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Protein

Cadherin-2

Gene

CDH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; 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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi262Calcium 1By similarity1
Metal bindingi262Calcium 2By similarity1
Metal bindingi293Calcium 3By similarity1

GO - Molecular functioni

  • alpha-catenin binding Source: BHF-UCL
  • beta-catenin binding Source: AgBase
  • calcium ion binding Source: InterPro
  • gamma-catenin binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170558-MONOMER.
ReactomeiR-HSA-375170. CDO in myogenesis.
R-HSA-418990. Adherens junctions interactions.
SIGNORiP19022.

Names & Taxonomyi

Protein namesi
Recommended name:
Cadherin-2
Alternative name(s):
CDw325
Neural cadherin
Short name:
N-cadherin
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

HGNCiHGNC:1759. CDH2.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein Sequence analysis

  • Note: Colocalizes with TMEM65 at the intercalated disk in cardiomyocytes.By similarity

Topology

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

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • basolateral plasma membrane Source: Ensembl
  • catenin complex Source: BHF-UCL
  • cell-cell adherens junction Source: UniProtKB
  • cell-cell junction Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • fascia adherens Source: Ensembl
  • focal adhesion Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • intercalated disc Source: BHF-UCL
  • lamellipodium Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • plasma membrane raft Source: Ensembl
  • synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

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...)Sequence analysis1
Glycosylationi273N-linked (GlcNAc...)1 Publication1
Glycosylationi325N-linked (GlcNAc...)Sequence analysis1
Glycosylationi402N-linked (GlcNAc...)1 Publication1
Glycosylationi572N-linked (GlcNAc...)1 Publication1
Glycosylationi651N-linked (GlcNAc...)Sequence analysis1
Glycosylationi692N-linked (GlcNAc...)1 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

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Phosphoprotein

Proteomic databases

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

PTM databases

iPTMnetiP19022.
PhosphoSitePlusiP19022.
UniCarbKBiP19022.

Miscellaneous databases

PMAP-CutDBP19022.

Expressioni

Gene expression databases

BgeeiENSG00000170558.
CleanExiHS_CDH2.
ExpressionAtlasiP19022. baseline and differential.
GenevisibleiP19022. HS.

Organism-specific databases

HPAiCAB000141.
CAB018580.
HPA058574.

Interactioni

Subunit structurei

Interacts with CDCP1. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with PCDH8; this complex may also include TAOK2. The interaction with PCDH8 may lead to internalization through TAOK2/p38 MAPK pathway (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CTNNB1P352223EBI-2256711,EBI-491549

GO - Molecular functioni

  • alpha-catenin binding Source: BHF-UCL
  • beta-catenin binding Source: AgBase
  • gamma-catenin binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107435. 54 interactors.
DIPiDIP-43894N.
IntActiP19022. 16 interactors.
MINTiMINT-441636.
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).By similarity

Sequence similaritiesi

Contains 5 cadherin domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.40.60. 6 hits.
4.10.900.10. 1 hit.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR014868. Cadherin_pro_dom.
IPR027397. Catenin_binding_dom.
IPR030051. CDH2.
[Graphical view]
PANTHERiPTHR24027:SF79. PTHR24027:SF79. 1 hit.
PfamiPF00028. Cadherin. 5 hits.
PF01049. Cadherin_C. 1 hit.
PF08758. Cadherin_pro. 1 hit.
[Graphical view]
PRINTSiPR00205. CADHERIN.
SMARTiSM00112. CA. 5 hits.
SM01055. Cadherin_pro. 1 hit.
[Graphical view]
SUPFAMiSSF49313. SSF49313. 6 hits.
PROSITEiPS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 5 hits.
[Graphical view]

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

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

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 rs17495042dbSNPEnsembl.1
Natural variantiVAR_028255118A → T.Corresponds to variant rs17445840dbSNPEnsembl.1
Natural variantiVAR_028256196S → T.1 PublicationCorresponds to variant rs1041970dbSNPEnsembl.1
Natural variantiVAR_028257212I → L.1 PublicationCorresponds to variant rs1041972dbSNPEnsembl.1
Natural variantiVAR_048503454T → A.1 PublicationCorresponds to variant rs17857112dbSNPEnsembl.1
Natural variantiVAR_028258845N → S.Corresponds to variant rs2289664dbSNPEnsembl.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

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. 54 interactors.
DIPiDIP-43894N.
IntActiP19022. 16 interactors.
MINTiMINT-441636.
STRINGi9606.ENSP00000269141.

Chemistry databases

BindingDBiP19022.
ChEMBLiCHEMBL1697669.

PTM databases

iPTMnetiP19022.
PhosphoSitePlusiP19022.
UniCarbKBiP19022.

Polymorphism and mutation databases

BioMutaiCDH2.
DMDMi116241277.

Proteomic databases

EPDiP19022.
MaxQBiP19022.
PaxDbiP19022.
PeptideAtlasiP19022.
PRIDEiP19022.
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.
GeneCardsiCDH2.
H-InvDBHIX0027368.
HGNCiHGNC:1759. CDH2.
HPAiCAB000141.
CAB018580.
HPA058574.
MIMi114020. gene.
neXtProtiNX_P19022.
OpenTargetsiENSG00000170558.
PharmGKBiPA26293.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170558-MONOMER.
ReactomeiR-HSA-375170. CDO in myogenesis.
R-HSA-418990. Adherens junctions interactions.
SIGNORiP19022.

Miscellaneous databases

ChiTaRSiCDH2. human.
GeneWikiiCDH2.
GenomeRNAii1000.
PMAP-CutDBP19022.
PROiP19022.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170558.
CleanExiHS_CDH2.
ExpressionAtlasiP19022. baseline and differential.
GenevisibleiP19022. HS.

Family and domain databases

Gene3Di2.60.40.60. 6 hits.
4.10.900.10. 1 hit.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR014868. Cadherin_pro_dom.
IPR027397. Catenin_binding_dom.
IPR030051. CDH2.
[Graphical view]
PANTHERiPTHR24027:SF79. PTHR24027:SF79. 1 hit.
PfamiPF00028. Cadherin. 5 hits.
PF01049. Cadherin_C. 1 hit.
PF08758. Cadherin_pro. 1 hit.
[Graphical view]
PRINTSiPR00205. CADHERIN.
SMARTiSM00112. CA. 5 hits.
SM01055. Cadherin_pro. 1 hit.
[Graphical view]
SUPFAMiSSF49313. SSF49313. 6 hits.
PROSITEiPS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 5 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCADH2_HUMAN
AccessioniPrimary (citable) accession number: P19022
Secondary accession number(s): A8MWK3
, B0YIY6, Q14923, Q8N173
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 169 of the entry and version 4 of the sequence. [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 cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.