ID CADH2_HUMAN Reviewed; 906 AA. AC P19022; A8MWK3; B0YIY6; Q14923; Q8N173; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 4. DT 27-MAR-2024, entry version 217. DE RecName: Full=Cadherin-2; DE AltName: Full=CDw325; DE AltName: Full=Neural cadherin; DE Short=N-cadherin {ECO:0000303|PubMed:2216790}; DE AltName: CD_antigen=CD325; DE Flags: Precursor; GN Name=CDH2; Synonyms=CDHN, NCAD; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-196. RX PubMed=2216790; DOI=10.1093/nar/18.19.5896; RA Reid R.A., Hemperly J.J.; RT "Human N-cadherin: nucleotide and deduced amino acid sequence."; RL Nucleic Acids Res. 18:5896-5896(1990). RN [2] RP SEQUENCE REVISION TO 341; 699 AND 705. RA Reid R.A.; RL Submitted (NOV-1990) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1500442; DOI=10.1242/jcs.102.1.7; RA Salomon D., Ayalon O., Patel-King R., Hynes R.O., Geiger B.; RT "Extrajunctional distribution of N-cadherin in cultured human endothelial RT cells."; RL J. Cell Sci. 102:7-17(1992). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J., RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-454. RC TISSUE=Brain; 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 160-906 (ISOFORM 1), AND VARIANT LEU-212. RX PubMed=2384753; DOI=10.1111/j.1471-4159.1990.tb04563.x; RA Walsh F.S., Barton C.H., Putt W., Moore S.E., Kelsell D., Spurr N., RA Goodfellow P.N.; RT "N-cadherin gene maps to human chromosome 18 and is not linked to the E- RT cadherin gene."; RL J. Neurochem. 55:805-812(1990). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20. RX PubMed=7959764; DOI=10.1006/geno.1994.1358; RA Wallis J.A., Fox M., Walsh F.S.; RT "Structure of the human N-cadherin gene: YAC analysis and fine chromosomal RT mapping to 18q11.2."; RL Genomics 22:172-179(1994). RN [11] RP INTERACTION WITH CDCP1. RX PubMed=16007225; DOI=10.1038/sj.onc.1208582; RA Bhatt A.S., Erdjument-Bromage H., Tempst P., Craik C.S., Moasser M.M.; RT "Adhesion signaling by a novel mitotic substrate of src kinases."; RL Oncogene 24:5333-5343(2005). RN [12] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-273; ASN-402; ASN-572 AND RP ASN-692. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [13] RP PHOSPHORYLATION AT SER-96 AND SER-135. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=28169360; DOI=10.1038/srep42125; RA Liu J., Li J., Li P., Wang Y., Liang Z., Jiang Y., Li J., Feng C., Wang R., RA Chen H., Zhou C., Zhang J., Yang J., Liu P.; RT "Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo RT signaling pathway."; RL Sci. Rep. 7:42125-42125(2017). RN [15] RP INTERACTION WITH FBXO45. RX PubMed=32341084; DOI=10.1128/mcb.00539-19; RA Na Y., Calvo-Jimenez E., Kon E., Cao H., Jossin Y., Cooper J.A.; RT "Fbxo45 Binds SPRY Motifs in the Extracellular Domain of N-Cadherin and RT Regulates Neuron Migration during Brain Development."; RL Mol. Cell. Biol. 40:0-0(2020). RN [16] RP INVOLVEMENT IN ARVD14, AND VARIANTS ARVD14 PRO-229 AND ASN-407. RX PubMed=28280076; DOI=10.1161/circgenetics.116.001605; RA Mayosi B.M., Fish M., Shaboodien G., Mastantuono E., Kraus S., Wieland T., RA Kotta M.C., Chin A., Laing N., Ntusi N.B., Chong M., Horsfall C., RA Pimstone S.N., Gentilini D., Parati G., Strom T.M., Meitinger T., Pare G., RA Schwartz P.J., Crotti L.; RT "Identification of cadherin 2 (CDH2) mutations in arrhythmogenic right RT ventricular cardiomyopathy."; RL Circ. Cardiovasc. Genet. 10:0-0(2017). RN [17] RP INVOLVEMENT IN ARVD14, AND VARIANT ARVD14 ASN-407. RX PubMed=28326674; DOI=10.1111/chd.12462; RA Turkowski K.L., Tester D.J., Bos J.M., Haugaa K.H., Ackerman M.J.; RT "Whole exome sequencing with genomic triangulation implicates CDH2-encoded RT N-cadherin as a novel pathogenic substrate for arrhythmogenic RT cardiomyopathy."; RL Congenit. Heart Dis. 12:226-235(2017). RN [18] RP INVOLVEMENT IN ACOGS, FUNCTION, VARIANTS ACOGS ASN-353; ASN-597; TYR-597; RP THR-601; TRP-613; GLY-627 AND CYS-676, AND CHARACTERIZATION OF VARIANTS RP ACOGS ASN-353; ASN-597; THR-601; TRP-613; GLY-627 AND CYS-676. RX PubMed=31585109; DOI=10.1016/j.ajhg.2019.09.005; RG Undiagnosed Diseases Network; RA Accogli A., Calabretta S., St-Onge J., Boudrahem-Addour N., RA Dionne-Laporte A., Joset P., Azzarello-Burri S., Rauch A., Krier J., RA Fieg E., Pallais J.C., McConkie-Rosell A., McDonald M., Freedman S.F., RA Riviere J.B., Lafond-Lapalme J., Simpson B.N., Hopkin R.J., Trimouille A., RA Van-Gils J., Begtrup A., McWalter K., Delphine H., Keren B., Genevieve D., RA Argilli E., Sherr E.H., Severino M., Rouleau G.A., Yam P.T., Charron F., RA Srour M.; RT "De novo pathogenic variants in N-cadherin cause a syndromic RT neurodevelopmental disorder with corpus collosum, axon, cardiac, ocular, RT and genital defects."; RL Am. J. Hum. Genet. 105:854-868(2019). RN [19] RP INVOLVEMENT IN ACOGS, AND VARIANTS ACOGS ASP-162; GLY-525 AND SER-603. 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] RP VARIANT ADHD8 TYR-150, CHARACTERIZATION OF VARIANT ADHD8 TYR-150, AND RP INVOLVEMENT IN ADHD8. 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). CC -!- FUNCTION: Calcium-dependent cell adhesion protein; preferentially CC mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain CC from another cell. Cadherins may thus contribute to the sorting of CC heterogeneous cell types. Acts as a regulator of neural stem cells CC quiescence by mediating anchorage of neural stem cells to ependymocytes CC in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated CC anchorage is affected, leading to modulate neural stem cell quiescence. CC Plays a role in cell-to-cell junction formation between pancreatic beta CC cells and neural crest stem (NCS) cells, promoting the formation of CC processes by NCS cells (By similarity). Required for proper neurite CC branching. Required for pre- and postsynaptic organization (By CC similarity). CDH2 may be involved in neuronal recognition mechanism. In CC hippocampal neurons, may regulate dendritic spine density. CC {ECO:0000250|UniProtKB:P10288, ECO:0000250|UniProtKB:P15116, CC ECO:0000269|PubMed:31585109}. CC -!- SUBUNIT: Homodimer (via extracellular region). Can also form CC heterodimers with other cadherins (via extracellular region). CC Dimerization occurs in trans, i.e. with a cadherin chain from another CC cell (By similarity). Interacts with CDCP1 (PubMed:16007225). Interacts CC with 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. May interact with CC OBSCN (via protein kinase domain 2) (By similarity). Interacts with CC FBXO45 (PubMed:32341084). {ECO:0000250|UniProtKB:P15116, CC ECO:0000250|UniProtKB:Q9Z1Y3, ECO:0000269|PubMed:16007225, CC ECO:0000269|PubMed:32341084}. CC -!- INTERACTION: CC P19022; P35222: CTNNB1; NbExp=8; IntAct=EBI-2256711, EBI-491549; CC P19022; P14923: JUP; NbExp=2; IntAct=EBI-2256711, EBI-702484; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P15116}; CC Single-pass type I membrane protein {ECO:0000255}. Cell membrane, CC sarcolemma {ECO:0000250|UniProtKB:P15116}. Cell junction CC {ECO:0000269|PubMed:28169360}. Cell surface CC {ECO:0000250|UniProtKB:P15116}. Cell junction, desmosome CC {ECO:0000250|UniProtKB:P15116}. Cell junction, adherens junction CC {ECO:0000250|UniProtKB:P15116}. Note=Colocalizes with TMEM65 at the CC intercalated disk in cardiomyocytes. Colocalizes with OBSCN at the CC intercalated disk and at sarcolemma in cardiomyocytes. CC {ECO:0000250|UniProtKB:P15116}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P19022-1; Sequence=Displayed; CC Name=2; CC IsoId=P19022-2; Sequence=VSP_056448; 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:0000250|UniProtKB:P15116}. CC -!- PTM: Cleaved by MMP24. Ectodomain cleavage leads to the generation of a CC soluble 90 kDa N-terminal soluble fragment and a 45 kDa membrane-bound CC C-terminal fragment 1 (CTF1), which is further cleaved by gamma- CC secretase into a 35 kDa (By similarity). Cleavage in neural stem cells CC by MMP24 affects CDH2-mediated anchorage of neural stem cells to CC ependymocytes in the adult subependymal zone, leading to modulate CC neural stem cell quiescence (By similarity). CC {ECO:0000250|UniProtKB:P15116}. CC -!- PTM: May be phosphorylated by OBSCN. {ECO:0000250|UniProtKB:P15116}. CC -!- DISEASE: Arrhythmogenic right ventricular dysplasia, familial, 14 CC (ARVD14) [MIM:618920]: A congenital heart disease characterized by CC infiltration of adipose and fibrous tissue into the right ventricle and CC loss of myocardial cells, resulting in ventricular and supraventricular CC arrhythmias. {ECO:0000269|PubMed:28280076, CC ECO:0000269|PubMed:28326674}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Agenesis of corpus callosum, cardiac, ocular, and genital CC syndrome (ACOGS) [MIM:618929]: An autosomal dominant, syndromic CC neurodevelopmental disorder characterized by global developmental delay CC and/or intellectual disability, corpus callosum agenesis or hypoplasia, CC mirror movements, dysmorphic features, and ocular, cardiac, and genital CC anomalies. {ECO:0000269|PubMed:31585109, ECO:0000269|PubMed:31650526}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Attention deficit-hyperactivity disorder 8 (ADHD8) CC [MIM:619957]: A form of attention deficit-hyperactivity disorder, a CC neurobehavioral developmental condition primarily characterized by the CC coexistence of attentional problems and hyperactivity, with each CC feature occurring infrequently alone. ADHD8 is an autosomal recessive CC form with onset in early childhood, usually by age 3 years. ADHD8 CC patients may manifest mild developmental delay with autism. CC {ECO:0000269|PubMed:34702855}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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; X54315; CAA38213.1; -; mRNA. DR EMBL; S42303; AAB22854.1; -; mRNA. DR EMBL; AK302831; BAH13814.1; -; mRNA. DR EMBL; AC006249; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC015933; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC110015; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; EF444966; ACA05964.1; -; Genomic_DNA. DR EMBL; CH471088; EAX01240.1; -; Genomic_DNA. DR EMBL; BC036470; AAH36470.1; -; mRNA. DR EMBL; M34064; AAA03236.1; -; mRNA. DR EMBL; X57548; CAA40773.1; -; mRNA. DR EMBL; Z27420; CAA81799.1; -; Genomic_DNA. DR CCDS; CCDS11891.1; -. [P19022-1] DR CCDS; CCDS77172.1; -. [P19022-2] DR PIR; A38870; IJHUCN. DR RefSeq; NP_001295105.1; NM_001308176.1. [P19022-2] DR RefSeq; NP_001783.2; NM_001792.4. [P19022-1] DR AlphaFoldDB; P19022; -. DR SMR; P19022; -. DR BioGRID; 107435; 111. DR CORUM; P19022; -. DR DIP; DIP-43894N; -. DR IntAct; P19022; 36. DR MINT; P19022; -. DR STRING; 9606.ENSP00000269141; -. DR BindingDB; P19022; -. DR ChEMBL; CHEMBL1697669; -. DR GlyConnect; 733; 11 N-Linked glycans (4 sites). DR GlyCosmos; P19022; 7 sites, 12 glycans. DR GlyGen; P19022; 10 sites, 12 N-linked glycans (4 sites), 1 O-linked glycan (1 site). DR iPTMnet; P19022; -. DR PhosphoSitePlus; P19022; -. DR BioMuta; CDH2; -. DR DMDM; 116241277; -. DR CPTAC; CPTAC-5769; -. DR CPTAC; CPTAC-5770; -. DR CPTAC; non-CPTAC-5371; -. DR CPTAC; non-CPTAC-5373; -. DR CPTAC; non-CPTAC-5374; -. DR CPTAC; non-CPTAC-5543; -. DR CPTAC; non-CPTAC-5544; -. DR EPD; P19022; -. DR jPOST; P19022; -. DR MassIVE; P19022; -. DR MaxQB; P19022; -. DR PaxDb; 9606-ENSP00000269141; -. DR PeptideAtlas; P19022; -. DR ProteomicsDB; 2250; -. DR ProteomicsDB; 53628; -. [P19022-1] DR Pumba; P19022; -. DR TopDownProteomics; P19022-1; -. [P19022-1] DR ABCD; P19022; 4 sequenced antibodies. DR Antibodypedia; 4558; 1940 antibodies from 53 providers. DR CPTC; P19022; 5 antibodies. DR DNASU; 1000; -. DR Ensembl; ENST00000269141.8; ENSP00000269141.3; ENSG00000170558.10. [P19022-1] DR Ensembl; ENST00000399380.7; ENSP00000382312.3; ENSG00000170558.10. [P19022-2] DR GeneID; 1000; -. DR KEGG; hsa:1000; -. DR MANE-Select; ENST00000269141.8; ENSP00000269141.3; NM_001792.5; NP_001783.2. DR UCSC; uc002kwg.3; human. [P19022-1] DR AGR; HGNC:1759; -. DR CTD; 1000; -. DR DisGeNET; 1000; -. DR GeneCards; CDH2; -. DR HGNC; HGNC:1759; CDH2. DR HPA; ENSG00000170558; Tissue enhanced (heart). DR MalaCards; CDH2; -. DR MIM; 114020; gene. DR MIM; 618920; phenotype. DR MIM; 618929; phenotype. DR MIM; 619957; phenotype. DR neXtProt; NX_P19022; -. DR OpenTargets; ENSG00000170558; -. DR Orphanet; 293910; Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant. DR PharmGKB; PA26293; -. DR VEuPathDB; HostDB:ENSG00000170558; -. DR eggNOG; KOG3594; Eukaryota. DR GeneTree; ENSGT00940000155981; -. DR HOGENOM; CLU_005284_2_0_1; -. DR InParanoid; P19022; -. DR OMA; PRQLTKH; -. DR OrthoDB; 5306553at2759; -. DR PhylomeDB; P19022; -. DR TreeFam; TF316817; -. DR PathwayCommons; P19022; -. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-418990; Adherens junctions interactions. DR Reactome; R-HSA-525793; Myogenesis. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SignaLink; P19022; -. DR SIGNOR; P19022; -. DR BioGRID-ORCS; 1000; 62 hits in 1154 CRISPR screens. DR ChiTaRS; CDH2; human. DR GeneWiki; CDH2; -. DR GenomeRNAi; 1000; -. DR Pharos; P19022; Tbio. DR PRO; PR:P19022; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; P19022; Protein. DR Bgee; ENSG00000170558; Expressed in heart right ventricle and 170 other cell types or tissues. DR ExpressionAtlas; P19022; 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; IEA:Ensembl. DR GO; GO:0016327; C:apicolateral plasma membrane; IEA:Ensembl. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl. DR GO; GO:0016342; C:catenin complex; IDA:BHF-UCL. DR GO; GO:0030054; C:cell junction; IDA:UniProtKB. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005911; C:cell-cell junction; IDA:BHF-UCL. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0030057; C:desmosome; ISS:UniProtKB. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005916; C:fascia adherens; IEA:Ensembl. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0014704; C:intercalated disc; ISS:BHF-UCL. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. 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; IEA:Ensembl. DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell. DR GO; GO:0045294; F:alpha-catenin binding; IPI:BHF-UCL. DR GO; GO:0008013; F:beta-catenin binding; IPI:UniProtKB. DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0045295; F:gamma-catenin binding; IPI:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; IEA:Ensembl. DR GO; GO:0034332; P:adherens junction organization; IBA:GO_Central. DR GO; GO:0048514; P:blood vessel morphogenesis; IBA:GO_Central. DR GO; GO:0007420; P:brain development; IBA:GO_Central. DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl. DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; IBA:GO_Central. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central. DR GO; GO:0098609; P:cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; ISS:UniProtKB. DR GO; GO:0007043; P:cell-cell junction assembly; ISS:UniProtKB. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0035995; P:detection of muscle stretch; TAS:BHF-UCL. DR GO; GO:0010001; P:glial cell differentiation; ISS:UniProtKB. DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IEA:Ensembl. DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl. DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IBA:GO_Central. DR GO; GO:0090497; P:mesenchymal cell migration; IEA:Ensembl. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0014032; P:neural crest cell development; ISS:UniProtKB. DR GO; GO:0060563; P:neuroepithelial cell differentiation; IEA:Ensembl. DR GO; GO:0097118; P:neuroligin clustering involved in postsynaptic membrane assembly; IEA:Ensembl. DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISS:UniProtKB. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl. DR GO; GO:2000809; P:positive regulation of synaptic vesicle clustering; IEA:Ensembl. DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0060019; P:radial glial cell differentiation; IEA:Ensembl. DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central. DR GO; GO:0070445; P:regulation of oligodendrocyte progenitor proliferation; IEA:Ensembl. DR GO; GO:1902897; P:regulation of postsynaptic density protein 95 clustering; IEA:Ensembl. DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central. DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl. DR GO; GO:0007416; P:synapse assembly; IBA:GO_Central. DR GO; GO:0097091; P:synaptic vesicle clustering; ISS:UniProtKB. DR GO; GO:0003323; P:type B pancreatic cell development; ISS: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; P19022; HS. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cardiomyopathy; Cell adhesion; KW Cell junction; Cell membrane; Cleavage on pair of basic residues; KW Disease variant; Glycoprotein; Intellectual disability; Membrane; KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT PROPEP 26..159 FT /id="PRO_0000003731" FT CHAIN 160..906 FT /note="Cadherin-2" FT /id="PRO_0000003732" 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..714 FT /note="Cadherin 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT REGION 863..884 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:0000250|UniProtKB:P15116" FT BINDING 170 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 226 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 228 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 228 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 259 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 260 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 261 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 262 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 262 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 263 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 293 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 295 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 301 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P15116" FT BINDING 353 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P15116" FT MOD_RES 96 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT MOD_RES 135 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" 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:19159218" FT CARBOHYD 325 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 402 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 572 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 651 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 692 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT VAR_SEQ 1..57 FT /note="MCRIAGALRTLLPLLAALLQASVEASGEIALCKTGFPEDVYSAVLSKDVHEG FT QPLLN -> MFLLRRYVCIFTEKLKNQAELYVFLS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056448" FT VARIANT 21 FT /note="A -> T (in dbSNP:rs17495042)" FT /id="VAR_028254" FT VARIANT 118 FT /note="A -> T (in dbSNP:rs17445840)" FT /id="VAR_028255" FT VARIANT 150 FT /note="H -> Y (in ADHD8; decreased propeptide cleavage)" FT /evidence="ECO:0000269|PubMed:34702855" FT /id="VAR_087507" FT VARIANT 162 FT /note="V -> D (in ACOGS; uncertain significance; FT dbSNP:rs2013111940)" FT /evidence="ECO:0000269|PubMed:31650526" FT /id="VAR_084438" FT VARIANT 196 FT /note="S -> T (in dbSNP:rs1041970)" FT /evidence="ECO:0000269|PubMed:2216790" FT /id="VAR_028256" FT VARIANT 212 FT /note="I -> L (in dbSNP:rs1041972)" FT /evidence="ECO:0000269|PubMed:2384753" FT /id="VAR_028257" FT VARIANT 229 FT /note="Q -> P (in ARVD14; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28280076" FT /id="VAR_084439" FT VARIANT 353 FT /note="D -> N (in ACOGS; decreased function in cell-cell FT adhesion; dbSNP:rs1599017933)" FT /evidence="ECO:0000269|PubMed:31585109" FT /id="VAR_084440" FT VARIANT 407 FT /note="D -> N (in ARVD14; uncertain significance; FT dbSNP:rs568089577)" FT /evidence="ECO:0000269|PubMed:28280076, FT ECO:0000269|PubMed:28326674" FT /id="VAR_084441" FT VARIANT 454 FT /note="T -> A (in dbSNP:rs17857112)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_048503" FT VARIANT 525 FT /note="D -> G (in ACOGS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31650526" FT /id="VAR_084442" FT VARIANT 597 FT /note="D -> N (in ACOGS; decreased function in cell-cell FT adhesion; dbSNP:rs1599011050)" FT /evidence="ECO:0000269|PubMed:31585109" FT /id="VAR_084443" FT VARIANT 597 FT /note="D -> Y (in ACOGS; dbSNP:rs1599011050)" FT /evidence="ECO:0000269|PubMed:31585109" FT /id="VAR_084444" FT VARIANT 601 FT /note="N -> T (in ACOGS; decreased function in cell-cell FT adhesion; dbSNP:rs201775968)" FT /evidence="ECO:0000269|PubMed:31585109" FT /id="VAR_084445" FT VARIANT 603 FT /note="P -> S (in ACOGS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31650526" FT /id="VAR_084446" FT VARIANT 613 FT /note="C -> W (in ACOGS; decreased function in cell-cell FT adhesion; dbSNP:rs754880999)" FT /evidence="ECO:0000269|PubMed:31585109" FT /id="VAR_084447" FT VARIANT 627 FT /note="D -> G (in ACOGS; decreased function in cell-cell FT adhesion; dbSNP:rs1599010918)" FT /evidence="ECO:0000269|PubMed:31585109" FT /id="VAR_084448" FT VARIANT 676 FT /note="Y -> C (in ACOGS; decreased function in cell-cell FT adhesion; dbSNP:rs199984052)" FT /evidence="ECO:0000269|PubMed:31585109" FT /id="VAR_084449" FT VARIANT 845 FT /note="N -> S (in dbSNP:rs2289664)" FT /id="VAR_028258" FT CONFLICT 12 FT /note="Missing (in Ref. 3; AAB22854)" FT /evidence="ECO:0000305" FT CONFLICT 16 FT /note="A -> L (in Ref. 1; CAA38213)" FT /evidence="ECO:0000305" FT CONFLICT 164 FT /note="P -> S (in Ref. 8; AAH36470)" FT /evidence="ECO:0000305" FT CONFLICT 357 FT /note="N -> I (in Ref. 1; CAA38213)" FT /evidence="ECO:0000305" FT CONFLICT 437 FT /note="P -> Q (in Ref. 8; AAH36470)" FT /evidence="ECO:0000305" FT CONFLICT 484 FT /note="V -> M (in Ref. 8; AAH36470)" FT /evidence="ECO:0000305" FT CONFLICT 629 FT /note="D -> G (in Ref. 8; AAH36470)" FT /evidence="ECO:0000305" FT CONFLICT 867 FT /note="A -> L (in Ref. 3; AAB22854)" FT /evidence="ECO:0000305" SQ SEQUENCE 906 AA; 99809 MW; 7267E2A00489DF94 CRC64; MCRIAGALRT LLPLLAALLQ ASVEASGEIA LCKTGFPEDV YSAVLSKDVH EGQPLLNVKF SNCNGKRKVQ YESSEPADFK VDEDGMVYAV RSFPLSSEHA KFLIYAQDKE TQEKWQVAVK LSLKPTLTEE SVKESAEVEE IVFPRQFSKH SGHLQRQKRD WVIPPINLPE NSRGPFPQEL VRIRSDRDKN LSLRYSVTGP GADQPPTGIF IINPISGQLS VTKPLDREQI ARFHLRAHAV DINGNQVENP IDIVINVIDM NDNRPEFLHQ VWNGTVPEGS KPGTYVMTVT AIDADDPNAL NGMLRYRIVS QAPSTPSPNM FTINNETGDI ITVAAGLDRE KVQQYTLIIQ ATDMEGNPTY GLSNTATAVI TVTDVNDNPP EFTAMTFYGE VPENRVDIIV ANLTVTDKDQ PHTPAWNAVY RISGGDPTGR FAIQTDPNSN DGLVTVVKPI DFETNRMFVL TVAAENQVPL AKGIQHPPQS TATVSVTVID VNENPYFAPN PKIIRQEEGL HAGTMLTTFT AQDPDRYMQQ NIRYTKLSDP ANWLKIDPVN GQITTIAVLD RESPNVKNNI YNATFLASDN GIPPMSGTGT LQIYLLDIND NAPQVLPQEA ETCETPDPNS INITALDYDI DPNAGPFAFD LPLSPVTIKR NWTITRLNGD FAQLNLKIKF LEAGIYEVPI IITDSGNPPK SNISILRVKV CQCDSNGDCT DVDRIVGAGL GTGAIIAILL CIIILLILVL MFVVWMKRRD KERQAKQLLI DPEDDVRDNI LKYDEEGGGE EDQDYDLSQL QQPDTVEPDA IKPVGIRRMD ERPIHAEPQY PVRSAAPHPG DIGDFINEGL KAADNDPTAP PYDSLLVFDY EGSGSTAGSL SSLNSSSSGG EQDYDYLNDW GPRFKKLADM YGGGDD //