CADH2_MOUSE
ID CADH2_MOUSE Reviewed; 906 AA.
AC P15116; Q64260; Q6GU11;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Cadherin-2;
DE AltName: Full=Neural cadherin;
DE Short=N-cadherin;
DE AltName: CD_antigen=CD325;
DE Flags: Precursor;
GN Name=Cdh2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=2762814; DOI=10.1126/science.2762814;
RA Miyatani S., Shimamura K., Hatta M., Nagafuchi A., Nose A., Matsunaga M.,
RA Hatta K., Takeichi M.;
RT "Neural cadherin: role in selective cell-cell adhesion.";
RL Science 245:631-635(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tamura K.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=1528849; DOI=10.1073/pnas.89.18.8443;
RA Miyatani S., Copeland N.G., Gilbert D.J., Jenkins N.A., Takeichi M.;
RT "Genomic structure and chromosomal mapping of the mouse N-cadherin gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8443-8447(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=8879495; DOI=10.1095/biolreprod55.4.822;
RA Munro S.B., Blaschuk O.W.;
RT "A comprehensive survey of the cadherins expressed in the testes of fetal,
RT immature, and adult mice utilizing the polymerase chain reaction.";
RL Biol. Reprod. 55:822-827(1996).
RN [7]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH FGFR4; PLCG1; FRS2; SRC;
RP GAP43 AND CTTN.
RX PubMed=11433297; DOI=10.1038/35083041;
RA Cavallaro U., Niedermeyer J., Fuxa M., Christofori G.;
RT "N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor
RT signalling.";
RL Nat. Cell Biol. 3:650-657(2001).
RN [8]
RP FUNCTION, PCDH8-MEDIATED ENDOCYTOSIS, AND SUBCELLULAR LOCATION.
RX PubMed=17988630; DOI=10.1016/j.neuron.2007.08.020;
RA Yasuda S., Tanaka H., Sugiura H., Okamura K., Sakaguchi T., Tran U.,
RA Takemiya T., Mizoguchi A., Yagita Y., Sakurai T., De Robertis E.M.,
RA Yamagata K.;
RT "Activity-induced protocadherin arcadlin regulates dendritic spine number
RT by triggering N-cadherin endocytosis via TAO2beta and p38 MAP kinases.";
RL Neuron 56:456-471(2007).
RN [9]
RP PROTEOLYTIC PROCESSING.
RX PubMed=19805319; DOI=10.1073/pnas.0908507106;
RA Folgueras A.R., Valdes-Sanchez T., Llano E., Menendez L., Baamonde A.,
RA Denlinger B.L., Belmonte C., Juarez L., Lastra A., Garcia-Suarez O.,
RA Astudillo A., Kirstein M., Pendas A.M., Farinas I., Lopez-Otin C.;
RT "Metalloproteinase MT5-MMP is an essential modulator of neuro-immune
RT interactions in thermal pain stimulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:16451-16456(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Liver, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP CALCIUM-BINDING SITES, MUTAGENESIS OF ASP-262 AND ASP-293, AND DOMAIN.
RX PubMed=21366346; DOI=10.1021/bi101872b;
RA Vunnam N., Pedigo S.;
RT "Sequential binding of calcium leads to dimerization in neural cadherin.";
RL Biochemistry 50:2973-2982(2011).
RN [12]
RP INTERACTION WITH OBSCN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=23392350; DOI=10.1096/fj.12-221317;
RA Hu L.Y., Kontrogianni-Konstantopoulos A.;
RT "The kinase domains of obscurin interact with intercellular adhesion
RT proteins.";
RL FASEB J. 27:2001-2012(2013).
RN [13]
RP DEVELOPMENTAL STAGE.
RX PubMed=23001562; DOI=10.1093/hmg/dds398;
RA Alves C.H., Sanz A.S., Park B., Pellissier L.P., Tanimoto N., Beck S.C.,
RA Huber G., Murtaza M., Richard F., Sridevi Gurubaran I., Garcia Garrido M.,
RA Levelt C.N., Rashbass P., Le Bivic A., Seeliger M.W., Wijnholds J.;
RT "Loss of CRB2 in the mouse retina mimics human retinitis pigmentosa due to
RT mutations in the CRB1 gene.";
RL Hum. Mol. Genet. 22:35-50(2013).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=25232112; DOI=10.1523/jneurosci.1280-14.2014;
RA Wang S.H., Celic I., Choi S.Y., Riccomagno M., Wang Q., Sun L.O.,
RA Mitchell S.P., Vasioukhin V., Huganir R.L., Kolodkin A.L.;
RT "Dlg5 regulates dendritic spine formation and synaptogenesis by controlling
RT subcellular N-cadherin localization.";
RL J. Neurosci. 34:12745-12761(2014).
RN [15]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PROTEOLYTIC PROCESSING.
RX PubMed=24952463; DOI=10.1038/ncb2993;
RA Porlan E., Marti-Prado B., Morante-Redolat J.M., Consiglio A.,
RA Delgado A.C., Kypta R., Lopez-Otin C., Kirstein M., Farinas I.;
RT "MT5-MMP regulates adult neural stem cell functional quiescence through the
RT cleavage of N-cadherin.";
RL Nat. Cell Biol. 16:629-638(2014).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=26403541; DOI=10.1038/ncomms9391;
RA Sharma P., Abbasi C., Lazic S., Teng A.C., Wang D., Dubois N.,
RA Ignatchenko V., Wong V., Liu J., Araki T., Tiburcy M., Ackerley C.,
RA Zimmermann W.H., Hamilton R., Sun Y., Liu P.P., Keller G., Stagljar I.,
RA Scott I.C., Kislinger T., Gramolini A.O.;
RT "Evolutionarily conserved intercalated disc protein Tmem65 regulates
RT cardiac conduction and connexin 43 function.";
RL Nat. Commun. 6:8391-8391(2015).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26750727; DOI=10.1038/srep19006;
RA Wang X., Xie B., Qi Y., Wallerman O., Vasylovska S., Andersson L.,
RA Kozlova E.N., Welsh N.;
RT "Knock-down of ZBED6 in insulin-producing cells promotes N-cadherin
RT junctions between beta-cells and neural crest stem cells in vitro.";
RL Sci. Rep. 6:19006-19006(2016).
RN [18] {ECO:0007744|PDB:1NCG, ECO:0007744|PDB:1NCH, ECO:0007744|PDB:1NCI}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 160-267.
RX PubMed=7885471; DOI=10.1038/374327a0;
RA Shapiro L., Fannon A.M., Kwong P.D., Thompson A., Lehmann M.S., Gruebel G.,
RA Legrand J.-F., Als-Nielsen J., Colman D.R., Hendrickson W.A.;
RT "Structural basis of cell-cell adhesion by cadherins.";
RL Nature 374:327-337(1995).
RN [19]
RP DEVELOPMENTAL STAGE.
RX PubMed=31650526; DOI=10.1111/cge.13660;
RA Reis L.M., Houssin N.S., Zamora C., Abdul-Rahman O., Kalish J.M.,
RA Zackai E.H., Plageman T.F. Jr., Semina E.V.;
RT "Novel variants in CDH2 are associated with a new syndrome including Peters
RT anomaly.";
RL Clin. Genet. 97:502-508(2020).
RN [20] {ECO:0007744|PDB:1NCJ}
RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 160-374 IN COMPLEX WITH CALCIUM,
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-161; VAL-162;
RP ALA-237 AND ALA-239.
RX PubMed=9655503; DOI=10.1016/s0896-6273(00)80496-1;
RA Tamura K., Shan W.S., Hendrickson W.A., Colman D.R., Shapiro L.;
RT "Structure-function analysis of cell adhesion by neural (N-) cadherin.";
RL Neuron 20:1153-1163(1998).
RN [21] {ECO:0007744|PDB:3Q2W}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 160-712 IN COMPLEX WITH CALCIUM,
RP SUBUNIT, DOMAIN, GLYCOSYLATION ON SER AND THR RESIDUES, AND GLYCOSYLATION
RP AT ASN-273; ASN-325; ASN-402; ASN-572 AND ASN-651.
RX PubMed=21300292; DOI=10.1016/j.str.2010.11.016;
RA Harrison O.J., Jin X., Hong S., Bahna F., Ahlsen G., Brasch J., Wu Y.,
RA Vendome J., Felsovalyi K., Hampton C.M., Troyanovsky R.B., Ben-Shaul A.,
RA Frank J., Troyanovsky S.M., Shapiro L., Honig B.;
RT "The extracellular architecture of adherens junctions revealed by crystal
RT structures of type I cadherins.";
RL Structure 19:244-256(2011).
RN [22] {ECO:0007744|PDB:4NUM, ECO:0007744|PDB:4NUP, ECO:0007744|PDB:4NUQ}
RP X-RAY CRYSTALLOGRAPHY (2.12 ANGSTROMS) OF 160-374 IN COMPLEX WITH CALCIUM,
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF TRP-161 AND ARG-173.
RX PubMed=25253890; DOI=10.1073/pnas.1416737111;
RA Vendome J., Felsovalyi K., Song H., Yang Z., Jin X., Brasch J.,
RA Harrison O.J., Ahlsen G., Bahna F., Kaczynska A., Katsamba P.S., Edmond D.,
RA Hubbell W.L., Shapiro L., Honig B.;
RT "Structural and energetic determinants of adhesive binding specificity in
RT type I cadherins.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E4175-E4184(2014).
CC -!- FUNCTION: Calcium-dependent cell adhesion protein; preferentially
CC mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain
CC from another cell (PubMed:2762814, PubMed:11433297, PubMed:17988630,
CC PubMed:9655503, PubMed:25253890). Cadherins may thus contribute to the
CC sorting of heterogeneous cell types. Acts as a regulator of neural stem
CC cells quiescence by mediating anchorage of neural stem cells to
CC ependymocytes in the adult subependymal zone: upon cleavage by MMP24,
CC CDH2-mediated anchorage is affected, leading to modulate neural stem
CC cell quiescence (PubMed:24952463). Plays a role in cell-to-cell
CC junction formation between pancreatic beta cells and neural crest stem
CC (NCS) cells, promoting the formation of processes by NCS cells
CC (PubMed:26750727). CDH2 may be involved in neuronal recognition
CC mechanism. In hippocampal neurons, may regulate dendritic spine
CC density. {ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:17988630,
CC ECO:0000269|PubMed:24952463, ECO:0000269|PubMed:25253890,
CC ECO:0000269|PubMed:26750727, ECO:0000269|PubMed:2762814,
CC ECO:0000269|PubMed:9655503}.
CC -!- SUBUNIT: Homodimer (via extracellular region) (PubMed:21300292,
CC PubMed:25253890). Can also form heterodimers with other cadherins (via
CC extracellular region) (PubMed:25253890). Dimerization occurs in trans,
CC i.e. with a cadherin chain from another cell (PubMed:21300292,
CC PubMed:25253890). Interacts with CDCP1 (By similarity). Interacts with
CC PCDH8; this complex may also include TAOK2 (By similarity). The
CC interaction with PCDH8 may lead to internalization through TAOK2/p38
CC MAPK pathway (By similarity). Identified in a complex containing FGFR4,
CC NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN (PubMed:11433297).
CC May interact with OBSCN (via protein kinase domain 2)
CC (PubMed:23392350). {ECO:0000250|UniProtKB:P19022,
CC ECO:0000250|UniProtKB:Q9Z1Y3, ECO:0000269|PubMed:11433297,
CC ECO:0000269|PubMed:21300292, ECO:0000269|PubMed:23392350,
CC ECO:0000269|PubMed:25253890}.
CC -!- INTERACTION:
CC P15116; P15116: Cdh2; NbExp=4; IntAct=EBI-397974, EBI-397974;
CC P15116; P18031: PTPN1; Xeno; NbExp=3; IntAct=EBI-397974, EBI-968788;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17988630,
CC ECO:0000269|PubMed:26403541, ECO:0000269|PubMed:9655503}; Single-pass
CC type I membrane protein {ECO:0000255}. Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:23392350}. Cell junction
CC {ECO:0000269|PubMed:26750727}. Cell surface
CC {ECO:0000269|PubMed:25232112, ECO:0000269|PubMed:9655503}.
CC Note=Colocalizes with TMEM65 at the intercalated disk in cardiomyocytes
CC (PubMed:26403541). Colocalizes with OBSCN at the intercalated disk and
CC sarcolemma in cardiomyocytes (PubMed:23392350).
CC {ECO:0000269|PubMed:23392350, ECO:0000269|PubMed:26403541}.
CC -!- TISSUE SPECIFICITY: Expressed in cardiac muscle (at protein level).
CC {ECO:0000269|PubMed:23392350}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all stages of testicular development
CC with the highest expression levels found in testes of 21-day-old mice
CC (PubMed:8879495). Expressed at the outer limiting membrane of the
CC retina at 3 months of age (PubMed:23001562). Expression is restricted
CC to the lens stalk region between 10 and 11 dpc. At later stages (17.5
CC dpc), it is expressed in the developing lens and corneal endothelium
CC (PubMed:31650526). {ECO:0000269|PubMed:23001562,
CC ECO:0000269|PubMed:31650526, ECO:0000269|PubMed:8879495}.
CC -!- DOMAIN: Three calcium ions are usually bound at the interface of each
CC cadherin domain and rigidify the connections, imparting a strong
CC curvature to the full-length ectodomain. Calcium-binding sites are
CC occupied sequentially in the order of site 3, then site 2 and site 1.
CC {ECO:0000269|PubMed:21300292, ECO:0000269|PubMed:21366346}.
CC -!- PTM: Cleaved by MMP24 (PubMed:19805319, PubMed:24952463). Ectodomain
CC cleavage leads to the generation of a soluble 90 kDa N-terminal soluble
CC fragment and a 45 kDa membrane-bound C-terminal fragment 1 (CTF1),
CC which is further cleaved by gamma-secretase into a 35 kDa
CC (PubMed:24952463). Cleavage in neural stem cells by MMP24 affects CDH2-
CC mediated anchorage of neural stem cells to ependymocytes in the adult
CC subependymal zone, leading to modulate neural stem cell quiescence
CC (PubMed:24952463). {ECO:0000269|PubMed:19805319,
CC ECO:0000269|PubMed:24952463}.
CC -!- PTM: May be phosphorylated by OBSCN. {ECO:0000269|PubMed:23392350}.
CC -!- PTM: O-glycosylated on Ser and Thr residues.
CC {ECO:0000269|PubMed:21300292}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality.
CC {ECO:0000269|PubMed:24952463}.
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DR EMBL; M31131; AAA37353.1; -; mRNA.
DR EMBL; AB008811; BAA23549.1; -; mRNA.
DR EMBL; S45011; AAB23356.1; -; Genomic_DNA.
DR EMBL; CH466557; EDK96930.1; -; Genomic_DNA.
DR EMBL; BC022107; AAH22107.1; -; mRNA.
DR CCDS; CCDS29076.1; -.
DR PIR; A32759; IJMSCN.
DR RefSeq; NP_031690.3; NM_007664.5.
DR PDB; 1NCG; X-ray; 2.10 A; A=160-267.
DR PDB; 1NCH; X-ray; 2.10 A; A/B=160-267.
DR PDB; 1NCI; X-ray; 2.10 A; A/B=160-267.
DR PDB; 1NCJ; X-ray; 3.40 A; A=160-374.
DR PDB; 1OP4; NMR; -; A=24-159.
DR PDB; 2QVI; X-ray; 3.01 A; A=160-374.
DR PDB; 3Q2W; X-ray; 3.20 A; A=160-712.
DR PDB; 4NUM; X-ray; 3.30 A; A/B/C/D=160-374.
DR PDB; 4NUP; X-ray; 2.70 A; A/B/C=162-374.
DR PDB; 4NUQ; X-ray; 2.12 A; A=160-374.
DR PDBsum; 1NCG; -.
DR PDBsum; 1NCH; -.
DR PDBsum; 1NCI; -.
DR PDBsum; 1NCJ; -.
DR PDBsum; 1OP4; -.
DR PDBsum; 2QVI; -.
DR PDBsum; 3Q2W; -.
DR PDBsum; 4NUM; -.
DR PDBsum; 4NUP; -.
DR PDBsum; 4NUQ; -.
DR AlphaFoldDB; P15116; -.
DR SMR; P15116; -.
DR BioGRID; 198637; 36.
DR CORUM; P15116; -.
DR DIP; DIP-31564N; -.
DR IntAct; P15116; 17.
DR MINT; P15116; -.
DR STRING; 10090.ENSMUSP00000025166; -.
DR GlyConnect; 2169; 7 N-Linked glycans (3 sites).
DR GlyGen; P15116; 16 sites, 7 N-linked glycans (3 sites).
DR iPTMnet; P15116; -.
DR PhosphoSitePlus; P15116; -.
DR jPOST; P15116; -.
DR MaxQB; P15116; -.
DR PaxDb; P15116; -.
DR PeptideAtlas; P15116; -.
DR PRIDE; P15116; -.
DR ProteomicsDB; 265498; -.
DR Antibodypedia; 4558; 1714 antibodies from 53 providers.
DR DNASU; 12558; -.
DR Ensembl; ENSMUST00000025166; ENSMUSP00000025166; ENSMUSG00000024304.
DR GeneID; 12558; -.
DR KEGG; mmu:12558; -.
DR UCSC; uc008edx.2; mouse.
DR CTD; 1000; -.
DR MGI; MGI:88355; Cdh2.
DR VEuPathDB; HostDB:ENSMUSG00000024304; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT00940000155981; -.
DR InParanoid; P15116; -.
DR OMA; NVRFQSC; -.
DR OrthoDB; 191117at2759; -.
DR PhylomeDB; P15116; -.
DR TreeFam; TF316817; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-418990; Adherens junctions interactions.
DR Reactome; R-MMU-525793; Myogenesis.
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 12558; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Cdh2; mouse.
DR EvolutionaryTrace; P15116; -.
DR PRO; PR:P15116; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P15116; protein.
DR Bgee; ENSMUSG00000024304; Expressed in median eminence of neurohypophysis and 305 other tissues.
DR ExpressionAtlas; P15116; baseline and differential.
DR Genevisible; P15116; MM.
DR GO; GO:0005912; C:adherens junction; IDA:MGI.
DR GO; GO:0045177; C:apical part of cell; IBA:GO_Central.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0016327; C:apicolateral plasma membrane; IDA:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
DR GO; GO:0016342; C:catenin complex; ISO:MGI.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005916; C:fascia adherens; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; ISO:MGI.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; ISO:MGI.
DR GO; GO:0014704; C:intercalated disc; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0030315; C:T-tubule; ISO:MGI.
DR GO; GO:0045294; F:alpha-catenin binding; ISO:MGI.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0045295; F:gamma-catenin binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050998; F:nitric-oxide synthase binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0048854; P:brain morphogenesis; IGI:MGI.
DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; IDA:MGI.
DR GO; GO:0007155; P:cell adhesion; IDA:MGI.
DR GO; GO:0016477; P:cell migration; IDA:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; IDA:UniProtKB.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0007043; P:cell-cell junction assembly; IMP:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IGI:MGI.
DR GO; GO:0010001; P:glial cell differentiation; IDA:UniProtKB.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IDA:MGI.
DR GO; GO:0048872; P:homeostasis of number of cells; IGI:MGI.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IDA:MGI.
DR GO; GO:0090497; P:mesenchymal cell migration; IMP:MGI.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0014032; P:neural crest cell development; IMP:UniProtKB.
DR GO; GO:0060563; P:neuroepithelial cell differentiation; IGI:MGI.
DR GO; GO:0097118; P:neuroligin clustering involved in postsynaptic membrane assembly; IMP:BHF-UCL.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IGI:MGI.
DR GO; GO:2000809; P:positive regulation of synaptic vesicle clustering; IMP:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
DR GO; GO:0060019; P:radial glial cell differentiation; IGI:MGI.
DR GO; GO:0050770; P:regulation of axonogenesis; ISO:MGI.
DR GO; GO:0031641; P:regulation of myelination; ISO:MGI.
DR GO; GO:0070445; P:regulation of oligodendrocyte progenitor proliferation; IGI:MGI.
DR GO; GO:1902897; P:regulation of postsynaptic density protein 95 clustering; IMP:BHF-UCL.
DR GO; GO:0032880; P:regulation of protein localization; ISO:MGI.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; ISO:MGI.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISO:MGI.
DR GO; GO:0051146; P:striated muscle cell differentiation; IGI:MGI.
DR GO; GO:0007416; P:synapse assembly; ISO:MGI.
DR GO; GO:0021537; P:telencephalon development; IGI:MGI.
DR GO; GO:0003323; P:type B pancreatic cell development; IMP:UniProtKB.
DR Gene3D; 4.10.900.10; -; 1.
DR InterPro; IPR039808; Cadherin.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR000233; Cadherin_cytoplasmic-dom.
DR InterPro; IPR014868; Cadherin_pro_dom.
DR InterPro; IPR027397; Catenin-bd_sf.
DR InterPro; IPR030051; CDH2.
DR PANTHER; PTHR24027; PTHR24027; 1.
DR PANTHER; PTHR24027:SF79; PTHR24027:SF79; 1.
DR Pfam; PF00028; Cadherin; 5.
DR Pfam; PF01049; Cadherin_C; 1.
DR Pfam; PF08758; Cadherin_pro; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 5.
DR SMART; SM01055; Cadherin_pro; 1.
DR SUPFAM; SSF49313; SSF49313; 6.
DR PROSITE; PS00232; CADHERIN_1; 3.
DR PROSITE; PS50268; CADHERIN_2; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell adhesion; Cell junction; Cell membrane;
KW Cleavage on pair of basic residues; Glycoprotein; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..159
FT /evidence="ECO:0000255"
FT /id="PRO_0000003733"
FT CHAIN 160..906
FT /note="Cadherin-2"
FT /id="PRO_0000003734"
FT TOPO_DOM 160..724
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 725..745
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 746..906
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 160..267
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 268..382
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 383..497
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 498..603
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 604..717
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 863..883
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 864..883
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 226
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 259
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 260
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 261
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 262
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21366346,
FT ECO:0000269|PubMed:25253890, ECO:0007744|PDB:4NUQ"
FT BINDING 262
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:21366346,
FT ECO:0000269|PubMed:25253890, ECO:0007744|PDB:4NUQ"
FT BINDING 263
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 293
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:21366346,
FT ECO:0000269|PubMed:25253890, ECO:0007744|PDB:4NUQ"
FT BINDING 295
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 301
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT BINDING 353
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:25253890,
FT ECO:0007744|PDB:4NUQ"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21300292,
FT ECO:0007744|PDB:3Q2W"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21300292,
FT ECO:0007744|PDB:3Q2W"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21300292,
FT ECO:0007744|PDB:3Q2W"
FT CARBOHYD 572
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21300292,
FT ECO:0007744|PDB:3Q2W"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21300292,
FT ECO:0007744|PDB:3Q2W"
FT CARBOHYD 692
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 161
FT /note="W->A,Y: Loss of calcium-dependent cell-cell
FT adhesion."
FT /evidence="ECO:0000269|PubMed:9655503"
FT MUTAGEN 161
FT /note="W->A: Loss of dimerization; when associated with E-
FT 173."
FT /evidence="ECO:0000269|PubMed:25253890"
FT MUTAGEN 162
FT /note="V->A: Decreased calcium-dependent cell-cell
FT adhesion."
FT /evidence="ECO:0000269|PubMed:9655503"
FT MUTAGEN 173
FT /note="R->E: Loss of dimerization; when associated with A-
FT 161."
FT /evidence="ECO:0000269|PubMed:25253890"
FT MUTAGEN 237
FT /note="A->M: Loss of calcium-dependent cell-cell adhesion."
FT /evidence="ECO:0000269|PubMed:9655503"
FT MUTAGEN 239
FT /note="A->M: Loss of calcium-dependent cell-cell adhesion."
FT /evidence="ECO:0000269|PubMed:9655503"
FT MUTAGEN 262
FT /note="D->A: Abolishes dimerization."
FT /evidence="ECO:0000269|PubMed:21366346"
FT MUTAGEN 293
FT /note="D->A: Severely impaired the binding of calcium to
FT all three sites."
FT /evidence="ECO:0000269|PubMed:21366346"
FT CONFLICT 7..9
FT /note="APR -> GRG (in Ref. 1; AAA37353)"
FT /evidence="ECO:0000305"
FT CONFLICT 565..567
FT /note="NVK -> YVQ (in Ref. 1; AAA37353)"
FT /evidence="ECO:0000305"
FT CONFLICT 624
FT /note="T -> A (in Ref. 1; AAA37353)"
FT /evidence="ECO:0000305"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:1OP4"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:1OP4"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:1OP4"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:1OP4"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:1OP4"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:1OP4"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:1OP4"
FT STRAND 100..108
FT /evidence="ECO:0007829|PDB:1OP4"
FT TURN 109..112
FT /evidence="ECO:0007829|PDB:1OP4"
FT STRAND 113..121
FT /evidence="ECO:0007829|PDB:1OP4"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:1NCG"
FT STRAND 176..182
FT /evidence="ECO:0007829|PDB:1NCG"
FT HELIX 186..190
FT /evidence="ECO:0007829|PDB:1NCG"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:1NCG"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:1NCG"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:1NCG"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:1NCG"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:1NCG"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:1NCG"
FT TURN 227..229
FT /evidence="ECO:0007829|PDB:1NCG"
FT STRAND 232..240
FT /evidence="ECO:0007829|PDB:1NCG"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:2QVI"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:1NCI"
FT STRAND 251..258
FT /evidence="ECO:0007829|PDB:1NCG"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:4NUQ"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:4NUQ"
FT STRAND 285..288
FT /evidence="ECO:0007829|PDB:4NUQ"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:4NUQ"
FT STRAND 305..313
FT /evidence="ECO:0007829|PDB:4NUQ"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:4NUQ"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:4NUQ"
FT STRAND 329..332
FT /evidence="ECO:0007829|PDB:4NUQ"
FT TURN 339..341
FT /evidence="ECO:0007829|PDB:4NUQ"
FT STRAND 344..353
FT /evidence="ECO:0007829|PDB:4NUQ"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:4NUQ"
FT TURN 358..360
FT /evidence="ECO:0007829|PDB:4NUQ"
FT STRAND 363..373
FT /evidence="ECO:0007829|PDB:4NUQ"
FT STRAND 381..394
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 396..406
FT /evidence="ECO:0007829|PDB:3Q2W"
FT TURN 414..416
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 421..425
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 431..435
FT /evidence="ECO:0007829|PDB:3Q2W"
FT TURN 437..439
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 441..446
FT /evidence="ECO:0007829|PDB:3Q2W"
FT TURN 452..454
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 456..463
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:3Q2W"
FT HELIX 478..480
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 481..489
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 496..508
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 515..518
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 526..528
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 532..538
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 544..546
FT /evidence="ECO:0007829|PDB:3Q2W"
FT TURN 548..550
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 552..557
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 561..563
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 568..579
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 581..583
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 586..596
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 604..606
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 621..623
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 633..636
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 638..640
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 643..645
FT /evidence="ECO:0007829|PDB:3Q2W"
FT HELIX 646..651
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 652..656
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 658..660
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 662..666
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 674..683
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 685..688
FT /evidence="ECO:0007829|PDB:3Q2W"
FT STRAND 691..700
FT /evidence="ECO:0007829|PDB:3Q2W"
SQ SEQUENCE 906 AA; 99796 MW; BDAB8063A23E1F13 CRC64;
MCRIAGAPRT LLPLLAALLQ ASVEASGEIA LCKTGFPEDV YSAVLPKDVH EGQPLLNVKF
SNCNRKRKVQ YESSEPADFK VDEDGTVYAV RSFPLTAEQA KFLIYAQDKE TQEKWQVAVN
LSREPTLTEE PMKEPHEIEE IVFPRQLAKH SGALQRQKRD WVIPPINLPE NSRGPFPQEL
VRIRSDRDKN LSLRYSVTGP GADQPPTGIF IINPISGQLS VTKPLDRELI ARFHLRAHAV
DINGNQVENP IDIVINVIDM NDNRPEFLHQ VWNGSVPEGS KPGTYVMTVT AIDADDPNAL
NGMLRYRILS QAPSTPSPNM FTINNETGDI ITVAAGLDRE KVQQYTLIIQ ATDMEGNPTY
GLSNTATAVI TVTDVNDNPP EFTAMTFYGE VPENRVDVIV ANLTVTDKDQ PHTPAWNAAY
RISGGDPTGR FAILTDPNSN DGLVTVVKPI DFETNRMFVL TVAAENQVPL AKGIQHPPQS
TATVSVTVID VNENPYFAPN PKIIRQEEGL HAGTMLTTLT AQDPDRYMQQ NIRYTKLSDP
ANWLKIDPVN GQITTIAVLD RESPNVKNNI YNATFLASDN GIPPMSGTGT LQIYLLDIND
NAPQVLPQEA ETCETPEPNS INITALDYDI DPNAGPFAFD LPLSPVTIKR NWTINRLNGD
FAQLNLKIKF LEAGIYEVPI IITDSGNPPK SNISILRVKV CQCDSNGDCT DVDRIVGAGL
GTGAIIAILL CIIILLILVL MFVVWMKRRD KERQAKQLLI DPEDDVRDNI LKYDEEGGGE
EDQDYDLSQL QQPDTVEPDA IKPVGIRRLD ERPIHAEPQY PVRSAAPHPG DIGDFINEGL
KAADNDPTAP PYDSLLVFDY EGSGSTAGSL SSLNSSSSGG DQDYDYLNDW GPRFKKLADM
YGGGDD
