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Q10743 (ADA10_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:Madm
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length544 AA.
Sequence statusFragment.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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. 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.

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. Interacts with EPHA2, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Expressed in brain, kidney, lung, spleen, ovary and testis.

Domain

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
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 signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

in utero embryonic development

Inferred from sequence or structural similarity. Source: UniProtKB

membrane protein ectodomain proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of osteoclast differentiation

Non-traceable author statement PubMed 10423016. Source: RGD

   Cellular_componentGolgi-associated vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface

Inferred from sequence or structural similarity. Source: UniProtKB

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 10423016. Source: RGD

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

trans-Golgi network

Inferred from direct assay PubMed 10423016. Source: RGD

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

metalloendopeptidase activity

Inferred from direct assay PubMed 10423016. Source: RGD

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide‹1 – 9›9 Potential
PRO_0000029070
Chain10 – 544535Disintegrin and metalloproteinase domain-containing protein 10
PRO_0000029071

Regions

Topological domain10 – 468459Extracellular Potential
Transmembrane469 – 49224Helical; Potential
Topological domain493 – 54452Cytoplasmic Potential
Domain16 – 252237Peptidase M12B
Domain253 – 34795Disintegrin
Motif504 – 5118SH3-binding Potential
Motif518 – 5247SH3-binding Potential
Compositional bias347 – 468122Cys-rich

Sites

Active site1801 By similarity
Metal binding1791Zinc; catalytic By similarity
Metal binding1831Zinc; catalytic By similarity
Metal binding1891Zinc; catalytic By similarity

Amino acid modifications

Glycosylation631N-linked (GlcNAc...) Potential
Glycosylation741N-linked (GlcNAc...) Potential
Glycosylation2351N-linked (GlcNAc...) Potential
Glycosylation3471N-linked (GlcNAc...) Potential
Disulfide bond18 ↔ 109 By similarity
Disulfide bond140 ↔ 247 By similarity
Disulfide bond195 ↔ 231 By similarity
Disulfide bond280 ↔ 311 By similarity
Disulfide bond299 ↔ 307 By similarity
Disulfide bond320 ↔ 339 By similarity
Disulfide bond326 ↔ 358 By similarity
Disulfide bond351 ↔ 363 By similarity
Disulfide bond368 ↔ 394 By similarity
Disulfide bond376 ↔ 403 By similarity
Disulfide bond378 ↔ 393 By similarity
Disulfide bond390 ↔ 435 By similarity
Disulfide bond428 ↔ 441 By similarity

Experimental info

Non-terminal residue11

Sequences

Sequence LengthMass (Da)Tools
Q10743 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: F75E0E8D6C88A7DD

FASTA54460,445
        10         20         30         40         50         60 
GPELLRKKRT TLPERNTCQL YIQTDHLFFK SYGTREAVIA QISSHVKAID AIYQTTDFSG 

        70         80         90        100        110        120 
IRNISFMVKR IRINTTSDEK DPTNPFRFPN IGVEKFLELN SEQNHDDYCL AYVFTDRDFD 

       130        140        150        160        170        180 
DGVLGLAWVG APSGSSGGIC EKSKLYSDGK KKSLNTGIIT VQNYGSHVPP KVSHITFAHE 

       190        200        210        220        230        240 
VGHNFGSPHD SGTECTPGES KNLGQKENGN YIMYARATSG DKLNNNKFSL CSIRNISQVL 

       250        260        270        280        290        300 
EKKRNNCFVE SGQPICGNGM VEQGEECDCG YSDQCKDECC FDANQPEGKK CKLKPGKQCS 

       310        320        330        340        350        360 
PSQGPCCTAQ CAFKSKSEKC RDDSDCAKEG ICNGFTALCP ASDPKPNFTD CNRHTQVCIN 

       370        380        390        400        410        420 
GQCAGSICEK YDLEECTCAS SDGKDDKELC HVCCMKKMAP STCASTGSLQ WNKQFTGRTI 

       430        440        450        460        470        480 
TLQPGSPCND FRGYCDVFMR CRLVDADGPL ARLKKAIFSP QLYENIAEWI VAHWWAVLLM 

       490        500        510        520        530        540 
GIALIMLMAG FIKICSVHTP SSNPKLPPPK PLPGTLKRRR PPQPIQQPQR QRPRESYQMG 


HMRR 

« Hide

References

[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].
Strain: Sprague-Dawley.
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z48444 mRNA. Translation: CAA88359.1.
IPIIPI01016310.
PIRS52477.
UniGeneRn.42924.

3D structure databases

ProteinModelPortalQ10743.
SMRQ10743. Positions 292-442.
ModBaseSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000021066.

Protein family/group databases

MEROPSM12.210.

Proteomic databases

PaxDbQ10743.
PRIDEQ10743.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:2032. rat.

Organism-specific databases

RGD2032. Adam10.

Phylogenomic databases

eggNOGNOG271989.
HOVERGENHBG050455.
InParanoidQ10743.

Gene expression databases

GenevestigatorQ10743.
GermOnlineENSRNOG00000015038. Rattus norvegicus.

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.
[Graphical view]
PANTHERPTHR11905:SF4. PTHR11905:SF4. 1 hit.
PfamPF00200. Disintegrin. 1 hit.
[Graphical view]
SMARTSM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMSSF57552. Disintegrin. 1 hit.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS00546. CYSTEINE_SWITCH. False negative.
PS00427. DISINTEGRIN_1. False negative.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameADA10_RAT
AccessionPrimary (citable) accession number: Q10743
Entry history
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1996
Last modified: April 3, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Recent format changes

Overview of recent format changes

Recent format changes (XML)

Overview of recent format changes in the XML format

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families