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O00548 (DLL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Delta-like protein 1
Alternative name(s):
Drosophila Delta homolog 1
Short name=Delta1
Short name=H-Delta-1
Gene names
Name:DLL1
ORF Names:UNQ146/PRO172
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length723 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Acts as a ligand for Notch receptors. Blocks the differentiation of progenitor cells into the B-cell lineage while promoting the emergence of a population of cells with the characteristics of a T-cell/NK-cell precursor. Ref.8

Subunit structure

Interacts with Notch receptors.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Expressed in heart and pancreas, with lower expression in brain and muscle and almost no expression in placenta, lung, liver and kidney.

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 processDifferentiation
Notch signaling pathway
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainEGF-like domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch receptor processing

Traceable author statement. Source: Reactome

Notch signaling pathway

Inferred from mutant phenotype PubMed 19682396. Source: UniProtKB

cell differentiation

Traceable author statement PubMed 11912004. Source: UniProtKB

cell fate determination

Non-traceable author statement Ref.8. Source: UniProtKB

cell-cell signaling

Inferred from electronic annotation. Source: Ensembl

compartment pattern specification

Inferred from electronic annotation. Source: Ensembl

determination of left/right symmetry

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

heart looping

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

hemopoiesis

Non-traceable author statement Ref.8. Source: UniProtKB

inner ear development

Inferred from electronic annotation. Source: Ensembl

left/right axis specification

Inferred from electronic annotation. Source: Ensembl

loop of Henle development

Inferred from electronic annotation. Source: Ensembl

negative regulation of auditory receptor cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-10 production

Inferred from mutant phenotype PubMed 23086448. Source: UniProt

negative regulation of myeloid cell differentiation

Inferred from electronic annotation. Source: Ensembl

neuronal stem cell maintenance

Inferred from expression pattern PubMed 19682396. Source: UniProtKB

positive regulation of Notch signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

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

proximal tubule development

Inferred from electronic annotation. Source: Ensembl

regulation of cell adhesion

Traceable author statement PubMed 11912004. Source: UniProtKB

somite specification

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

extracellular region

Non-traceable author statement PubMed 11823422. Source: UniProtKB

integral component of plasma membrane

Non-traceable author statement Ref.1. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionNotch binding

Inferred from physical interaction Ref.1PubMed 11823422. Source: UniProtKB

calcium ion binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction Ref.1PubMed 11823422. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 723706Delta-like protein 1
PRO_0000007506

Regions

Topological domain18 – 545528Extracellular Potential
Transmembrane546 – 56823Helical; Potential
Topological domain569 – 723155Cytoplasmic Potential
Domain177 – 22145DSL
Domain226 – 25429EGF-like 1
Domain257 – 28529EGF-like 2
Domain292 – 32534EGF-like 3
Domain332 – 36332EGF-like 4; calcium-binding Potential
Domain370 – 40233EGF-like 5
Domain409 – 44032EGF-like 6
Domain447 – 47832EGF-like 7; calcium-binding Potential
Domain485 – 51632EGF-like 8

Amino acid modifications

Glycosylation4771N-linked (GlcNAc...) Potential
Disulfide bond179 ↔ 188 By similarity
Disulfide bond192 ↔ 204 By similarity
Disulfide bond212 ↔ 221 By similarity
Disulfide bond226 ↔ 237 By similarity
Disulfide bond230 ↔ 243 By similarity
Disulfide bond245 ↔ 254 By similarity
Disulfide bond257 ↔ 268 By similarity
Disulfide bond263 ↔ 274 By similarity
Disulfide bond276 ↔ 285 By similarity
Disulfide bond292 ↔ 304 By similarity
Disulfide bond298 ↔ 314 By similarity
Disulfide bond316 ↔ 325 By similarity
Disulfide bond332 ↔ 343 By similarity
Disulfide bond337 ↔ 352 By similarity
Disulfide bond354 ↔ 363 By similarity
Disulfide bond370 ↔ 381 By similarity
Disulfide bond375 ↔ 391 By similarity
Disulfide bond393 ↔ 402 By similarity
Disulfide bond409 ↔ 420 By similarity
Disulfide bond414 ↔ 429 By similarity
Disulfide bond431 ↔ 440 By similarity
Disulfide bond447 ↔ 458 By similarity
Disulfide bond452 ↔ 467 By similarity
Disulfide bond469 ↔ 478 By similarity
Disulfide bond485 ↔ 496 By similarity
Disulfide bond490 ↔ 505 By similarity
Disulfide bond507 ↔ 516 By similarity

Natural variations

Natural variant4441V → M.
Corresponds to variant rs16901311 [ dbSNP | Ensembl ].
VAR_048976

Experimental info

Sequence conflict4981E → Q in AAF05834. Ref.2
Sequence conflict5021R → G in AAB61286. Ref.1
Sequence conflict5021R → G in AAF05834. Ref.2
Sequence conflict5021R → G in AAG09716. Ref.3
Sequence conflict5101G → S in AAF05834. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O00548 [UniParc].

Last modified October 31, 2006. Version 2.
Checksum: 094B8F235DFD899D

FASTA72378,056
        10         20         30         40         50         60 
MGSRCALALA VLSALLCQVW SSGVFELKLQ EFVNKKGLLG NRNCCRGGAG PPPCACRTFF 

        70         80         90        100        110        120 
RVCLKHYQAS VSPEPPCTYG SAVTPVLGVD SFSLPDGGGA DSAFSNPIRF PFGFTWPGTF 

       130        140        150        160        170        180 
SLIIEALHTD SPDDLATENP ERLISRLATQ RHLTVGEEWS QDLHSSGRTD LKYSYRFVCD 

       190        200        210        220        230        240 
EHYYGEGCSV FCRPRDDAFG HFTCGERGEK VCNPGWKGPY CTEPICLPGC DEQHGFCDKP 

       250        260        270        280        290        300 
GECKCRVGWQ GRYCDECIRY PGCLHGTCQQ PWQCNCQEGW GGLFCNQDLN YCTHHKPCKN 

       310        320        330        340        350        360 
GATCTNTGQG SYTCSCRPGY TGATCELGID ECDPSPCKNG GSCTDLENSY SCTCPPGFYG 

       370        380        390        400        410        420 
KICELSAMTC ADGPCFNGGR CSDSPDGGYS CRCPVGYSGF NCEKKIDYCS SSPCSNGAKC 

       430        440        450        460        470        480 
VDLGDAYLCR CQAGFSGRHC DDNVDDCASS PCANGGTCRD GVNDFSCTCP PGYTGRNCSA 

       490        500        510        520        530        540 
PVSRCEHAPC HNGATCHERG HRYVCECARG YGGPNCQFLL PELPPGPAVV DLTEKLEGQG 

       550        560        570        580        590        600 
GPFPWVAVCA GVILVLMLLL GCAAVVVCVR LRLQKHRPPA DPCRGETETM NNLANCQREK 

       610        620        630        640        650        660 
DISVSIIGAT QIKNTNKKAD FHGDHSADKN GFKARYPAVD YNLVQDLKGD DTAVRDAHSK 

       670        680        690        700        710        720 
RDTKCQPQGS SGEEKGTPTT LRGGEASERK RPDSGCSTSK DTKYQSVYVI SEEKDECVIA 


TEV 

« Hide

References

« Hide 'large scale' references
[1]"Human ligands of the Notch receptor."
Gray G.E., Mann R.S., Mitsiadis E., Henrique D., Carcangiu M.-L., Banks A., Leiman J., Ward D., Ish-Horowitz D., Artavanis-Tsakonas S.
Am. J. Pathol. 154:785-794(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells."
Han W., Ye Q., Moore M.A.S.
Blood 95:1616-1625(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Human Delta 1 gene sequence."
Oda T., Chandrasekharappa S.C.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation."
Jaleco A.C., Neves H., Hooijberg E., Gameiro P., Clode N., Haury M., Henrique D., Parreira L.
J. Exp. Med. 194:991-1001(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF003522 mRNA. Translation: AAB61286.1.
AF196571 mRNA. Translation: AAF05834.1.
AF222310 Genomic DNA. Translation: AAG09716.1.
AY358892 mRNA. Translation: AAQ89251.1.
AK314234 mRNA. Translation: BAG36904.1.
AL078605 Genomic DNA. Translation: CAB89569.1.
CH471051 Genomic DNA. Translation: EAW47425.1.
CCDSCCDS5313.1.
RefSeqNP_005609.3. NM_005618.3.
UniGeneHs.379912.

3D structure databases

ProteinModelPortalO00548.
SMRO00548. Positions 22-551.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118391. 6 interactions.
STRING9606.ENSP00000355718.

PTM databases

PhosphoSiteO00548.

Proteomic databases

PaxDbO00548.
PRIDEO00548.

Protocols and materials databases

DNASU28514.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366756; ENSP00000355718; ENSG00000198719.
GeneID28514.
KEGGhsa:28514.
UCSCuc003qxm.3. human.

Organism-specific databases

CTD28514.
GeneCardsGC06M170591.
HGNCHGNC:2908. DLL1.
MIM606582. gene.
neXtProtNX_O00548.
Orphanet93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBPA27364.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249767.
HOGENOMHOG000267024.
HOVERGENHBG007139.
InParanoidO00548.
KOK06051.
OMARCTDNPD.
OrthoDBEOG7GQXZ5.
PhylomeDBO00548.
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.
SignaLinkO00548.

Gene expression databases

BgeeO00548.
CleanExHS_DLL1.
GenevestigatorO00548.

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.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR011651. Notch_ligand_N.
[Graphical view]
PfamPF01414. DSL. 1 hit.
PF00008. EGF. 6 hits.
PF07657. MNNL. 1 hit.
[Graphical view]
SMARTSM00051. DSL. 1 hit.
SM00181. EGF. 4 hits.
SM00179. EGF_CA. 4 hits.
[Graphical view]
SUPFAMSSF57184. SSF57184. 2 hits.
PROSITEPS00010. ASX_HYDROXYL. 3 hits.
PS51051. DSL. 1 hit.
PS00022. EGF_1. 8 hits.
PS01186. EGF_2. 8 hits.
PS50026. EGF_3. 7 hits.
PS01187. EGF_CA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDLL1. human.
GeneWikiDelta-like_1.
GenomeRNAi28514.
NextBio50984.
PROO00548.
SOURCESearch...

Entry information

Entry nameDLL1_HUMAN
AccessionPrimary (citable) accession number: O00548
Secondary accession number(s): B2RAK7, Q9NU41, Q9UJV2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 31, 2006
Last modified: July 9, 2014
This is version 142 of the entry and version 2 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 6

Human chromosome 6: entries, gene names and cross-references to MIM