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Protein

Cadherin-2

Gene

CDH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence. CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi170Calcium 1By similarity1
Metal bindingi170Calcium 2By similarity1
Metal bindingi226Calcium 1By similarity1
Metal bindingi228Calcium 1By similarity1
Metal bindingi228Calcium 2By similarity1
Metal bindingi259Calcium 2By similarity1
Metal bindingi260Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi261Calcium 3By similarity1
Metal bindingi262Calcium 1By similarity1
Metal bindingi262Calcium 2By similarity1
Metal bindingi263Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi293Calcium 3By similarity1
Metal bindingi295Calcium 2By similarity1
Metal bindingi301Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi353Calcium 3By similarity1

GO - Molecular functioni

  • alpha-catenin binding Source: BHF-UCL
  • beta-catenin binding Source: UniProtKB
  • cadherin binding Source: GO_Central
  • calcium ion binding Source: GO_Central
  • cytoskeletal protein binding Source: GO_Central
  • gamma-catenin binding Source: BHF-UCL
  • protein homodimerization activity Source: GO_Central
  • protein kinase binding Source: Ensembl
  • protein phosphatase binding Source: Ensembl

GO - Biological processi

Keywordsi

Biological processCell adhesion
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-375170 CDO in myogenesis
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-418990 Adherens junctions interactions
R-HSA-8957275 Post-translational protein phosphorylation
SIGNORiP19022

Names & Taxonomyi

Protein namesi
Recommended name:
Cadherin-2
Alternative name(s):
CDw325
Neural cadherin
Short name:
N-cadherin1 Publication
CD_antigen: CD325
Gene namesi
Name:CDH2
Synonyms:CDHN, NCAD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000170558.8
HGNCiHGNC:1759 CDH2
MIMi114020 gene
neXtProtiNX_P19022

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini160 – 724ExtracellularSequence analysisAdd BLAST565
Transmembranei725 – 745HelicalSequence analysisAdd BLAST21
Topological domaini746 – 906CytoplasmicSequence analysisAdd BLAST161

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi1000
OpenTargetsiENSG00000170558
PharmGKBiPA26293

Chemistry databases

ChEMBLiCHEMBL1697669

Polymorphism and mutation databases

BioMutaiCDH2
DMDMi116241277

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
PropeptideiPRO_000000373126 – 159Add BLAST134
ChainiPRO_0000003732160 – 906Cadherin-2Add BLAST747

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei96Phosphoserine; by FAM20C1 Publication1
Modified residuei135Phosphoserine; by FAM20C1 Publication1
Glycosylationi190N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi273N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi325N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi402N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi572N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi651N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi692N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

Cleaved by MMP24. Ectodomain cleavage leads to the generation of a soluble 90 kDa amino-terminal soluble fragment and a 45 kDa membrane-bound carboxy-terminal fragment 1 (CTF1), which is further cleaved by gamma-secretase into a 35 kDa. Cleavage in neural stem cells by MMP24 affects CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate neural stem cell quiescence (By similarity).By similarity
May be phosphorylated by OBSCN.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP19022
MaxQBiP19022
PaxDbiP19022
PeptideAtlasiP19022
PRIDEiP19022
ProteomicsDBi53628
TopDownProteomicsiP19022-1 [P19022-1]

PTM databases

GlyConnecti733
iPTMnetiP19022
PhosphoSitePlusiP19022
UniCarbKBiP19022

Miscellaneous databases

PMAP-CutDBiP19022

Expressioni

Gene expression databases

BgeeiENSG00000170558 Expressed in 199 organ(s), highest expression level in cardiac ventricle
CleanExiHS_CDH2
ExpressionAtlasiP19022 baseline and differential
GenevisibleiP19022 HS

Organism-specific databases

HPAiCAB000141
CAB018580
CAB078686
HPA058574

Interactioni

Subunit structurei

Homodimer (via extracellular region). Can also form heterodimers with other cadherins (via extracellular region). Dimerization occurs in trans, i.e. with a cadherin chain from another cell (By similarity). Interacts with CDCP1 (PubMed:16007225). Interacts with PCDH8; this complex may also include TAOK2 (By similarity). The interaction with PCDH8 may lead to internalization through TAOK2/p38 MAPK pathway (By similarity). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. May interact with OBSCN (via protein kinase domain 2) (By similarity).By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107435, 60 interactors
CORUMiP19022
DIPiDIP-43894N
IntActiP19022, 21 interactors
MINTiP19022
STRINGi9606.ENSP00000269141

Chemistry databases

BindingDBiP19022

Structurei

3D structure databases

ProteinModelPortaliP19022
SMRiP19022
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini160 – 267Cadherin 1PROSITE-ProRule annotationAdd BLAST108
Domaini268 – 382Cadherin 2PROSITE-ProRule annotationAdd BLAST115
Domaini383 – 497Cadherin 3PROSITE-ProRule annotationAdd BLAST115
Domaini498 – 603Cadherin 4PROSITE-ProRule annotationAdd BLAST106
Domaini604 – 714Cadherin 5PROSITE-ProRule annotationAdd BLAST111

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi863 – 878Ser-richAdd BLAST16

Domaini

Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1.By similarity

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3594 Eukaryota
ENOG410XQHI LUCA
GeneTreeiENSGT00760000118906
HOGENOMiHOG000231254
HOVERGENiHBG106438
InParanoidiP19022
KOiK06736
OMAiMYNATFL
OrthoDBiEOG091G01FV
PhylomeDBiP19022
TreeFamiTF316817

Family and domain databases

Gene3Di4.10.900.10, 1 hit
InterProiView protein in InterPro
IPR039808 Cadherin
IPR002126 Cadherin-like_dom
IPR015919 Cadherin-like_sf
IPR020894 Cadherin_CS
IPR000233 Cadherin_cytoplasmic-dom
IPR014868 Cadherin_pro_dom
IPR027397 Catenin_binding_dom_sf
IPR030051 CDH2
PANTHERiPTHR24027 PTHR24027, 1 hit
PTHR24027:SF79 PTHR24027:SF79, 1 hit
PfamiView protein in Pfam
PF00028 Cadherin, 5 hits
PF01049 Cadherin_C, 1 hit
PF08758 Cadherin_pro, 1 hit
PRINTSiPR00205 CADHERIN
SMARTiView protein in SMART
SM00112 CA, 5 hits
SM01055 Cadherin_pro, 1 hit
SUPFAMiSSF49313 SSF49313, 6 hits
PROSITEiView protein in PROSITE
PS00232 CADHERIN_1, 3 hits
PS50268 CADHERIN_2, 5 hits

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P19022-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MCRIAGALRT LLPLLAALLQ ASVEASGEIA LCKTGFPEDV YSAVLSKDVH
60 70 80 90 100
EGQPLLNVKF SNCNGKRKVQ YESSEPADFK VDEDGMVYAV RSFPLSSEHA
110 120 130 140 150
KFLIYAQDKE TQEKWQVAVK LSLKPTLTEE SVKESAEVEE IVFPRQFSKH
160 170 180 190 200
SGHLQRQKRD WVIPPINLPE NSRGPFPQEL VRIRSDRDKN LSLRYSVTGP
210 220 230 240 250
GADQPPTGIF IINPISGQLS VTKPLDREQI ARFHLRAHAV DINGNQVENP
260 270 280 290 300
IDIVINVIDM NDNRPEFLHQ VWNGTVPEGS KPGTYVMTVT AIDADDPNAL
310 320 330 340 350
NGMLRYRIVS QAPSTPSPNM FTINNETGDI ITVAAGLDRE KVQQYTLIIQ
360 370 380 390 400
ATDMEGNPTY GLSNTATAVI TVTDVNDNPP EFTAMTFYGE VPENRVDIIV
410 420 430 440 450
ANLTVTDKDQ PHTPAWNAVY RISGGDPTGR FAIQTDPNSN DGLVTVVKPI
460 470 480 490 500
DFETNRMFVL TVAAENQVPL AKGIQHPPQS TATVSVTVID VNENPYFAPN
510 520 530 540 550
PKIIRQEEGL HAGTMLTTFT AQDPDRYMQQ NIRYTKLSDP ANWLKIDPVN
560 570 580 590 600
GQITTIAVLD RESPNVKNNI YNATFLASDN GIPPMSGTGT LQIYLLDIND
610 620 630 640 650
NAPQVLPQEA ETCETPDPNS INITALDYDI DPNAGPFAFD LPLSPVTIKR
660 670 680 690 700
NWTITRLNGD FAQLNLKIKF LEAGIYEVPI IITDSGNPPK SNISILRVKV
710 720 730 740 750
CQCDSNGDCT DVDRIVGAGL GTGAIIAILL CIIILLILVL MFVVWMKRRD
760 770 780 790 800
KERQAKQLLI DPEDDVRDNI LKYDEEGGGE EDQDYDLSQL QQPDTVEPDA
810 820 830 840 850
IKPVGIRRMD ERPIHAEPQY PVRSAAPHPG DIGDFINEGL KAADNDPTAP
860 870 880 890 900
PYDSLLVFDY EGSGSTAGSL SSLNSSSSGG EQDYDYLNDW GPRFKKLADM

YGGGDD
Length:906
Mass (Da):99,809
Last modified:October 17, 2006 - v4
Checksum:i7267E2A00489DF94
GO
Isoform 2 (identifier: P19022-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: MCRIAGALRT...DVHEGQPLLN → MFLLRRYVCIFTEKLKNQAELYVFLS

Note: No experimental confirmation available.
Show »
Length:875
Mass (Da):97,040
Checksum:i04DCB2F62C61C998
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J8J8C9J8J8_HUMAN
Cadherin-2
CDH2
191Annotation score:
C9J126C9J126_HUMAN
Cadherin-2
CDH2
120Annotation score:
C9JMH2C9JMH2_HUMAN
Cadherin-2
CDH2
73Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12Missing in AAB22854 (PubMed:1500442).Curated1
Sequence conflicti16A → L in CAA38213 (PubMed:2216790).Curated1
Sequence conflicti164P → S in AAH36470 (PubMed:15489334).Curated1
Sequence conflicti357N → I in CAA38213 (PubMed:2216790).Curated1
Sequence conflicti437P → Q in AAH36470 (PubMed:15489334).Curated1
Sequence conflicti484V → M in AAH36470 (PubMed:15489334).Curated1
Sequence conflicti629D → G in AAH36470 (PubMed:15489334).Curated1
Sequence conflicti867A → L in AAB22854 (PubMed:1500442).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02825421A → T. Corresponds to variant dbSNP:rs17495042Ensembl.1
Natural variantiVAR_028255118A → T. Corresponds to variant dbSNP:rs17445840Ensembl.1
Natural variantiVAR_028256196S → T1 PublicationCorresponds to variant dbSNP:rs1041970Ensembl.1
Natural variantiVAR_028257212I → L1 PublicationCorresponds to variant dbSNP:rs1041972Ensembl.1
Natural variantiVAR_048503454T → A1 PublicationCorresponds to variant dbSNP:rs17857112Ensembl.1
Natural variantiVAR_028258845N → S. Corresponds to variant dbSNP:rs2289664Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564481 – 57MCRIA…QPLLN → MFLLRRYVCIFTEKLKNQAE LYVFLS in isoform 2. 1 PublicationAdd BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54315 mRNA Translation: CAA38213.1
S42303 mRNA Translation: AAB22854.1
AK302831 mRNA Translation: BAH13814.1
AC006249 Genomic DNA No translation available.
AC015933 Genomic DNA No translation available.
AC110015 Genomic DNA No translation available.
EF444966 Genomic DNA Translation: ACA05964.1
CH471088 Genomic DNA Translation: EAX01240.1
BC036470 mRNA Translation: AAH36470.1
M34064 mRNA Translation: AAA03236.1
X57548 mRNA Translation: CAA40773.1
Z27420 Genomic DNA Translation: CAA81799.1
CCDSiCCDS11891.1 [P19022-1]
CCDS77172.1 [P19022-2]
PIRiA38870 IJHUCN
RefSeqiNP_001295105.1, NM_001308176.1 [P19022-2]
NP_001783.2, NM_001792.4 [P19022-1]
UniGeneiHs.464829
Hs.606106

Genome annotation databases

EnsembliENST00000269141; ENSP00000269141; ENSG00000170558 [P19022-1]
ENST00000399380; ENSP00000382312; ENSG00000170558 [P19022-2]
GeneIDi1000
KEGGihsa:1000
UCSCiuc002kwg.3 human [P19022-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54315 mRNA Translation: CAA38213.1
S42303 mRNA Translation: AAB22854.1
AK302831 mRNA Translation: BAH13814.1
AC006249 Genomic DNA No translation available.
AC015933 Genomic DNA No translation available.
AC110015 Genomic DNA No translation available.
EF444966 Genomic DNA Translation: ACA05964.1
CH471088 Genomic DNA Translation: EAX01240.1
BC036470 mRNA Translation: AAH36470.1
M34064 mRNA Translation: AAA03236.1
X57548 mRNA Translation: CAA40773.1
Z27420 Genomic DNA Translation: CAA81799.1
CCDSiCCDS11891.1 [P19022-1]
CCDS77172.1 [P19022-2]
PIRiA38870 IJHUCN
RefSeqiNP_001295105.1, NM_001308176.1 [P19022-2]
NP_001783.2, NM_001792.4 [P19022-1]
UniGeneiHs.464829
Hs.606106

3D structure databases

ProteinModelPortaliP19022
SMRiP19022
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107435, 60 interactors
CORUMiP19022
DIPiDIP-43894N
IntActiP19022, 21 interactors
MINTiP19022
STRINGi9606.ENSP00000269141

Chemistry databases

BindingDBiP19022
ChEMBLiCHEMBL1697669

PTM databases

GlyConnecti733
iPTMnetiP19022
PhosphoSitePlusiP19022
UniCarbKBiP19022

Polymorphism and mutation databases

BioMutaiCDH2
DMDMi116241277

Proteomic databases

EPDiP19022
MaxQBiP19022
PaxDbiP19022
PeptideAtlasiP19022
PRIDEiP19022
ProteomicsDBi53628
TopDownProteomicsiP19022-1 [P19022-1]

Protocols and materials databases

DNASUi1000
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269141; ENSP00000269141; ENSG00000170558 [P19022-1]
ENST00000399380; ENSP00000382312; ENSG00000170558 [P19022-2]
GeneIDi1000
KEGGihsa:1000
UCSCiuc002kwg.3 human [P19022-1]

Organism-specific databases

CTDi1000
DisGeNETi1000
EuPathDBiHostDB:ENSG00000170558.8
GeneCardsiCDH2
H-InvDBiHIX0027368
HGNCiHGNC:1759 CDH2
HPAiCAB000141
CAB018580
CAB078686
HPA058574
MIMi114020 gene
neXtProtiNX_P19022
OpenTargetsiENSG00000170558
PharmGKBiPA26293
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3594 Eukaryota
ENOG410XQHI LUCA
GeneTreeiENSGT00760000118906
HOGENOMiHOG000231254
HOVERGENiHBG106438
InParanoidiP19022
KOiK06736
OMAiMYNATFL
OrthoDBiEOG091G01FV
PhylomeDBiP19022
TreeFamiTF316817

Enzyme and pathway databases

ReactomeiR-HSA-375170 CDO in myogenesis
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-418990 Adherens junctions interactions
R-HSA-8957275 Post-translational protein phosphorylation
SIGNORiP19022

Miscellaneous databases

ChiTaRSiCDH2 human
GeneWikiiCDH2
GenomeRNAii1000
PMAP-CutDBiP19022
PROiPR:P19022
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170558 Expressed in 199 organ(s), highest expression level in cardiac ventricle
CleanExiHS_CDH2
ExpressionAtlasiP19022 baseline and differential
GenevisibleiP19022 HS

Family and domain databases

Gene3Di4.10.900.10, 1 hit
InterProiView protein in InterPro
IPR039808 Cadherin
IPR002126 Cadherin-like_dom
IPR015919 Cadherin-like_sf
IPR020894 Cadherin_CS
IPR000233 Cadherin_cytoplasmic-dom
IPR014868 Cadherin_pro_dom
IPR027397 Catenin_binding_dom_sf
IPR030051 CDH2
PANTHERiPTHR24027 PTHR24027, 1 hit
PTHR24027:SF79 PTHR24027:SF79, 1 hit
PfamiView protein in Pfam
PF00028 Cadherin, 5 hits
PF01049 Cadherin_C, 1 hit
PF08758 Cadherin_pro, 1 hit
PRINTSiPR00205 CADHERIN
SMARTiView protein in SMART
SM00112 CA, 5 hits
SM01055 Cadherin_pro, 1 hit
SUPFAMiSSF49313 SSF49313, 6 hits
PROSITEiView protein in PROSITE
PS00232 CADHERIN_1, 3 hits
PS50268 CADHERIN_2, 5 hits
ProtoNetiSearch...

Entry informationi

Entry nameiCADH2_HUMAN
AccessioniPrimary (citable) accession number: P19022
Secondary accession number(s): A8MWK3
, B0YIY6, Q14923, Q8N173
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: October 17, 2006
Last modified: November 7, 2018
This is version 186 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  5. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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