Overview
| Uniprot ID | O14672 |
|---|
| Protein Name | Disintegrin and metalloproteinase domain-containing protein 10 |
|---|
| Gene Name | ADAM10 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 405 |
ECTPGESKNLGQKEN |
Function
Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins, including adhesion proteins, growth factor precursors and cytokines being essential for development and tissue homeostasis (PubMed:11786905, PubMed:12475894, PubMed:20592283, PubMed:24990881, PubMed:26686862, PubMed:28600292, PubMed:31792032, PubMed:31792032). Associates with six members of the tetraspanin superfamily TspanC8 which regulate its exit from the endoplasmic reticulum and its substrate selectivity (PubMed:26686862, PubMed:28600292, PubMed:31792032, PubMed:34739841, PubMed:37516108). Cleaves the membrane-bound precursor of TNF at '76-Ala-|-Val-77' to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) (PubMed:11786905, PubMed:26686862, PubMed:29224781, PubMed:34739841, PubMed:33731436). Contributes to the normal cleavage of the cellular prion protein (PubMed:11477090). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (PubMed:12475894). Also controls the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity). Required for the development of type 1 transitional B cells into marginal zone B cells, probably by cleaving Notch (By similarity). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (PubMed:17557115). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (PubMed:19114711, PubMed:21288900). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the release of secreted forms of IL6R and IL11RA (PubMed:26876177). Enhances the cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By similarity). Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:24990881). Involved in the development and maturation of glomerular and coronary vasculature (By similarity). During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions (By similarity). May regulate the EFNA5-EPHA3 signaling (PubMed:16239146). Regulates leukocyte transmigration as a sheddase for the adherens junction protein VE-cadherin/CDH5 in endothelial cells (PubMed:28600292)
Protein Sequence
10
MVLLRVLILL
20
LSWAAGMGGQ
30
YGNPLNKYIR
40
HYEGLSYNVD
50
SLHQKHQRAK
60
RAVSHEDQFL
70
RLDFHAHGRH
80
FNLRMKRDTS
90
LFSDEFKVET
100
SNKVLDYDTS
110
HIYTGHIYGE
120
EGSFSHGSVI
130
DGRFEGFIQT
140
RGGTFYVEPA
150
ERYIKDRTLP
160
FHSVIYHEDD
170
INYPHKYGPQ
180
GGCADHSVFE
190
RMRKYQMTGV
200
EEVTQIPQEE
210
HAANGPELLR
220
KKRTTSAEKN
230
TCQLYIQTDH
240
LFFKYYGTRE
250
AVIAQISSHV
260
KAIDTIYQTT
270
DFSGIRNISF
280
MVKRIRINTT
290
ADEKDPTNPF
300
RFPNIGVEKF
310
LELNSEQNHD
320
DYCLAYVFTD
330
RDFDDGVLGL
340
AWVGAPSGSS
350
GGICEKSKLY
360
SDGKKKSLNT
370
GIITVQNYGS
380
HVPPKVSHIT
390
FAHEVGHNFG
400
SPHDSGTECT
410
PGESKNLGQK
420
ENGNYIMYAR
430
ATSGDKLNNN
440
KFSLCSIRNI
450
SQVLEKKRNN
460
CFVESGQPIC
470
GNGMVEQGEE
480
CDCGYSDQCK
490
DECCFDANQP
500
EGRKCKLKPG
510
KQCSPSQGPC
520
CTAQCAFKSK
530
SEKCRDDSDC
540
AREGICNGFT
550
ALCPASDPKP
560
NFTDCNRHTQ
570
VCINGQCAGS
580
ICEKYGLEEC
590
TCASSDGKDD
600
KELCHVCCMK
610
KMDPSTCAST
620
GSVQWSRHFS
630
GRTITLQPGS
640
PCNDFRGYCD
650
VFMRCRLVDA
660
DGPLARLKKA
670
IFSPELYENI
680
AEWIVAHWWA
690
VLLMGIALIM
700
LMAGFIKICS
710
VHTPSSNPKL
720
PPPKPLPGTL
730
KRRRPPQPIQ
740
QPQRQRPRES
YQMGHMRR
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005912 |
adherens junction |
| Biological Process |
GO:0140249 |
protein catabolic process at postsynapse |
| Biological Process |
GO:0016485 |
protein processing |
| Biological Process |
GO:0098696 |
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane |
| Biological Process |
GO:0008593 |
regulation of Notch signaling pathway |
| Biological Process |
GO:0099175 |
regulation of postsynapse organization |
| Biological Process |
GO:1901342 |
regulation of vasculature development |
| Biological Process |
GO:0034612 |
response to tumor necrosis factor |
| Cellular Component |
GO:0030424 |
axon |
| Cellular Component |
GO:0009986 |
cell surface |
| Cellular Component |
GO:0030136 |
clathrin-coated vesicle |
| Cellular Component |
GO:0030425 |
dendrite |
| Cellular Component |
GO:0005788 |
endoplasmic reticulum lumen |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0005925 |
focal adhesion |
| Cellular Component |
GO:0098978 |
glutamatergic synapse |
| Cellular Component |
GO:0005794 |
Golgi apparatus |
| Cellular Component |
GO:0000139 |
Golgi membrane |
| Cellular Component |
GO:0005798 |
Golgi-associated vesicle |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0097038 |
perinuclear endoplasmic reticulum |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0046930 |
pore complex |
| Cellular Component |
GO:0014069 |
postsynaptic density |
| Cellular Component |
GO:0035579 |
specific granule membrane |
| Cellular Component |
GO:0097060 |
synaptic membrane |
| Cellular Component |
GO:0070821 |
tertiary granule membrane |
| Cellular Component |
GO:0097197 |
tetraspanin-enriched microdomain |
| Molecular Function |
GO:0004175 |
endopeptidase activity |
| Molecular Function |
GO:0005178 |
integrin binding |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0070573 |
metallodipeptidase activity |
| Molecular Function |
GO:0004222 |
metalloendopeptidase activity |
| Molecular Function |
GO:1902945 |
metalloendopeptidase activity involved in amyloid precursor protein catabolic process |
| Molecular Function |
GO:0008237 |
metallopeptidase activity |
| Molecular Function |
GO:0042803 |
protein homodimerization activity |
| Molecular Function |
GO:0017124 |
SH3 domain binding |
| Biological Process |
GO:0034332 |
adherens junction organization |
| Biological Process |
GO:0042987 |
amyloid precursor protein catabolic process |
| Biological Process |
GO:0007267 |
cell-cell signaling |
| Biological Process |
GO:0090102 |
cochlea development |
| Biological Process |
GO:0051089 |
constitutive protein ectodomain proteolysis |
| Biological Process |
GO:0038004 |
epidermal growth factor receptor ligand maturation |
| Biological Process |
GO:0022617 |
extracellular matrix disassembly |
| Biological Process |
GO:0001701 |
in utero embryonic development |
| Biological Process |
GO:0007229 |
integrin-mediated signaling pathway |
| Biological Process |
GO:0006509 |
membrane protein ectodomain proteolysis |
| Biological Process |
GO:0042117 |
monocyte activation |
| Biological Process |
GO:0007162 |
negative regulation of cell adhesion |
| Biological Process |
GO:0010629 |
negative regulation of gene expression |
| Biological Process |
GO:0007219 |
Notch signaling pathway |
| Biological Process |
GO:0046931 |
pore complex assembly |
| Biological Process |
GO:0030307 |
positive regulation of cell growth |
| Biological Process |
GO:0030335 |
positive regulation of cell migration |
| Biological Process |
GO:0008284 |
positive regulation of cell population proliferation |
| Biological Process |
GO:0010820 |
positive regulation of T cell chemotaxis |
| Biological Process |
GO:0032760 |
positive regulation of tumor necrosis factor production |
| Biological Process |
GO:1903265 |
positive regulation of tumor necrosis factor-mediated signaling pathway |
| Biological Process |
GO:0099173 |
postsynapse organization |
Reference
PMID: N/A