ID   CADH2_OTOGA             Reviewed;         906 AA.
AC   B4USZ0;
DT   26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 1.
DT   03-MAY-2023, entry version 58.
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   Otolemur garnettii (Small-eared galago) (Garnett's greater bushbaby).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Strepsirrhini; Lorisiformes;
OC   Galagidae; Otolemur.
OX   NCBI_TaxID=30611;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG   The Broad Institute Genome Sequencing Platform;
RA   Di Palma F., Johnson J., Lander E.S., Lindblad-Toh K., Jaffe D.B.,
RA   Gnerre S., MacCallum I., Przybylski D., Ribeiro F.J., Burton J.N.,
RA   Walker B.J., Sharpe T., Hall G.;
RT   "Version 3 of the genome sequence of Otolemur garnettii(Bushbaby).";
RL   Submitted (MAR-2011) to the EMBL/GenBank/DDBJ databases.
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   -!- 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P15116,
CC       ECO:0000250|UniProtKB:P19022, ECO:0000250|UniProtKB:Q9Z1Y3}.
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:0000250|UniProtKB:P19022}. 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 (By similarity). Colocalizes with
CC       OBSCN at the intercalated disk and sarcolemma in cardiomyocytes (By
CC       similarity). {ECO:0000250|UniProtKB:P15116}.
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}.
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DR   EMBL; DP000883; ACG69456.1; -; Genomic_DNA.
DR   AlphaFoldDB; B4USZ0; -.
DR   SMR; B4USZ0; -.
DR   STRING; 30611.ENSOGAP00000002127; -.
DR   GlyCosmos; B4USZ0; 8 sites, No reported glycans.
DR   eggNOG; KOG3594; Eukaryota.
DR   InParanoid; B4USZ0; -.
DR   Proteomes; UP000005225; Unassembled WGS sequence.
DR   GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR   GO; GO:0030054; C:cell junction; ISS:UniProtKB.
DR   GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR   GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR   GO; GO:0030057; C:desmosome; ISS:UniProtKB.
DR   GO; GO:0014704; C:intercalated disc; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098793; C:presynapse; IEA:GOC.
DR   GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0098609; P:cell-cell adhesion; ISS: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:0010001; P:glial cell differentiation; ISS:UniProtKB.
DR   GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR   GO; GO:0014032; P:neural crest cell development; ISS:UniProtKB.
DR   GO; GO:0097150; P:neuronal stem cell population maintenance; ISS:UniProtKB.
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.
PE   3: Inferred from homology;
KW   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:0000250"
FT                   /id="PRO_0000375877"
FT   CHAIN           160..906
FT                   /note="Cadherin-2"
FT                   /id="PRO_0000375878"
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"
FT                   /evidence="ECO:0000250|UniProtKB:P19022"
FT   MOD_RES         135
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P19022"
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:0000255"
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:0000255"
FT   CARBOHYD        572
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        622
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
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:0000255"
SQ   SEQUENCE   906 AA;  99825 MW;  5F7C057DDA43D60E CRC64;
     MCRIAGAPRT LLPLLAALLQ ASVEASGEIA LCKTGFPEDV YSAVLSKDVH EGQPLLSVKF
     SNCNGKRKVQ YESSEPADFK VDEDGMVYAV RSFPLSSEHS KFLIYAQDKE TQEKWQVAVK
     LSLKPTLTEE SVKESPEIEE IVFPRQLTKH NGYLQRQKRD WVIPPINLPE NSRGPFPQEL
     VRIRSDRDKN LSLRYSVTGP GADQPPTGIF IINPISGQLS VTKPLDRELI ARFHLRAHAV
     DINGNQVENP IDIVINVIDM NDNRPEFLHQ VWNGTVPEGS KPGTYVMTVT AIDADDPNAL
     NGMLRYRILS QAPSTPSPNM FTINNETGDI ITVAAGLDRE KVQQYTLIIQ ATDMEGNPTY
     GLSNTATAII TVTDVNDNPP EFTAMTFYGE VPENRVDVIV ANLTVTDKDQ PHTQAWNAVY
     RISGGDPAGR FAIQTDPNSN DGLVTVVKPI DFETNRMFVL TVAAENQVPL AKGIQHPPQS
     TATVSVTVID VNENPYFAPN PKIIRQEEGL HSGTMLTTFT AQDPDRYMQQ NIRYTKLSDP
     ANWLKIDPVN GQITTIAVLD RESPNVKNNI YNATFLASDN GIPPMSGTGT LQIYLLDIND
     NAPQVLPQEA ETCETPDPNS INITALDYDI DPNAGPFAFD LPLSPGTIKR NWTITRLNGD
     FAQLNLKIKF LEAGIYEVPI IITDSGNPPK SNISILRVKV CQCDSNGDCT DVDRIVGAGL
     GTGAIIAILL CIIILLILVL MFVVWMKRRD KERQAKQLLI DPEDDVRDNI LKYDEEGGGE
     EDQDYDLSQL QQPDTVEPDA IKPVGIRRLD ERPIHAEPQY PVRSAAPHPG DIGDFINEGL
     KAADNDPTAP PYDSLLVFDY EGSGSTAGSL SSLNSSSSGG EQDYDYLNDW GPRFKKLAEM
     YGGGDD
//