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Q61824 (ADA12_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified November 16, 2011. Version 110. Feed History...

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

Names and origin

Protein namesRecommended name:
Disintegrin and metalloproteinase domain-containing protein 12
Short name=ADAM 12
EC=3.4.24.-
Alternative name(s):
Meltrin-alpha
Gene names
Name:Adam12
Synonyms:Mltna
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length903 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Interacts with FST3. Interacts with GNB2L1/RACK1; the interaction is required for PKC-dependent translocation of ADAM12 to the cell membrane By similarity. Ref.3

Subcellular location

Membrane; Single-pass type I membrane protein.

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ACTN2P356093EBI-77785,EBI-77797From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Propeptide32 – 205174 By similarity
PRO_0000029080
Chain206 – 903698Disintegrin and metalloproteinase domain-containing protein 12
PRO_0000029081

Regions

Topological domain206 – 706501Extracellular Potential
Transmembrane707 – 72721Helical; Potential
Topological domain728 – 903176Cytoplasmic Potential
Domain212 – 414203Peptidase M12B
Domain422 – 50887Disintegrin
Domain654 – 68633EGF-like
Motif175 – 1828Cysteine switch By similarity
Motif824 – 8307SH3-binding; class II
Motif830 – 8378SH3-binding; class I
Motif846 – 8527SH3-binding; class II
Motif852 – 8587SH3-binding; class I
Motif881 – 8877SH3-binding; class I
Compositional bias509 – 653145Cys-rich

Sites

Active site3491 By similarity
Metal binding1771Zinc; in inhibited form By similarity
Metal binding3481Zinc; catalytic By similarity
Metal binding3521Zinc; catalytic By similarity
Metal binding3581Zinc; catalytic By similarity

Amino acid modifications

Modified residue9011Phosphotyrosine; by SRC
Glycosylation1121N-linked (GlcNAc...) Potential
Glycosylation1471N-linked (GlcNAc...) Potential
Glycosylation1571N-linked (GlcNAc...) Potential
Glycosylation1821N-linked (GlcNAc...) Potential
Glycosylation1851N-linked (GlcNAc...) Potential
Glycosylation4501N-linked (GlcNAc...) Potential
Glycosylation6491N-linked (GlcNAc...) Potential
Disulfide bond323 ↔ 409 By similarity
Disulfide bond365 ↔ 393 By similarity
Disulfide bond367 ↔ 376 By similarity
Disulfide bond480 ↔ 500 By similarity
Disulfide bond658 ↔ 668 By similarity
Disulfide bond662 ↔ 674 By similarity
Disulfide bond676 ↔ 685 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q61824 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6EB0208D2023DCE3

FASTA90398,601
        10         20         30         40         50         60 
MAERPARRAP PARALLLALA GALLAPRAAR GMSLWDQRGA YEVARASLLS KDPGIPGQSI 

        70         80         90        100        110        120 
PAKDHPDVLT VQLQLESRDL ILSLERNEGL IANGFTETHY LQDGTDVSLT RNHTDHCYYH 

       130        140        150        160        170        180 
GHVQGDAASV VSLSTCSDLR GLIMFENKTY SLEPMKNTTD SYKLVPAESM TNIQGLCGSQ 

       190        200        210        220        230        240 
HNKSNLTMED VSPGTSQMRA RRHKRETLKM TKYVELVIVA DNREFQRQGK DLEKVKQRLI 

       250        260        270        280        290        300 
EIANHVDKFY RPLNIRIVLV GVEVWNDIDK CSISQDPFTR LHEFLDWRKI KLLPRKSHDN 

       310        320        330        340        350        360 
AQLISGVYFQ GTTIGMAPIM SMCTAEQSGG VVMDHSDSPL GAAVTLAHEL GHNFGMNHDT 

       370        380        390        400        410        420 
LERGCSCRMA AEKGGCIMNP STGFPFPMVF SSCSRKDLEA SLEKGMGMCL FNLPEVKQAF 

       430        440        450        460        470        480 
GGRKCGNGYV EEGEECDCGE PEECTNRCCN ATTCTLKPDA VCAHGQCCED CQLKPPGTAC 

       490        500        510        520        530        540 
RGSSNSCDLP EFCTGTAPHC PANVYLHDGH PCQGVDGYCY NGICQTHEQQ CVTLWGPGAK 

       550        560        570        580        590        600 
PAPGICFERV NSAGDPYGNC GKDSKSAFAK CELRDAKCGK IQCQGGASRP VIGTNAVSIE 

       610        620        630        640        650        660 
TNIPQQEGGR ILCRGTHVYL GDDMPDPGLV LAGTKCAEGK ICLNRRCQNI SVFGVHKCAM 

       670        680        690        700        710        720 
QCHGRGVCNN RKNCHCEAHW APPFCDKFGF GGSTDSGPIR QADNQGLTVG ILVSILCLLA 

       730        740        750        760        770        780 
AGFVVYLKRK TLMRLLFTHK KTTMEKLRCV HPSRTPSGPH LGQAHHTPGK GLLMNRAPHF 

       790        800        810        820        830        840 
NTPKDRHSLK CQNMDISRPL DARAVPQLQS PQRVLLPLHQ TPRAPSGPAR PLPASPAVRQ 

       850        860        870        880        890        900 
AQGIRKPSPP QKPLPADPLS RTSRLTSALV RTPGQQEPGH RPAPIRPAPK HQVPRPSHNA 


YIK

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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

EMBL
GenBank
DDBJ		D50411 mRNA. Translation: BAA08912.1.
IPIIPI00126140.
PIRS60257.
RefSeqNP_031426.2. NM_007400.2.
UniGeneMm.439714.

3D structure databases

ProteinModelPortalQ61824.
SMRQ61824. Positions 206-691.
ModBaseSearch...

Protein-protein interaction databases

IntActQ61824. 1 interaction.
MINTMINT-154663.
STRINGQ61824.

Protein family/group databases

MEROPSM12.212.

PTM databases

PhosphoSiteQ61824.

Proteomic databases

PRIDEQ61824.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID11489.
KEGGmmu:11489.
UCSCuc009kdo.1. mouse.

Organism-specific databases

CTD8038.
MGIMGI:105378. Adam12.

Phylogenomic databases

GeneTreeENSGT00590000082827.
HOGENOMHBG507118.
HOVERGENHBG006978.
InParanoidQ61824.
OrthoDBEOG42JNQX.

Enzyme and pathway databases

ReactomeREACT_115202. Signal Transduction.

Gene expression databases

ArrayExpressQ61824.
BgeeQ61824.
GenevestigatorQ61824.
GermOnlineENSMUSG00000054555. Mus musculus.

Family and domain databases

InterProIPR006586. ADAM_Cys-rich.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR000742. EGF_3.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
Gene3DG3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.
G3DSA:3.40.390.10. G3DSA:3.40.390.10. 1 hit.
KOK06835.
PfamPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSPR00289. DISINTEGRIN.
SMARTSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMSSF57552. Disintegrin. 1 hit.
PROSITEPS50215. 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]
ProtoNetSearch...

Other

NextBio278856.
SOURCESearch...

Entry information

Entry nameADA12_MOUSE
AccessionPrimary (citable) accession number: Q61824
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: November 1, 1996
Last modified: November 16, 2011
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents