Q9NYJ7 (DLL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Delta-like protein 3

Alternative name(s):
Drosophila Delta homolog 3
Short name=Delta3

Gene names

Name:

DLL3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	618 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	Inhibits primary neurogenesis. May be required to divert neurons along a specific differentiation pathway. Plays a role in the formation of somite boundaries during segmentation of the paraxial mesoderm By similarity.
Subunit structure	Can bind and activate Notch-1 or another Notch receptor By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein Probable.
Domain	The 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.
Involvement in disease	Defects in DLL3 are the cause of spondylocostal dysostosis type 1 (SCDO1) [MIM:277300]. An autosomal recessive condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf-like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life. Ref.1
Sequence similarities	Contains 1 DSL domain. Contains 6 EGF-like domains.

Ontologies

Keywords
Biological process	Differentiation Notch signaling pathway
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Disulfide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Notch signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW skeletal system development Inferred from mutant phenotype Ref.1. Source: UniProtKB
Cellular component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	Notch binding Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 618	592	Delta-like protein 3		PRO_0000007509
Regions
	Topological domain	27 – 492	466	Extracellular Potential
	Transmembrane	493 – 513	21	Helical; Potential
	Topological domain	514 – 618	105	Cytoplasmic Potential
	Domain	176 – 215	40	DSL
	Domain	216 – 249	34	EGF-like 1
	Domain	274 – 310	37	EGF-like 2
	Domain	312 – 351	40	EGF-like 3
	Domain	353 – 389	37	EGF-like 4
	Domain	391 – 427	37	EGF-like 5
	Domain	429 – 465	37	EGF-like 6
Amino acid modifications
	Disulfide bond	220 ↔ 231		By similarity
	Disulfide bond	224 ↔ 237		By similarity
	Disulfide bond	239 ↔ 248		By similarity
	Disulfide bond	278 ↔ 289		By similarity
	Disulfide bond	283 ↔ 298		By similarity
	Disulfide bond	300 ↔ 309		By similarity
	Disulfide bond	316 ↔ 327		By similarity
	Disulfide bond	321 ↔ 339		By similarity
	Disulfide bond	341 ↔ 350		By similarity
	Disulfide bond	357 ↔ 368		By similarity
	Disulfide bond	362 ↔ 377		By similarity
	Disulfide bond	379 ↔ 388		By similarity
	Disulfide bond	395 ↔ 406		By similarity
	Disulfide bond	400 ↔ 415		By similarity
	Disulfide bond	417 ↔ 426		By similarity
	Disulfide bond	433 ↔ 444		By similarity
	Disulfide bond	438 ↔ 453		By similarity
	Disulfide bond	455 ↔ 464		By similarity
Natural variations
	Natural variant	115	1	A → T. Ref.3		VAR_046782
	Natural variant	142	1	L → Q. Ref.3 Corresponds to variant rs55741253 [ dbSNP | Ensembl ].		VAR_046783
	Natural variant	172	1	F → C. Ref.3 Corresponds to variant rs8107127 [ dbSNP | Ensembl ].		VAR_046784
	Natural variant	218	1	L → P. Ref.3 Corresponds to variant rs1110627 [ dbSNP | Ensembl ].		VAR_016776
	Natural variant	385	1	G → D in SCDO1. Ref.1		VAR_009952

Sequences

	Sequence		Length	Mass (Da)
	Q9NYJ7 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 58A9BC0A7DEAD1A0	FASTA	618	64,618
	10 20 30 40 50 60 MVSPRMSGLL SQTVILALIF LPQTRPAGVF ELQIHSFGPG PGPGAPRSPC SARLPCRLFF 70 80 90 100 110 120 RVCLKPGLSE EAAESPCALG AALSARGPVY TEQPGAPAPD LPLPDGLLQV PFRDAWPGTF 130 140 150 160 170 180 SFIIETWREE LGDQIGGPAW SLLARVAGRR RLAAGGPWAR DIQRAGAWEL RFSYRARCEP 190 200 210 220 230 240 PAVGTACTRL CRPRSAPSRC GPGLRPCAPL EDECEAPLVC RAGCSPEHGF CEQPGECRCL 250 260 270 280 290 300 EGWTGPLCTV PVSTSSCLSP RGPSSATTGC LVPGPGPCDG NPCANGGSCS ETPRSFECTC 310 320 330 340 350 360 PRGFYGLRCE VSGVTCADGP CFNGGLCVGG ADPDSAYICH CPPGFQGSNC EKRVDRCSLQ 370 380 390 400 410 420 PCRNGGLCLD LGHALRCRCR AGFAGPRCEH DLDDCAGRAC ANGGTCVEGG GAHRCSCALG 430 440 450 460 470 480 FGGRDCRERA DPCAARPCAH GGRCYAHFSG LVCACAPGYM GARCEFPVHP DGASALPAAP 490 500 510 520 530 540 PGLRPGDPQR YLLPPALGLL VAAGVAGAAL LLVHVRRRGH SQDAGSRLLA GTPEPSVHAL 550 560 570 580 590 600 PDALNNLRTQ EGSGDGPSSS VDWNRPEDVD PQGIYVISAP SIYAREVATP LFPPLHTGRA 610 GQRQHLLFPY PSSILSVK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis." Bulman M.P., Kusumi K., Frayling T.M., McKeown C., Garrett C., Lander E.S., Krumlauf R., Hattersley A.T., Ellard S., Turnpenny P.D. Nat. Genet. 24:438-441(2000) [PubMed: 10742114] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT SCDO1 ASP-385.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome." Cornier A.S., Staehling-Hampton K., Delventhal K.M., Saga Y., Caubet J.-F., Sasaki N., Ellard S., Young E., Ramirez N., Carlo S.E., Torres J., Emans J.B., Turnpenny P.D., Pourquie O. Am. J. Hum. Genet. 82:1334-1341(2008) [PubMed: 18485326] [Abstract] Cited for: VARIANTS THR-115; GLN-142; CYS-172 AND PRO-218.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF241373 , AF241367, AF241368, AF241369, AF241370, AF241371, AF241372 Genomic DNA. Translation: AAF62542.1. BC000218 mRNA. Translation: AAH00218.1.
IPI	IPI00021010.
RefSeq	NP_058637.1. NM_016941.3. NP_982353.1. NM_203486.2.
UniGene	Hs.127792.
3D structure databases
ProteinModelPortal	Q9NYJ7.
SMR	Q9NYJ7. Positions 177-466.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9NYJ7.
Polymorphism databases
DMDM	12229810.
Proteomic databases
PRIDE	Q9NYJ7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000205143; ENSP00000205143; ENSG00000090932.
GeneID	10683.
KEGG	hsa:10683.
UCSC	uc002olw.2. human.
Organism-specific databases
CTD	10683.
GeneCards	GC19P039989.
H-InvDB	HIX0015121.
HGNC	HGNC:2909. DLL3.
MIM	277300. phenotype. 602768. gene.
neXtProt	NX_Q9NYJ7.
Orphanet	2311. Autosomal recessive spondylocostal dysostosis.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00600000084206.
HOGENOM	HBG403082.
HOVERGEN	HBG007139.
InParanoid	Q9NYJ7.
OMA	FPVHPDG.
PhylomeDB	Q9NYJ7.
Gene expression databases
ArrayExpress	Q9NYJ7.
Bgee	Q9NYJ7.
CleanEx	HS_DLL3.
Genevestigator	Q9NYJ7.
GermOnline	ENSG00000090932. Homo sapiens.
Family and domain databases
InterPro	IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR011651. Notch_ligand_N. [Graphical view]
KO	K06051.
Pfam	PF00008. EGF. 3 hits. PF07657. MNNL. 1 hit. [Graphical view]
SMART	SM00181. EGF. 6 hits. [Graphical view]
PROSITE	PS51051. DSL. False negative. PS00022. EGF_1. 6 hits. PS01186. EGF_2. 6 hits. PS50026. EGF_3. 6 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	40615.
SOURCE	Search...

Entry information

Entry name

DLL3_HUMAN

Accession

Primary (citable) accession number: Q9NYJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 112 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.