DLLD_DANRE
ID DLLD_DANRE Reviewed; 717 AA.
AC Q8UWJ4; P87357;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Delta-like protein D;
DE Short=DeltaD;
DE AltName: Full=After eight protein;
DE Flags: Precursor;
GN Name=dld; Synonyms=aei;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=9203139; DOI=10.1016/s0925-4773(97)00037-3;
RA Dornseifer P., Takke C., Campos-Ortega J.A.;
RT "Overexpression of a zebrafish homologue of the Drosophila neurogenic gene
RT delta perturbs differentiation of primary neurons and somitic
RT development.";
RL Mech. Dev. 63:159-171(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=12361969; DOI=10.1242/dev.129.20.4773;
RA Hans S., Campos-Ortega J.A.;
RT "On the organisation of the regulatory region of the zebrafish deltaD
RT gene.";
RL Development 129:4773-4784(2002).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=9425132; DOI=10.1242/dev.125.3.359;
RA Haddon C., Smithers L., Schneider-Maunoury S., Coche T., Henrique D.,
RA Lewis J.;
RT "Multiple delta genes and lateral inhibition in zebrafish primary
RT neurogenesis.";
RL Development 125:359-370(1998).
RN [4]
RP FUNCTION.
RX PubMed=11100729; DOI=10.1038/35044091;
RA Jiang Y.-J., Aerne B.L., Smithers L., Haddon C., Ish-Horowicz D., Lewis J.;
RT "Notch signalling and the synchronization of the somite segmentation
RT clock.";
RL Nature 408:475-479(2000).
RN [5]
RP INTERACTION WITH MIB.
RX PubMed=15013799; DOI=10.1016/j.ydbio.2003.11.010;
RA Chen W., Corliss D.C.;
RT "Three modules of zebrafish Mind bomb work cooperatively to promote Delta
RT ubiquitination and endocytosis.";
RL Dev. Biol. 267:361-373(2004).
RN [6]
RP UBIQUITINATION.
RX PubMed=12530964; DOI=10.1016/s1534-5807(02)00409-4;
RA Itoh M., Kim C.-H., Palardy G., Oda T., Jiang Y.-J., Maust D., Yeo S.-Y.,
RA Lorick K., Wright G.J., Ariza-McNaughton L., Weissman A.M., Lewis J.,
RA Chandrasekharappa S.C., Chitnis A.B.;
RT "Mind bomb is a ubiquitin ligase that is essential for efficient activation
RT of Notch signaling by Delta.";
RL Dev. Cell 4:67-82(2003).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=15068793; DOI=10.1016/s1534-5807(04)00097-8;
RA Cheng Y.-C., Amoyel M., Qiu X., Jiang Y.-J., Xu Q., Wilkinson D.G.;
RT "Notch activation regulates the segregation and differentiation of
RT rhombomere boundary cells in the zebrafish hindbrain.";
RL Dev. Cell 6:539-550(2004).
CC -!- FUNCTION: Acts as a ligand for Notch receptors and is involved in
CC primary neurogenesis and somitogenesis. Can activate Notch receptors,
CC thereby playing a key role in lateral inhibition, a process that
CC prevents the immediate neighbors of each nascent neural cell from
CC simultaneously embarking on neural differentiation. Required in somite
CC segmentation to keep the oscillations of neighboring presomitic
CC mesoderm cells synchronized. {ECO:0000269|PubMed:11100729}.
CC -!- SUBUNIT: Interacts with mib. {ECO:0000269|PubMed:15013799}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in both mesodermal and neuroectodermal
CC regions. In the developing nervous system, it is expressed in
CC overlapping regions with deltaB (dlb) and deltaA (dla); in the neural
CC plate, dld is expressed in patches of contiguous cells with dla, while
CC dlb is confined to scattered cells within those patches that will
CC differentiate as neurons. In somites, it marks the anterior part of
CC each formed somite, while deltaC (dlc) marks the posterior part. In 24
CC hours embryos, expressed in the hindbrain in stripes adjacent to
CC rhombomere boundaries, but not in the actual boundary cells.
CC {ECO:0000269|PubMed:12361969, ECO:0000269|PubMed:15068793,
CC ECO:0000269|PubMed:9203139, ECO:0000269|PubMed:9425132}.
CC -!- PTM: Ubiquitinated by mib, leading to its endocytosis and subsequent
CC degradation. {ECO:0000269|PubMed:12530964}.
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DR EMBL; Y11760; CAA72425.1; -; mRNA.
DR EMBL; AF426384; AAL31528.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8UWJ4; -.
DR SMR; Q8UWJ4; -.
DR STRING; 7955.ENSDARP00000089996; -.
DR PaxDb; Q8UWJ4; -.
DR ZFIN; ZDB-GENE-990415-47; dld.
DR eggNOG; KOG1217; Eukaryota.
DR InParanoid; Q8UWJ4; -.
DR PhylomeDB; Q8UWJ4; -.
DR SignaLink; Q8UWJ4; -.
DR PRO; PR:Q8UWJ4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:ZFIN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:ZFIN.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IGI:ZFIN.
DR GO; GO:0005886; C:plasma membrane; IDA:ZFIN.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005112; F:Notch binding; IBA:GO_Central.
DR GO; GO:0030165; F:PDZ domain binding; IDA:ZFIN.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:ZFIN.
DR GO; GO:0060271; P:cilium assembly; IMP:ZFIN.
DR GO; GO:0003140; P:determination of left/right asymmetry in lateral mesoderm; IGI:ZFIN.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:ZFIN.
DR GO; GO:0071910; P:determination of liver left/right asymmetry; IMP:ZFIN.
DR GO; GO:0035469; P:determination of pancreatic left/right asymmetry; IMP:ZFIN.
DR GO; GO:0048546; P:digestive tract morphogenesis; IMP:ZFIN.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:ZFIN.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IMP:ZFIN.
DR GO; GO:0046331; P:lateral inhibition; IMP:ZFIN.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:ZFIN.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; IMP:ZFIN.
DR GO; GO:0061056; P:sclerotome development; IGI:ZFIN.
DR GO; GO:0021523; P:somatic motor neuron differentiation; IMP:ZFIN.
DR GO; GO:0001756; P:somitogenesis; IMP:ZFIN.
DR GO; GO:0021514; P:ventral spinal cord interneuron differentiation; IMP:ZFIN.
DR InterPro; IPR001774; DSL.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR011651; Notch_ligand_N.
DR Pfam; PF01414; DSL; 1.
DR Pfam; PF00008; EGF; 5.
DR Pfam; PF12661; hEGF; 1.
DR Pfam; PF07657; MNNL; 1.
DR SMART; SM00051; DSL; 1.
DR SMART; SM00181; EGF; 8.
DR SMART; SM00179; EGF_CA; 6.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 3.
DR PROSITE; PS51051; DSL; 1.
DR PROSITE; PS00022; EGF_1; 8.
DR PROSITE; PS01186; EGF_2; 8.
DR PROSITE; PS50026; EGF_3; 8.
DR PROSITE; PS01187; EGF_CA; 2.
PE 1: Evidence at protein level;
KW Calcium; Developmental protein; Differentiation; Disulfide bond;
KW EGF-like domain; Glycoprotein; Membrane; Neurogenesis;
KW Notch signaling pathway; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..717
FT /note="Delta-like protein D"
FT /id="PRO_0000007517"
FT TOPO_DOM 20..547
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..568
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 569..717
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 175..219
FT /note="DSL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00377"
FT DOMAIN 220..253
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 257..284
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 286..324
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 326..362
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 364..401
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 403..439
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 441..477
FT /note="EGF-like 7; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 479..515
FT /note="EGF-like 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 649..693
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 475
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 177..186
FT /evidence="ECO:0000250"
FT DISULFID 190..202
FT /evidence="ECO:0000250"
FT DISULFID 210..219
FT /evidence="ECO:0000250"
FT DISULFID 224..235
FT /evidence="ECO:0000250"
FT DISULFID 228..241
FT /evidence="ECO:0000250"
FT DISULFID 243..252
FT /evidence="ECO:0000250"
FT DISULFID 261..266
FT /evidence="ECO:0000250"
FT DISULFID 274..283
FT /evidence="ECO:0000250"
FT DISULFID 290..302
FT /evidence="ECO:0000250"
FT DISULFID 296..312
FT /evidence="ECO:0000250"
FT DISULFID 314..323
FT /evidence="ECO:0000250"
FT DISULFID 330..341
FT /evidence="ECO:0000250"
FT DISULFID 335..350
FT /evidence="ECO:0000250"
FT DISULFID 352..361
FT /evidence="ECO:0000250"
FT DISULFID 368..379
FT /evidence="ECO:0000250"
FT DISULFID 373..389
FT /evidence="ECO:0000250"
FT DISULFID 391..400
FT /evidence="ECO:0000250"
FT DISULFID 407..418
FT /evidence="ECO:0000250"
FT DISULFID 412..427
FT /evidence="ECO:0000250"
FT DISULFID 429..438
FT /evidence="ECO:0000250"
FT DISULFID 445..456
FT /evidence="ECO:0000250"
FT DISULFID 450..465
FT /evidence="ECO:0000250"
FT DISULFID 467..476
FT /evidence="ECO:0000250"
FT DISULFID 483..494
FT /evidence="ECO:0000250"
FT DISULFID 488..503
FT /evidence="ECO:0000250"
FT DISULFID 505..514
FT /evidence="ECO:0000250"
FT CONFLICT 95
FT /note="E -> D (in Ref. 2; AAL31528)"
FT /evidence="ECO:0000305"
FT CONFLICT 717
FT /note="V -> ISEC (in Ref. 2; AAL31528)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 717 AA; 79061 MW; 9C5A0162504593E4 CRC64;
MGRLMIAVLL CVMISQGFCS GVFELKLQEF LNKKGVTGNA NCCKGSAAEG HQCECKTFFR
ICLKHYQANV SPDPPCTYGG AVTPVLGSNS FQVPESFPDS SFTNPIPFAF GFTWPGTFSL
IIEALHTDST DDLSTENPDR LISRMTTQRH LTVGEEWSQD LQVGGRTELK YSYRFVCDEH
YYGEGCSVFC RPRDDTFGHF TCGERGEIIC NSGWKGQYCT EPICLPGCDE DHGFCDKPGE
CKCRVGFSGK YCDDCIRYPG CLHGTCQQPW QCNCQEGWGG LFCNQDLNYC THHKPCQNGA
TCTNTGQGSY TCSCRPGFTG DSCEIEVNEC SGSPCRNGGS CTDLENTYSC TCPPGFYGRN
CELSAMTCAD GPCFNGGHCA DNPEGGYFCQ CPMGYAGFNC EKKIDHCSSN PCSNDAQCLD
LVDSYLCQCP EGFTGTHCED NIDECATYPC QNGGTCQDGL SDYTCTCPPG YTGKNCTSAV
NKCLHNPCHN GATCHEMDNR YVCACIPGYG GRNCQFLLPE NPQGQAIVEG ADKRYSYEED
DGGFPWTAVC AGIILVLLVL IGGSVFVIYI RLKLQQRSQQ IDSHSEIETM NNLTNNRSRE
KDLSVSIIGA TQVKNINKKV DFQSDGDKNG FKSRYSLVDY NLVHELKQED LGKEDSERSE
ATKCEPLDSD SEEKHRNHLK SDSSERKRTE SLCKDTKYQS VFVLSEEKDE CIIATEV
