GenomeNet

Database: UniProt
Entry: D3ZHH1
LinkDB: D3ZHH1
Original site: D3ZHH1 
ID   DLL4_RAT                Reviewed;         686 AA.
AC   D3ZHH1;
DT   11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2015, sequence version 3.
DT   16-JAN-2019, entry version 78.
DE   RecName: Full=Delta-like protein 4 {ECO:0000303|PubMed:25700513};
DE   AltName: Full=Drosophila Delta homolog 4 {ECO:0000305};
DE            Short=Delta4 {ECO:0000305};
DE   Flags: Precursor;
GN   Name=Dll4 {ECO:0000312|Ensembl:ENSRNOP00000018970,
GN   ECO:0000312|RGD:1309740};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116 {ECO:0000312|Ensembl:ENSRNOP00000018970};
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T.,
RA   Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A.,
RA   Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M.,
RA   Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K.,
RA   Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S.,
RA   Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J.,
RA   Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y.,
RA   Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A.,
RA   Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J.,
RA   D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R.,
RA   Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A.,
RA   Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E.,
RA   Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E.,
RA   Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D.,
RA   Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M.,
RA   Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O.,
RA   Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O.,
RA   Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H.,
RA   Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S.,
RA   Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J.,
RA   Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E.,
RA   Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F.,
RA   Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K.,
RA   Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S.,
RA   Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M.,
RA   Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M.,
RA   Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A.,
RA   Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S.,
RA   Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G.,
RA   Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H.,
RA   Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R.,
RA   Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M.,
RA   Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H.,
RA   Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S.,
RA   Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into
RT   mammalian evolution.";
RL   Nature 428:493-521(2004).
RN   [2] {ECO:0000244|PDB:4XL1, ECO:0000244|PDB:4XLW}
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 28-284 OF
RP   SER-29/LEU-108/PRO-207 MUTANT IN COMPLEX WITH NOTCH1, FUNCTION,
RP   GLYCOSYLATION AT ASN-79; ASN-109 AND ASN-162, DISULFIDE BONDS, AND
RP   MUTAGENESIS OF HIS-65; TYR-66; PHE-196 AND TYR-217.
RX   PubMed=25700513; DOI=10.1126/science.1261093;
RA   Luca V.C., Jude K.M., Pierce N.W., Nachury M.V., Fischer S.,
RA   Garcia K.C.;
RT   "Structural biology. Structural basis for Notch1 engagement of Delta-
RT   like 4.";
RL   Science 347:847-853(2015).
CC   -!- FUNCTION: Involved in the Notch signaling pathway as Notch ligand.
CC       Activates NOTCH1 and NOTCH4 (PubMed:25700513). Involved in
CC       angiogenesis; negatively regulates endothelial cell proliferation
CC       and migration and angiogenic sprouting. Essential for retinal
CC       progenitor proliferation. Required for suppressing rod fates in
CC       late retinal progenitors as well as for proper generation of other
CC       retinal cell types. During spinal cord neurogenesis, inhibits V2a
CC       interneuron fate (By similarity). {ECO:0000250|UniProtKB:Q9JI71,
CC       ECO:0000250|UniProtKB:Q9NR61, ECO:0000269|PubMed:25700513}.
CC   -!- SUBUNIT: Interacts with NOTCH4 (By similarity). Interacts (via N-
CC       terminal DSL and MNNL domains) with NOTCH1 (via EGF-like domains)
CC       (PubMed:25700513). {ECO:0000250|UniProtKB:Q9JI71,
CC       ECO:0000269|PubMed:25700513}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:25700513};
CC       Single-pass type I membrane protein
CC       {ECO:0000255|RuleBase:RU280815}.
DR   EMBL; AC132987; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; XP_006234827.1; XM_006234765.2.
DR   UniGene; Rn.147393; -.
DR   PDB; 4XL1; X-ray; 2.30 A; B/E=28-253.
DR   PDB; 4XLW; X-ray; 3.39 A; B/D/F/H=28-284.
DR   PDBsum; 4XL1; -.
DR   PDBsum; 4XLW; -.
DR   SMR; D3ZHH1; -.
DR   IntAct; D3ZHH1; 2.
DR   STRING; 10116.ENSRNOP00000018970; -.
DR   iPTMnet; D3ZHH1; -.
DR   PaxDb; D3ZHH1; -.
DR   PRIDE; D3ZHH1; -.
DR   Ensembl; ENSRNOT00000018970; ENSRNOP00000018970; ENSRNOG00000014011.
DR   GeneID; 311332; -.
DR   UCSC; RGD:1309740; rat.
DR   CTD; 54567; -.
DR   RGD; 1309740; Dll4.
DR   eggNOG; KOG1217; Eukaryota.
DR   eggNOG; ENOG410XP6K; LUCA.
DR   GeneTree; ENSGT00940000157441; -.
DR   InParanoid; D3ZHH1; -.
DR   OMA; DCARSPC; -.
DR   OrthoDB; 406049at2759; -.
DR   PhylomeDB; D3ZHH1; -.
DR   TreeFam; TF351835; -.
DR   Reactome; R-RNO-2979096; NOTCH2 Activation and Transmission of Signal to the Nucleus.
DR   Reactome; R-RNO-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR   PRO; PR:D3ZHH1; -.
DR   Proteomes; UP000002494; Chromosome 3.
DR   Bgee; ENSRNOG00000014011; Expressed in 9 organ(s), highest expression level in lung.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0005112; F:Notch binding; IEA:Ensembl.
DR   GO; GO:0072554; P:blood vessel lumenization; IEA:Ensembl.
DR   GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR   GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl.
DR   GO; GO:0003209; P:cardiac atrium morphogenesis; IEA:Ensembl.
DR   GO; GO:0035912; P:dorsal aorta morphogenesis; IEA:Ensembl.
DR   GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IEA:Ensembl.
DR   GO; GO:0045746; P:negative regulation of Notch signaling pathway; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0061314; P:Notch signaling involved in heart development; IEA:Ensembl.
DR   GO; GO:0003344; P:pericardium morphogenesis; IEA:Ensembl.
DR   GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IEA:Ensembl.
DR   GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl.
DR   GO; GO:0061074; P:regulation of neural retina development; IEA:Ensembl.
DR   GO; GO:0050767; P:regulation of neurogenesis; IEA:Ensembl.
DR   GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
DR   GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IEA:Ensembl.
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; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR011651; Notch_ligand_N.
DR   Pfam; PF01414; DSL; 1.
DR   Pfam; PF00008; EGF; 4.
DR   Pfam; PF12661; hEGF; 1.
DR   Pfam; PF07657; MNNL; 1.
DR   SMART; SM00051; DSL; 1.
DR   SMART; SM00181; EGF; 9.
DR   SMART; SM00179; EGF_CA; 6.
DR   SUPFAM; SSF57184; SSF57184; 1.
DR   PROSITE; PS00010; ASX_HYDROXYL; 1.
DR   PROSITE; PS51051; DSL; 1.
DR   PROSITE; PS00022; EGF_1; 8.
DR   PROSITE; PS01186; EGF_2; 7.
DR   PROSITE; PS50026; EGF_3; 8.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Complete proteome; Developmental protein;
KW   Disulfide bond; EGF-like domain; Glycoprotein; Membrane;
KW   Reference proteome; Repeat; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL        1     27       {ECO:0000255}.
FT   CHAIN        28    686       Delta-like protein 4.
FT                                /FTId=PRO_5003053341.
FT   TOPO_DOM     28    530       Extracellular. {ECO:0000305}.
FT   TRANSMEM    531    551       Helical. {ECO:0000255}.
FT   TOPO_DOM    552    686       Cytoplasmic. {ECO:0000305}.
FT   DOMAIN      174    218       DSL. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00377}.
FT   DOMAIN      219    252       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      256    283       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      285    323       EGF-like 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      325    361       EGF-like 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      363    401       EGF-like 5. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      403    439       EGF-like 6. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      441    477       EGF-like 7. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      481    519       EGF-like 8. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   REGION      186    188       Interaction with Notch1.
FT                                {ECO:0000269|PubMed:25700513}.
FT   REGION      192    196       Interaction with Notch1.
FT                                {ECO:0000269|PubMed:25700513}.
FT   SITE        111    111       Interaction with Notch1.
FT                                {ECO:0000269|PubMed:25700513}.
FT   SITE        217    217       Interaction with Notch1.
FT                                {ECO:0000269|PubMed:25700513}.
FT   CARBOHYD     79     79       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000244|PDB:4XL1,
FT                                ECO:0000269|PubMed:25700513}.
FT   CARBOHYD    109    109       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000244|PDB:4XL1,
FT                                ECO:0000269|PubMed:25700513}.
FT   CARBOHYD    162    162       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000244|PDB:4XL1,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID     51     55       {ECO:0000244|PDB:4XL1,
FT                                ECO:0000244|PDB:4XLW,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID     62     75       {ECO:0000244|PDB:4XL1,
FT                                ECO:0000244|PDB:4XLW,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    176    185       {ECO:0000244|PDB:4XL1,
FT                                ECO:0000244|PDB:4XLW,
FT                                ECO:0000255|PROSITE-ProRule:PRU00377,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    189    201       {ECO:0000244|PDB:4XL1,
FT                                ECO:0000244|PDB:4XLW,
FT                                ECO:0000255|PROSITE-ProRule:PRU00377,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    209    218       {ECO:0000244|PDB:4XL1,
FT                                ECO:0000244|PDB:4XLW,
FT                                ECO:0000255|PROSITE-ProRule:PRU00377,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    223    234       {ECO:0000244|PDB:4XL1,
FT                                ECO:0000244|PDB:4XLW,
FT                                ECO:0000255|PROSITE-ProRule:PRU00076,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    227    240       {ECO:0000244|PDB:4XL1,
FT                                ECO:0000244|PDB:4XLW,
FT                                ECO:0000255|PROSITE-ProRule:PRU00076,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    242    251       {ECO:0000244|PDB:4XL1,
FT                                ECO:0000244|PDB:4XLW,
FT                                ECO:0000255|PROSITE-ProRule:PRU00076,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    254    265       {ECO:0000244|PDB:4XLW,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    260    271       {ECO:0000244|PDB:4XLW,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    273    282       {ECO:0000244|PDB:4XLW,
FT                                ECO:0000255|PROSITE-ProRule:PRU00076,
FT                                ECO:0000269|PubMed:25700513}.
FT   DISULFID    289    301       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    295    311       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    313    322       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    329    340       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    334    349       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    351    360       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    367    378       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    372    389       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    391    400       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    407    418       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    412    427       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    429    438       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    445    456       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    450    465       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    467    476       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    485    496       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    490    507       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    509    518       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   MUTAGEN      65     65       H->A: Strongly decreased binding to
FT                                Notch1. {ECO:0000269|PubMed:25700513}.
FT   MUTAGEN      66     66       Y->A: Decreased binding to Notch1.
FT                                {ECO:0000269|PubMed:25700513}.
FT   MUTAGEN     196    196       F->A: Strongly decreased binding to
FT                                Notch1. {ECO:0000269|PubMed:25700513}.
FT   MUTAGEN     217    217       Y->A: No binding to Notch1.
FT                                {ECO:0000269|PubMed:25700513}.
FT   STRAND       29     39       {ECO:0000244|PDB:4XL1}.
FT   STRAND       52     54       {ECO:0000244|PDB:4XL1}.
FT   STRAND       56     64       {ECO:0000244|PDB:4XL1}.
FT   STRAND       68     70       {ECO:0000244|PDB:4XLW}.
FT   STRAND       78     81       {ECO:0000244|PDB:4XL1}.
FT   STRAND       86     91       {ECO:0000244|PDB:4XL1}.
FT   STRAND      102    110       {ECO:0000244|PDB:4XL1}.
FT   STRAND      114    124       {ECO:0000244|PDB:4XL1}.
FT   STRAND      129    131       {ECO:0000244|PDB:4XL1}.
FT   HELIX       132    134       {ECO:0000244|PDB:4XL1}.
FT   STRAND      139    149       {ECO:0000244|PDB:4XL1}.
FT   STRAND      157    165       {ECO:0000244|PDB:4XL1}.
FT   STRAND      167    176       {ECO:0000244|PDB:4XL1}.
FT   STRAND      180    182       {ECO:0000244|PDB:4XL1}.
FT   STRAND      197    201       {ECO:0000244|PDB:4XL1}.
FT   STRAND      207    209       {ECO:0000244|PDB:4XL1}.
FT   TURN        229    231       {ECO:0000244|PDB:4XL1}.
FT   TURN        248    251       {ECO:0000244|PDB:4XL1}.
FT   STRAND      261    264       {ECO:0000244|PDB:4XLW}.
FT   STRAND      266    269       {ECO:0000244|PDB:4XLW}.
FT   TURN        279    282       {ECO:0000244|PDB:4XLW}.
SQ   SEQUENCE   686 AA;  74961 MW;  BB6B5EDC50CA8498 CRC64;
     MTPGSRSACR WALLLLAVLW PQQRAAGSGI FQLRLQEFAN ERGMLANGRP CEPGCRTFFR
     ICLKHYQATF SEGPCTFGNV STPVLGTNSF VIRDKNSGSG RNPLQLPFNF TWPGTFSLNI
     QAWHTPGDDL RPETSPGNSL ISQIIIQGSL AVGKNWKSDE QNNTLTRLRY SYRVVCSDNY
     YGDSCSRLCK KRDDHFGHYE CQPDGSLSCL PGWTGKYCDQ PICLSGCHEQ NGYCSKPDEC
     NCRPGWQGPL CNECIPHNGC RHGTCTIPWQ CACDEGWGGL FCDQDLNYCT HHSPCKNGST
     CSNSGPRGYT CTCLPGYTGE HCELELSKCA SNPCRNGGSC KDHENSYHCL CPPGYYGQHC
     EHSTLTCADS PCFNGGSCRE RNQGASYACE CPPNFTGSNC EKKVDRCTSN PCANGGQCLN
     RGPSRTCRCR PGFTGTHCEL HISDCARSPC AHGGTCHDLE NGPVCTCPAG FSGRRCEVRI
     TNDACASGPC FNGATCYTGL SPNNFVCNCP YGFVGSRCEF PVGLPPSFPW VAVSLGVGLV
     VLLVLLVMVA VAVRQLRLRR PDDDSREAMN NLSDFQKDNL IPAAQLKNTN QKKELEVDCG
     LDKSNCGKLQ NHTLDYNLAP GFLGRGSTPG KYPHSDKSLG EKVPLRLHSE KPACRISAIC
     SPRDSMYQSV CLISEERNEC VIATEV
//
DBGET integrated database retrieval system