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 27-MAR-2024, entry version 216. 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 SUBCELLULAR LOCATION. RX PubMed=15479741; DOI=10.1083/jcb.200402096; RA Grossmann K.S., Grund C., Huelsken J., Behrend M., Erdmann B., Franke W.W., RA Birchmeier W.; RT "Requirement of plakophilin 2 for heart morphogenesis and cardiac junction RT formation."; RL J. Cell Biol. 167:149-160(2004). RN [9] 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] {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 [20] 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 [21] RP MUTAGENESIS OF HIS-150. RX PubMed=34702855; DOI=10.1038/s41467-021-26426-1; RA Halperin D., Stavsky A., Kadir R., Drabkin M., Wormser O., Yogev Y., RA Dolgin V., Proskorovski-Ohayon R., Perez Y., Nudelman H., Stoler O., RA Rotblat B., Lifschytz T., Lotan A., Meiri G., Gitler D., Birk O.S.; RT "CDH2 mutation affecting N-cadherin function causes attention-deficit RT hyperactivity disorder in humans and mice."; RL Nat. Commun. 12:6187-6187(2021). RN [22] {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 [23] {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 [24] {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). Required for proper neurite branching. Required for CC pre- and postsynaptic organization (By similarity). CDH2 may be CC involved in neuronal recognition mechanism. In hippocampal neurons, may CC regulate dendritic spine density. {ECO:0000250|UniProtKB:P10288, CC 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). Interacts with FBXO45 (By similarity). CC {ECO:0000250|UniProtKB:P19022, ECO:0000250|UniProtKB:Q9Z1Y3, CC ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:21300292, CC ECO:0000269|PubMed:23392350, 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 junction, adherens junction CC {ECO:0000269|PubMed:15479741}. Cell junction, desmosome CC {ECO:0000269|PubMed:15479741}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P15116; 7 sites, 7 glycans. DR GlyGen; P15116; 17 sites, 7 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P15116; -. DR PhosphoSitePlus; P15116; -. DR SwissPalm; P15116; -. DR jPOST; P15116; -. DR MaxQB; P15116; -. DR PaxDb; 10090-ENSMUSP00000025166; -. DR PeptideAtlas; P15116; -. DR ProteomicsDB; 265498; -. DR Pumba; P15116; -. DR Antibodypedia; 4558; 1940 antibodies from 53 providers. DR DNASU; 12558; -. DR Ensembl; ENSMUST00000025166.14; ENSMUSP00000025166.8; ENSMUSG00000024304.15. DR GeneID; 12558; -. DR KEGG; mmu:12558; -. DR UCSC; uc008edx.2; mouse. DR AGR; MGI:88355; -. DR CTD; 1000; -. DR MGI; MGI:88355; Cdh2. DR VEuPathDB; HostDB:ENSMUSG00000024304; -. DR eggNOG; KOG3594; Eukaryota. DR GeneTree; ENSGT00940000155981; -. DR InParanoid; P15116; -. DR OMA; PRQLTKH; -. DR OrthoDB; 5306553at2759; -. 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 79 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 309 other cell types or tissues. DR ExpressionAtlas; P15116; baseline and differential. DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB. 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; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0030057; C:desmosome; IDA:UniProtKB. DR GO; GO:0005916; C:fascia adherens; IDA:MGI. DR GO; GO:0098978; C:glutamatergic synapse; 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:0099634; C:postsynaptic specialization membrane; ISO:MGI. DR GO; GO:0048787; C:presynaptic active zone membrane; ISO:MGI. 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:0034332; P:adherens junction organization; IBA:GO_Central. 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:0000902; P:cell morphogenesis; IBA:GO_Central. 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: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:0097091; P:synaptic vesicle clustering; IMP:UniProtKB. DR GO; GO:0021537; P:telencephalon development; IGI:MGI. DR GO; GO:0003323; P:type B pancreatic cell development; IMP:UniProtKB. DR CDD; cd11304; Cadherin_repeat; 3. DR Gene3D; 2.60.40.60; Cadherins; 6. DR Gene3D; 4.10.900.10; TCF3-CBD (Catenin binding domain); 1. DR InterPro; IPR039808; Cadherin. DR InterPro; IPR002126; Cadherin-like_dom. DR InterPro; IPR015919; Cadherin-like_sf. DR InterPro; IPR020894; Cadherin_CS. DR InterPro; IPR014868; Cadherin_pro_dom. DR InterPro; IPR000233; Cadherin_Y-type_LIR. DR InterPro; IPR027397; Catenin-bd_sf. DR PANTHER; PTHR24027:SF79; CADHERIN-2; 1. DR PANTHER; PTHR24027; CADHERIN-23; 1. DR Pfam; PF01049; CADH_Y-type_LIR; 1. DR Pfam; PF00028; Cadherin; 5. DR Pfam; PF08758; Cadherin_pro; 1. DR PRINTS; PR00205; CADHERIN. DR PRINTS; PR01820; DESMOCOLLIN. DR SMART; SM00112; CA; 5. DR SMART; SM01055; Cadherin_pro; 1. DR SUPFAM; SSF49313; Cadherin-like; 6. DR PROSITE; PS00232; CADHERIN_1; 3. DR PROSITE; PS50268; CADHERIN_2; 5. DR Genevisible; P15116; MM. 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 150 FT /note="H->Y: CRISPR/Cas9-mutated knockin mice manifest FT motor-associated features of hyperactivity such as greater FT traveling distance, increased velocity and prolonged FT mobility time compared with control mice. Synaptic release FT is attenuated in neuron from mutant mice and synaptic FT vesicle clusters size is reduced in presynaptic terminals." FT /evidence="ECO:0000269|PubMed:34702855" 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 FT E-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 FT A-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 //