KEGG   PATHWAY: hsa04530
Entry
hsa04530                    Pathway                                
Name
Tight junction - Homo sapiens (human)
Description
Tight junctions (TJs) are essential for establishing a selectively permeable barrier to diffusion through the paracellular space between neighboring cells. TJs are composed of at least three types of transmembrane protein -occludin, claudin and junctional adhesion molecules (JAMs)- and a cytoplasmic 'plaque' consisting of many different proteins that form large complexes. These are proposed to be involved in junction assembly, barrier regulation, cell polarity, gene transcription, and other pathways.
Class
Cellular Processes; Cellular community - eukaryotes
Pathway map
hsa04530  Tight junction
hsa04530

Network
  Element
N00340  The Scribble/Dlg/Lgl polarity module
N00344  CRB3-Pals1-PATJ complex
N01287  Tight junction-Actin signaling pathway
Drug
D11527  Zolbetuximab (USAN/INN)
D12722  Bexotegrast (USAN/INN)
D12781  Osemitamab (USAN/INN)
Other DBs
GO: 0005923
Organism
Homo sapiens (human) [GN:hsa]
Gene
92359  CRB3; crumbs cell polarity complex component 3 [KO:K06090]
1364  CLDN4; claudin 4 [KO:K06087]
1365  CLDN3; claudin 3 [KO:K06087]
1366  CLDN7; claudin 7 [KO:K06087]
149461  CLDN19; claudin 19 [KO:K06087]
10686  CLDN16; claudin 16 [KO:K06087]
23562  CLDN14; claudin 14 [KO:K06087]
24146  CLDN15; claudin 15 [KO:K06087]
26285  CLDN17; claudin 17 [KO:K06087]
49861  CLDN20; claudin 20 [KO:K06087]
5010  CLDN11; claudin 11 [KO:K06087]
51208  CLDN18; claudin 18 [KO:K06087]
53842  CLDN22; claudin 22 [KO:K06087]
7122  CLDN5; claudin 5 [KO:K06087]
9071  CLDN10; claudin 10 [KO:K06087]
9073  CLDN8; claudin 8 [KO:K06087]
9074  CLDN6; claudin 6 [KO:K06087]
9075  CLDN2; claudin 2 [KO:K06087]
9076  CLDN1; claudin 1 [KO:K06087]
9080  CLDN9; claudin 9 [KO:K06087]
137075  CLDN23; claudin 23 [KO:K06087]
100288814  CLDN34; claudin 34 [KO:K06087]
644672  CLDN25; claudin 25 [KO:K06087]
100132463  CLDN24; claudin 24 [KO:K06087]
9069  CLDN12; claudin 12 [KO:K06087]
100506658  OCLN; occludin [KO:K06088]
50848  F11R; F11 receptor [KO:K06089]
58494  JAM2; junctional adhesion molecule 2 [KO:K06735]
83700  JAM3; junctional adhesion molecule 3 [KO:K06785]
11149  BVES; blood vessel epicardial substance [KO:K21108]
998  CDC42; cell division cycle 42 [KO:K04393]
50855  PARD6A; par-6 family cell polarity regulator alpha [KO:K06093]
84552  PARD6G; par-6 family cell polarity regulator gamma [KO:K06093]
84612  PARD6B; par-6 family cell polarity regulator beta [KO:K06093]
64398  PALS1; protein associated with LIN7 1, MAGUK p55 family member [KO:K06091]
58538  MPP4; MAGUK p55 scaffold protein 4 [KO:K21109]
27134  TJP3; tight junction protein 3 [KO:K06097]
10207  PATJ; PATJ crumbs cell polarity complex component [KO:K06092]
8777  MPDZ; multiple PDZ domain crumbs cell polarity complex component [KO:K06095]
5590  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
5584  PRKCI; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
154796  AMOT; angiomotin [KO:K16819]
154810  AMOTL1; angiomotin like 1 [KO:K06104]
51421  AMOTL2; angiomotin like 2 [KO:K06104]
55114  ARHGAP17; Rho GTPase activating protein 17 [KO:K20638]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
4771  NF2; NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [KO:K16684]
3993  LLGL2; LLGL scribble cell polarity complex component 2 [KO:K06094]
3996  LLGL1; LLGL scribble cell polarity complex component 1 [KO:K06094]
1739  DLG1; discs large MAGUK scaffold protein 1 [KO:K12076]
23513  SCRIB; scribble planar cell polarity protein [KO:K16175]
5515  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
5516  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
5519  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
5518  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
5520  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
5521  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
5522  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
55844  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
56288  PARD3; par-3 family cell polarity regulator [KO:K04237]
7074  TIAM1; TIAM Rac1 associated GEF 1 [KO:K05731]
7082  TJP1; tight junction protein 1 [KO:K05701]
93643  TJAP1; tight junction associated protein 1 [KO:K06105]
1740  DLG2; discs large MAGUK scaffold protein 2 [KO:K12075]
1741  DLG3; discs large MAGUK scaffold protein 3 [KO:K21098]
4734  NEDD4; NEDD4 E3 ubiquitin protein ligase [KO:K10591] [EC:2.3.2.26]
23327  NEDD4L; NEDD4 like E3 ubiquitin protein ligase [KO:K13305] [EC:2.3.2.26]
57530  CGN; cingulin [KO:K06102]
84952  CGNL1; cingulin like 1 [KO:K21110]
9181  ARHGEF2; Rho/Rac guanine nucleotide exchange factor 2 [KO:K12791]
387  RHOA; ras homolog family member A [KO:K04513]
2626  GATA4; GATA binding protein 4 [KO:K09183]
91862  MARVELD3; MARVEL domain containing 3 [KO:K21099]
4214  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
909  CD1A; CD1a molecule [KO:K06448]
910  CD1B; CD1b molecule [KO:K06448]
911  CD1C; CD1c molecule [KO:K06448]
912  CD1D; CD1d molecule [KO:K06448]
913  CD1E; CD1e molecule [KO:K06448]
1080  CFTR; CF transmembrane conductance regulator [KO:K05031] [EC:5.6.1.6]
1019  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
8531  YBX3; Y-box binding protein 3 [KO:K06099]
8189  SYMPK; symplekin scaffold protein [KO:K06100]
5111  PCNA; proliferating cell nuclear antigen [KO:K04802]
595  CCND1; cyclin D1 [KO:K04503]
2064  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
861  RUNX1; RUNX family transcription factor 1 [KO:K08367]
3308  HSPA4; heat shock protein family A (Hsp70) member 4 [KO:K09489]
9368  NHERF1; NHERF family PDZ scaffold protein 1 [KO:K13365]
7430  EZR; ezrin [KO:K08007]
5962  RDX; radixin [KO:K05762]
4478  MSN; moesin [KO:K05763]
5581  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
71  ACTG1; actin gamma 1 [KO:K05692]
60  ACTB; actin beta [KO:K05692]
776  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
4217  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
5609  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
6714  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
2017  CTTN; cortactin [KO:K06106]
3059  HCLS1; hematopoietic cell-specific Lyn substrate 1 [KO:K06106]
10097  ACTR2; actin related protein 2 [KO:K17260]
57180  ACTR3B; actin related protein 3B [KO:K18584]
653857  ACTR3C; actin related protein 3C [KO:K18584]
10096  ACTR3; actin related protein 3 [KO:K18584]
10095  ARPC1B; actin related protein 2/3 complex subunit 1B [KO:K05757]
10552  ARPC1A; actin related protein 2/3 complex subunit 1A [KO:K05757]
10109  ARPC2; actin related protein 2/3 complex subunit 2 [KO:K05758]
10094  ARPC3; actin related protein 2/3 complex subunit 3 [KO:K05756]
10093  ARPC4; actin related protein 2/3 complex subunit 4 [KO:K05755]
10092  ARPC5; actin related protein 2/3 complex subunit 5 [KO:K05754]
81873  ARPC5L; actin related protein 2/3 complex subunit 5 like [KO:K05754]
123720  WHAMM; WASP homolog associated with actin, golgi membranes and microtubules [KO:K20479]
7454  WAS; WASP actin nucleation promoting factor [KO:K05747]
7408  VASP; vasodilator stimulated phosphoprotein [KO:K06274]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
5872  RAB13; RAB13, member RAS oncogene family [KO:K06109]
23370  ARHGEF18; Rho/Rac guanine nucleotide exchange factor 18 [KO:K21066]
6093  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
9475  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
4633  MYL2; myosin light chain 2 [KO:K10351]
54566  EPB41L4B; erythrocyte membrane protein band 4.1 like 4B [KO:K21111]
6794  STK11; serine/threonine kinase 11 [KO:K07298] [EC:2.7.11.1]
5562  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
5563  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
5564  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
5565  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
5571  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
53632  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
51422  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
4627  MYH9; myosin heavy chain 9 [KO:K10352]
4628  MYH10; myosin heavy chain 10 [KO:K10352]
4629  MYH11; myosin heavy chain 11 [KO:K10352]
79784  MYH14; myosin heavy chain 14 [KO:K10352]
140465  MYL6B; myosin light chain 6B [KO:K12751]
4637  MYL6; myosin light chain 6 [KO:K12751]
10398  MYL9; myosin light chain 9 [KO:K12755]
103910  MYL12B; myosin light chain 12B [KO:K12757]
10627  MYL12A; myosin light chain 12A [KO:K12757]
150084  IGSF5; immunoglobulin superfamily member 5 [KO:K06786]
9223  MAGI1; membrane associated guanylate kinase, WW and PDZ domain containing 1 [KO:K05631]
11346  SYNPO; synaptopodin [KO:K21112]
87  ACTN1; actinin alpha 1 [KO:K05699]
81  ACTN4; actinin alpha 4 [KO:K05699]
79778  MICALL2; MICAL like 2 [KO:K21068]
4218  RAB8A; RAB8A, member RAS oncogene family [KO:K07901]
51762  RAB8B; RAB8B, member RAS oncogene family [KO:K07902]
51735  RAPGEF6; Rap guanine nucleotide exchange factor 6 [KO:K08020]
5906  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
3688  ITGB1; integrin subunit beta 1 [KO:K05719]
4301  AFDN; afadin, adherens junction formation factor [KO:K05702]
9414  TJP2; tight junction protein 2 [KO:K06098]
9693  RAPGEF2; Rap guanine nucleotide exchange factor 2 [KO:K08018]
57826  RAP2C; RAP2C, member of RAS oncogene family [KO:K07839]
153562  MARVELD2; MARVEL domain containing 2 [KO:K17291]
10376  TUBA1B; tubulin alpha 1b [KO:K07374]
7277  TUBA4A; tubulin alpha 4a [KO:K07374]
7278  TUBA3C; tubulin alpha 3c [KO:K07374]
7846  TUBA1A; tubulin alpha 1a [KO:K07374]
84790  TUBA1C; tubulin alpha 1c [KO:K07374]
51807  TUBA8; tubulin alpha 8 [KO:K07374]
112714  TUBA3E; tubulin alpha 3e [KO:K07374]
113457  TUBA3D; tubulin alpha 3d [KO:K07374]
79861  TUBAL3; tubulin alpha like 3 [KO:K07374]
Compound
C00076  Calcium cation
Reference
PMID:27353478
  Authors
Zihni C, Mills C, Matter K, Balda MS
  Title
Tight junctions: from simple barriers to multifunctional molecular gates.
  Journal
Nat Rev Mol Cell Biol 17:564-80 (2016)
DOI:10.1038/nrm.2016.80
Reference
PMID:22169974
  Authors
Martin-Belmonte F, Perez-Moreno M
  Title
Epithelial cell polarity, stem cells and cancer.
  Journal
Nat Rev Cancer 12:23-38 (2011)
DOI:10.1038/nrc3169
Reference
PMID:17525755
  Authors
Weber C, Fraemohs L, Dejana E
  Title
The role of junctional adhesion molecules in vascular inflammation.
  Journal
Nat Rev Immunol 7:467-77 (2007)
DOI:10.1038/nri2096
Reference
PMID:15820555
  Authors
Miyoshi J, Takai Y
  Title
Molecular perspective on tight-junction assembly and epithelial polarity.
  Journal
Adv Drug Deliv Rev 57:815-55 (2005)
DOI:10.1016/j.addr.2005.01.008
Reference
PMID:16650994
  Authors
Mertens AE, Pegtel DM, Collard JG
  Title
Tiam1 takes PARt in cell polarity.
  Journal
Trends Cell Biol 16:308-16 (2006)
DOI:10.1016/j.tcb.2006.04.001
Reference
PMID:16771626
  Authors
Shin K, Fogg VC, Margolis B
  Title
Tight junctions and cell polarity.
  Journal
Annu Rev Cell Dev Biol 22:207-35 (2006)
DOI:10.1146/annurev.cellbio.22.010305.104219
Reference
PMID:17182900
  Authors
Kooistra MR, Dube N, Bos JL
  Title
Rap1: a key regulator in cell-cell junction formation.
  Journal
J Cell Sci 120:17-22 (2007)
DOI:10.1242/jcs.03306
Reference
PMID:17950242
  Authors
Gonzalez-Mariscal L, Tapia R, Chamorro D
  Title
Crosstalk of tight junction components with signaling pathways.
  Journal
Biochim Biophys Acta 1778:729-56 (2008)
DOI:10.1016/j.bbamem.2007.08.018
Reference
PMID:18005931
  Authors
Assemat E, Bazellieres E, Pallesi-Pocachard E, Le Bivic A, Massey-Harroche D
  Title
Polarity complex proteins.
  Journal
Biochim Biophys Acta 1778:614-30 (2008)
DOI:10.1016/j.bbamem.2007.08.029
Reference
PMID:18946474
  Authors
Iden S, Collard JG
  Title
Crosstalk between small GTPases and polarity proteins in cell polarization.
  Journal
Nat Rev Mol Cell Biol 9:846-59 (2008)
DOI:10.1038/nrm2521
Reference
PMID:20094051
  Authors
Rosse C, Linch M, Kermorgant S, Cameron AJ, Boeckeler K, Parker PJ
  Title
PKC and the control of localized signal dynamics.
  Journal
Nat Rev Mol Cell Biol 11:103-12 (2010)
DOI:10.1038/nrm2847
Reference
PMID:20134025
  Authors
Terry S, Nie M, Matter K, Balda MS
  Title
Rho signaling and tight junction functions.
  Journal
Physiology (Bethesda) 25:16-26 (2010)
DOI:10.1152/physiol.00034.2009
Reference
PMID:21283798
  Authors
Russ PK, Pino CJ, Williams CS, Bader DM, Haselton FR, Chang MS
  Title
Bves modulates tight junction associated signaling.
  Journal
PLoS One 6:e14563 (2011)
DOI:10.1371/journal.pone.0014563
Reference
PMID:21781017
  Authors
Citi S, Spadaro D, Schneider Y, Stutz J, Pulimeno P
  Title
Regulation of small GTPases at epithelial cell-cell junctions.
  Journal
Mol Membr Biol 28:427-44 (2011)
DOI:10.3109/09687688.2011.603101
Reference
PMID:22896795
  Authors
Lickert H, Van Campenhout CA
  Title
Evolution of the Discs large gene family provides new insights into the establishment of apical epithelial polarity and the etiology of mental retardation.
  Journal
Commun Integr Biol 5:287-90 (2012)
DOI:10.4161/cib.19792
Reference
PMID:22928510
  Authors
Spadaro D, Tapia R, Pulimeno P, Citi S
  Title
The control of gene expression and cell proliferation by the epithelial apical junctional complex.
  Journal
Essays Biochem 53:83-93 (2012)
DOI:10.1042/bse0530083
Reference
PMID:24548561
  Authors
Moleirinho S, Guerrant W, Kissil JL
  Title
The Angiomotins--from discovery to function.
  Journal
FEBS Lett 588:2693-703 (2014)
DOI:10.1016/j.febslet.2014.02.006
Reference
PMID:24651541
  Authors
Rodriguez-Boulan E, Macara IG
  Title
Organization and execution of the epithelial polarity programme.
  Journal
Nat Rev Mol Cell Biol 15:225-42 (2014)
DOI:10.1038/nrm3775
Reference
PMID:25152334
  Authors
Gonzalez-Mariscal L, Dominguez-Calderon A, Raya-Sandino A, Ortega-Olvera JM, Vargas-Sierra O, Martinez-Revollar G
  Title
Tight junctions and the regulation of gene expression.
  Journal
Semin Cell Dev Biol 36:213-23 (2014)
DOI:10.1016/j.semcdb.2014.08.009
Reference
PMID:25469537
  Authors
Mack NA, Georgiou M
  Title
The interdependence of the Rho GTPases and apicobasal cell polarity.
  Journal
Small GTPases 5:10 (2014)
DOI:10.4161/21541248.2014.973768
Reference
PMID:25483301
  Authors
Citi S, Guerrera D, Spadaro D, Shah J
  Title
Epithelial junctions and Rho family GTPases: the zonular signalosome.
  Journal
Small GTPases 5:1-15 (2014)
DOI:10.4161/21541248.2014.973760
Reference
PMID:25757376
  Authors
Zihni C, Terry SJ
  Title
RhoGTPase signalling at epithelial tight junctions: Bridging the GAP between polarity and cancer.
  Journal
Int J Biochem Cell Biol 64:120-5 (2015)
DOI:10.1016/j.biocel.2015.02.020
Reference
PMID:22892070
  Authors
Nakano A, Takashima S
  Title
LKB1 and AMP-activated protein kinase: regulators of cell polarity.
  Journal
Genes Cells 17:737-47 (2012)
DOI:10.1111/j.1365-2443.2012.01629.x
Reference
PMID:12042308
  Authors
Patrie KM, Drescher AJ, Welihinda A, Mundel P, Margolis B
  Title
Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4, with the tight junction protein MAGI-1.
  Journal
J Biol Chem 277:30183-90 (2002)
DOI:10.1074/jbc.M203072200
Reference
PMID:18094055
  Authors
Yamamura R, Nishimura N, Nakatsuji H, Arase S, Sasaki T
  Title
The interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of tight junctions and adherens junctions.
  Journal
Mol Biol Cell 19:971-83 (2008)
DOI:10.1091/mbc.E07-06-0551
Reference
PMID:23885123
  Authors
Monteiro AC, Sumagin R, Rankin CR, Leoni G, Mina MJ, Reiter DM, Stehle T, Dermody TS, Schaefer SA, Hall RA, Nusrat A, Parkos CA
  Title
JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function.
  Journal
Mol Biol Cell 24:2849-60 (2013)
DOI:10.1091/mbc.E13-06-0298
Related
pathway
hsa04520  Adherens junction
hsa04810  Regulation of actin cytoskeleton
KO pathway
ko04530   
LinkDB

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