CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000269
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Disintegrin and metalloproteinase domain-containing protein 10 
Protein Synonyms/Alias
 ADAM 10; CDw156; Kuzbanian protein homolog; Mammalian disintegrin-metalloprotease; CD156c 
Gene Name
 ADAM10 
Gene Synonyms/Alias
 KUZ; MADM 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
45NVDSLHQKHQRAKRAubiquitination[1]
93FKVETSNKVLDYDTSubiquitination[2]
166DDINYPHKYGPQGGCubiquitination[1]
184SVFERMRKYQMTGVEubiquitination[1]
284INTTADEKDPTNPFRubiquitination[3]
410ESKNLGQKENGNYIMubiquitination[1]
601CHVCCMKKMDPSTCAubiquitination[1]
721KPLPGTLKRRRPPQPubiquitination[1]
Reference
 [1] 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]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] 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] 
Functional Description
 Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' 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 heparin-binding epidermal growth- like factor, ephrin-A2 and for constitutive and regulated alpha- secretase cleavage of amyloid precursor protein (APP). Contributes to the normal cleavage of the cellular prion protein. Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity. Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis. Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form. Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B. May regulate the EFNA5-EPHA3 signaling. 
Sequence Annotation
 DOMAIN 220 456 Peptidase M12B.
 DOMAIN 457 551 Disintegrin.
 MOTIF 171 178 Cysteine switch (By similarity).
 MOTIF 708 715 SH3-binding (Potential).
 MOTIF 722 728 SH3-binding (Potential).
 ACT_SITE 384 384
 METAL 173 173 Zinc; in inhibited form (By similarity).
 METAL 383 383 Zinc; catalytic.
 METAL 387 387 Zinc; catalytic.
 METAL 393 393 Zinc; catalytic.
 CARBOHYD 267 267 N-linked (GlcNAc...) (Potential).
 CARBOHYD 278 278 N-linked (GlcNAc...).
 CARBOHYD 439 439 N-linked (GlcNAc...) (Potential).
 CARBOHYD 551 551 N-linked (GlcNAc...) (Potential).
 DISULFID 222 313 By similarity.
 DISULFID 344 451 By similarity.
 DISULFID 399 435 By similarity.
 DISULFID 484 515 By similarity.
 DISULFID 503 511 By similarity.
 DISULFID 524 543 By similarity.
 DISULFID 530 562 By similarity.
 DISULFID 555 567 By similarity.
 DISULFID 572 598 By similarity.
 DISULFID 580 607 By similarity.
 DISULFID 582 597 By similarity.
 DISULFID 594 639 By similarity.
 DISULFID 632 645 By similarity.  
Keyword
 3D-structure; Cell membrane; Cleavage on pair of basic residues; Complete proteome; Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; Notch signaling pathway; Polymorphism; Protease; Reference proteome; SH3-binding; Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 748 AA 
Protein Sequence
MVLLRVLILL LSWAAGMGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK RAVSHEDQFL 60
RLDFHAHGRH FNLRMKRDTS LFSDEFKVET SNKVLDYDTS HIYTGHIYGE EGSFSHGSVI 120
DGRFEGFIQT RGGTFYVEPA ERYIKDRTLP FHSVIYHEDD INYPHKYGPQ GGCADHSVFE 180
RMRKYQMTGV EEVTQIPQEE HAANGPELLR KKRTTSAEKN TCQLYIQTDH LFFKYYGTRE 240
AVIAQISSHV KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF 300
LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY SDGKKKSLNT 360
GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT PGESKNLGQK ENGNYIMYAR 420
ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN CFVESGQPIC GNGMVEQGEE CDCGYSDQCK 480
DECCFDANQP EGRKCKLKPG KQCSPSQGPC CTAQCAFKSK SEKCRDDSDC AREGICNGFT 540
ALCPASDPKP NFTDCNRHTQ VCINGQCAGS ICEKYGLEEC TCASSDGKDD KELCHVCCMK 600
KMDPSTCAST GSVQWSRHFS GRTITLQPGS PCNDFRGYCD VFMRCRLVDA DGPLARLKKA 660
IFSPELYENI AEWIVAHWWA VLLMGIALIM LMAGFIKICS VHTPSSNPKL PPPKPLPGTL 720
KRRRPPQPIQ QPQRQRPRES YQMGHMRR 748 
Gene Ontology
 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
 GO:0005798; C:Golgi-associated vesicle; IDA:UniProtKB.
 GO:0016021; C:integral to membrane; NAS:UniProtKB.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0014069; C:postsynaptic density; IEA:Compara.
 GO:0005178; F:integrin binding; NAS:UniProtKB.
 GO:0004222; F:metalloendopeptidase activity; IMP:UniProtKB.
 GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
 GO:0019901; F:protein kinase binding; ISS:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0007267; P:cell-cell signaling; NAS:UniProtKB.
 GO:0030574; P:collagen catabolic process; TAS:Reactome.
 GO:0051089; P:constitutive protein ectodomain proteolysis; IDA:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
 GO:0001701; P:in utero embryonic development; ISS:UniProtKB.
 GO:0007229; P:integrin-mediated signaling pathway; NAS:UniProtKB.
 GO:0042117; P:monocyte activation; IMP:BHF-UCL.
 GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB.
 GO:0007220; P:Notch receptor processing; TAS:Reactome.
 GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
 GO:0051088; P:PMA-inducible membrane protein ectodomain proteolysis; IMP: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:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL.
 GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
 GO:0034612; P:response to tumor necrosis factor; IDA:BHF-UCL. 
Interpro
 IPR027053; ADAM_10.
 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