O00548 (DLL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	723 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Differentiation Notch signaling pathway
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Notch receptor processing Traceable author statement. Source: Reactome Notch signaling pathway Inferred from mutant phenotype. Source: UniProtKB cell fate determination Non-traceable author statement Ref.8. Source: UniProtKB hemopoiesis Non-traceable author statement Ref.8. Source: UniProtKB neuronal stem cell maintenance Inferred from expression pattern. Source: UniProtKB regulation of cell adhesion Traceable author statement. Source: UniProtKB
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	Notch binding Inferred from physical interaction Ref.1. Source: UniProtKB 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 – 17	17	Potential
	Chain	18 – 723	706	Delta-like protein 1		PRO_0000007506
Regions
	Topological domain	18 – 545	528	Extracellular Potential
	Transmembrane	546 – 568	23	Helical; Potential
	Topological domain	569 – 723	155	Cytoplasmic Potential
	Domain	177 – 221	45	DSL
	Domain	226 – 254	29	EGF-like 1
	Domain	257 – 285	29	EGF-like 2
	Domain	292 – 325	34	EGF-like 3
	Domain	332 – 363	32	EGF-like 4; calcium-binding Potential
	Domain	370 – 402	33	EGF-like 5
	Domain	409 – 440	32	EGF-like 6
	Domain	447 – 478	32	EGF-like 7; calcium-binding Potential
	Domain	485 – 516	32	EGF-like 8
Amino acid modifications
	Glycosylation	477	1	N-linked (GlcNAc...) Potential
	Disulfide bond	179 ↔ 188		By similarity
	Disulfide bond	192 ↔ 204		By similarity
	Disulfide bond	212 ↔ 221		By similarity
	Disulfide bond	226 ↔ 237		By similarity
	Disulfide bond	230 ↔ 243		By similarity
	Disulfide bond	245 ↔ 254		By similarity
	Disulfide bond	257 ↔ 268		By similarity
	Disulfide bond	263 ↔ 274		By similarity
	Disulfide bond	276 ↔ 285		By similarity
	Disulfide bond	292 ↔ 304		By similarity
	Disulfide bond	298 ↔ 314		By similarity
	Disulfide bond	316 ↔ 325		By similarity
	Disulfide bond	332 ↔ 343		By similarity
	Disulfide bond	337 ↔ 352		By similarity
	Disulfide bond	354 ↔ 363		By similarity
	Disulfide bond	370 ↔ 381		By similarity
	Disulfide bond	375 ↔ 391		By similarity
	Disulfide bond	393 ↔ 402		By similarity
	Disulfide bond	409 ↔ 420		By similarity
	Disulfide bond	414 ↔ 429		By similarity
	Disulfide bond	431 ↔ 440		By similarity
	Disulfide bond	447 ↔ 458		By similarity
	Disulfide bond	452 ↔ 467		By similarity
	Disulfide bond	469 ↔ 478		By similarity
	Disulfide bond	485 ↔ 496		By similarity
	Disulfide bond	490 ↔ 505		By similarity
	Disulfide bond	507 ↔ 516		By similarity
Natural variations
	Natural variant	444	1	V → M. Corresponds to variant rs16901311 [ dbSNP | Ensembl ].		VAR_048976
Experimental info
	Sequence conflict	498	1	E → Q in AAF05834. Ref.2
	Sequence conflict	502	1	R → G in AAB61286. Ref.1
	Sequence conflict	502	1	R → G in AAF05834. Ref.2
	Sequence conflict	502	1	R → G in AAG09716. Ref.3
	Sequence conflict	510	1	G → S in AAF05834. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O00548 [UniParc]. Last modified October 31, 2006. Version 2. Checksum: 094B8F235DFD899D	FASTA	723	78,056
	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

References

	« Hide 'large scale' referencesShow '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: 10079256] [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: 10688816] [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. , 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: 12975309] [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. , 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: 14702039] [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. , 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: 14574404] [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. , 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: 11581320] [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.
IPI	IPI00413521.
RefSeq	NP_005609.3. NM_005618.3.
UniGene	Hs.379912.
3D structure databases
ProteinModelPortal	O00548.
SMR	O00548. Positions 178-548.
ModBase	Search...
Protein-protein interaction databases
STRING	O00548.
Proteomic databases
PRIDE	O00548.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366756; ENSP00000355718; ENSG00000198719.
GeneID	28514.
KEGG	hsa:28514.
UCSC	uc003qxm.1. human.
Organism-specific databases
CTD	28514.
GeneCards	GC06M170508.
H-InvDB	HIX0032757.
HGNC	HGNC:2908. DLL1.
MIM	606582. gene.
neXtProt	NX_O00548.
PharmGKB	PA27364.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13951.
GeneTree	ENSGT00600000084206.
HOGENOM	HBG403082.
HOVERGEN	HBG007139.
InParanoid	O00548.
OMA	GFYGRIC.
OrthoDB	EOG469QT9.
PhylomeDB	O00548.
Enzyme and pathway databases
Pathway_Interaction_DB	ps1pathway. Presenilin action in Notch and Wnt signaling.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	O00548.
Bgee	O00548.
CleanEx	HS_DLL1.
Genevestigator	O00548.
GermOnline	ENSG00000198719. Homo sapiens.
Family and domain databases
InterPro	IPR001774. DSL. IPR006209. EGF. IPR006210. EGF-like. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_reg_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR000742. EGF_3. IPR018097. EGF_Ca-bd_CS. IPR011651. Notch_ligand_N. [Graphical view]
KO	K06051.
Pfam	PF01414. DSL. 1 hit. PF00008. EGF. 6 hits. PF07657. MNNL. 1 hit. [Graphical view]
SMART	SM00051. DSL. 1 hit. SM00181. EGF. 4 hits. SM00179. EGF_CA. 4 hits. [Graphical view]
PROSITE	PS00010. 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]
ProtoNet	Search...
Other
NextBio	50984.
SOURCE	Search...

Entry information

Entry name

DLL1_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 118 of the entry and version 2 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.