KEGG   PATHWAY: hsa04530Help
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
BRITE hierarchy
Pathway map
Tight junction
hsa04530

All organismsOrtholog table
Disease
H00578  
MYH9-related kidney diseases
H00594  
Distal muscular dystrophies
H00606  
Early infantile epileptic encephalopathy
H00656  
Scapuloperoneal myopathy (SPM)
H00703  
Myosin storage myopathy (MSM)
H00742  
Neonatal ichthyosis-sclerosing cholangitis (NISCH) syndrome
H00801  
Familial thoracic aortic aneurysm and dissection (TAAD)
H00811  
Distal arthrogryposis (DA)
H00840  
Band-like calcification with simplified gyration and polymicrogyria (BLC-PMG)
H00872  
Trismus-pseudocamptodactyly syndrome
H00894  
FG syndrome (FGS)
H00947  
Pilomatricoma
H01195  
VACTERL/VATER association
H01210  
Hypomagnesemia
H01229  
Inclusion body myopathy 3 (IBM3)
H01255  
Juvenile-onset dystonia
H01301  
Hemorrhagic destruction of the brain, subependymal calcification, and cataracts
H01677  
Congenital hydrocephalus
Drug
D04510  
Imciromab pentetate (USAN)
D09671  
Sotrastaurin (USAN/INN)
D09718  
Sotrastaurin acetate (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
92359  
CRB3; crumbs 3, cell polarity complex component [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]
644672  
CLDN25; claudin 25 [KO:K06087]
CLDN24; claudin 24 [KO:K06087]
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  
MPP5; membrane palmitoylated protein 5 [KO:K06091]
58538  
MPP4; membrane palmitoylated 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; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
4771  
NF2; neurofibromin 2 [KO:K16684]
3993  
LLGL2; LLGL2, scribble cell polarity complex component [KO:K06094]
3996  
LLGL1; LLGL1, scribble cell polarity complex component [KO:K06094]
1739  
DLG1; discs large MAGUK scaffold protein 1 [KO:K12076]
23513  
SCRIB; scribbled 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; T-cell lymphoma invasion and metastasis 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; neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase [KO:K10591] [EC:2.3.2.26]
23327  
NEDD4L; neural precursor cell expressed, developmentally down-regulated 4-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; cystic fibrosis transmembrane conductance regulator [KO:K05031] [EC:3.6.3.49]
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 [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; runt related transcription factor 1 [KO:K08367]
3308  
HSPA4; heat shock protein family A (Hsp70) member 4 [KO:K09489]
9368  
SLC9A3R1; SLC9A3 regulator 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]
60  
ACTB; actin beta [KO:K05692]
71  
ACTG1; actin gamma 1 [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; ARP2 actin related protein 2 homolog [KO:K17260]
57180  
ACTR3B; ARP3 actin related protein 3 homolog B [KO:K18584]
653857  
ACTR3C; ARP3 actin-related protein 3 homolog C [KO:K18584]
10096  
ACTR3; ARP3 actin related protein 3 homolog [KO:K18584]
123720  
WHAMM; WAS protein homolog associated with actin, golgi membranes and microtubules [KO:K20479]
7454  
WAS; Wiskott-Aldrich syndrome [KO:K05747]
8976  
WASL; Wiskott-Aldrich syndrome like [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]
5562  
PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.11]
5563  
PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.11]
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]
22989  
MYH15; myosin heavy chain 15 [KO:K10352]
4619  
MYH1; myosin heavy chain 1 [KO:K10352]
4620  
MYH2; myosin heavy chain 2 [KO:K10352]
4621  
MYH3; myosin heavy chain 3 [KO:K10352]
4622  
MYH4; myosin heavy chain 4 [KO:K10352]
4626  
MYH8; myosin heavy chain 8 [KO:K10352]
4627  
MYH9; myosin heavy chain 9 [KO:K10352]
4628  
MYH10; myosin heavy chain 10 [KO:K10352]
4629  
MYH11; myosin heavy chain 11 [KO:K10352]
57644  
MYH7B; myosin heavy chain 7B [KO:K10352]
79784  
MYH14; myosin heavy chain 14 [KO:K10352]
8735  
MYH13; myosin heavy chain 13 [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
  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)
Reference
  Authors
Martin-Belmonte F, Perez-Moreno M
  Title
Epithelial cell polarity, stem cells and cancer.
  Journal
Nat Rev Cancer 12:23-38 (2011)
Reference
  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)
Reference
  Authors
Miyoshi J, Takai Y
  Title
Molecular perspective on tight-junction assembly and epithelial polarity.
  Journal
Adv Drug Deliv Rev 57:815-55 (2005)
Reference
  Authors
Mertens AE, Pegtel DM, Collard JG
  Title
Tiam1 takes PARt in cell polarity.
  Journal
Trends Cell Biol 16:308-16 (2006)
Reference
  Authors
Shin K, Fogg VC, Margolis B
  Title
Tight junctions and cell polarity.
  Journal
Annu Rev Cell Dev Biol 22:207-35 (2006)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Terry S, Nie M, Matter K, Balda MS
  Title
Rho signaling and tight junction functions.
  Journal
Physiology (Bethesda) 25:16-26 (2010)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Moleirinho S, Guerrant W, Kissil JL
  Title
The Angiomotins--from discovery to function.
  Journal
FEBS Lett 588:2693-703 (2014)
Reference
  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)
Reference
  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)
Reference
  Authors
Mack NA, Georgiou M
  Title
The interdependence of the Rho GTPases and apicobasal cell polarity.
  Journal
Small GTPases 5:10 (2014)
Reference
  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)
Reference
  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)
Reference
  Authors
Nakano A, Takashima S
  Title
LKB1 and AMP-activated protein kinase: regulators of cell polarity.
  Journal
Genes Cells 17:737-47 (2012)
Reference
  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)
Reference
  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)
Reference
  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)
KO pathway
 

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