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P33151 (CADH5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cadherin-5
Alternative name(s):
7B4 antigen
Vascular endothelial cadherin
Short name=VE-cadherin
CD_antigen=CD144
Gene names
Name:CDH5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length784 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. It associates with alpha-catenin forming a link to the cytoskeleton. Acts in concert with KRIT1 to establish and maintain correct endothelial cell polarity and vascular lumen. These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for activation of PRKCZ and for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction. Ref.10 Ref.11

Subunit structure

Interacts (via cadherin 5 domain) with PTPRB By similarity. Interacts with TRPC4. Interacts with KRIT1. Interacts with PARD3 By similarity. Ref.9 Ref.10

Subcellular location

Cell junction. Cell membrane; Single-pass type I membrane protein Probable. Note: Found at cell-cell boundaries and probably at cell-matrix boundaries. KRIT1 and CDH5 reciprocally regulate their localization to endothelial cell-cell junctions. Ref.10

Tissue specificity

Endothelial tissues and brain.

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 By similarity.

Post-translational modification

Phosphorylated on tyrosine residues by KDR/VEGFR-2. Dephosphorylated by PTPRB By similarity.

O-glycosylated. Ref.8 Ref.11

Sequence similarities

Contains 5 cadherin domains.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCell junction
Cell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   PTMCleavage on pair of basic residues
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadherens junction organization

Traceable author statement. Source: Reactome

blood vessel maturation

Inferred from electronic annotation. Source: Ensembl

cell junction assembly

Traceable author statement. Source: Reactome

cell-cell junction organization

Traceable author statement. Source: Reactome

homophilic cell adhesion

Traceable author statement Ref.2. Source: ProtInc

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of establishment of cell polarity

Inferred from mutant phenotype Ref.10. Source: UniProtKB

   Cellular_componentcell junction

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell junction

Inferred from direct assay Ref.10. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Traceable author statement Ref.2. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

tight junction

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionbeta-catenin binding

Inferred from physical interaction PubMed 18287330. Source: BHF-UCL

calcium ion binding

Inferred from electronic annotation. Source: InterPro

ion channel binding

Inferred from physical interaction Ref.9. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.10. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 12088286. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P33151-1)

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.
Isoform 2 (identifier: P33151-2)

The sequence of this isoform differs from the canonical sequence as follows:
     380-494: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Propeptide26 – 4722 Potential
PRO_0000003755
Chain48 – 784737Cadherin-5
PRO_0000003756

Regions

Topological domain48 – 599552Extracellular Potential
Transmembrane600 – 62021Helical; Potential
Topological domain621 – 784164Cytoplasmic Potential
Domain48 – 151104Cadherin 1
Domain152 – 258107Cadherin 2
Domain259 – 372114Cadherin 3
Domain373 – 477105Cadherin 4
Domain478 – 593116Cadherin 5
Compositional bias736 – 75318Ser-rich

Sites

Metal binding581Calcium 1 By similarity
Metal binding581Calcium 2 By similarity
Metal binding591Calcium 1 By similarity
Metal binding1091Calcium 1 By similarity
Metal binding1111Calcium 1 By similarity
Metal binding1111Calcium 2 By similarity
Metal binding1431Calcium 2 By similarity
Metal binding1441Calcium 2; via carbonyl oxygen By similarity
Metal binding1451Calcium 3 By similarity
Metal binding1461Calcium 1 By similarity
Metal binding1461Calcium 2 By similarity
Metal binding1471Calcium 3; via carbonyl oxygen By similarity
Metal binding1771Calcium 3 By similarity
Metal binding1791Calcium 2 By similarity
Metal binding1791Calcium 3 By similarity
Metal binding1861Calcium 3; via carbonyl oxygen By similarity
Metal binding2311Calcium 3 By similarity

Amino acid modifications

Glycosylation611N-linked (GlcNAc...) (complex) Ref.8 Ref.11
Glycosylation1121N-linked (GlcNAc...) (complex) Ref.7 Ref.8 Ref.11
Glycosylation1571N-linked (GlcNAc...) Ref.11
Glycosylation3621N-linked (GlcNAc...) Ref.11
Glycosylation4421N-linked (GlcNAc...) (complex) Ref.7 Ref.8 Ref.11
Glycosylation5231N-linked (GlcNAc...) Ref.7
Glycosylation5351N-linked (GlcNAc...) Ref.7

Natural variations

Alternative sequence380 – 494115Missing in isoform 2.
VSP_053861
Natural variant5031I → T.
Corresponds to variant rs16956504 [ dbSNP | Ensembl ].
VAR_028003
Natural variant5171I → T. Ref.1 Ref.3 Ref.4
Corresponds to variant rs1049970 [ dbSNP | Ensembl ].
VAR_028004

Experimental info

Sequence conflict6021V → A in AAH96363. Ref.4
Sequence conflict6021V → A in AAI17521. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 8, 2011. Version 5.
Checksum: 6DBEBFC4DA6899D1

FASTA78487,528
        10         20         30         40         50         60 
MQRLMMLLAT SGACLGLLAV AAVAAAGANP AQRDTHSLLP THRRQKRDWI WNQMHIDEEK 

        70         80         90        100        110        120 
NTSLPHHVGK IKSSVSRKNA KYLLKGEYVG KVFRVDAETG DVFAIERLDR ENISEYHLTA 

       130        140        150        160        170        180 
VIVDKDTGEN LETPSSFTIK VHDVNDNWPV FTHRLFNASV PESSAVGTSV ISVTAVDADD 

       190        200        210        220        230        240 
PTVGDHASVM YQILKGKEYF AIDNSGRIIT ITKSLDREKQ ARYEIVVEAR DAQGLRGDSG 

       250        260        270        280        290        300 
TATVLVTLQD INDNFPFFTQ TKYTFVVPED TRVGTSVGSL FVEDPDEPQN RMTKYSILRG 

       310        320        330        340        350        360 
DYQDAFTIET NPAHNEGIIK PMKPLDYEYI QQYSFIVEAT DPTIDLRYMS PPAGNRAQVI 

       370        380        390        400        410        420 
INITDVDEPP IFQQPFYHFQ LKENQKKPLI GTVLAMDPDA ARHSIGYSIR RTSDKGQFFR 

       430        440        450        460        470        480 
VTKKGDIYNE KELDREVYPW YNLTVEAKEL DSTGTPTGKE SIVQVHIEVL DENDNAPEFA 

       490        500        510        520        530        540 
KPYQPKVCEN AVHGQLVLQI SAIDKDITPR NVKFKFILNT ENNFTLTDNH DNTANITVKY 

       550        560        570        580        590        600 
GQFDREHTKV HFLPVVISDN GMPSRTGTST LTVAVCKCNE QGEFTFCEDM AAQVGVSIQA 

       610        620        630        640        650        660 
VVAILLCILT ITVITLLIFL RRRLRKQARA HGKSVPEIHE QLVTYDEEGG GEMDTTSYDV 

       670        680        690        700        710        720 
SVLNSVRRGG AKPPRPALDA RPSLYAQVQK PPRHAPGAHG GPGEMAAMIE VKKDEADHDG 

       730        740        750        760        770        780 
DGPPYDTLHI YGYEGSESIA ESLSSLGTDS SDSDVDYDFL NDWGPRFKML AELYGSDPRE 


ELLY 

« Hide

Isoform 2 [UniParc].

Checksum: 379A177E6E279C9A
Show »

FASTA66974,499

References

« Hide 'large scale' references
[1]"Functional properties of human vascular endothelial cadherin (7B4/cadherin-5), an endothelium-specific cadherin."
Breviario F., Caveda L., Corada M., Martin-Padura I., Navarro P., Golay J., Introna M., Gulino D., Lampugnani M.G., Dejana E.
Arterioscler. Thromb. Vasc. Biol. 15:1229-1239(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-517.
Tissue: Endothelial cell.
[2]"Vascular endothelial cadherin (VE-cadherin): cloning and role in endothelial cell-cell adhesion."
Ali J., Liao F., Martens E., Muller W.A.
Microcirculation 4:267-277(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[3]"Identification of three human type-II classic cadherins and frequent heterophilic interactions between different subclasses of type-II classic cadherins."
Shimoyama Y., Tsujimoto G., Kitajima M., Natori M.
Biochem. J. 349:159-167(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-517.
[4]"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] (ISOFORM 2), VARIANT THR-517.
[5]"Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue."
Suzuki S., Sano K., Tanihara H.
Cell Regul. 2:261-270(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-784 (ISOFORM 1).
Tissue: Brain.
[6]"A novel endothelial-specific membrane protein is a marker of cell-cell contacts."
Lampugnani M.G., Resnati M., Raiteri M., Pigott R., Pisacane A., Houen G., Ruco L.P., Dejana E.
J. Cell Biol. 118:1511-1522(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
Tissue: Endothelial cell.
[7]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-112; ASN-442; ASN-523 AND ASN-535.
Tissue: Plasma.
[8]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-61; ASN-112 AND ASN-442.
[9]"Cell-cell contact formation governs Ca2+ signaling by TRPC4 in the vascular endothelium: evidence for a regulatory TRPC4-beta-catenin interaction."
Graziani A., Poteser M., Heupel W.M., Schleifer H., Krenn M., Drenckhahn D., Romanin C., Baumgartner W., Groschner K.
J. Biol. Chem. 285:4213-4223(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRPC4.
[10]"CCM1 regulates vascular-lumen organization by inducing endothelial polarity."
Lampugnani M.G., Orsenigo F., Rudini N., Maddaluno L., Boulday G., Chapon F., Dejana E.
J. Cell Sci. 123:1073-1080(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH KRIT1.
[11]"Structure and binding mechanism of vascular endothelial cadherin: a divergent classical cadherin."
Brasch J., Harrison O.J., Ahlsen G., Carnally S.M., Henderson R.M., Honig B., Shapiro L.
J. Mol. Biol. 408:57-73(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, GLYCOSYLATION AT ASN-61; ASN-112; ASN-157; ASN-362 AND ASN-442.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X79981 mRNA. Translation: CAA56306.1.
U84722 mRNA. Translation: AAB41796.1.
AB035304 mRNA. Translation: BAA87418.1.
BC096363 mRNA. Translation: AAH96363.1.
BC096364 mRNA. Translation: AAH96364.3.
BC117520 mRNA. Translation: AAI17521.1.
X59796 mRNA. Translation: CAA42468.1.
CCDSCCDS10804.1.
PIRIJHUC5. S49893.
RefSeqNP_001786.2. NM_001795.3. [P33151-1]
UniGeneHs.76206.

3D structure databases

ProteinModelPortalP33151.
SMRP33151. Positions 48-576, 679-775.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107438. 13 interactions.
DIPDIP-41172N.
IntActP33151. 10 interactions.
MINTMINT-235470.
STRING9606.ENSP00000344115.

PTM databases

PhosphoSiteP33151.
UniCarbKBP33151.

Polymorphism databases

DMDM322510142.

Proteomic databases

PaxDbP33151.
PRIDEP33151.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000341529; ENSP00000344115; ENSG00000179776.
GeneID1003.
KEGGhsa:1003.
UCSCuc002eom.4. human. [P33151-1]

Organism-specific databases

CTD1003.
GeneCardsGC16P066400.
H-InvDBHIX0038527.
HGNCHGNC:1764. CDH5.
HPACAB028366.
HPA030562.
MIM601120. gene.
neXtProtNX_P33151.
PharmGKBPA26301.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG270902.
HOVERGENHBG005217.
InParanoidP33151.
KOK06533.
OMAYGYEGSE.
OrthoDBEOG773XFF.
PhylomeDBP33151.
TreeFamTF329887.

Enzyme and pathway databases

ReactomeREACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpressP33151.
BgeeP33151.
CleanExHS_CDH5.
GenevestigatorP33151.

Family and domain databases

Gene3D2.60.40.60. 5 hits.
4.10.900.10. 1 hit.
InterProIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR027397. Catenin_binding_dom.
[Graphical view]
PfamPF00028. Cadherin. 5 hits.
PF01049. Cadherin_C. 1 hit.
[Graphical view]
PRINTSPR00205. CADHERIN.
SMARTSM00112. CA. 5 hits.
[Graphical view]
SUPFAMSSF49313. SSF49313. 5 hits.
PROSITEPS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCDH5. human.
GeneWikiVE-cadherin.
GenomeRNAi1003.
NextBio4216.
PMAP-CutDBP33151.
PROP33151.
SOURCESearch...

Entry information

Entry nameCADH5_HUMAN
AccessionPrimary (citable) accession number: P33151
Secondary accession number(s): Q4VAI5, Q4VAI6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: February 8, 2011
Last modified: July 9, 2014
This is version 132 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

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List of human entries with polymorphisms or disease mutations

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