Q9NR61 (DLL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Delta-like protein 4

Alternative name(s):
Drosophila Delta homolog 4
Short name=Delta4

Gene names

Name:	DLL4
ORF Names:	UNQ1895/PRO4341

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	685 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	Plays a role in the Notch signaling pathway. Activates Notch-1 and Notch-4 By similarity.
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 process	Differentiation Notch signaling pathway
Cellular component	Membrane
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Notch receptor processing Traceable author statement. Source: Reactome Notch signaling involved in heart development 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: Compara blood vessel remodeling Inferred from sequence or structural similarity. Source: BHF-UCL cardiac atrium morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL dorsal aorta morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of blood vessel endothelial cell migration Inferred from electronic annotation. Source: Compara 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: Compara ventricular trabecula myocardium morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	Notch binding Traceable author statement Ref.1. Source: ProtInc 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 – 26	26	Ref.6
	Chain	27 – 685	659	Delta-like protein 4		PRO_0000007512
Regions
	Topological domain	27 – 529	503	Extracellular Potential
	Transmembrane	530 – 550	21	Helical; Potential
	Topological domain	551 – 685	135	Cytoplasmic Potential
	Domain	173 – 217	45	DSL
	Domain	218 – 251	34	EGF-like 1
	Domain	252 – 282	31	EGF-like 2
	Domain	284 – 322	39	EGF-like 3
	Domain	324 – 360	37	EGF-like 4
	Domain	362 – 400	39	EGF-like 5
	Domain	402 – 438	37	EGF-like 6
	Domain	440 – 476	37	EGF-like 7
	Domain	480 – 518	39	EGF-like 8
Amino acid modifications
	Glycosylation	108	1	N-linked (GlcNAc...) Potential
	Glycosylation	183	1	N-linked (GlcNAc...) Potential
	Glycosylation	205	1	N-linked (GlcNAc...) Potential
	Glycosylation	393	1	N-linked (GlcNAc...) Potential
	Disulfide bond	175 ↔ 184		By similarity
	Disulfide bond	188 ↔ 200		By similarity
	Disulfide bond	208 ↔ 217		By similarity
	Disulfide bond	222 ↔ 233		By similarity
	Disulfide bond	226 ↔ 239		By similarity
	Disulfide bond	241 ↔ 250		By similarity
	Disulfide bond	253 ↔ 264		By similarity
	Disulfide bond	259 ↔ 270		By similarity
	Disulfide bond	272 ↔ 281		By similarity
	Disulfide bond	288 ↔ 300		By similarity
	Disulfide bond	294 ↔ 310		By similarity
	Disulfide bond	312 ↔ 321		By similarity
	Disulfide bond	328 ↔ 339		By similarity
	Disulfide bond	333 ↔ 348		By similarity
	Disulfide bond	350 ↔ 359		By similarity
	Disulfide bond	366 ↔ 377		By similarity
	Disulfide bond	371 ↔ 388		By similarity
	Disulfide bond	390 ↔ 399		By similarity
	Disulfide bond	406 ↔ 417		By similarity
	Disulfide bond	411 ↔ 426		By similarity
	Disulfide bond	428 ↔ 437		By similarity
	Disulfide bond	444 ↔ 455		By similarity
	Disulfide bond	449 ↔ 464		By similarity
	Disulfide bond	466 ↔ 475		By similarity
	Disulfide bond	484 ↔ 495		By similarity
	Disulfide bond	489 ↔ 506		By similarity
	Disulfide bond	508 ↔ 517		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9NR61 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 6CF89D3C220ACC89	FASTA	685	74,605
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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.
IPI	IPI00015994.
PIR	JC7570.
RefSeq	NP_061947.1. NM_019074.3.
UniGene	Hs.511076.
3D structure databases
ProteinModelPortal	Q9NR61.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000249749.
Polymorphism databases
DMDM	13431490.
Proteomic databases
PaxDb	Q9NR61.
PRIDE	Q9NR61.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000249749; ENSP00000249749; ENSG00000128917.
GeneID	54567.
KEGG	hsa:54567.
UCSC	uc001zng.2. human.
Organism-specific databases
CTD	54567.
GeneCards	GC15P041221.
HGNC	HGNC:2910. DLL4.
HPA	HPA023392.
MIM	605185. gene.
neXtProt	NX_Q9NR61.
PharmGKB	PA27366.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG249767.
HOGENOM	HOG000267024.
HOVERGEN	HBG007139.
InParanoid	Q9NR61.
KO	K06051.
OMA	LPFNFTW.
OrthoDB	EOG4PZJ63.
PhylomeDB	Q9NR61.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_2001. Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor.
Gene expression databases
Bgee	Q9NR61.
CleanEx	HS_DLL4.
Genevestigator	Q9NR61.
GermOnline	ENSG00000128917. Homo sapiens.
Family and domain databases
InterPro	IPR001774. DSL. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR011651. Notch_ligand_N. [Graphical view]
Pfam	PF01414. DSL. 1 hit. PF00008. EGF. 4 hits. PF12661. hEGF. 2 hits. PF07657. MNNL. 1 hit. [Graphical view]
SMART	SM00051. DSL. 1 hit. SM00181. EGF. 6 hits. SM00179. EGF_CA. 2 hits. [Graphical view]
PROSITE	PS00010. 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]
ProtoNet	Search...
Other
GenomeRNAi	54567.
NextBio	57056.
SOURCE	Search...

Entry information

Entry name

DLL4_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 121 of the entry and version 1 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.