CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010429
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Disintegrin and metalloproteinase domain-containing protein 17 
Protein Synonyms/Alias
 ADAM 17; Snake venom-like protease; TNF-alpha convertase; TNF-alpha-converting enzyme; CD156b 
Gene Name
 ADAM17 
Gene Synonyms/Alias
 CSVP; TACE 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
168DKRMLVYKSEDIKNVubiquitination[1]
302EKHYNMAKSYPNEEKubiquitination[1, 2]
392TSTKNYGKTILTKEAubiquitination[3]
728SASVRIIKPFPAPQTubiquitination[1, 4]
779MDEDGFEKDPFPNSSubiquitination[1]
790PNSSTAAKSFEDLTDubiquitination[1]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473] 
Functional 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. Also involved in the activation of Notch pathway (By similarity). 
Sequence Annotation
 DOMAIN 223 474 Peptidase M12B.
 DOMAIN 475 563 Disintegrin.
 REGION 603 671 Crambin-like.
 MOTIF 182 189 Cysteine switch (By similarity).
 MOTIF 731 738 SH3-binding (Potential).
 MOTIF 741 748 SH3-binding (Potential).
 ACT_SITE 406 406
 METAL 184 184 Zinc; in inhibited form (By similarity).
 METAL 405 405 Zinc; catalytic.
 METAL 409 409 Zinc; catalytic.
 METAL 415 415 Zinc; catalytic.
 MOD_RES 735 735 Phosphothreonine; by MAPK14.
 MOD_RES 791 791 Phosphoserine.
 MOD_RES 819 819 Phosphoserine.
 CARBOHYD 103 103 N-linked (GlcNAc...) (Potential).
 CARBOHYD 157 157 N-linked (GlcNAc...) (Potential).
 CARBOHYD 174 174 N-linked (GlcNAc...) (Potential).
 CARBOHYD 264 264 N-linked (GlcNAc...) (Potential).
 CARBOHYD 452 452 N-linked (GlcNAc...) (Potential).
 CARBOHYD 498 498 N-linked (GlcNAc...) (Potential).
 CARBOHYD 539 539 N-linked (GlcNAc...) (Potential).
 CARBOHYD 551 551 N-linked (GlcNAc...) (Potential).
 CARBOHYD 594 594 N-linked (GlcNAc...) (Potential).
 DISULFID 225 333
 DISULFID 365 469
 DISULFID 423 453
 DISULFID 534 555 By similarity.
 DISULFID 573 582 By similarity.
 DISULFID 578 591 By similarity.
 DISULFID 593 600 By similarity.  
Keyword
 3D-structure; Alternative splicing; Cleavage on pair of basic residues; Complete proteome; Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; Notch signaling pathway; Phosphoprotein; Polymorphism; Protease; Reference proteome; SH3-binding; Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 824 AA 
Protein Sequence
MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI QQHSVRKRDL 60
QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD GKNESEYTVK WQDFFTGHVV 120
GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS 180
PKVCGYLKVD NEELLPKGLV DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG 240
RGEESTTTNY LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM 300
AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL AYVGSPRANS 360
HGGVCPKAYY SPVGKKNIYL NSGLTSTKNY GKTILTKEAD LVTTHELGHN FGAEHDPDGL 420
AECAPNEDQG GKYVMYPIAV SGDHENNKMF SNCSKQSIYK TIESKAQECF QERSNKVCGN 480
SRVDEGEECD PGIMYLNNDT CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA 540
TCKGVSYCTG NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC 600
KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE RFWDFIDQLS 660
INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK QYESLSLFHP SNVEMLSSMD 720
SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA APKLDHQRMD TIQEDPSTDS HMDEDGFEKD 780
PFPNSSTAAK SFEDLTDHPV TRSEKAASFK LQRQNRVDSK ETEC 824 
Gene Ontology
 GO:0015629; C:actin cytoskeleton; IDA:BHF-UCL.
 GO:0016324; C:apical plasma membrane; IDA:BHF-UCL.
 GO:0009986; C:cell surface; IDA:BHF-UCL.
 GO:0005737; C:cytoplasm; IEA:Compara.
 GO:0005887; C:integral to plasma membrane; IDA:BHF-UCL.
 GO:0045121; C:membrane raft; IDA:BHF-UCL.
 GO:0004222; F:metalloendopeptidase activity; IDA:BHF-UCL.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0030183; P:B cell differentiation; ISS:BHF-UCL.
 GO:0033627; P:cell adhesion mediated by integrin; IDA:BHF-UCL.
 GO:0030574; P:collagen catabolic process; TAS:Reactome.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:BHF-UCL.
 GO:0035625; P:epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway; IMP:BHF-UCL.
 GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
 GO:0002467; P:germinal center formation; ISS:BHF-UCL.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
 GO:0031293; P:membrane protein intracellular domain proteolysis; TAS:Reactome.
 GO:0032717; P:negative regulation of interleukin-8 production; IMP:BHF-UCL.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0002446; P:neutrophil mediated immunity; IC:BHF-UCL.
 GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
 GO:0051088; P:PMA-inducible membrane protein ectodomain proteolysis; IDA:BHF-UCL.
 GO:0030307; P:positive regulation of cell growth; IMP:BHF-UCL.
 GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL.
 GO:0032722; P:positive regulation of chemokine production; IMP:BHF-UCL.
 GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
 GO:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL.
 GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISS:BHF-UCL.
 GO:0033025; P:regulation of mast cell apoptotic process; ISS:BHF-UCL.
 GO:0042493; P:response to drug; ISS:BHF-UCL.
 GO:0055099; P:response to high density lipoprotein particle stimulus; IDA:BHF-UCL.
 GO:0001666; P:response to hypoxia; IDA:BHF-UCL.
 GO:0032496; P:response to lipopolysaccharide; IDA:BHF-UCL.
 GO:0048536; P:spleen development; ISS:BHF-UCL.
 GO:0033077; P:T cell differentiation in thymus; ISS:BHF-UCL.
 GO:0035313; P:wound healing, spreading of epidermal cells; IEP:BHF-UCL. 
Interpro
 IPR001762; Blood-coag_inhib_Disintegrin.
 IPR024079; MetalloPept_cat_dom.
 IPR001590; Peptidase_M12B.
 IPR002870; Peptidase_M12B_N. 
Pfam
 PF00200; Disintegrin
 PF01562; Pep_M12B_propep 
SMART
 SM00050; DISIN 
PROSITE
 PS50215; ADAM_MEPRO
 PS00546; CYSTEINE_SWITCH
 PS00427; DISINTEGRIN_1
 PS50214; DISINTEGRIN_2
 PS00142; ZINC_PROTEASE 
PRINTS