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O35598 (ADA10_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Disintegrin and metalloproteinase domain-containing protein 10

Short name=ADAM 10
EC=3.4.24.81
Alternative name(s):
Kuzbanian protein homolog
Mammalian disintegrin-metalloprotease
CD_antigen=CD156c
Gene names
Name:Adam10
Synonyms:Kuz, Madm
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length749 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) at '687-Lys-|-Leu-688'. 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. 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 By similarity.

Catalytic activity

Endopeptidase of broad specificity.

Cofactor

Binds 1 zinc ion By similarity.

Subunit structure

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. Ref.5

Subcellular location

Membrane; Single-pass type I membrane protein.

Developmental stage

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

Domain

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.

Post-translational modification

The precursor is cleaved by a furin endopeptidase By similarity.

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 peptidase M12B domain.

Ontologies

Keywords
   Biological processNotch signaling pathway
   Cellular componentMembrane
   DomainSH3-binding
Signal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Zymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch receptor processing

Non-traceable author statement PubMed 12354787. Source: UniProtKB

Notch signaling pathway

Inferred from mutant phenotype PubMed 12354787. Source: UniProtKB

PMA-inducible membrane protein ectodomain proteolysis

Inferred from electronic annotation. Source: Ensembl

constitutive protein ectodomain proteolysis

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from mutant phenotype PubMed 12354787. Source: UniProtKB

membrane protein ectodomain proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

monocyte activation

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

nucleocytoplasmic transport

Non-traceable author statement PubMed 12176995. Source: UniProtKB

positive regulation of T cell chemotaxis

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay PubMed 12176995. Source: UniProtKB

response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

Golgi-associated vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 12176995. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from direct assay PubMed 12176995. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic density

Inferred from direct assay PubMed 17301176. Source: MGI

   Molecular_functionSH2 domain binding

Non-traceable author statement PubMed 12176995. Source: UniProtKB

endopeptidase activity

Inferred from direct assay PubMed 12794186. Source: MGI

metalloendopeptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

metallopeptidase activity

Inferred from mutant phenotype PubMed 12354787. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12176995. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction PubMed 12176995. Source: UniProtKB

protein kinase binding

Inferred from direct assay PubMed 12176995. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Propeptide20 – 214195 By similarity
PRO_0000029068
Chain215 – 749535Disintegrin and metalloproteinase domain-containing protein 10
PRO_0000029069

Regions

Topological domain20 – 673654Extracellular Potential
Transmembrane674 – 69421Helical; Potential
Topological domain695 – 74955Cytoplasmic Potential
Domain221 – 457237Peptidase M12B
Domain458 – 55295Disintegrin
Motif171 – 1788Cysteine switch By similarity
Motif709 – 7168SH3-binding Potential
Motif723 – 7297SH3-binding Potential
Compositional bias553 – 673121Cys-rich

Sites

Active site3851 By similarity
Metal binding1731Zinc; in inhibited form By similarity
Metal binding3841Zinc; catalytic
Metal binding3881Zinc; catalytic
Metal binding3941Zinc; catalytic

Amino acid modifications

Glycosylation2681N-linked (GlcNAc...) Potential
Glycosylation2791N-linked (GlcNAc...) Ref.6
Glycosylation4401N-linked (GlcNAc...) Potential
Glycosylation5521N-linked (GlcNAc...) Potential
Disulfide bond223 ↔ 314 By similarity
Disulfide bond345 ↔ 452 By similarity
Disulfide bond400 ↔ 436 By similarity
Disulfide bond485 ↔ 516 By similarity
Disulfide bond504 ↔ 512 By similarity
Disulfide bond525 ↔ 544 By similarity
Disulfide bond531 ↔ 563 By similarity
Disulfide bond556 ↔ 568 By similarity
Disulfide bond573 ↔ 599 By similarity
Disulfide bond581 ↔ 608 By similarity
Disulfide bond583 ↔ 598 By similarity
Disulfide bond595 ↔ 640 By similarity
Disulfide bond633 ↔ 646 By similarity

Experimental info

Sequence conflict5911D → N in AAC53303. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O35598 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 6AA2230B2251ABDA

FASTA74983,968
        10         20         30         40         50         60 
MVLPTVLILL LSWAAGLGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK RAVSHEDQFL 

        70         80         90        100        110        120 
LLDFHAHGRQ FNLRMKRDTS LFSDEFKVET SNKVLDYDTS HIYTGHIYGE EGSFSHGSVI 

       130        140        150        160        170        180 
DGRFEGFIKT RGGTFYIEPA ERYIKDRILP FHSVIYHEDD INYPHKYGPQ GGCADHSVFE 

       190        200        210        220        230        240 
RMRKYQMTGV EEGARAHPEK HAASSGPELL RKKRTTLAER NTCQLYIQTD HLFFKYYGTR 

       250        260        270        280        290        300 
EAVIAQISSH VKAIDTIYQT TDFSGIRNIS FMVKRIRINT TSDEKDPTNP FRFPNIGVEK 

       310        320        330        340        350        360 
FLELNSEQNH DDYCLAYVFT DRDFDDGVLG LAWVGAPSGS SGGICEKSKL YSDGKKKSLN 

       370        380        390        400        410        420 
TGIITVQNYG SHVPPKVSHI TFAHEVGHNF GSPHDSGTEC TPGESKNLGQ KENGNYIMYA 

       430        440        450        460        470        480 
RATSGDKLNN NKFSLCSIRN ISQVLEKKRN NCFVESGQPI CGNGMVEQGE ECDCGYSDQC 

       490        500        510        520        530        540 
KDDCCFDANQ PEGKKCKLKP GKQCSPSQGP CCTAQCAFKS KSEKCRDDSD CAKEGICNGF 

       550        560        570        580        590        600 
TALCPASDPK PNFTDCNRHT QVCINGQCAG SICEKYDLEE CTCASSDGKD DKELCHVCCM 

       610        620        630        640        650        660 
KKMAPSTCAS TGSLQWSKQF SGRTITLQPG SPCNDFRGYC DVFMRCRLVD ADGPLARLKK 

       670        680        690        700        710        720 
AIFSPQLYEN IAEWIVAHWW AVLLMGIALI MLMAGFIKIC SVHTPSSNPK LPPPKPLPGT 

       730        740 
LKRRRPPQPI QQPPRQRPRE SYQMGHMRR 

« Hide

References

« Hide 'large scale' references
[1]"Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis."
Pan D., Rubin G.M.
Cell 90:271-280(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 252-749.
Strain: C57BL/6J.
Tissue: Bone and Vagina.
[5]"Regulated cleavage of a contact-mediated axon repellent."
Hattori M., Osterfield M., Flanagan J.G.
Science 289:1360-1365(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPHA2.
[6]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-279.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS23323.1.
RefSeqNP_031425.2. NM_007399.3.
UniGeneMm.3037.

3D structure databases

ProteinModelPortalO35598.
SMRO35598. Positions 220-647.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid197960. 2 interactions.
IntActO35598. 1 interaction.
MINTMINT-4086890.
STRING10090.ENSMUSP00000063839.

Protein family/group databases

MEROPSM12.210.

PTM databases

PhosphoSiteO35598.

Proteomic databases

MaxQBO35598.
PaxDbO35598.
PRIDEO35598.

Protocols and materials databases

DNASU11487.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000067880; ENSMUSP00000063839; ENSMUSG00000054693.
GeneID11487.
KEGGmmu:11487.
UCSCuc009qor.1. mouse.

Organism-specific databases

CTD102.
MGIMGI:109548. Adam10.

Phylogenomic databases

eggNOGNOG271989.
GeneTreeENSGT00670000097974.
HOGENOMHOG000008148.
HOVERGENHBG050455.
InParanoidO35598.
KOK06704.
OMAHEDDIKY.
OrthoDBEOG7SBNNQ.
TreeFamTF352021.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.
REACT_189085. Disease.

Gene expression databases

ArrayExpressO35598.
BgeeO35598.
CleanExMM_ADAM10.
GenevestigatorO35598.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProIPR027053. ADAM_10.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERPTHR11905:SF113. PTHR11905:SF113. 1 hit.
PfamPF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
[Graphical view]
SMARTSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMSSF57552. SSF57552. 1 hit.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio278848.
PROO35598.
SOURCESearch...

Entry information

Entry nameADA10_MOUSE
AccessionPrimary (citable) accession number: O35598
Secondary accession number(s): B8JJJ0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot