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Protein

Disintegrin and metalloproteinase domain-containing protein 10

Gene

ADAM10

Organism
Bos taurus (Bovine)
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 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). 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 similarity1 Publication

Catalytic activityi

Endopeptidase of broad specificity.

Cofactori

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi173 – 1731Zinc; in inhibited formBy similarity
Metal bindingi383 – 3831Zinc; catalyticBy similarity
Active sitei384 – 38411 Publication
Metal bindingi387 – 3871Zinc; catalyticBy similarity
Metal bindingi393 – 3931Zinc; catalyticBy similarity

GO - Molecular functioni

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

ReactomeiR-BTA-1474228. Degradation of the extracellular matrix.
R-BTA-1980148. Signaling by NOTCH3.
R-BTA-1980150. Signaling by NOTCH4.
R-BTA-3928665. EPH-ephrin mediated repulsion of cells.

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
Myelin-associated metalloproteinase
CD_antigen: CD156c
Gene namesi
Name:ADAM10
Synonyms:MADM
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 10

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 672653ExtracellularSequence analysisAdd
BLAST
Transmembranei673 – 69624HelicalSequence analysisAdd
BLAST
Topological domaini697 – 74852CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi384 – 3841E → A: Decreased stimulated and constitutive secretion of APP. 1 Publication
Mutagenesisi573 – 5731E → A: Abrogates EFNA5 cleavage; when associated with Ala-578 and 579. 1 Publication
Mutagenesisi578 – 5781E → A: Abrogates EFNA5 cleavage; when associated with Ala-573 and 579. 1 Publication
Mutagenesisi579 – 5791E → A: Abrogates EFNA5 cleavage; when associated with Ala-573 and 578. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Propeptidei20 – 2131941 PublicationPRO_0000029064Add
BLAST
Chaini214 – 748535Disintegrin and metalloproteinase domain-containing protein 10PRO_0000029065Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi222 ↔ 313By similarity
Glycosylationi267 – 2671N-linked (GlcNAc...)Sequence analysis
Glycosylationi278 – 2781N-linked (GlcNAc...)Sequence analysis
Disulfide bondi344 ↔ 451By similarity
Disulfide bondi399 ↔ 435By similarity
Glycosylationi439 – 4391N-linked (GlcNAc...)Sequence analysis
Disulfide bondi484 ↔ 5151 Publication
Disulfide bondi503 ↔ 5111 Publication
Disulfide bondi524 ↔ 5431 Publication
Disulfide bondi530 ↔ 5621 Publication
Glycosylationi551 – 5511N-linked (GlcNAc...)Sequence analysis
Disulfide bondi555 ↔ 5671 Publication
Disulfide bondi572 ↔ 5981 Publication
Disulfide bondi580 ↔ 6071 Publication
Disulfide bondi582 ↔ 5971 Publication
Disulfide bondi594 ↔ 6391 Publication
Disulfide bondi632 ↔ 6451 Publication
Modified residuei719 – 7191PhosphothreonineBy 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

PaxDbiQ10741.
PRIDEiQ10741.

Expressioni

Tissue specificityi

Expressed at low level in kidney, spleen, lung, adrenal, heart and peripheral nerve.

Inductioni

By interleukin-1 alpha in nasal cartilage.

Interactioni

Subunit structurei

Interacts with EPHA2 (By similarity). Constitutively associates with EphA3. 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. Interacts with NGF in a divalent cation-dependent manner (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-48422N.
STRINGi9913.ENSBTAP00000042110.

Structurei

Secondary structure

1
748
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi505 – 5073Combined sources
Beta strandi523 – 5253Combined sources
Beta strandi529 – 5313Combined sources
Turni556 – 5594Combined sources
Beta strandi560 – 56910Combined sources
Helixi571 – 5755Combined sources
Beta strandi578 – 5803Combined sources
Helixi592 – 5943Combined sources
Beta strandi597 – 5993Combined sources
Helixi604 – 6063Combined sources
Helixi616 – 6194Combined sources
Turni633 – 6364Combined sources
Beta strandi637 – 6393Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2AO7X-ray2.90A455-646[»]
ProteinModelPortaliQ10741.
SMRiQ10741. Positions 483-646.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ10741.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini220 – 456237Peptidase M12BPROSITE-ProRule annotationAdd
BLAST
Domaini457 – 55195DisintegrinPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi171 – 1788Cysteine switchBy similarity
Motifi708 – 7158SH3-bindingSequence analysis
Motifi722 – 7287SH3-bindingSequence analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi555 – 59541Cys-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.

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.
InParanoidiQ10741.
KOiK06704.
OMAiEGFIQTH.
OrthoDBiEOG7SBNNQ.
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.

Q10741-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLLRVLILL LSWVAGLGGQ YGNPLNKYIR HYEGLSYDVD SLHQKHQRAK
60 70 80 90 100
RAVSHEDQFL RLDFHAHGRH FNLRMKRDTS LFSEEFRVET SNAVLDYDTS
110 120 130 140 150
HIYTGHIYGE EGSFSHGSVI DGRFEGFIQT HGGTFYVEPA ERYIKDRTLP
160 170 180 190 200
FHSVIYHEDD IKYPHKYGPQ GGCADHSVFE RMRKYQMTGV EEVTQTPQEK
210 220 230 240 250
HAINGPELLR KKRTTVAEKN TCQLYIQTDH LFFKYYGTRE AVIAQISSHV
260 270 280 290 300
KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF
310 320 330 340 350
LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY
360 370 380 390 400
SDGKKKSLNT GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT
410 420 430 440 450
PGESKNLGQK ENGNYIMYAR ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN
460 470 480 490 500
CFVESGQPIC GNGMVEQGEE CDCGYSDQCK DECCYDANQP EGKKCKLKPG
510 520 530 540 550
KQCSPSQGPC CTAHCAFKSK TEKCRDDSDC AKEGICNGIT ALCPASDPKP
560 570 580 590 600
NFTDCNRHTQ VCINGQCAGS ICEKHGLEEC TCASSDGKDD KELCHVCCMK
610 620 630 640 650
KMEPSTCAST GSVQWNKYFL GRTITLQPGS PCNDFRGYCD VFMRCRLVDA
660 670 680 690 700
DGPLARLKKA IFSPELYENI AEWIVAYWWA VLLMGIALIM LMAGFIKICS
710 720 730 740
VHTPSSNPKL PPPKPLPGTL KRRRPPQPIQ QPQRQRPRES YQMGHMRR
Length:748
Mass (Da):84,188
Last modified:November 1, 1996 - v1
Checksum:i202E29830611F9E1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z21961 mRNA. Translation: CAA79973.1.
BC153863 mRNA. Translation: AAI53864.1.
PIRiS66129.
RefSeqiNP_776921.1. NM_174496.2.
UniGeneiBt.49218.

Genome annotation databases

EnsembliENSBTAT00000044627; ENSBTAP00000042110; ENSBTAG00000005481.
GeneIDi282132.
KEGGibta:282132.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z21961 mRNA. Translation: CAA79973.1.
BC153863 mRNA. Translation: AAI53864.1.
PIRiS66129.
RefSeqiNP_776921.1. NM_174496.2.
UniGeneiBt.49218.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2AO7X-ray2.90A455-646[»]
ProteinModelPortaliQ10741.
SMRiQ10741. Positions 483-646.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-48422N.
STRINGi9913.ENSBTAP00000042110.

Protein family/group databases

MEROPSiM12.210.

Proteomic databases

PaxDbiQ10741.
PRIDEiQ10741.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000044627; ENSBTAP00000042110; ENSBTAG00000005481.
GeneIDi282132.
KEGGibta:282132.

Organism-specific databases

CTDi102.

Phylogenomic databases

eggNOGiKOG3658. Eukaryota.
ENOG410XQWB. LUCA.
GeneTreeiENSGT00670000097974.
HOGENOMiHOG000008148.
HOVERGENiHBG050455.
InParanoidiQ10741.
KOiK06704.
OMAiEGFIQTH.
OrthoDBiEOG7SBNNQ.
TreeFamiTF352021.

Enzyme and pathway databases

ReactomeiR-BTA-1474228. Degradation of the extracellular matrix.
R-BTA-1980148. Signaling by NOTCH3.
R-BTA-1980150. Signaling by NOTCH4.
R-BTA-3928665. EPH-ephrin mediated repulsion of cells.

Miscellaneous databases

EvolutionaryTraceiQ10741.
NextBioi20805967.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types."
    Howard L., Mitchell S., Lu X., Griffiths S., Glynn P.
    Biochem. J. 317:45-50(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease."
    Lammich S., Kojro E., Postina R., Gilbert S., Pfeiffer R., Jasionowski M., Haass C., Fahrenholz F.
    Proc. Natl. Acad. Sci. U.S.A. 96:3922-3927(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 214-233, FUNCTION, ACTIVE SITE, MUTAGENESIS OF GLU-384.
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Basal ganglia.
  4. "Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans."
    Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H., Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B.
    Cell 123:291-304(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 455-646, DISULFIDE BONDS, SUBUNIT, MUTAGENESIS OF GLU-573; GLU-578 AND GLU-579.

Entry informationi

Entry nameiADA10_BOVIN
AccessioniPrimary (citable) accession number: Q10741
Secondary accession number(s): A8E663
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1996
Last modified: February 17, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.