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Database: UniProt
Entry: Q6DI48
LinkDB: Q6DI48
Original site: Q6DI48 
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   23-MAY-2018, entry version 109.
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   Cyprinidae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND
RP   DEVELOPMENTAL STAGE.
RX   PubMed=9425133;
RA   Appel B., Eisen J.S.;
RT   "Regulation of neuronal specification in the zebrafish spinal cord by
RT   Delta 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;
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.,
RA   Riley B.B.;
RT   "Delta-mediated specification of midline cell fates in zebrafish
RT   embryos.";
RL   Curr. Biol. 9:247-256(1999).
RN   [5]
RP   FUNCTION.
RX   PubMed=10572043;
RA   Riley B.B., Chiang M.-Y., Farmer L., Heck R.;
RT   "The deltaA gene of zebrafish mediates lateral inhibition of hair
RT   cells in 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
RT   Delta 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
RT   boundary 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
CC       playing a key role in lateral inhibition, a process that prevents
CC       the immediate neighbors of each nascent neural cell from
CC       simultaneously embarking on neural differentiation. Required for
CC       boundary formation during segmentation of the hindbrain. Required
CC       for midline cell fate specification prior to germ layer formation;
CC       regulates specification of floorplate, notochord and hypochord. In
CC       inner ear, it prevents adjacent cells from adopting the same cell
CC       fate. Plays a role in angiogenesis. {ECO:0000269|PubMed:10074451,
CC       ECO:0000269|PubMed:10572043, ECO:0000269|PubMed:15659486,
CC       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
CC       stripes adjacent to rhombomere boundaries, but not in the actual
CC       boundary cells. During gastrulation and tail formation, expressed
CC       in embryonic 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
CC       dld. In the developing trunk neural plate and neural tube, it is
CC       initiated in the epiblast prior to completion of gastrulation. At
CC       the 2- to 3-somite stage (10.5 hours) low levels are distributed
CC       throughout the trunk CNS, with cells expressing higher levels
CC       found in the medial and lateral regions of the neural plate. These
CC       regions correspond to the positions at which primary motoneurons
CC       and Rohon Beard neurons (RBs) originate. Cells expressing high
CC       levels do not form contiguous domains. Rather, single cells or
CC       small clusters of several cells showing high expression are
CC       interspersed with cells having lower expression. Expression is
CC       specific to the developing nervous system, and continues to be
CC       expressed broadly in the CNS throughout neurogenesis. Expressed in
CC       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
CC       as neuronal specification occurs and is subsequently down-
CC       regulated in cells that have acquired specific neuronal fates.
CC       {ECO:0000269|PubMed:9425133}.
CC   -!- PTM: Ubiquitinated by mib, leading to its endocytosis and
CC       subsequent degradation. {ECO:0000269|PubMed:15013799}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC41249.1; Type=Frameshift; Positions=726; Evidence={ECO:0000305};
DR   EMBL; AF030031; AAC41249.1; ALT_SEQ; mRNA.
DR   EMBL; BC075742; AAH75742.1; -; mRNA.
DR   UniGene; Dr.30326; -.
DR   ProteinModelPortal; Q6DI48; -.
DR   SMR; Q6DI48; -.
DR   BioGrid; 78367; 2.
DR   STRING; 7955.ENSDARP00000003059; -.
DR   PaxDb; Q6DI48; -.
DR   PRIDE; Q6DI48; -.
DR   ZFIN; ZDB-GENE-980526-29; dla.
DR   eggNOG; ENOG410IR7B; Eukaryota.
DR   eggNOG; ENOG410XUNS; LUCA.
DR   HOGENOM; HOG000267024; -.
DR   HOVERGEN; HBG007139; -.
DR   InParanoid; Q6DI48; -.
DR   PhylomeDB; Q6DI48; -.
DR   PRO; PR:Q6DI48; -.
DR   Proteomes; UP000000437; 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: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:0014032; P:neural crest cell development; IMP:ZFIN.
DR   GO; GO:0022008; P:neurogenesis; IMP:ZFIN.
DR   GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
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; Complete proteome; Developmental protein;
KW   Differentiation; Disulfide bond; EGF-like domain; Glycoprotein;
KW   Membrane; Neurogenesis; Notch signaling pathway; Reference proteome;
KW   Repeat; Signal; Transmembrane; Transmembrane helix; Ubl conjugation.
FT   SIGNAL        1     20       {ECO:0000255}.
FT   CHAIN        21    772       Delta-like protein A.
FT                                /FTId=PRO_0000007514.
FT   TOPO_DOM     21    536       Extracellular. {ECO:0000255}.
FT   TRANSMEM    537    557       Helical. {ECO:0000255}.
FT   TOPO_DOM    558    772       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      179    223       DSL. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00377}.
FT   DOMAIN      225    257       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      257    288       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      290    328       EGF-like 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      330    366       EGF-like 4; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      368    405       EGF-like 5. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      407    443       EGF-like 6. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      445    481       EGF-like 7. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      483    519       EGF-like 8. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   COMPBIAS    697    746       Ser-rich.
FT   CARBOHYD    479    479       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    181    190       {ECO:0000250}.
FT   DISULFID    194    206       {ECO:0000250}.
FT   DISULFID    214    223       {ECO:0000250}.
FT   DISULFID    228    239       {ECO:0000250}.
FT   DISULFID    232    245       {ECO:0000250}.
FT   DISULFID    259    270       {ECO:0000250}.
FT   DISULFID    265    276       {ECO:0000250}.
FT   DISULFID    278    287       {ECO:0000250}.
FT   DISULFID    294    306       {ECO:0000250}.
FT   DISULFID    300    316       {ECO:0000250}.
FT   DISULFID    318    327       {ECO:0000250}.
FT   DISULFID    334    345       {ECO:0000250}.
FT   DISULFID    339    354       {ECO:0000250}.
FT   DISULFID    356    365       {ECO:0000250}.
FT   DISULFID    372    383       {ECO:0000250}.
FT   DISULFID    377    393       {ECO:0000250}.
FT   DISULFID    395    404       {ECO:0000250}.
FT   DISULFID    411    422       {ECO:0000250}.
FT   DISULFID    416    431       {ECO:0000250}.
FT   DISULFID    433    442       {ECO:0000250}.
FT   DISULFID    449    460       {ECO:0000250}.
FT   DISULFID    454    469       {ECO:0000250}.
FT   DISULFID    471    480       {ECO:0000250}.
FT   DISULFID    487    498       {ECO:0000250}.
FT   DISULFID    492    507       {ECO:0000250}.
FT   DISULFID    509    518       {ECO:0000250}.
FT   MUTAGEN     270    270       C->Y: In dla(dx2); excess numbers of
FT                                early-specified neurons, reduced numbers
FT                                of floorplate and hypochord cells, excess
FT                                numbers of notochord cells.
FT                                {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
//
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