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Q9NYJ7 (DLL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Delta-like protein 3
Alternative name(s):
Drosophila Delta homolog 3
Short name=Delta3
Gene names
Name:DLL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length618 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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

Spondylocostal dysostosis 1, autosomal recessive (SCDO1) [MIM:277300]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence similarities

Contains 1 DSL domain.

Contains 6 EGF-like domains.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NYJ7-1)

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: Q9NYJ7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     587-618: VATPLFPPLHTGRAGQRQHLLFPYPSSILSVK → A
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 618592Delta-like protein 3
PRO_0000007509

Regions

Topological domain27 – 492466Extracellular Potential
Transmembrane493 – 51321Helical; Potential
Topological domain514 – 618105Cytoplasmic Potential
Domain176 – 21540DSL
Domain216 – 24934EGF-like 1
Domain274 – 31037EGF-like 2
Domain312 – 35140EGF-like 3
Domain353 – 38937EGF-like 4
Domain391 – 42737EGF-like 5
Domain429 – 46537EGF-like 6

Amino acid modifications

Disulfide bond220 ↔ 231 By similarity
Disulfide bond224 ↔ 237 By similarity
Disulfide bond239 ↔ 248 By similarity
Disulfide bond278 ↔ 289 By similarity
Disulfide bond283 ↔ 298 By similarity
Disulfide bond300 ↔ 309 By similarity
Disulfide bond316 ↔ 327 By similarity
Disulfide bond321 ↔ 339 By similarity
Disulfide bond341 ↔ 350 By similarity
Disulfide bond357 ↔ 368 By similarity
Disulfide bond362 ↔ 377 By similarity
Disulfide bond379 ↔ 388 By similarity
Disulfide bond395 ↔ 406 By similarity
Disulfide bond400 ↔ 415 By similarity
Disulfide bond417 ↔ 426 By similarity
Disulfide bond433 ↔ 444 By similarity
Disulfide bond438 ↔ 453 By similarity
Disulfide bond455 ↔ 464 By similarity

Natural variations

Alternative sequence587 – 61832VATPL…ILSVK → A in isoform 2.
VSP_045249
Natural variant1151A → T. Ref.5
VAR_046782
Natural variant1421L → Q. Ref.5
Corresponds to variant rs55741253 [ dbSNP | Ensembl ].
VAR_046783
Natural variant1721F → C. Ref.2 Ref.5
Corresponds to variant rs8107127 [ dbSNP | Ensembl ].
VAR_046784
Natural variant2181L → P. Ref.2 Ref.5
Corresponds to variant rs1110627 [ dbSNP | Ensembl ].
VAR_016776
Natural variant3851G → D in SCDO1. Ref.1
VAR_009952

Experimental info

Sequence conflict3181D → N in BAC11535. Ref.2
Sequence conflict4351A → V in BAC11535. Ref.2

Sequences

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

Last modified October 1, 2000. Version 1.
Checksum: 58A9BC0A7DEAD1A0

FASTA61864,618
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 66503288EABBFECE
Show »

FASTA58761,178

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT SCDO1 ASP-385.
[2]"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. expand/collapse author list , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS CYS-172 AND PRO-218.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 1).
Tissue: Brain.
[5]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-115; GLN-142; CYS-172 AND PRO-218.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF241373 expand/collapse EMBL AC list , AF241367, AF241368, AF241369, AF241370, AF241371, AF241372 Genomic DNA. Translation: AAF62542.1.
AK075302 mRNA. Translation: BAC11535.1.
AC011500 Genomic DNA. No translation available.
BC000218 mRNA. Translation: AAH00218.1.
CCDSCCDS12537.1. [Q9NYJ7-2]
CCDS12538.1. [Q9NYJ7-1]
RefSeqNP_058637.1. NM_016941.3. [Q9NYJ7-1]
NP_982353.1. NM_203486.2. [Q9NYJ7-2]
UniGeneHs.127792.

3D structure databases

ProteinModelPortalQ9NYJ7.
SMRQ9NYJ7. Positions 27-465.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115922. 1 interaction.
STRING9606.ENSP00000205143.

Polymorphism databases

DMDM12229810.

Proteomic databases

PaxDbQ9NYJ7.
PRIDEQ9NYJ7.

Protocols and materials databases

DNASU10683.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000205143; ENSP00000205143; ENSG00000090932. [Q9NYJ7-1]
ENST00000356433; ENSP00000348810; ENSG00000090932. [Q9NYJ7-2]
GeneID10683.
KEGGhsa:10683.
UCSCuc002olx.2. human. [Q9NYJ7-1]

Organism-specific databases

CTD10683.
GeneCardsGC19P039989.
GeneReviewsDLL3.
HGNCHGNC:2909. DLL3.
HPAHPA056533.
MIM277300. phenotype.
602768. gene.
neXtProtNX_Q9NYJ7.
Orphanet2311. Autosomal recessive spondylocostal dysostosis.
PharmGKBPA27365.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG244272.
HOGENOMHOG000267024.
HOVERGENHBG007139.
InParanoidQ9NYJ7.
KOK06051.
OMADECRCLE.
OrthoDBEOG7P8P7B.
PhylomeDBQ9NYJ7.
TreeFamTF351835.

Enzyme and pathway databases

SignaLinkQ9NYJ7.

Gene expression databases

ArrayExpressQ9NYJ7.
BgeeQ9NYJ7.
CleanExHS_DLL3.
GenevestigatorQ9NYJ7.

Family and domain databases

InterProIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR011651. Notch_ligand_N.
[Graphical view]
PfamPF00008. EGF. 3 hits.
PF12661. hEGF. 2 hits.
PF07657. MNNL. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 6 hits.
[Graphical view]
SUPFAMSSF57184. SSF57184. 1 hit.
PROSITEPS00022. EGF_1. 6 hits.
PS01186. EGF_2. 6 hits.
PS50026. EGF_3. 6 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDLL3.
GenomeRNAi10683.
NextBio40615.
PROQ9NYJ7.
SOURCESearch...

Entry information

Entry nameDLL3_HUMAN
AccessionPrimary (citable) accession number: Q9NYJ7
Secondary accession number(s): E9PFG2, Q8NBS4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 139 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM