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Protein

Disintegrin and metalloproteinase domain-containing protein 10

Gene

Adam10

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Cofactori

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

Sites

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

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Notch signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.81. 3474.
ReactomeiR-MMU-1474228. Degradation of the extracellular matrix.
R-MMU-177929. Signaling by EGFR.
R-MMU-1980148. Signaling by NOTCH3.
R-MMU-1980150. Signaling by NOTCH4.
R-MMU-2979096. NOTCH2 Activation and Transmission of Signal to the Nucleus.
R-MMU-3928665. EPH-ephrin mediated repulsion of cells.
R-MMU-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiM12.210.

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 10 (EC:3.4.24.81)
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:109548. Adam10.

Subcellular locationi

Topology

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

GO - Cellular componenti

Complete GO annotation...

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...)Sequence analysis1
Glycosylationi279N-linked (GlcNAc...)1 Publication1
Disulfide bondi345 ↔ 452By similarity
Disulfide bondi400 ↔ 436By similarity
Glycosylationi440N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi485 ↔ 516By similarity
Disulfide bondi504 ↔ 512By similarity
Disulfide bondi525 ↔ 544By similarity
Disulfide bondi531 ↔ 563By similarity
Glycosylationi552N-linked (GlcNAc...)Sequence 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 a furin endopeptidase.By similarity

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.
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 interacations regulate ADAM10 substrate specificity (PubMed:26668317, PubMed:23035126).By similarity3 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi197960. 2 interactors.
IntActiO35598. 1 interactor.
MINTiMINT-4086890.
STRINGi10090.ENSMUSP00000063839.

Structurei

3D structure databases

ProteinModelPortaliO35598.
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 switchBy similarity8
Motifi709 – 716SH3-bindingSequence analysis8
Motifi723 – 729SH3-bindingSequence analysis7

Compositional bias

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

Domaini

The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
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

Sequence similaritiesi

Contains 1 disintegrin domain.PROSITE-ProRule annotation
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

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

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR027053. ADAM_10.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERiPTHR11905:SF4. PTHR11905:SF4. 1 hit.
PfamiPF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
[Graphical view]
SMARTiSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

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.

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi197960. 2 interactors.
IntActiO35598. 1 interactor.
MINTiMINT-4086890.
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-177929. Signaling by EGFR.
R-MMU-1980148. Signaling by NOTCH3.
R-MMU-1980150. Signaling by NOTCH4.
R-MMU-2979096. NOTCH2 Activation and Transmission of Signal to the Nucleus.
R-MMU-3928665. EPH-ephrin mediated repulsion of cells.
R-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

PROiO35598.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000054693.
CleanExiMM_ADAM10.
ExpressionAtlasiO35598. baseline and differential.
GenevisibleiO35598. MM.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR027053. ADAM_10.
IPR001762. Disintegrin_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERiPTHR11905:SF4. PTHR11905:SF4. 1 hit.
PfamiPF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
[Graphical view]
SMARTiSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADA10_MOUSE
AccessioniPrimary (citable) accession number: O35598
Secondary accession number(s): B8JJJ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 158 of the entry and version 2 of the sequence. [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
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.