DLLA_DANRE
ID DLLA_DANRE Reviewed; 772 AA.
AC Q6DI48; O57462;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Delta-like protein A;
DE Short=DeltaA;
DE Flags: Precursor;
GN Name=dla;
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], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=9425133; DOI=10.1242/dev.125.3.371;
RA Appel B., Eisen J.S.;
RT "Regulation of neuronal specification in the zebrafish spinal cord by Delta
RT function.";
RL Development 125:371-380(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
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, MUTAGENESIS OF CYS-270, AND TISSUE SPECIFICITY.
RX PubMed=10074451; DOI=10.1016/s0960-9822(99)80113-4;
RA Appel B., Fritz A., Westerfield M., Grunwald D.J., Eisen J.S., Riley B.B.;
RT "Delta-mediated specification of midline cell fates in zebrafish embryos.";
RL Curr. Biol. 9:247-256(1999).
RN [5]
RP FUNCTION.
RX PubMed=10572043; DOI=10.1242/dev.126.24.5669;
RA Riley B.B., Chiang M.-Y., Farmer L., Heck R.;
RT "The deltaA gene of zebrafish mediates lateral inhibition of hair cells in
RT the inner ear and is regulated by pax2.1.";
RL Development 126:5669-5678(1999).
RN [6]
RP INTERACTION WITH MIB, AND UBIQUITINATION.
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 [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).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15659486; DOI=10.1242/dev.01616;
RA Amoyel M., Cheng Y.-C., Jiang Y.-J., Wilkinson D.G.;
RT "Wnt1 regulates neurogenesis and mediates lateral inhibition of boundary
RT cell specification in the zebrafish hindbrain.";
RL Development 132:775-785(2005).
CC -!- FUNCTION: Acts as a ligand for Notch receptors and is involved in
CC primary neurogenesis. Can activate Notch receptors, thereby playing a
CC key role in lateral inhibition, a process that prevents the immediate
CC neighbors of each nascent neural cell from simultaneously embarking on
CC neural differentiation. Required for boundary formation during
CC segmentation of the hindbrain. Required for midline cell fate
CC specification prior to germ layer formation; regulates specification of
CC floorplate, notochord and hypochord. In inner ear, it prevents adjacent
CC cells from adopting the same cell fate. Plays a role in angiogenesis.
CC {ECO:0000269|PubMed:10074451, ECO:0000269|PubMed:10572043,
CC ECO:0000269|PubMed:15659486, ECO:0000269|PubMed:9425133}.
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 nervous system. In the developing
CC nervous system, it is expressed in overlapping regions with deltaB
CC (dlb) and deltaD (dld); in the neural plate, dla is expressed in
CC patches of contiguous cells with dld, while dlb is confined to
CC scattered cells within those patches that will differentiate as
CC neurons. In 24 hours embryos, expressed in the hindbrain in stripes
CC adjacent to rhombomere boundaries, but not in the actual boundary
CC cells. During gastrulation and tail formation, expressed in embryonic
CC midline cells. Expressed in hair cells of inner ear.
CC {ECO:0000269|PubMed:10074451, ECO:0000269|PubMed:15068793,
CC ECO:0000269|PubMed:15659486, ECO:0000269|PubMed:9425132,
CC ECO:0000269|PubMed:9425133}.
CC -!- DEVELOPMENTAL STAGE: Initiated in the neuroectoderm before that of dld.
CC In the developing trunk neural plate and neural tube, it is initiated
CC in the epiblast prior to completion of gastrulation. At the 2- to 3-
CC somite stage (10.5 hours) low levels are distributed throughout the
CC trunk CNS, with cells expressing higher levels found in the medial and
CC lateral regions of the neural plate. These regions correspond to the
CC positions at which primary motoneurons and Rohon Beard neurons (RBs)
CC originate. Cells expressing high levels do not form contiguous domains.
CC Rather, single cells or small clusters of several cells showing high
CC expression are interspersed with cells having lower expression.
CC Expression is specific to the developing nervous system, and continues
CC to be expressed broadly in the CNS throughout neurogenesis. Expressed
CC in cells specified for neuronal fates. At 24 hours, and throughout
CC later embryogenesis, it is broadly expressed in the spinal cord,
CC suggesting that it is expressed by many types of cells. Expressed as
CC neuronal specification occurs and is subsequently down-regulated in
CC cells that have acquired specific neuronal fates.
CC {ECO:0000269|PubMed:9425133}.
CC -!- PTM: Ubiquitinated by mib, leading to its endocytosis and subsequent
CC degradation. {ECO:0000269|PubMed:15013799}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC41249.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF030031; AAC41249.1; ALT_SEQ; mRNA.
DR EMBL; BC075742; AAH75742.1; -; mRNA.
DR AlphaFoldDB; Q6DI48; -.
DR SMR; Q6DI48; -.
DR BioGRID; 78367; 2.
DR STRING; 7955.ENSDARP00000003059; -.
DR PaxDb; Q6DI48; -.
DR ZFIN; ZDB-GENE-980526-29; dla.
DR eggNOG; KOG1217; Eukaryota.
DR InParanoid; Q6DI48; -.
DR PhylomeDB; Q6DI48; -.
DR SignaLink; Q6DI48; -.
DR PRO; PR:Q6DI48; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005938; C:cell cortex; IDA:ZFIN.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0021536; P:diencephalon development; IMP:ZFIN.
DR GO; GO:0009880; P:embryonic pattern specification; IMP:ZFIN.
DR GO; GO:0033504; P:floor plate development; IMP:ZFIN.
DR GO; GO:0055016; P:hypochord development; IMP:ZFIN.
DR GO; GO:0060113; P:inner ear receptor cell differentiation; IMP:ZFIN.
DR GO; GO:0030901; P:midbrain development; IGI:ZFIN.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0014032; P:neural crest cell development; IMP:ZFIN.
DR GO; GO:0022008; P:neurogenesis; IMP:ZFIN.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0060034; P:notochord cell differentiation; IMP:ZFIN.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; 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; 2.
DR PROSITE; PS51051; DSL; 1.
DR PROSITE; PS00022; EGF_1; 8.
DR PROSITE; PS01186; EGF_2; 8.
DR PROSITE; PS50026; EGF_3; 7.
DR PROSITE; PS01187; EGF_CA; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Calcium; Developmental protein; Differentiation;
KW Disulfide bond; EGF-like domain; Glycoprotein; Membrane; Neurogenesis;
KW Notch signaling pathway; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..772
FT /note="Delta-like protein A"
FT /id="PRO_0000007514"
FT TOPO_DOM 21..536
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 537..557
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 558..772
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 179..223
FT /note="DSL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00377"
FT DOMAIN 225..257
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 257..288
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 290..328
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 330..366
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 368..405
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 407..443
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 445..481
FT /note="EGF-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 483..519
FT /note="EGF-like 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 688..722
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 688..721
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 181..190
FT /evidence="ECO:0000250"
FT DISULFID 194..206
FT /evidence="ECO:0000250"
FT DISULFID 214..223
FT /evidence="ECO:0000250"
FT DISULFID 228..239
FT /evidence="ECO:0000250"
FT DISULFID 232..245
FT /evidence="ECO:0000250"
FT DISULFID 259..270
FT /evidence="ECO:0000250"
FT DISULFID 265..276
FT /evidence="ECO:0000250"
FT DISULFID 278..287
FT /evidence="ECO:0000250"
FT DISULFID 294..306
FT /evidence="ECO:0000250"
FT DISULFID 300..316
FT /evidence="ECO:0000250"
FT DISULFID 318..327
FT /evidence="ECO:0000250"
FT DISULFID 334..345
FT /evidence="ECO:0000250"
FT DISULFID 339..354
FT /evidence="ECO:0000250"
FT DISULFID 356..365
FT /evidence="ECO:0000250"
FT DISULFID 372..383
FT /evidence="ECO:0000250"
FT DISULFID 377..393
FT /evidence="ECO:0000250"
FT DISULFID 395..404
FT /evidence="ECO:0000250"
FT DISULFID 411..422
FT /evidence="ECO:0000250"
FT DISULFID 416..431
FT /evidence="ECO:0000250"
FT DISULFID 433..442
FT /evidence="ECO:0000250"
FT DISULFID 449..460
FT /evidence="ECO:0000250"
FT DISULFID 454..469
FT /evidence="ECO:0000250"
FT DISULFID 471..480
FT /evidence="ECO:0000250"
FT DISULFID 487..498
FT /evidence="ECO:0000250"
FT DISULFID 492..507
FT /evidence="ECO:0000250"
FT DISULFID 509..518
FT /evidence="ECO:0000250"
FT MUTAGEN 270
FT /note="C->Y: In dla(dx2); excess numbers of early-specified
FT neurons, reduced numbers of floorplate and hypochord cells,
FT excess numbers of notochord cells."
FT /evidence="ECO:0000269|PubMed:10074451"
SQ SEQUENCE 772 AA; 84969 MW; 716A014158938576 CRC64;
MGRHLLLLLF SILYMLLCQA SSSGVFELKL QEFLNKKGVQ GNKNCCKGGL TTSYQQCECK
TFFRICLKHY QPNASPEPPC TYGGTVTPVL GSNSFQVPDT LPDGSFTNPI RMNFGFTWPG
TFSLIIEALH ADSKEDLTTE NPERIISTMT TQRHLTVGED WSQDLHSVGR TELKYSYRFV
CDEHYYGEGC SVFCRPRDDA FGHFTCGERG EIICDAGWKG QYCTEPICLP GCDEEHGFCE
KPGECKCRVG FKGRYCDECI RYPGCLHGTC QQPWQCNCQE GWGGLFCNQD LNYCTHHKPC
LNGATCSNTG QGSYTCSCRP GFSGASCEIE VNECTGNPCR NGGSCTDMEN TYSCTCPPGF
YGKNCELSAM TCADGPCFNG GRCADNPDGG YFCQCPTGYA GFNCEKKIDH CSSSPCSNGA
RCVDLVNSYL CQCPDGFTGM NCDRAGDECS MYPCQNGGTC QEGASGYMCT CPPGYTGRNC
SSPVSRCQHN PCHNGATCHE RNNRYVCACV SGYGGRNCQF LLPDRASQIA SDVPWTAVGS
GVLLVLLLVV ACAVVVVCVR SKVQQRRRDR EDEVANGENE TINNLTNNCH RDKDLAVSVV
GVAPVKNINK KIDFSSDHDD LSLTTEKRSY KTRHAPADYN LVHEVKFEVK HEVKLEHAGK
ETTMANELSD SCEDIKCQSL QDSSECTEEK RRKRLKSDAS EKSKYSESRY SESKYSESKY
SESKYSDVSL YSESACASAC ASASTSACVD TKYKSVMVMS EEKDECVIAT EV
