10         20         30         40         50         60
         |          |          |          |          |          |
MRSPRTRGRS GRPLSLLLAL LCALRAKVCG ASGQFELEIL SMQNVNGELQ NGNCCGGARN - 60
PGDRKCTRDE CDTYFKVCLK EYQSRVTAGG PCSFGSGSTP VIGGNTFNLK ASRGNDRNRI - 120
VLPFSFAWPR SYTLLVEAWD SSNDTVQPDS IIEKASHSGM INPSRQWQTL KQNTGVAHFE - 180
YQIRVTCDDY YYGFGCNKFC RPRDDFFGHY ACDQNGNKTC MEGWMGPECN RAICRQGCSP - 240
KHGSCKLPGD CRCQYGWQGL YCDKCIPHPG CVHGICNEPW QCLCETNWGG QLCDKDLNYC - 300
GTHQPCLNGG TCSNTGPDKY QCSCPEGYSG PNCEIAEHAC LSDPCHNRGS CKETSLGFEC - 360
ECSPGWTGPT CSTNIDDCSP NNCSHGGTCQ DLVNGFKCVC PPQWTGKTCQ LDANECEAKP - 420
CVNAKSCKNL IASYYCDCLP GWMGQNCDIN INDCLGQCQN DASCRDLVNG YRCICPPGYA - 480
GDHCERDIDE CASNPCLNGG HCQNEINRFQ CLCPTGFSGN LCQLDIDYCE PNPCQNGAQC - 540
YNRASDYFCK CPEDYEGKNC SHLKDHCRTT PCEVIDSCTV AMASNDTPEG VRYISSNVCG - 600
PHGKCKSQSG GKFTCDCNKG FTGTYCHENI NDCESNPCRN GGTCIDGVNS YKCICSDGWE - 660
GAYCETNIND CSQNPCHNGG TCRDLVNDFY CDCKNGWKGK TCHSRDSQCD EATCNNGGTC - 720
YDEGDAFKCM CPGGWEGTTC NIARNSSCLP NPCHNGGTCV VNGESFTCVC KEGWEGPICA - 780
QNTNDCSPHP CYNSGTCVDG DNWYRCECAP GFAGPDCRIN INECQSSPCA FGATCVDEIN - 840
GYRCVCPPGH SGAKCQEVSG RPCITMGSVI PDGAKWDDDC NTCQCLNGRI ACSKVWCGPR - 900
PCLLHKGHSE CPSGQSCIPI LDDQCFVHPC TGVGECRSSS LQPVKTKCTS DSYYQDNCAN - 960
ITFTFNKEMM SPGLTTEHIC SELRNLNILK NVSAEYSIYI ACEPSPSANN EIHVAISAED - 1020
IRDDGNPIKE ITDKIIDLVS KRDGNSSLIA AVAEVRVQRR PLKNRTDFLV PLLSSVLTVA - 1080
WICCLVTAFY WCLRKRRKPG SHTHSASEDN TTNNVREQLN QIKNPIEKHG ANTVPIKDYE - 1140
NKNSKMSKIR THNSEVEEDD MDKHQQKARF AKQPAYTLVD REEKPPNGTP TKHPNWTNKQ - 1200
DNRDLESAQS LNRMEYIV

The type I membrane-spanning proteins Jagged (Jagged-1 and -2) and Delta (Delta-1, -3 and - 4) are the human ligands of Notch receptors, which mediate key signaling events in cell differentiation and morphogenesis. Binding of Jagged and Delta proteins to Notch receptors triggers a series of proteolytic cleavages eventually leading to the release of the intracellular part of the receptor from the membrane, its translocation to the nucleus, and the activation of transcription factors. ADAM and presenilin/gamma-secretase, the proteases involved in Notch receptor processing, have been recently shown to be involved also in the proteolytic cleavage of Jagged and Delta, with the consequent release of signaling fragments from the membrane. Furthermore, Delta-1, -2, -4 (but not Delta-3) and Jagged-1 (but not Jagged-2) contain a PDZ binding motif at the C-terminus of their cytoplasmic tail, suggesting their involvement in Notch-independent signaling, as well as a possible role of their intracellular region in the cross-talk between Notch signaling and other signal transduction pathways. The cytoplasmic tail of Jagged-1 has been shown to bind the PDZ domain of AF6, a protein belonging to the cell adhesion system and containing two Ras association domains. Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation. Enhances fibroblast growth factor-induced angiogenesis (in vitro).