DLL1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: DLL1_HUMAN
• UniProt AC: O00548
• Protein Name: Delta-like protein 1
• Gene Name: DLL1
• Organism: Homo sapiens (Human).
• Sequence Length: 723
• Subcellular Localization: Apical cell membrane ; Single-pass type I membrane protein . Cell junction, adherens junction . Membrane raft . Distributed around adherens junction in the apical endfeet through interactions with MAGI1.
• Protein Description: Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner. [PubMed: 11006133 Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerisation; these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) (By similarity Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme; the DLL1-induced Notch signaling is mediated through an intercellular communication that regulates cell lineage, cell specification, cell patterning and morphogenesis through effects on differentiation and proliferation]
• Protein Sequence: MGSRCALALAVLSALLCQVWSSGVFELKLQEFVNKKGLLGNRNCCRGGAGPPPCACRTFFRVCLKHYQASVSPEPPCTYGSAVTPVLGVDSFSLPDGGGADSAFSNPIRFPFGFTWPGTFSLIIEALHTDSPDDLATENPERLISRLATQRHLTVGEEWSQDLHSSGRTDLKYSYRFVCDEHYYGEGCSVFCRPRDDAFGHFTCGERGEKVCNPGWKGPYCTEPICLPGCDEQHGFCDKPGECKCRVGWQGRYCDECIRYPGCLHGTCQQPWQCNCQEGWGGLFCNQDLNYCTHHKPCKNGATCTNTGQGSYTCSCRPGYTGATCELGIDECDPSPCKNGGSCTDLENSYSCTCPPGFYGKICELSAMTCADGPCFNGGRCSDSPDGGYSCRCPVGYSGFNCEKKIDYCSSSPCSNGAKCVDLGDAYLCRCQAGFSGRHCDDNVDDCASSPCANGGTCRDGVNDFSCTCPPGYTGRNCSAPVSRCEHAPCHNGATCHERGHRYVCECARGYGGPNCQFLLPELPPGPAVVDLTEKLEGQGGPFPWVAVCAGVILVLMLLLGCAAVVVCVRLRLQKHRPPADPCRGETETMNNLANCQREKDISVSIIGATQIKNTNKKADFHGDHSADKNGFKARYPAVDYNLVQDLKGDDTAVRDAHSKRDTKCQPQGSSGEEKGTPTTLRGGEASERKRPDSGCSTSKDTKYQSVYVISEEKDECVIATEV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
35	Acetylation	KLQEFVNKKGLLGNR HHHHHHHHCCCCCCC	42.80	30588195
174	Phosphorylation	GRTDLKYSYRFVCDE CCCCCEEEEEEEECC	14.29	24719451
477	N-linked_Glycosylation	PPGYTGRNCSAPVSR CCCCCCCCCCCCCCC	25.99	UniProtKB CARBOHYD
603	Phosphorylation	CQREKDISVSIIGAT CHHCCCCEEEEEEEE	21.68	-
641	Phosphorylation	ARYPAVDYNLVQDLK CCCCCCCCCCCHHHC	12.09	27642862
663	Phosphorylation	DAHSKRDTKCQPQGS CHHCCCCCCCCCCCC	37.44	26270265
670	Phosphorylation	TKCQPQGSSGEEKGT CCCCCCCCCCCCCCC	29.89	26270265
671	Phosphorylation	KCQPQGSSGEEKGTP CCCCCCCCCCCCCCC	57.98	26270265
677	Phosphorylation	SSGEEKGTPTTLRGG CCCCCCCCCCEECCC	28.64	27794612
679	Phosphorylation	GEEKGTPTTLRGGEA CCCCCCCCEECCCCC	38.00	27794612
680	Phosphorylation	EEKGTPTTLRGGEAS CCCCCCCEECCCCCC	18.70	27794612
694	Phosphorylation	SERKRPDSGCSTSKD CCCCCCCCCCCCCCC	44.36	29978859
697	Phosphorylation	KRPDSGCSTSKDTKY CCCCCCCCCCCCCCC	38.96	29978859
698	Phosphorylation	RPDSGCSTSKDTKYQ CCCCCCCCCCCCCCC	43.82	29978859
699	Phosphorylation	PDSGCSTSKDTKYQS CCCCCCCCCCCCCCE	16.55	29978859
702	Phosphorylation	GCSTSKDTKYQSVYV CCCCCCCCCCCEEEE	35.07	29978859
704	Phosphorylation	STSKDTKYQSVYVIS CCCCCCCCCEEEEEE	14.23	22461510
706	Phosphorylation	SKDTKYQSVYVISEE CCCCCCCEEEEEECC	16.60	22461510

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
694	S	Phosphorylation	Kinase	PKB	P31749	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	MIB1	Q86YT6	PMID:18676613
-	K	Ubiquitination	E3 ubiquitin ligase	MIB2	Q96AX9	PMID:18676613
-	K	Ubiquitination	E3 ubiquitin ligase	NEURL1B	A8MQ27	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
613	K	ubiquitylation	Multi-ubiquitination of LYS-613 by MIB1 promotes both cis and trans-interaction with NOTCH1, as well as activation of Notch signaling.	-
694	S	Phosphorylation	Phosphorylation at Ser-697 requires the presence of Ser-694, whereas phosphorylation at Ser-694 occurs independently of the other site.	-
697	S	Phosphorylation	Phosphorylation at Ser-697 requires the presence of Ser-694, whereas phosphorylation at Ser-694 occurs independently of the other site.	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of DLL1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NOTC2_HUMAN	NOTCH2	physical	11346656
NOTC2_HUMAN	NOTCH2	physical	9244302
EPN1_HUMAN	EPN1	physical	22658936
MIB1_HUMAN	MIB1	physical	27510968

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.