dbPTM

ADA17_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	ADA17_HUMAN
UniProt AC	P78536
Protein Name	Disintegrin and metalloproteinase domain-containing protein 17
Gene Name	ADAM17
Organism	Homo sapiens (Human).
Sequence Length	824
Subcellular Localization	Membrane Single-pass type I membrane protein.
Protein Description	Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2..
Protein Sequence	MRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDLQTSTHVETLLTFSALKRHFKLYLTSSTERFSQNFKVVVVDGKNESEYTVKWQDFFTGHVVGEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQSPKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGEKHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANSHGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINATCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCEKRVQDVIERFWDFIDQLSINTFGKFLADNIVGSVLVFSLIFWIPFSILVHCVDKKLDKQYESLSLFHPSNVEMLSSMDSASVRIIKPFPAPQTPGRLQPAPVIPSAPAAPKLDHQRMDTIQEDPSTDSHMDEDGFEKDPFPNSSTAAKSFEDLTDHPVTRSEKAASFKLQRQNRVDSKETEC

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
4	Phosphorylation	----MRQSLLFLTSV ----CCCHHHHHHCC	19.37	27732954
9	Phosphorylation	RQSLLFLTSVVPFVL CCHHHHHHCCCCEEE	16.49	27732954
10	Phosphorylation	QSLLFLTSVVPFVLA CHHHHHHCCCCEEEC	24.22	27732954
82	Phosphorylation	LKRHFKLYLTSSTER HHHHHEEEECCCCHH	14.44	-
84	Phosphorylation	RHFKLYLTSSTERFS HHHEEEECCCCHHHC	13.69	27362937
87	Phosphorylation	KLYLTSSTERFSQNF EEEECCCCHHHCCCE	30.83	27362937
102	Ubiquitination	KVVVVDGKNESEYTV EEEEECCCCCCEEEE	53.75	-
103	N-linked_Glycosylation	VVVVDGKNESEYTVK EEEECCCCCCEEEEE	64.65	UniProtKB CARBOHYD
157	N-linked_Glycosylation	EPLWRFVNDTKDKRM HHHHHHHCCCCCCEE	48.82	UniProtKB CARBOHYD
168 (in isoform 2)	Ubiquitination	-	39.63	21906983
168 (in isoform 1)	Ubiquitination	-	39.63	21890473
168	Ubiquitination	DKRMLVYKSEDIKNV CCEEEEEECHHHCCH	39.63	21906983
174	N-linked_Glycosylation	YKSEDIKNVSRLQSP EECHHHCCHHHCCCC	37.01	UniProtKB CARBOHYD
180	Phosphorylation	KNVSRLQSPKVCGYL CCHHHCCCCCCCCEE	31.14	26091039
182	Ubiquitination	VSRLQSPKVCGYLKV HHHCCCCCCCCEEEE	56.24	-
186	Phosphorylation	QSPKVCGYLKVDNEE CCCCCCCEEEECCHH	9.75	23403867
197	Ubiquitination	DNEELLPKGLVDREP CCHHHCCCCCCCCCC	65.92	-
262	Phosphorylation	IDRVDDIYRNTSWDN HHHHHHHHHCCCCCC	12.57	29978859
264	N-linked_Glycosylation	RVDDIYRNTSWDNAG HHHHHHHCCCCCCCC	22.84	UniProtKB CARBOHYD
265	Phosphorylation	VDDIYRNTSWDNAGF HHHHHHCCCCCCCCC	23.38	29978859
266	Phosphorylation	DDIYRNTSWDNAGFK HHHHHCCCCCCCCCC	35.66	29978859
273 (in isoform 2)	Ubiquitination	-	50.75	-
302	Ubiquitination	EKHYNMAKSYPNEEK CCCCCCCCCCCCCCC	39.49	21906983
302 (in isoform 2)	Ubiquitination	-	39.49	21906983
302 (in isoform 1)	Ubiquitination	-	39.49	21890473
309	Ubiquitination	KSYPNEEKDAWDVKM CCCCCCCCCHHHHHH	46.71	-
360	Phosphorylation	VGSPRANSHGGVCPK ECCCCCCCCCCCCCC	23.64	30631047
376	Ubiquitination	YYSPVGKKNIYLNSG CCCCCCCCEEEECCC	42.52	-
379	Phosphorylation	PVGKKNIYLNSGLTS CCCCCEEEECCCCCC	14.82	22817900
382	Phosphorylation	KKNIYLNSGLTSTKN CCEEEECCCCCCCCC	32.36	22817900
388	Ubiquitination	NSGLTSTKNYGKTIL CCCCCCCCCCCCEEE	48.19	-
392	Ubiquitination	TSTKNYGKTILTKEA CCCCCCCCEEEECCC	23.25	-
433	Phosphorylation	NEDQGGKYVMYPIAV CCCCCCCEEEEEEEE	8.17	-
436	Phosphorylation	QGGKYVMYPIAVSGD CCCCEEEEEEEEECC	4.97	-
452	N-linked_Glycosylation	ENNKMFSNCSKQSIY CCCCCCCCCCHHHHH	23.86	UniProtKB CARBOHYD
460	Ubiquitination	CSKQSIYKTIESKAQ CCHHHHHHHHHHHHH	41.16	-
465	Ubiquitination	IYKTIESKAQECFQE HHHHHHHHHHHHHHH	41.10	-
498	N-linked_Glycosylation	PGIMYLNNDTCCNSD CCCEEECCCCCCCCC	43.29	UniProtKB CARBOHYD
539	N-linked_Glycosylation	KKCQEAINATCKGVS HHHHHHHHHHHCCCH	35.92	UniProtKB CARBOHYD
551	N-linked_Glycosylation	GVSYCTGNSSECPPP CCHHCCCCCCCCCCC	24.98	UniProtKB CARBOHYD
594	N-linked_Glycosylation	QLESCACNETDNSCK HHHHHHCCCCCCCCE	36.36	17660510
608	Phosphorylation	KVCCRDLSGRCVPYV EEEEECCCCCEEECC	28.60	22210691
614	Phosphorylation	LSGRCVPYVDAEQKN CCCCEEECCCHHHHC	7.20	22210691
620	Ubiquitination	PYVDAEQKNLFLRKG ECCCHHHHCEEECCC	47.31	-
631	Phosphorylation	LRKGKPCTVGFCDMN ECCCCCCEEEEECCC	31.99	29759185
702	Phosphorylation	DKKLDKQYESLSLFH CHHHHHHHHHCCCCC	17.15	27642862
706	Phosphorylation	DKQYESLSLFHPSNV HHHHHHCCCCCHHHH	37.96	-
711	Phosphorylation	SLSLFHPSNVEMLSS HCCCCCHHHHHHHHC	44.96	22210691
717	Phosphorylation	PSNVEMLSSMDSASV HHHHHHHHCCCCCEE	23.47	22210691
718	Phosphorylation	SNVEMLSSMDSASVR HHHHHHHCCCCCEEE	23.73	28348404
721	Phosphorylation	EMLSSMDSASVRIIK HHHHCCCCCEEEEEC	17.50	28857561
723	Phosphorylation	LSSMDSASVRIIKPF HHCCCCCEEEEECCC	18.84	28857561
728 (in isoform 1)	Ubiquitination	-	37.93	21890473
728	Ubiquitination	SASVRIIKPFPAPQT CCEEEEECCCCCCCC	37.93	21890473
735	Phosphorylation	KPFPAPQTPGRLQPA CCCCCCCCCCCCCCC	27.01	30266825
747	Phosphorylation	QPAPVIPSAPAAPKL CCCCCCCCCCCCCCC	35.44	23312004
753	Ubiquitination	PSAPAAPKLDHQRMD CCCCCCCCCCCCCCC	62.92	-
761	Phosphorylation	LDHQRMDTIQEDPST CCCCCCCCCCCCCCC	18.41	30266825
767	Phosphorylation	DTIQEDPSTDSHMDE CCCCCCCCCCCCCCC	58.11	30266825
768	Phosphorylation	TIQEDPSTDSHMDED CCCCCCCCCCCCCCC	47.08	30266825
770	Phosphorylation	QEDPSTDSHMDEDGF CCCCCCCCCCCCCCC	22.31	30266825
779	Ubiquitination	MDEDGFEKDPFPNSS CCCCCCCCCCCCCCH	69.32	21906983
779 (in isoform 1)	Ubiquitination	-	69.32	21890473
785	Phosphorylation	EKDPFPNSSTAAKSF CCCCCCCCHHHHHHH	29.33	30266825
786	Phosphorylation	KDPFPNSSTAAKSFE CCCCCCCHHHHHHHH	28.80	30266825
787	Phosphorylation	DPFPNSSTAAKSFED CCCCCCHHHHHHHHH	30.38	30266825
790	Ubiquitination	PNSSTAAKSFEDLTD CCCHHHHHHHHHHCC	53.89	2190698
790 (in isoform 1)	Ubiquitination	-	53.89	21890473
791	Phosphorylation	NSSTAAKSFEDLTDH CCHHHHHHHHHHCCC	29.19	29255136
791	Dephosphorylation	NSSTAAKSFEDLTDH CCHHHHHHHHHHCCC	29.19	12621058
796	Phosphorylation	AKSFEDLTDHPVTRS HHHHHHHCCCCCCCC	44.58	23927012
801	Phosphorylation	DLTDHPVTRSEKAAS HHCCCCCCCCHHHHH	32.69	23403867
805	Ubiquitination	HPVTRSEKAASFKLQ CCCCCCHHHHHHHHH	50.96	-
808	Phosphorylation	TRSEKAASFKLQRQN CCCHHHHHHHHHHHC	27.98	27422710
810	Ubiquitination	SEKAASFKLQRQNRV CHHHHHHHHHHHCCC	41.01	-
819	Phosphorylation	QRQNRVDSKETEC-- HHHCCCCCCCCCC--	29.54	23898821
822	Phosphorylation	NRVDSKETEC----- CCCCCCCCCC-----	46.52	28102081

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
735	T	Phosphorylation	Kinase	PRKCA	P17252	GPS
735	T	Phosphorylation	Kinase	PRKCD	Q05655	GPS
735	T	Phosphorylation	Kinase	PRKCE	Q02156	GPS
735	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
735	T	Phosphorylation	Kinase	MAPK3	P27361	GPS
735	T	Phosphorylation	Kinase	P38A	Q16539	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
735	T	Phosphorylation	12058067
Phosphorylation at THR-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding.
791	S	Phosphorylation	17081983
Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791.
819	S	Phosphorylation	12621058
Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of ADA17_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
DLG1_HUMAN	DLG1	physical	12668732
MK01_HUMAN	MAPK1	physical	12058067
MD2L1_HUMAN	MAD2L1	physical	10527948
MD2L1_HUMAN	MAD2L1	physical	11741929
TNR1A_HUMAN	TNFRSF1A	physical	17010968
TNR1B_HUMAN	TNFRSF1B	physical	17010968
DLG1_HUMAN	DLG1	physical	18930083
SDK2_HUMAN	SDK2	physical	28514442
LRRC3_HUMAN	LRRC3	physical	28514442

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
614328	Inflammatory skin and bowel disease, neonatal, 1 (NISBD1)
Kegg Drug
D08859	Apratastat (USAN/INN)
D09320	Aderbasib (USAN/INN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of ADA17_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-379; SER-382 ANDSER-791, AND MASS SPECTROMETRY.	17081983 [Abstract]
"Direct activation of TACE-mediated ectodomain shedding by p38 MAPkinase regulates EGF receptor-dependent cell proliferation."; Xu P., Derynck R.; Mol. Cell 37:551-566(2010). Cited for: PHOSPHORYLATION AT THR-735, AND INTERACTION WITH MAPK14.	20188673 [Abstract]
"Extracellular signal-regulated kinase phosphorylates tumor necrosisfactor alpha-converting enzyme at threonine 735: a potential role inregulated shedding."; Diaz-Rodriguez E., Montero J.C., Esparis-Ogando A., Yuste L.,Pandiella A.; Mol. Biol. Cell 13:2031-2044(2002). Cited for: PHOSPHORYLATION AT THR-735.	12058067 [Abstract]

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