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Protein

Disintegrin and metalloproteinase domain-containing protein 10

Gene

Adam10

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (By similarity). 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) at '687-Lys-|-Leu-688' (By similarity). Contributes to the normal cleavage of the cellular prion protein (By similarity). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (By similarity). Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (PubMed:9244301). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (By similarity). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (By similarity). May regulate the EFNA5-EPHA3 signaling (By similarity).By similarity1 Publication

Catalytic activityi

Endopeptidase of broad specificity.By similarity

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Activity regulationi

Catalytically inactive when the propeptide is intact and associated with the mature enzyme (By similarity). The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi173Zinc; in inhibited formBy similarity1
Metal bindingi384Zinc; via tele nitrogen; catalyticBy similarity1
Active sitei385PROSITE-ProRule annotation1
Metal bindingi388Zinc; via tele nitrogen; catalyticBy similarity1
Metal bindingi394Zinc; via tele nitrogen; catalyticBy similarity1

GO - Molecular functioni

  • endopeptidase activity Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: UniProtKB
  • metallopeptidase activity Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processNotch signaling pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.81 3474
ReactomeiR-MMU-1474228 Degradation of the extracellular matrix
R-MMU-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-MMU-6798695 Neutrophil degranulation
R-MMU-8957275 Post-translational protein phosphorylation
R-MMU-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus

Protein family/group databases

MEROPSiM12.210

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 10 (EC:3.4.24.81By similarity)
Short name:
ADAM 10
Alternative name(s):
Kuzbanian protein homolog
Mammalian disintegrin-metalloprotease
CD_antigen: CD156c
Gene namesi
Name:Adam10
Synonyms:Kuz, Madm
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:109548 Adam10

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 673ExtracellularSequence analysisAdd BLAST654
Transmembranei674 – 694HelicalSequence analysisAdd BLAST21
Topological domaini695 – 749CytoplasmicSequence analysisAdd BLAST55

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000002906820 – 214By similarityAdd BLAST195
ChainiPRO_0000029069215 – 749Disintegrin and metalloproteinase domain-containing protein 10Add BLAST535

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi223 ↔ 314By similarity
Glycosylationi268N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi279N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi345 ↔ 452By similarity
Disulfide bondi400 ↔ 436By similarity
Glycosylationi440N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi461 ↔ 496By similarity
Disulfide bondi472 ↔ 485By similarity
Disulfide bondi474 ↔ 480By similarity
Disulfide bondi484 ↔ 516By similarity
Disulfide bondi504 ↔ 512By similarity
Disulfide bondi511 ↔ 537By similarity
Disulfide bondi525 ↔ 544By similarity
Disulfide bondi531 ↔ 563By similarity
Glycosylationi552N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi556 ↔ 568By similarity
Disulfide bondi573 ↔ 599By similarity
Disulfide bondi581 ↔ 608By similarity
Disulfide bondi583 ↔ 598By similarity
Disulfide bondi595 ↔ 640By similarity
Disulfide bondi633 ↔ 646By similarity
Modified residuei720PhosphothreonineCombined sources1

Post-translational modificationi

The precursor is cleaved by furin and PCSK7.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei214 – 215Cleavage; by furin and PCSK7By similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

EPDiO35598
MaxQBiO35598
PaxDbiO35598
PeptideAtlasiO35598
PRIDEiO35598

PTM databases

iPTMnetiO35598
PhosphoSitePlusiO35598
SwissPalmiO35598

Expressioni

Developmental stagei

Widely expressed in the nervous system at 18 dpc, with high expression in the posterior midbrain, which diminished toward the anterior midbrain.

Gene expression databases

BgeeiENSMUSG00000054693 Expressed in 299 organ(s), highest expression level in pineal body
CleanExiMM_ADAM10
ExpressionAtlasiO35598 baseline and differential
GenevisibleiO35598 MM

Interactioni

Subunit structurei

Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells (By similarity). Interacts with EPHA2 (PubMed:10958785). Interacts with NGF in a divalent cation-dependent manner (By similarity). Interacts with TSPAN14; the interaction promotes ADAM10 maturation and cell surface expression (PubMed:26668317, PubMed:23035126). Interacts with TSPAN5, TSPAN10, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate ADAM10 substrate specificity (PubMed:26668317, PubMed:23035126).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi197960, 2 interactors
IntActiO35598, 1 interactor
MINTiO35598
STRINGi10090.ENSMUSP00000063839

Structurei

3D structure databases

ProteinModelPortaliO35598
SMRiO35598
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini221 – 457Peptidase M12BPROSITE-ProRule annotationAdd BLAST237
Domaini458 – 552DisintegrinPROSITE-ProRule annotationAdd BLAST95

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi171 – 178Cysteine switchCurated8
Motifi709 – 716SH3-bindingSequence analysis8
Motifi723 – 729SH3-bindingSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi553 – 673Cys-richAdd BLAST121

Domaini

The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 Complex but not the individual proteins (By similarity). Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (PubMed:26668317). Stalk region is sufficient for interaction with TSPAN15 (PubMed:26668317).By similarity1 Publication
The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-173) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.By similarity

Keywords - Domaini

SH3-binding, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3658 Eukaryota
ENOG410XQWB LUCA
GeneTreeiENSGT00670000097974
HOGENOMiHOG000008148
HOVERGENiHBG050455
InParanoidiO35598
KOiK06704
OMAiEGFIQTH
OrthoDBiEOG091G01J4
TreeFamiTF352021

Family and domain databases

CDDicd04270 ZnMc_TACE_like, 1 hit
Gene3Di3.40.390.10, 1 hit
4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR034025 ADAM10_ADAM17
IPR027053 ADAM_10
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
PANTHERiPTHR11905:SF4 PTHR11905:SF4, 1 hit
PfamiView protein in Pfam
PF00200 Disintegrin, 1 hit
PF01562 Pep_M12B_propep, 1 hit
SMARTiView protein in SMART
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS50214 DISINTEGRIN_2, 1 hit
PS00142 ZINC_PROTEASE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

O35598-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MVLPTVLILL LSWAAGLGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK
60 70 80 90 100
RAVSHEDQFL LLDFHAHGRQ FNLRMKRDTS LFSDEFKVET SNKVLDYDTS
110 120 130 140 150
HIYTGHIYGE EGSFSHGSVI DGRFEGFIKT RGGTFYIEPA ERYIKDRILP
160 170 180 190 200
FHSVIYHEDD INYPHKYGPQ GGCADHSVFE RMRKYQMTGV EEGARAHPEK
210 220 230 240 250
HAASSGPELL RKKRTTLAER NTCQLYIQTD HLFFKYYGTR EAVIAQISSH
260 270 280 290 300
VKAIDTIYQT TDFSGIRNIS FMVKRIRINT TSDEKDPTNP FRFPNIGVEK
310 320 330 340 350
FLELNSEQNH DDYCLAYVFT DRDFDDGVLG LAWVGAPSGS SGGICEKSKL
360 370 380 390 400
YSDGKKKSLN TGIITVQNYG SHVPPKVSHI TFAHEVGHNF GSPHDSGTEC
410 420 430 440 450
TPGESKNLGQ KENGNYIMYA RATSGDKLNN NKFSLCSIRN ISQVLEKKRN
460 470 480 490 500
NCFVESGQPI CGNGMVEQGE ECDCGYSDQC KDDCCFDANQ PEGKKCKLKP
510 520 530 540 550
GKQCSPSQGP CCTAQCAFKS KSEKCRDDSD CAKEGICNGF TALCPASDPK
560 570 580 590 600
PNFTDCNRHT QVCINGQCAG SICEKYDLEE CTCASSDGKD DKELCHVCCM
610 620 630 640 650
KKMAPSTCAS TGSLQWSKQF SGRTITLQPG SPCNDFRGYC DVFMRCRLVD
660 670 680 690 700
ADGPLARLKK AIFSPQLYEN IAEWIVAHWW AVLLMGIALI MLMAGFIKIC
710 720 730 740
SVHTPSSNPK LPPPKPLPGT LKRRRPPQPI QQPPRQRPRE SYQMGHMRR
Length:749
Mass (Da):83,968
Last modified:July 27, 2011 - v2
Checksum:i6AA2230B2251ABDA
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PYF2E9PYF2_MOUSE
Disintegrin and metalloproteinase d...
Adam10
513Annotation score:
D3Z1E6D3Z1E6_MOUSE
Disintegrin and metalloproteinase d...
Adam10
144Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti591D → N in AAC53303 (PubMed:9244301).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF011379 mRNA Translation: AAC53303.1
CT025701, AC091263, AC160636 Genomic DNA Translation: CAX15709.1
CH466522 Genomic DNA Translation: EDL26211.1
AK036883 mRNA Translation: BAC29620.1
AK036599 mRNA Translation: BAC29502.1
CCDSiCCDS23323.1
RefSeqiNP_031425.2, NM_007399.4
UniGeneiMm.3037

Genome annotation databases

EnsembliENSMUST00000067880; ENSMUSP00000063839; ENSMUSG00000054693
GeneIDi11487
KEGGimmu:11487
UCSCiuc009qor.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF011379 mRNA Translation: AAC53303.1
CT025701, AC091263, AC160636 Genomic DNA Translation: CAX15709.1
CH466522 Genomic DNA Translation: EDL26211.1
AK036883 mRNA Translation: BAC29620.1
AK036599 mRNA Translation: BAC29502.1
CCDSiCCDS23323.1
RefSeqiNP_031425.2, NM_007399.4
UniGeneiMm.3037

3D structure databases

ProteinModelPortaliO35598
SMRiO35598
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi197960, 2 interactors
IntActiO35598, 1 interactor
MINTiO35598
STRINGi10090.ENSMUSP00000063839

Protein family/group databases

MEROPSiM12.210

PTM databases

iPTMnetiO35598
PhosphoSitePlusiO35598
SwissPalmiO35598

Proteomic databases

EPDiO35598
MaxQBiO35598
PaxDbiO35598
PeptideAtlasiO35598
PRIDEiO35598

Protocols and materials databases

DNASUi11487
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000067880; ENSMUSP00000063839; ENSMUSG00000054693
GeneIDi11487
KEGGimmu:11487
UCSCiuc009qor.1 mouse

Organism-specific databases

CTDi102
MGIiMGI:109548 Adam10

Phylogenomic databases

eggNOGiKOG3658 Eukaryota
ENOG410XQWB LUCA
GeneTreeiENSGT00670000097974
HOGENOMiHOG000008148
HOVERGENiHBG050455
InParanoidiO35598
KOiK06704
OMAiEGFIQTH
OrthoDBiEOG091G01J4
TreeFamiTF352021

Enzyme and pathway databases

BRENDAi3.4.24.81 3474
ReactomeiR-MMU-1474228 Degradation of the extracellular matrix
R-MMU-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-MMU-6798695 Neutrophil degranulation
R-MMU-8957275 Post-translational protein phosphorylation
R-MMU-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus

Miscellaneous databases

PROiPR:O35598
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000054693 Expressed in 299 organ(s), highest expression level in pineal body
CleanExiMM_ADAM10
ExpressionAtlasiO35598 baseline and differential
GenevisibleiO35598 MM

Family and domain databases

CDDicd04270 ZnMc_TACE_like, 1 hit
Gene3Di3.40.390.10, 1 hit
4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR034025 ADAM10_ADAM17
IPR027053 ADAM_10
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
PANTHERiPTHR11905:SF4 PTHR11905:SF4, 1 hit
PfamiView protein in Pfam
PF00200 Disintegrin, 1 hit
PF01562 Pep_M12B_propep, 1 hit
SMARTiView protein in SMART
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS50214 DISINTEGRIN_2, 1 hit
PS00142 ZINC_PROTEASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiADA10_MOUSE
AccessioniPrimary (citable) accession number: O35598
Secondary accession number(s): B8JJJ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 174 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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