Reviewed,
UniProtKB/Swiss-Prot Q61824 (ADA12_MOUSE)
Last modified
June 16, 2009.
Version 88.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Disintegrin and metalloproteinase domain-containing protein 12 Short name=ADAM 12 EC=3.4.24.- Alternative name(s): Meltrin-alpha | ||||
| Gene names |
| ||||
| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 903 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Involved in skeletal muscle regeneration, specifically at the onset of cell fusion. Also involved in macrophage-derived giant cells (MGC) and osteoclast formation from mononuclear precursors. |
| Cofactor | Binds 1 zinc ion per subunit By similarity. |
| Subunit structure | Interacts with alpha-actinin-2 and with syndecans. Interacts with SH3PXD2A By similarity. |
| Subcellular location | |
| Tissue specificity | Expressed during early developing mesenchymal cells that give rise to skeletal muscle, bones and visceral organs. Not expressed in adult normal muscle but expressed in regenerating muscle. Ref.2 |
| Induction | At the onset of myoblast fusion. |
| Domain | The first 30 amino acids of the cytoplasmic domain contain a major binding site to alpha-actinin-2. This interaction is necessary to promote muscle cell fusion. The cysteine-rich domain supports cell adhesion through syndecans and triggers signaling events that lead to beta-1 integrin-dependent cell spreading. In carcinoma cells the binding of this domain to syndecans does not allow the integrin-mediated cell spreading By similarity. 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. |
| Post-translational modification | The precursor is cleaved by a furin endopeptidase By similarity. |
| Miscellaneous | Marker of skeletal muscle regeneration. |
| Sequence similarities | Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Cell adhesion |
| Cellular component | Membrane |
| Domain | EGF-like domain SH3-binding Signal Transmembrane |
| Ligand | Metal-binding Zinc |
| Molecular function | Hydrolase Metalloprotease Protease |
| PTM | Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein Zymogen |
| Gene Ontology (GO) | |
| Biological process | cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW proteolysisInferred from electronic annotation. Source: InterPro |
| Cellular component | integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membraneInferred from Experiment. Source: Reactome |
| Molecular function | SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activityInferred from electronic annotation. Source: InterPro zinc ion bindingInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| ACTN2 | P35609 | 2 | EBI-77785,EBI-77797 | From a different organism. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 31 | 31 | Potential | ||||||||
| Propeptide | 32 – 205 | 174 | By similarity | PRO_0000029080 | |||||||
| Chain | 206 – 903 | 698 | Disintegrin and metalloproteinase domain-containing protein 12 | PRO_0000029081 | |||||||
Regions | |||||||||||
| Topological domain | 206 – 706 | 501 | Extracellular Potential | ||||||||
| Transmembrane | 707 – 727 | 21 | Potential | ||||||||
| Topological domain | 728 – 903 | 176 | Cytoplasmic Potential | ||||||||
| Domain | 212 – 414 | 203 | Peptidase M12B | ||||||||
| Domain | 422 – 508 | 87 | Disintegrin | ||||||||
| Domain | 654 – 686 | 33 | EGF-like | ||||||||
| Motif | 175 – 182 | 8 | Cysteine switch By similarity | ||||||||
| Motif | 824 – 830 | 7 | SH3-binding; class II | ||||||||
| Motif | 830 – 837 | 8 | SH3-binding; class I | ||||||||
| Motif | 846 – 852 | 7 | SH3-binding; class II | ||||||||
| Motif | 852 – 858 | 7 | SH3-binding; class I | ||||||||
| Motif | 881 – 887 | 7 | SH3-binding; class I | ||||||||
| Compositional bias | 509 – 653 | 145 | Cys-rich | ||||||||
Sites | |||||||||||
| Active site | 349 | 1 | By similarity | ||||||||
| Metal binding | 177 | 1 | Zinc; in inhibited form By similarity | ||||||||
| Metal binding | 348 | 1 | Zinc; catalytic By similarity | ||||||||
| Metal binding | 352 | 1 | Zinc; catalytic By similarity | ||||||||
| Metal binding | 358 | 1 | Zinc; catalytic By similarity | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 901 | 1 | Phosphotyrosine; by SRC | ||||||||
| Glycosylation | 112 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 147 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 157 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 182 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 185 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 450 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 649 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Disulfide bond | 323 ↔ 409 | By similarity | |||||||||
| Disulfide bond | 365 ↔ 393 | By similarity | |||||||||
| Disulfide bond | 367 ↔ 376 | By similarity | |||||||||
| Disulfide bond | 480 ↔ 500 | By similarity | |||||||||
| Disulfide bond | 658 ↔ 668 | By similarity | |||||||||
| Disulfide bond | 662 ↔ 674 | By similarity | |||||||||
| Disulfide bond | 676 ↔ 685 | By similarity | |||||||||
Sequences
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References
| [1] | "A metalloprotease-disintegrin participating in myoblast fusion." Yagami-Hiromasa T., Sato T., Kurisaki T., Kamijo K., Nabeshima Y., Fujisawa-Sehara A. Nature 377:652-656(1995) [PubMed: 7566181] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Embryonic fibroblast. |
| [2] | "Spatially- and temporally-restricted expression of meltrin alpha (ADAM12) and beta (ADAM19) in mouse embryo." Kurisaki T., Masuda A., Osumi N., Nabeshima Y., Fujisawa-Sehara A. Mech. Dev. 73:211-215(1998) [PubMed: 9622634] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [3] | "Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha-actinin-2, is required for myoblast fusion." Galliano M.-F., Huet C., Frygelius J., Polgren A., Wewer U.M., Engvall E. J. Biol. Chem. 275:13933-13939(2000) [PubMed: 10788519] [Abstract] Cited for: INTERACTION WITH ALPHA-ACTININ-2. |
| [4] | "Meltrin alpha cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src." Suzuki A., Kadota N., Hara T., Nakagami Y., Izumi T., Takenawa T., Sabe H., Endo T. Oncogene 19:5842-5850(2000) [PubMed: 11127814] [Abstract] Cited for: PHOSPHORYLATION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| D50411 mRNA. Translation: BAA08912.1. | |
| IPI | IPI00126140. |
| PIR | S60257. |
| RefSeq | NP_031426.2. |
| UniGene | Mm.439714 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1FVL based on UniProtKB P18619. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q61824. 1 interaction. |
Protein family/group databases | |
| MEROPS | M12.212. |
PTM databases | |
| PhosphoSite | Q61824. |
Proteomic databases | |
| PRIDE | Q61824. |
Genome annotation databases | |
| Ensembl | ENSMUSG00000054555. Mus musculus. [Contig view] |
| GeneID | 11489. |
| KEGG | mmu:11489. |
Organism-specific databases | |
| MGI | MGI:105378. Adam12. |
Phylogenomic databases | |
| HOGENOM | Q61824. |
| HOVERGEN | Q61824. |
Gene expression databases | |
| ArrayExpress | Q61824. |
| Bgee | Q61824. |
| GermOnline | ENSMUSG00000054555. Mus musculus. |
Family and domain databases | |
| InterPro | IPR006586. ADAM_Cys-rich. IPR001762. Blood-coag_inhib_Disintegrin. IPR018358. Disintegrin_CS. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR013111. EGF_extracell. IPR001818. Pept_M10A_M12B. IPR006025. Pept_M_Zn_BS. IPR001590. Peptidase_M12B. IPR002870. Peptidase_M12B_N. [Graphical view] |
| Gene3D | G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit. |
| Pfam | PF08516. ADAM_CR. 1 hit. PF00200. Disintegrin. 1 hit. PF07974. EGF_2. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF01421. Reprolysin. 1 hit. [Graphical view] |
| PRINTS | PR00289. DISINTEGRIN. |
| ProDom | PD000664. Disintegrin. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00608. ACR. 1 hit. SM00050. DISIN. 1 hit. [Graphical view] |
| PROSITE | PS50215. ADAM_MEPRO. 1 hit. PS00546. CYSTEINE_SWITCH. False negative. PS00427. DISINTEGRIN_1. 1 hit. PS50214. DISINTEGRIN_2. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. False negative. PS50026. EGF_3. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 278856. |
| SOURCE | Search... |
Entry information
| Entry name | ADA12_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q61824 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with


