
PS50106. PDZ. 3 hits.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O95049.

NextBio

13603241.

SOURCE

Search...

Entry information

Entry name

ZO3_HUMAN

Accession

Primary (citable) accession number: O95049
Secondary accession number(s): A6NFP3, Q32N01

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	January 11, 2001
Last modified:	May 1, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.