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Q9NR61 (DLL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Delta-like protein 4
Alternative name(s):
Drosophila Delta homolog 4
Short name=Delta4
Gene names
Name:DLL4
ORF Names:UNQ1895/PRO4341
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length685 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Plays a role in the Notch signaling pathway. Activates Notch-1 and Notch-4 By similarity. Ref.8

Subunit structure

Binds to Notch-1 and Notch-4 By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein Probable.

Tissue specificity

Expressed in vascular endothelium.

Domain

The Delta-Serrate-Lag2 (DSL) domain is required for binding to the Notch receptor.

Post-translational modification

Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation By similarity.

Sequence similarities

Contains 1 DSL domain.

Contains 8 EGF-like domains.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
Notch signaling pathway
   Cellular componentMembrane
   DomainEGF-like domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processNotch receptor processing

Traceable author statement. Source: Reactome

Notch signaling involved in heart development

Inferred from sequence or structural similarity. Source: BHF-UCL

Notch signaling pathway

Traceable author statement. Source: Reactome

angiogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

blood circulation

Traceable author statement Ref.1. Source: ProtInc

blood vessel lumenization

Inferred from electronic annotation. Source: Ensembl

blood vessel remodeling

Inferred from sequence or structural similarity. Source: BHF-UCL

cardiac atrium morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cardiac ventricle morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to fibroblast growth factor stimulus

Inferred from direct assay Ref.8. Source: UniProtKB

cellular response to vascular endothelial growth factor stimulus

Inferred from mutant phenotype Ref.8. Source: UniProtKB

dorsal aorta morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cell migration involved in sprouting angiogenesis

Inferred from mutant phenotype Ref.8. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

negative regulation of endothelial cell migration

Inferred from mutant phenotype Ref.8. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

patterning of blood vessels

Inferred from sequence or structural similarity. Source: BHF-UCL

pericardium morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of neurogenesis

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

ventricular trabecula myocardium morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionNotch binding

Traceable author statement Ref.1. Source: ProtInc

calcium ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Ref.6
Chain27 – 685659Delta-like protein 4
PRO_0000007512

Regions

Topological domain27 – 529503Extracellular Potential
Transmembrane530 – 55021Helical; Potential
Topological domain551 – 685135Cytoplasmic Potential
Domain173 – 21745DSL
Domain218 – 25134EGF-like 1
Domain252 – 28231EGF-like 2
Domain284 – 32239EGF-like 3
Domain324 – 36037EGF-like 4
Domain362 – 40039EGF-like 5
Domain402 – 43837EGF-like 6
Domain440 – 47637EGF-like 7
Domain480 – 51839EGF-like 8

Amino acid modifications

Glycosylation1081N-linked (GlcNAc...) Potential
Glycosylation1831N-linked (GlcNAc...) Potential
Glycosylation2051N-linked (GlcNAc...) Potential
Glycosylation3931N-linked (GlcNAc...) Potential
Disulfide bond175 ↔ 184 By similarity
Disulfide bond188 ↔ 200 By similarity
Disulfide bond208 ↔ 217 By similarity
Disulfide bond222 ↔ 233 By similarity
Disulfide bond226 ↔ 239 By similarity
Disulfide bond241 ↔ 250 By similarity
Disulfide bond253 ↔ 264 By similarity
Disulfide bond259 ↔ 270 By similarity
Disulfide bond272 ↔ 281 By similarity
Disulfide bond288 ↔ 300 By similarity
Disulfide bond294 ↔ 310 By similarity
Disulfide bond312 ↔ 321 By similarity
Disulfide bond328 ↔ 339 By similarity
Disulfide bond333 ↔ 348 By similarity
Disulfide bond350 ↔ 359 By similarity
Disulfide bond366 ↔ 377 By similarity
Disulfide bond371 ↔ 388 By similarity
Disulfide bond390 ↔ 399 By similarity
Disulfide bond406 ↔ 417 By similarity
Disulfide bond411 ↔ 426 By similarity
Disulfide bond428 ↔ 437 By similarity
Disulfide bond444 ↔ 455 By similarity
Disulfide bond449 ↔ 464 By similarity
Disulfide bond466 ↔ 475 By similarity
Disulfide bond484 ↔ 495 By similarity
Disulfide bond489 ↔ 506 By similarity
Disulfide bond508 ↔ 517 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9NR61 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 6CF89D3C220ACC89

FASTA68574,605
        10         20         30         40         50         60 
MAAASRSASG WALLLLVALW QQRAAGSGVF QLQLQEFINE RGVLASGRPC EPGCRTFFRV 

        70         80         90        100        110        120 
CLKHFQAVVS PGPCTFGTVS TPVLGTNSFA VRDDSSGGGR NPLQLPFNFT WPGTFSLIIE 

       130        140        150        160        170        180 
AWHAPGDDLR PEALPPDALI SKIAIQGSLA VGQNWLLDEQ TSTLTRLRYS YRVICSDNYY 

       190        200        210        220        230        240 
GDNCSRLCKK RNDHFGHYVC QPDGNLSCLP GWTGEYCQQP ICLSGCHEQN GYCSKPAECL 

       250        260        270        280        290        300 
CRPGWQGRLC NECIPHNGCR HGTCSTPWQC TCDEGWGGLF CDQDLNYCTH HSPCKNGATC 

       310        320        330        340        350        360 
SNSGQRSYTC TCRPGYTGVD CELELSECDS NPCRNGGSCK DQEDGYHCLC PPGYYGLHCE 

       370        380        390        400        410        420 
HSTLSCADSP CFNGGSCRER NQGANYACEC PPNFTGSNCE KKVDRCTSNP CANGGQCLNR 

       430        440        450        460        470        480 
GPSRMCRCRP GFTGTYCELH VSDCARNPCA HGGTCHDLEN GLMCTCPAGF SGRRCEVRTS 

       490        500        510        520        530        540 
IDACASSPCF NRATCYTDLS TDTFVCNCPY GFVGSRCEFP VGLPPSFPWV AVSLGVGLAV 

       550        560        570        580        590        600 
LLVLLGMVAV AVRQLRLRRP DDGSREAMNN LSDFQKDNLI PAAQLKNTNQ KKELEVDCGL 

       610        620        630        640        650        660 
DKSNCGKQQN HTLDYNLAPG PLGRGTMPGK FPHSDKSLGE KAPLRLHSEK PECRISAICS 

       670        680 
PRDSMYQSVC LISEERNECV IATEV 

« Hide

References

« Hide 'large scale' references
[1]"Dll4, a novel Notch ligand expressed in arterial endothelium."
Shutter J.R., Scully S., Fan W., Richards W.G., Kitajewski J., Deblandre G.A., Kintner C.R., Stark K.L.
Genes Dev. 14:1313-1318(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Human Delta-2, Notch ligand gene."
Sakano S.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Molecular cloning of Delta-4, a new mouse and human Notch ligand."
Yoneya T., Tahara T., Nagao K., Yamada Y., Yamamoto T., Miyatani S., Nishikawa M.
J. Biochem. 129:27-34(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"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].
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 27-41.
[7]"A novel Delta gene expressed in embryonic and tumour vasculature."
Mailhos C., Modlich U., Lewis J., Harris A., Bicknell R., Ish-Horowicz D.
Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-685.
Tissue: Placenta.
[8]"Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis."
Brutsch R., Liebler S.S., Wustehube J., Bartol A., Herberich S.E., Adam M.G., Telzerow A., Augustin H.G., Fischer A.
Circ. Res. 107:592-601(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF253468 mRNA. Translation: AAF76427.1.
AB036931 mRNA. Translation: BAB16085.1.
AB043894 mRNA. Translation: BAB18581.1.
AY358894 mRNA. Translation: AAQ89253.1.
BC106950 mRNA. Translation: AAI06951.1.
AF279305 mRNA. Translation: AAF81912.1.
PIRJC7570.
RefSeqNP_061947.1. NM_019074.3.
UniGeneHs.511076.

3D structure databases

ProteinModelPortalQ9NR61.
SMRQ9NR61. Positions 131-518.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000249749.

Polymorphism databases

DMDM13431490.

Proteomic databases

PaxDbQ9NR61.
PRIDEQ9NR61.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000249749; ENSP00000249749; ENSG00000128917.
GeneID54567.
KEGGhsa:54567.
UCSCuc001zng.2. human.

Organism-specific databases

CTD54567.
GeneCardsGC15P041221.
HGNCHGNC:2910. DLL4.
HPAHPA023392.
MIM605185. gene.
neXtProtNX_Q9NR61.
PharmGKBPA27366.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249767.
HOGENOMHOG000267024.
HOVERGENHBG007139.
InParanoidQ9NR61.
KOK06051.
OMALPFNFTW.
OrthoDBEOG7GQXZ5.
PhylomeDBQ9NR61.
TreeFamTF351835.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_2001. Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor.
SignaLinkQ9NR61.

Gene expression databases

BgeeQ9NR61.
CleanExHS_DLL4.
GenevestigatorQ9NR61.

Family and domain databases

InterProIPR001774. DSL.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR009030. Growth_fac_rcpt_N_dom.
IPR011651. Notch_ligand_N.
[Graphical view]
PfamPF01414. DSL. 1 hit.
PF00008. EGF. 4 hits.
PF12661. hEGF. 2 hits.
PF07657. MNNL. 1 hit.
[Graphical view]
SMARTSM00051. DSL. 1 hit.
SM00181. EGF. 6 hits.
SM00179. EGF_CA. 2 hits.
[Graphical view]
SUPFAMSSF57184. SSF57184. 1 hit.
PROSITEPS00010. ASX_HYDROXYL. 1 hit.
PS51051. DSL. 1 hit.
PS00022. EGF_1. 8 hits.
PS01186. EGF_2. 7 hits.
PS50026. EGF_3. 8 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDLL4.
GenomeRNAi54567.
NextBio57056.
PROQ9NR61.
SOURCESearch...

Entry information

Entry nameDLL4_HUMAN
AccessionPrimary (citable) accession number: Q9NR61
Secondary accession number(s): Q3KP23, Q9NQT9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 130 of the entry and version 1 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 chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM