Table 1.

Interactions between tight junction–associated proteins

Name	Structural signatures	Binding partners

TRANSMEMBRANE PROTEINS
Claudin family
Claudins	Four transmembrane domains, two cytoplasmic tails, two extracellular loops, one intracellular linker, one C-terminal PDZ-binding motif	Claudins (extracellular domains),^c,e,f,h,i,k occludin (extracellular region),^j marvelD3,^h CD9,^j CD81 (extracellular loop),^g,i EpCAM,^d,g ZO-1 (PDZ-binding motifs),^a,b,e,f,h ZO-2,^a,b,e,f ZO-3,^a,b,e,f MUPP1 (PDZ-binding motifs),^a,c PATJ (PDZ-binding motif ),^b Clostridium perfringens enterotoxin (second extracellular loop)^a
Tight junction–associated MARVEL proteins (TAMPs)
Occludin	Four transmembrane domains (forming MARVEL domain), two cytoplasmic tails, two extracellular loops, one intracellular linker Occludin and tricellulin C-terminal tails contain an OCEL (coiled-coil) domain	Occludin,^b connexin26 (OCEL),^b TGFβ RI and RII (second extracellular loop),^d,j ZO-1 (OCEL),^b,h ZO-2,^a,b ZO-3,^b cingulin (C-terminal cytoplasmic tail),^b F-actin (C-terminal cytoplasmic tail),^a VAP33 (OCEL),^c,g,h c-Yes (OCEL),^b,d,g PI3 kinase p85 (C-terminal coiled coil),^b PKCζ (OCEL),^b PKCη (C-terminal tail),^a,e,h CK2 (C-terminal tail),^j Itch (N-terminal cytoplasmic tail),^c,d,e,h Nedd4-2 (C-terminal tail PY motif),^e focal adhesion kinase^d
Tricellulin		MarvelD3,^d ZO-1 (C-terminal cytoplasmic tail)^a
MarvelD3		Occludin,^d tricellulin^d
Junctional adhesion molecules (JAMs)
JAM-A/JAM-1	Immunoglobulin (Ig) superfamily: one N-terminal extracellular region, one transmembrane region, one C-terminal cytosplasmic tail, C-terminal PDZ-binding motif; extracellular region contains two V-type Ig domains	JAM-A (extracellular region),^b,j LFA-1/CD11a/CD18 (Ig domain 2),^c,j α_Vβ₃ integrin,^d ZO-1 (PDZ-binding motif),^a,b,d MUPP1 (PDZ-binding motif),^a,b,c PATJ (PDZ-binding motif ),^b Par3 (PDZ-binding motif ),^a,d,h AF-6 (PDZ-binding motif),^b,c,d,g cingulin (C-terminal cytoplasmic tail),^b,d PDZ-GEF2,^e,g reovirus sigma protein^a,j
JAM-B/JAM-2		JAM-C (extracellular region),^a,h,j α_Vβ₁ integrin,^j ZO-1 (PDZ-binding motif),^a,b,h Par3 (PDZ-binding motif)^b,h
JAM-C/JAM-3		JAM-B (V domain),^a,h,j JAM-C(V domain),^b,j CD11b/CD18 (extracellular region),^a,j ZO-1 (PDZ domain),^a,b Par3 (PDZ-binding motif )^b
JAM-4/IGSF5		JAM-4,^h,j MAGI-1 (PDZ-binding motif)^b,c,e,h
CAR-like CTX family proteins
CAR	CTX family of Ig superfamily proteins: extracellular loop contains one V-type and one C2-type Ig domain and C-terminal PDZ-binding motif	CAR (D1 domain),^a ZO-1,^d,f,g,h MUPP1 (PDZ-binding motif),^a,c,d,e,g,h LNX (PDZ-binding motif),^b,c,h F-actin (cytoplasmic tail),^a,b,g,h microtubule (cytoplasmic tail),^a,b,d,f,g Coxsackie virus,^j adenovirus (D1 domain)^a,b,j
ESAM		ESAM (extracellular region),^j MAGI-1 (PDZ-binding motif)^b,c,e
CLMP		None determined
Popeye family proteins
Bves/popeye 1	Three transmembrane domain, one N-terminal extracellular tail, one extracellular loop, one intracellular linker, one C-terminal cytoplasmic tail	Bves (extracellular region),^j ZO-1 (C-terminal cytoplasmic tail),^b,g VAMP3 (C-terminal cytoplasmic tail),^b,c,e,g GEFT (C-terminal cytoplasmic tail)^b,c,g
PERIPHERAL MEMBRANE PROTEINS
Zonula occludens (ZO) family
ZO-1	Three PDZ domains, one SH3 domain, one GuK domain, one actin-binding region; ZO-2 and ZO-3 have C-terminal PDZ-binding motifs	Claudins (PDZ1),^a,b,e,f,h occludin (SH3-Guk domain),^a,b JAM-A (PDZ3),^a,b,d JAM-B (PDZ1-3),^a,b,h JAM-C (PDZ1–3),^a,b tricellulin (aa 1–888),^a CAR,^d,f,g,h Bves,^b,g Neph1–3 (PDZ1),^b,e,g connexins (PDZ domains),^b,c,e,g ZO-2 (PDZ2),^a,b ZO-3 (PDZ2),^a,b AF6 (N-terminal to Guk domain),^a,b,f,g α-catenin (SH3-Guk domain),^a,b ARVCF (PDZ domains),^a,b,e,h α-actinin-4 (PDZ1),^b,d,e,g α-spectrin,^d F-actin (actin-binding region),^a,h,j ZONAB (SH3),^b,e,j tuba,^e,g,h Shroom2 (SH3-Guk),^b,c,e,g,h Csk,^b Gα(12) (SH3),^e,h phosphoinositide (PDZ2)^j
ZO-2		Claudins (PDZ1)^a,b,e,f,h, occludin (SH3-GuK)^b,e, connexins (PDZ domains),^b,e,h ZO-1 (PDZ2),^a,b α-catenin (SH3-GuK),^b,e ARVCF (PDZ domains),^a,b,h F-actin,^a sec6/8,^d,j protein 4.1R (aa 1,054–1,118)^b,c,d,e,g tuba,^e,g Csk (aa 487–652),^b,e Gα (12) (SH3),^e,h SAF-B (PDZ1),^b,c,e,h PKC,^j Fos,^b,d,g,j Jun,^b,d,g,j C/EBP,^b,d,g,j Scribble (C-terminal PDZ-binding motif),^b,e,h phosphoinositide (PDZ2)^j
ZO-3		Claudins (PDZ1),^a,b,e,f,h occludin,^b ZO-1 (PDZ2),^d,e MUPP1 (C-terminal PDZ-binding motif),^b PATJ (C-terminal PDZ-binding motif )^b,e,h,g F-actin,^a connexins (PDZ domains)^b,e,h
Cingulin family
Cingulin	Globular N-terminal head and C-terminal tail domains and central α-helical rod domain	JAM-A,^b,d ZO-1 (aa 1–378),^b,e ZO-2 (aa 1–378),^b,e ZO-3 (aa 1–378),^b AF-6 (aa 1–378),^b F-actin (aa 101–294),^a,b myosin (aa 377–1,368),^b GEF-H1 (aa 782–1,025)^b,d,g,h
Cingulin-L1/JACOP		None determined
Angiomotin (Amot)/JEAP family
Amot	Coiled-coil domains and C-terminal PDZ-binding motifs; contains a lipid-binding domain	Angiostatin (BIG3 domain),^b,c Rich1 (coiled-coil domain),^e Amot-like 1,^e MAGI-1,^e,g MUPP1 (PDZ-binding motif),^c,d,e PATJ (PDZ-binding motif),^b,e Syx (PDZ-binding motif)^b,e
Amotl1/JEAP		Amot (coiled coil),^e MUPP1 (PDZ-binding motif),^c,e PATJ (PDZ-binding motif),^e Syx (PDZ-binding motif )^b
Amotl2/MASCOT		MAGI-1,^e MUPP1 (PDZ-binding motif),^c,d,e PATJ (PDZ-binding motif),^e Syx (PDZ-binding motif )^b
MAGUK with inverted domain structure (MAGI) family
MAGI-1	Six PDZ domains, two WW domains, one Guk domain	JAM-4 (PDZ1 and PDZ4)^b,c,e,h ESAM,^b,c,e nephrin (PDZ2–3),^{a,b,c,d,e,f,g,h} megalin (PDZ5),^b,c Amot,^e,g Amot-like 2,^e β-catenin (PDZ5),^c,d synaptopodin (WW2)^b,e,h,j α-actinin-4 (PDZ5),^b,e,h PDZ-GEF1 (PDZ1),^d,e mNET1 (PDZ1),^b,c,f PTEN (PDZ2),^c,d,e,g,h TRIP6 (PDZ5)^c,e
MUPP/PATJ family
MUPP1/MPDZ	One L27 domain, 13 PDZ domains	Claudins (PDZ10),^a,c CAR(PDZ13),^a,c,d,e,g,h JAM-A (PDZ9),^a,b,c nectin (PDZ5),^b,h ZO-3 (PDZ7),^b PALS (L27),^a,b Amot (PDZ2–3),^c,e Amot-like 1 (PDZ3),^c,e Amot-like 2 (PDZ2–3),^c,e Par6,^b,e Syx^b
PATJ	One L27 domain, ten PDZ domains	Claudin-1 (PDZ8),^b JAM-A (PDZ3),^b nectin (PDZ5),^b,h ZO-3 (PDZ6)^b,e,h,g PALS1 (L27),^a,b Crumbs (N-terminal domain),^e Par6,^b,e Amot (PDZ3),^c,e Amot-like 1 (PDZ1),^c,e Amot-like 2 (PDZ2),^c,e Syx (PDZ10)^c
Other peripheral membrane proteins
AF-6/l-afadin	Two Ras-binding domains, one forkhead-associated domain, one class V myosin homology region, DIL, one PDZ domain, and an actin-binding domain	Nectin,^b,c,d,e,h JAM-A (PDZ),^b,c,d,g ZO-1 (Ras-binding domain),^a,b,f,g cingulin,^b F-actin (aa 1,631–1,829),^a profilin,^b,c c-Src (PDZ domain),^a,b,d,g ADIP (DIL domain),^a,b,e Ras,^b,c Rap1^c,e,h
Pilt		hDlg^b,c,g
Barmotin/7H6		None determined
Symplekin		ZONAB^a,b,c,f,g

Parenthetical text indicates the domain used to bind identified partners. A fully referenced version of this table is available online (Supplemental Table 1; follow the Supplemental Material link from the Annual Reviews home page at http://www.annualreviews.org).

In vitro binding of bacterially expressed or purified proteins.

GST (glutathione S-transferase) fusion protein or peptide pulldown from eukaryotic cell lysates.

Yeast two-hybrid assay.

Coimmunoprecipitation of endogenous proteins.

Coimmunoprecipitation of overexpressed proteins.

Colocalization (by electron microscopy).

Colocalization (of endogenous proteins by fluorescence microscopy).

Colocalization (of overexpressed proteins by fluorescence microscopy).

ⁱ

Fluorescent resonant energy transfer.

Other methods.