P33151 (CADH5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cadherin-5

Alternative name(s):
7B4 antigen
Vascular endothelial cadherin
Short name=VE-cadherin
CD_antigen=CD144

Gene names

Name:

CDH5

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	784 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. 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.8
Subunit structure	Interacts via cadherin 5 domain with PTPRB By similarity. Interacts with TRPC4. Interacts with KRIT1. Ref.7 Ref.8
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.8
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.
Sequence similarities	Contains 5 cadherin domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction 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 Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adherens junction organization Traceable author statement. Source: Reactome blood vessel maturation Inferred from electronic annotation. Source: Compara cell junction assembly 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: Compara regulation of establishment of cell polarity Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	cell-cell junction Inferred from direct assay Ref.8. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome tight junction Inferred from electronic annotation. Source: Compara
Molecular_function	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 – 47	22	Potential		PRO_0000003755
	Chain	48 – 784	737	Cadherin-5		PRO_0000003756
Regions
	Topological domain	48 – 599	552	Extracellular Potential
	Transmembrane	600 – 620	21	Helical; Potential
	Topological domain	621 – 784	164	Cytoplasmic Potential
	Domain	48 – 151	104	Cadherin 1
	Domain	152 – 258	107	Cadherin 2
	Domain	259 – 372	114	Cadherin 3
	Domain	373 – 477	105	Cadherin 4
	Domain	478 – 593	116	Cadherin 5
	Compositional bias	736 – 753	18	Ser-rich
Amino acid modifications
	Glycosylation	61	1	N-linked (GlcNAc...) Potential
	Glycosylation	112	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	157	1	N-linked (GlcNAc...) Potential
	Glycosylation	362	1	N-linked (GlcNAc...) Potential
	Glycosylation	442	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	523	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	535	1	N-linked (GlcNAc...) Ref.6
Natural variations
	Natural variant	503	1	I → T. Corresponds to variant rs16956504 [ dbSNP | Ensembl ].		VAR_028003
	Natural variant	517	1	I → T. Ref.1 Ref.3 Corresponds to variant rs1049970 [ dbSNP | Ensembl ].		VAR_028004

Sequences

	Sequence		Length	Mass (Da)
	P33151 [UniParc]. Last modified February 8, 2011. Version 5. Checksum: 6DBEBFC4DA6899D1	FASTA	784	87,528
	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

References

	« Hide 'large scale' referencesShow '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], 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]. 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], VARIANT THR-517.
[4]	"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. Tissue: Brain.
[5]	"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.
[6]	"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, MASS SPECTROMETRY. Tissue: Plasma.
[7]	"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.
[8]	"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.
+	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. X59796 mRNA. Translation: CAA42468.1.
IPI	IPI00012792.
PIR	IJHUC5. S49893.
RefSeq	NP_001786.2. NM_001795.3.
UniGene	Hs.76206.
3D structure databases
ProteinModelPortal	P33151.
SMR	P33151. Positions 48-576, 679-775.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-41172N.
IntAct	P33151. 3 interactions.
MINT	MINT-235470.
STRING	9606.ENSP00000344115.
PTM databases
GlycoSuiteDB	P33151.
PhosphoSite	P33151.
Polymorphism databases
DMDM	13432109.
Proteomic databases
PaxDb	P33151.
PRIDE	P33151.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000341529; ENSP00000344115; ENSG00000179776.
GeneID	1003.
KEGG	hsa:1003.
UCSC	uc002eom.4. human.
Organism-specific databases
CTD	1003.
GeneCards	GC16P066400.
H-InvDB	HIX0038527.
HGNC	HGNC:1764. CDH5.
HPA	CAB028366. HPA030562.
MIM	601120. gene.
neXtProt	NX_P33151.
PharmGKB	PA26301.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG270902.
HOVERGEN	HBG005217.
InParanoid	P33151.
KO	K06533.
OMA	YSIRRTS.
OrthoDB	EOG4T1HM2.
PhylomeDB	P33151.
Enzyme and pathway databases
Pathway_Interaction_DB	s1p_s1p2_pathway. S1P2 pathway. vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
Reactome	REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	P33151.
Bgee	P33151.
CleanEx	HS_CDH5.
Genevestigator	P33151.
GermOnline	ENSG00000179776. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.60. 5 hits.
InterPro	IPR002126. Cadherin. IPR015919. Cadherin-like. IPR020894. Cadherin_CS. IPR000233. Cadherin_cytoplasmic-dom. [Graphical view]
Pfam	PF00028. Cadherin. 5 hits. PF01049. Cadherin_C. 1 hit. [Graphical view]
PRINTS	PR00205. CADHERIN.
SMART	SM00112. CA. 5 hits. [Graphical view]
SUPFAM	SSF49313. Cadherin. 5 hits.
PROSITE	PS00232. CADHERIN_1. 3 hits. PS50268. CADHERIN_2. 5 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CDH5. human.
GenomeRNAi	1003.
NextBio	4216.
PMAP-CutDB	P33151.
SOURCE	Search...

Entry information

Entry name

CADH5_HUMAN

Accession

Primary (citable) accession number: P33151

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	February 8, 2011
Last modified:	May 1, 2013
This is version 120 of the entry and version 5 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.