DLL3_HUMAN
ID DLL3_HUMAN Reviewed; 618 AA.
AC Q9NYJ7; E9PFG2; Q8NBS4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Delta-like protein 3;
DE AltName: Full=Drosophila Delta homolog 3;
DE Short=Delta3;
DE Flags: Precursor;
GN Name=DLL3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT SCDO1
RP ASP-385.
RX PubMed=10742114; DOI=10.1038/74307;
RA Bulman M.P., Kusumi K., Frayling T.M., McKeown C., Garrett C., Lander E.S.,
RA Krumlauf R., Hattersley A.T., Ellard S., Turnpenny P.D.;
RT "Mutations in the human delta homologue, DLL3, cause axial skeletal defects
RT in spondylocostal dysostosis.";
RL Nat. Genet. 24:438-441(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS CYS-172
RP AND PRO-218.
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP VARIANTS THR-115; GLN-142; CYS-172 AND PRO-218.
RX PubMed=18485326; DOI=10.1016/j.ajhg.2008.04.014;
RA Cornier A.S., Staehling-Hampton K., Delventhal K.M., Saga Y., Caubet J.-F.,
RA Sasaki N., Ellard S., Young E., Ramirez N., Carlo S.E., Torres J.,
RA Emans J.B., Turnpenny P.D., Pourquie O.;
RT "Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin
RT syndrome.";
RL Am. J. Hum. Genet. 82:1334-1341(2008).
CC -!- FUNCTION: Inhibits primary neurogenesis. May be required to divert
CC neurons along a specific differentiation pathway. Plays a role in the
CC formation of somite boundaries during segmentation of the paraxial
CC mesoderm (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Can bind and activate Notch-1 or another Notch receptor.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NYJ7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NYJ7-2; Sequence=VSP_045249;
CC -!- DOMAIN: The DSL domain is required for binding to the Notch receptor.
CC -!- PTM: Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis
CC and subsequent degradation. {ECO:0000250}.
CC -!- DISEASE: Spondylocostal dysostosis 1, autosomal recessive (SCDO1)
CC [MIM:277300]: A condition of variable severity associated with
CC vertebral and rib segmentation defects. The main skeletal malformations
CC include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and
CC other rib malformations. Deformity of the chest and spine (severe
CC scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the
CC malformation and leads to a dwarf-like appearance. As the thorax is
CC small, infants frequently have respiratory insufficiency and repeated
CC respiratory infections resulting in life-threatening complications in
CC the first year of life. {ECO:0000269|PubMed:10742114}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
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DR EMBL; AF241373; AAF62542.1; -; Genomic_DNA.
DR EMBL; AF241367; AAF62542.1; JOINED; Genomic_DNA.
DR EMBL; AF241368; AAF62542.1; JOINED; Genomic_DNA.
DR EMBL; AF241369; AAF62542.1; JOINED; Genomic_DNA.
DR EMBL; AF241370; AAF62542.1; JOINED; Genomic_DNA.
DR EMBL; AF241371; AAF62542.1; JOINED; Genomic_DNA.
DR EMBL; AF241372; AAF62542.1; JOINED; Genomic_DNA.
DR EMBL; AK075302; BAC11535.1; -; mRNA.
DR EMBL; AC011500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000218; AAH00218.1; -; mRNA.
DR CCDS; CCDS12537.1; -. [Q9NYJ7-2]
DR CCDS; CCDS12538.1; -. [Q9NYJ7-1]
DR RefSeq; NP_058637.1; NM_016941.3. [Q9NYJ7-1]
DR RefSeq; NP_982353.1; NM_203486.2. [Q9NYJ7-2]
DR AlphaFoldDB; Q9NYJ7; -.
DR SMR; Q9NYJ7; -.
DR BioGRID; 115922; 16.
DR STRING; 9606.ENSP00000205143; -.
DR ChEMBL; CHEMBL4630888; -.
DR iPTMnet; Q9NYJ7; -.
DR PhosphoSitePlus; Q9NYJ7; -.
DR BioMuta; DLL3; -.
DR DMDM; 12229810; -.
DR jPOST; Q9NYJ7; -.
DR MassIVE; Q9NYJ7; -.
DR PaxDb; Q9NYJ7; -.
DR PeptideAtlas; Q9NYJ7; -.
DR PRIDE; Q9NYJ7; -.
DR ProteomicsDB; 20096; -.
DR ProteomicsDB; 83237; -. [Q9NYJ7-1]
DR ABCD; Q9NYJ7; 94 sequenced antibodies.
DR Antibodypedia; 30387; 281 antibodies from 32 providers.
DR DNASU; 10683; -.
DR Ensembl; ENST00000205143.4; ENSP00000205143.3; ENSG00000090932.11. [Q9NYJ7-1]
DR Ensembl; ENST00000356433.10; ENSP00000348810.4; ENSG00000090932.11. [Q9NYJ7-2]
DR GeneID; 10683; -.
DR KEGG; hsa:10683; -.
DR MANE-Select; ENST00000356433.10; ENSP00000348810.4; NM_203486.3; NP_982353.1. [Q9NYJ7-2]
DR UCSC; uc002olw.3; human. [Q9NYJ7-1]
DR CTD; 10683; -.
DR DisGeNET; 10683; -.
DR GeneCards; DLL3; -.
DR GeneReviews; DLL3; -.
DR HGNC; HGNC:2909; DLL3.
DR HPA; ENSG00000090932; Group enriched (brain, choroid plexus, pituitary gland, testis).
DR MalaCards; DLL3; -.
DR MIM; 277300; phenotype.
DR MIM; 602768; gene.
DR neXtProt; NX_Q9NYJ7; -.
DR OpenTargets; ENSG00000090932; -.
DR Orphanet; 2311; Autosomal recessive spondylocostal dysostosis.
DR PharmGKB; PA27365; -.
DR VEuPathDB; HostDB:ENSG00000090932; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000162127; -.
DR HOGENOM; CLU_033244_0_0_1; -.
DR InParanoid; Q9NYJ7; -.
DR OMA; WSHPEDG; -.
DR OrthoDB; 394787at2759; -.
DR PhylomeDB; Q9NYJ7; -.
DR TreeFam; TF351835; -.
DR PathwayCommons; Q9NYJ7; -.
DR SignaLink; Q9NYJ7; -.
DR SIGNOR; Q9NYJ7; -.
DR BioGRID-ORCS; 10683; 14 hits in 1074 CRISPR screens.
DR ChiTaRS; DLL3; human.
DR GeneWiki; DLL3; -.
DR GenomeRNAi; 10683; -.
DR Pharos; Q9NYJ7; Tbio.
DR PRO; PR:Q9NYJ7; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NYJ7; protein.
DR Bgee; ENSG00000090932; Expressed in ganglionic eminence and 38 other tissues.
DR ExpressionAtlas; Q9NYJ7; baseline and differential.
DR Genevisible; Q9NYJ7; HS.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005112; F:Notch binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007386; P:compartment pattern specification; IEA:Ensembl.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0048339; P:paraxial mesoderm development; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IMP:UniProtKB.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR Pfam; PF00008; EGF; 4.
DR Pfam; PF12661; hEGF; 1.
DR SMART; SM00181; EGF; 6.
DR SMART; SM00179; EGF_CA; 5.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS00022; EGF_1; 6.
DR PROSITE; PS01186; EGF_2; 6.
DR PROSITE; PS50026; EGF_3; 6.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Differentiation;
KW Disease variant; Disulfide bond; Dwarfism; EGF-like domain; Membrane;
KW Notch signaling pathway; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..618
FT /note="Delta-like protein 3"
FT /id="PRO_0000007509"
FT TOPO_DOM 27..492
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 493..513
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 514..618
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 176..215
FT /note="DSL"
FT DOMAIN 216..249
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 274..310
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 312..351
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 353..389
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 391..427
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 429..465
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 546..566
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 546..560
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 220..231
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 224..237
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 239..248
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 278..289
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 283..298
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 300..309
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 316..327
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 321..339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 341..350
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 357..368
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 362..377
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 379..388
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 395..406
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 400..415
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 417..426
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 433..444
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 438..453
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 455..464
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 587..618
FT /note="VATPLFPPLHTGRAGQRQHLLFPYPSSILSVK -> A (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16303743"
FT /id="VSP_045249"
FT VARIANT 115
FT /note="A -> T (in dbSNP:rs71647811)"
FT /evidence="ECO:0000269|PubMed:18485326"
FT /id="VAR_046782"
FT VARIANT 142
FT /note="L -> Q (in dbSNP:rs55741253)"
FT /evidence="ECO:0000269|PubMed:18485326"
FT /id="VAR_046783"
FT VARIANT 172
FT /note="F -> C (in dbSNP:rs8107127)"
FT /evidence="ECO:0000269|PubMed:16303743,
FT ECO:0000269|PubMed:18485326"
FT /id="VAR_046784"
FT VARIANT 218
FT /note="L -> P (in dbSNP:rs1110627)"
FT /evidence="ECO:0000269|PubMed:16303743,
FT ECO:0000269|PubMed:18485326"
FT /id="VAR_016776"
FT VARIANT 385
FT /note="G -> D (in SCDO1; dbSNP:rs104894674)"
FT /evidence="ECO:0000269|PubMed:10742114"
FT /id="VAR_009952"
FT CONFLICT 318
FT /note="D -> N (in Ref. 2; BAC11535)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="A -> V (in Ref. 2; BAC11535)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 618 AA; 64618 MW; 58A9BC0A7DEAD1A0 CRC64;
MVSPRMSGLL SQTVILALIF LPQTRPAGVF ELQIHSFGPG PGPGAPRSPC SARLPCRLFF
RVCLKPGLSE EAAESPCALG AALSARGPVY TEQPGAPAPD LPLPDGLLQV PFRDAWPGTF
SFIIETWREE LGDQIGGPAW SLLARVAGRR RLAAGGPWAR DIQRAGAWEL RFSYRARCEP
PAVGTACTRL CRPRSAPSRC GPGLRPCAPL EDECEAPLVC RAGCSPEHGF CEQPGECRCL
EGWTGPLCTV PVSTSSCLSP RGPSSATTGC LVPGPGPCDG NPCANGGSCS ETPRSFECTC
PRGFYGLRCE VSGVTCADGP CFNGGLCVGG ADPDSAYICH CPPGFQGSNC EKRVDRCSLQ
PCRNGGLCLD LGHALRCRCR AGFAGPRCEH DLDDCAGRAC ANGGTCVEGG GAHRCSCALG
FGGRDCRERA DPCAARPCAH GGRCYAHFSG LVCACAPGYM GARCEFPVHP DGASALPAAP
PGLRPGDPQR YLLPPALGLL VAAGVAGAAL LLVHVRRRGH SQDAGSRLLA GTPEPSVHAL
PDALNNLRTQ EGSGDGPSSS VDWNRPEDVD PQGIYVISAP SIYAREVATP LFPPLHTGRA
GQRQHLLFPY PSSILSVK
