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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 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).By similarity

Catalytic activityi

Endopeptidase of broad specificity.

Cofactori

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi173 – 1731Zinc; in inhibited formBy similarity
Metal bindingi384 – 3841Zinc; catalytic
Active sitei385 – 3851PROSITE-ProRule annotation
Metal bindingi388 – 3881Zinc; catalytic
Metal bindingi394 – 3941Zinc; catalytic

GO - Molecular functioni

  • endopeptidase activity Source: MGI
  • metalloendopeptidase activity Source: UniProtKB
  • metallopeptidase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • zinc ion binding Source: InterPro

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.
ReactomeiREACT_275864. Degradation of the extracellular matrix.
REACT_279153. Signaling by NOTCH3.
REACT_284350. Signaling by EGFR.
REACT_286692. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_312443. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_313067. Collagen degradation.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_345101. Signaling by NOTCH4.

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
ProteomesiUP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:109548. Adam10.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 673654ExtracellularSequence AnalysisAdd
BLAST
Transmembranei674 – 69421HelicalSequence AnalysisAdd
BLAST
Topological domaini695 – 74955CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence AnalysisAdd
BLAST
Propeptidei20 – 214195By similarityPRO_0000029068Add
BLAST
Chaini215 – 749535Disintegrin and metalloproteinase domain-containing protein 10PRO_0000029069Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi223 ↔ 314By similarity
Glycosylationi268 – 2681N-linked (GlcNAc...)Sequence Analysis
Glycosylationi279 – 2791N-linked (GlcNAc...)1 Publication
Disulfide bondi345 ↔ 452By similarity
Disulfide bondi400 ↔ 436By similarity
Glycosylationi440 – 4401N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi485 ↔ 516By similarity
Disulfide bondi504 ↔ 512By similarity
Disulfide bondi525 ↔ 544By similarity
Disulfide bondi531 ↔ 563By similarity
Glycosylationi552 – 5521N-linked (GlcNAc...)Sequence Analysis
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 residuei720 – 7201PhosphothreonineBy similarity

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

MaxQBiO35598.
PaxDbiO35598.
PRIDEiO35598.

PTM databases

PhosphoSiteiO35598.

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

BgeeiO35598.
CleanExiMM_ADAM10.
ExpressionAtlasiO35598. baseline and differential.
GenevestigatoriO35598.

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. Interacts with NGF in a divalent cation-dependent manner (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi197960. 2 interactions.
IntActiO35598. 1 interaction.
MINTiMINT-4086890.
STRINGi10090.ENSMUSP00000063839.

Structurei

3D structure databases

ProteinModelPortaliO35598.
SMRiO35598. Positions 220-647.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini221 – 457237Peptidase M12BPROSITE-ProRule annotationAdd
BLAST
Domaini458 – 55295DisintegrinPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi171 – 1788Cysteine switchBy similarity
Motifi709 – 7168SH3-bindingSequence Analysis
Motifi723 – 7297SH3-bindingSequence Analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi553 – 673121Cys-richAdd
BLAST

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

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

eggNOGiNOG271989.
GeneTreeiENSGT00670000097974.
HOGENOMiHOG000008148.
HOVERGENiHBG050455.
InParanoidiO35598.
KOiK06704.
OMAiHEDDIKY.
OrthoDBiEOG7SBNNQ.
TreeFamiTF352021.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR027053. ADAM_10.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERiPTHR11905:SF113. PTHR11905:SF113. 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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti591 – 5911D → N in AAC53303 (PubMed:9244301).Curated

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_007399.3.
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_007399.3.
UniGeneiMm.3037.

3D structure databases

ProteinModelPortaliO35598.
SMRiO35598. Positions 220-647.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi197960. 2 interactions.
IntActiO35598. 1 interaction.
MINTiMINT-4086890.
STRINGi10090.ENSMUSP00000063839.

Protein family/group databases

MEROPSiM12.210.

PTM databases

PhosphoSiteiO35598.

Proteomic databases

MaxQBiO35598.
PaxDbiO35598.
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

eggNOGiNOG271989.
GeneTreeiENSGT00670000097974.
HOGENOMiHOG000008148.
HOVERGENiHBG050455.
InParanoidiO35598.
KOiK06704.
OMAiHEDDIKY.
OrthoDBiEOG7SBNNQ.
TreeFamiTF352021.

Enzyme and pathway databases

BRENDAi3.4.24.81. 3474.
ReactomeiREACT_275864. Degradation of the extracellular matrix.
REACT_279153. Signaling by NOTCH3.
REACT_284350. Signaling by EGFR.
REACT_286692. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_312443. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_313067. Collagen degradation.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_345101. Signaling by NOTCH4.

Miscellaneous databases

NextBioi278848.
PROiO35598.
SOURCEiSearch...

Gene expression databases

BgeeiO35598.
CleanExiMM_ADAM10.
ExpressionAtlasiO35598. baseline and differential.
GenevestigatoriO35598.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR027053. ADAM_10.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERiPTHR11905:SF113. PTHR11905:SF113. 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...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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.

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: May 27, 2015
This is version 143 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

External Data

Dasty 3

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 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.