P19022 (CADH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cadherin-2

Alternative name(s):
CDw325
Neural cadherin
Short name=N-cadherin
CD_antigen=CD325

Gene names

Name:	CDH2
Synonyms:	CDHN, NCAD

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	906 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density By similarity.
Subunit structure	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. Ref.9
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Domain	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.
Sequence similarities	Contains 5 cadherin domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
PTM	Cleavage on pair of basic residues Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adherens junction organization Traceable author statement. Source: Reactome blood vessel morphogenesis Inferred from electronic annotation. Source: Compara calcium-dependent cell-cell adhesion Inferred from electronic annotation. Source: Compara cell adhesion Traceable author statement Ref.7. Source: ProtInc cell junction assembly Traceable author statement. Source: Reactome cell migration Inferred from electronic annotation. Source: Compara heterophilic cell-cell adhesion Inferred from electronic annotation. Source: Compara homophilic cell adhesion Inferred from electronic annotation. Source: Compara muscle cell differentiation Traceable author statement. Source: Reactome negative regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of MAPK cascade Inferred from electronic annotation. Source: Compara positive regulation of muscle cell differentiation Traceable author statement. Source: Reactome striated muscle cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	catenin complex Inferred from direct assay PubMed 7650039. Source: BHF-UCL cell-cell adherens junction Inferred from direct assay PubMed 19101069. Source: BHF-UCL fascia adherens Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intercalated disc Inferred from sequence or structural similarity. Source: BHF-UCL lamellipodium Inferred from electronic annotation. Source: Compara synapse Inferred from electronic annotation. Source: Compara
Molecular_function	beta-catenin binding Traceable author statement PubMed 16344550. Source: AgBase calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Propeptide	26 – 159	134			PRO_0000003731
	Chain	160 – 906	747	Cadherin-2		PRO_0000003732
Regions
	Topological domain	160 – 724	565	Extracellular Potential
	Transmembrane	725 – 745	21	Helical; Potential
	Topological domain	746 – 906	161	Cytoplasmic Potential
	Domain	160 – 267	108	Cadherin 1
	Domain	268 – 382	115	Cadherin 2
	Domain	383 – 497	115	Cadherin 3
	Domain	498 – 603	106	Cadherin 4
	Domain	604 – 714	111	Cadherin 5
	Compositional bias	863 – 878	16	Ser-rich
Sites
	Metal binding	262	1	Calcium 1 By similarity
	Metal binding	262	1	Calcium 2 By similarity
	Metal binding	293	1	Calcium 3 By similarity
Amino acid modifications
	Glycosylation	190	1	N-linked (GlcNAc...) Potential
	Glycosylation	273	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	325	1	N-linked (GlcNAc...) Potential
	Glycosylation	402	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	572	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	651	1	N-linked (GlcNAc...) Potential
	Glycosylation	692	1	N-linked (GlcNAc...) Ref.10
Natural variations
	Natural variant	21	1	A → T. Corresponds to variant rs17495042 [ dbSNP | Ensembl ].		VAR_028254
	Natural variant	118	1	A → T. Corresponds to variant rs17445840 [ dbSNP | Ensembl ].		VAR_028255
	Natural variant	196	1	S → T. Ref.1 Corresponds to variant rs1041970 [ dbSNP | Ensembl ].		VAR_028256
	Natural variant	212	1	I → L. Ref.7 Corresponds to variant rs1041972 [ dbSNP | Ensembl ].		VAR_028257
	Natural variant	454	1	T → A. Ref.6 Corresponds to variant rs17857112 [ dbSNP | Ensembl ].		VAR_048503
	Natural variant	845	1	N → S. Corresponds to variant rs2289664 [ dbSNP | Ensembl ].		VAR_028258
Experimental info
	Sequence conflict	12	1	Missing in AAB22854. Ref.3
	Sequence conflict	16	1	A → L in CAA38213. Ref.1
	Sequence conflict	164	1	P → S in AAH36470. Ref.6
	Sequence conflict	357	1	N → I in CAA38213. Ref.1
	Sequence conflict	437	1	P → Q in AAH36470. Ref.6
	Sequence conflict	484	1	V → M in AAH36470. Ref.6
	Sequence conflict	629	1	D → G in AAH36470. Ref.6
	Sequence conflict	867	1	A → L in AAB22854. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P19022 [UniParc]. Last modified October 17, 2006. Version 4. Checksum: 7267E2A00489DF94	FASTA	906	99,809
	10 20 30 40 50 60 MCRIAGALRT LLPLLAALLQ ASVEASGEIA LCKTGFPEDV YSAVLSKDVH EGQPLLNVKF 70 80 90 100 110 120 SNCNGKRKVQ YESSEPADFK VDEDGMVYAV RSFPLSSEHA KFLIYAQDKE TQEKWQVAVK 130 140 150 160 170 180 LSLKPTLTEE SVKESAEVEE IVFPRQFSKH SGHLQRQKRD WVIPPINLPE NSRGPFPQEL 190 200 210 220 230 240 VRIRSDRDKN LSLRYSVTGP GADQPPTGIF IINPISGQLS VTKPLDREQI ARFHLRAHAV 250 260 270 280 290 300 DINGNQVENP IDIVINVIDM NDNRPEFLHQ VWNGTVPEGS KPGTYVMTVT AIDADDPNAL 310 320 330 340 350 360 NGMLRYRIVS QAPSTPSPNM FTINNETGDI ITVAAGLDRE KVQQYTLIIQ ATDMEGNPTY 370 380 390 400 410 420 GLSNTATAVI TVTDVNDNPP EFTAMTFYGE VPENRVDIIV ANLTVTDKDQ PHTPAWNAVY 430 440 450 460 470 480 RISGGDPTGR FAIQTDPNSN DGLVTVVKPI DFETNRMFVL TVAAENQVPL AKGIQHPPQS 490 500 510 520 530 540 TATVSVTVID VNENPYFAPN PKIIRQEEGL HAGTMLTTFT AQDPDRYMQQ NIRYTKLSDP 550 560 570 580 590 600 ANWLKIDPVN GQITTIAVLD RESPNVKNNI YNATFLASDN GIPPMSGTGT LQIYLLDIND 610 620 630 640 650 660 NAPQVLPQEA ETCETPDPNS INITALDYDI DPNAGPFAFD LPLSPVTIKR NWTITRLNGD 670 680 690 700 710 720 FAQLNLKIKF LEAGIYEVPI IITDSGNPPK SNISILRVKV CQCDSNGDCT DVDRIVGAGL 730 740 750 760 770 780 GTGAIIAILL CIIILLILVL MFVVWMKRRD KERQAKQLLI DPEDDVRDNI LKYDEEGGGE 790 800 810 820 830 840 EDQDYDLSQL QQPDTVEPDA IKPVGIRRMD ERPIHAEPQY PVRSAAPHPG DIGDFINEGL 850 860 870 880 890 900 KAADNDPTAP PYDSLLVFDY EGSGSTAGSL SSLNSSSSGG EQDYDYLNDW GPRFKKLADM YGGGDD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human N-cadherin: nucleotide and deduced amino acid sequence." Reid R.A., Hemperly J.J. Nucleic Acids Res. 18:5896-5896(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-196.
[2]	Reid R.A. Submitted (NOV-1990) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 341; 699 AND 705.
[3]	"Extrajunctional distribution of N-cadherin in cultured human endothelial cells." Salomon D., Ayalon O., Patel-King R., Hynes R.O., Geiger B. J. Cell Sci. 102:7-17(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-454. Tissue: Brain.
[7]	"N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene." Walsh F.S., Barton C.H., Putt W., Moore S.E., Kelsell D., Spurr N., Goodfellow P.N. J. Neurochem. 55:805-812(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 160-906, VARIANT LEU-212.
[8]	"Structure of the human N-cadherin gene: YAC analysis and fine chromosomal mapping to 18q11.2." Wallis J.A., Fox M., Walsh F.S. Genomics 22:172-179(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
[9]	"Adhesion signaling by a novel mitotic substrate of src kinases." Bhatt A.S., Erdjument-Bromage H., Tempst P., Craik C.S., Moasser M.M. Oncogene 24:5333-5343(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDCP1.
[10]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-273; ASN-402; ASN-572 AND ASN-692, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X54315 mRNA. Translation: CAA38213.1. S42303 mRNA. Translation: AAB22854.1. 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.
IPI	IPI00290085.
PIR	IJHUCN. A38870.
RefSeq	NP_001783.2. NM_001792.3.
UniGene	Hs.464829. Hs.606106.
3D structure databases
ProteinModelPortal	P19022.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-43894N.
IntAct	P19022. 15 interactions.
MINT	MINT-441636.
STRING	9606.ENSP00000269141.
PTM databases
PhosphoSite	P19022.
Polymorphism databases
DMDM	116241277.
Proteomic databases
PaxDb	P19022.
PeptideAtlas	P19022.
PRIDE	P19022.
Protocols and materials databases
DNASU	1000.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000269141; ENSP00000269141; ENSG00000170558.
GeneID	1000.
KEGG	hsa:1000.
UCSC	uc002kwg.2. human.
Organism-specific databases
CTD	1000.
GeneCards	GC18M025530.
H-InvDB	HIX0027368.
HGNC	HGNC:1759. CDH2.
HPA	CAB000141. CAB018580.
MIM	114020. gene.
neXtProt	NX_P19022.
PharmGKB	PA26293.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG251747.
HOGENOM	HOG000231254.
HOVERGEN	HBG106438.
InParanoid	P19022.
KO	K06736.
OMA	HSGHLQR.
OrthoDB	EOG483D43.
PhylomeDB	P19022.
Enzyme and pathway databases
Pathway_Interaction_DB	fgf_pathway. FGF signaling pathway. ptp1bpathway. Signaling events mediated by PTP1B.
Reactome	REACT_111045. Developmental Biology. REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	P19022.
Bgee	P19022.
CleanEx	HS_CDH2.
Genevestigator	P19022.
GermOnline	ENSG00000170558. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.60. 6 hits.
InterPro	IPR002126. Cadherin. IPR015919. Cadherin-like. IPR009124. Cadherin/Desmocollin. IPR020894. Cadherin_CS. IPR000233. Cadherin_cytoplasmic-dom. IPR014868. Cadherin_pro_dom. [Graphical view]
Pfam	PF00028. Cadherin. 5 hits. PF01049. Cadherin_C. 1 hit. PF08758. Cadherin_pro. 1 hit. [Graphical view]
PRINTS	PR00205. CADHERIN. PR01820. DESMOCOLLIN.
SMART	SM00112. CA. 5 hits. SM01055. Cadherin_pro. 1 hit. [Graphical view]
SUPFAM	SSF49313. Cadherin. 6 hits.
PROSITE	PS00232. CADHERIN_1. 3 hits. PS50268. CADHERIN_2. 5 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P19022.
ChEMBL	CHEMBL1697669.
ChiTaRS	CDH2. human.
GenomeRNAi	1000.
NextBio	4204.
PMAP-CutDB	P19022.
SOURCE	Search...

Entry information

Entry name

CADH2_HUMAN

Accession

Primary (citable) accession number: P19022
Secondary accession number(s): B0YIY6, Q14923, Q8N173

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 133 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.