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Q61824

- ADA12_MOUSE

UniProt

Q61824 - ADA12_MOUSE

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Protein
Disintegrin and metalloproteinase domain-containing protein 12
Gene
Adam12, Mltna
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

Cofactori

Binds 1 zinc ion per subunit By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi177 – 1771Zinc; in inhibited form By similarity
Metal bindingi348 – 3481Zinc; catalytic By similarity
Active sitei349 – 3491 By similarity
Metal bindingi352 – 3521Zinc; catalytic By similarity
Metal bindingi358 – 3581Zinc; catalytic By similarity

GO - Molecular functioni

  1. metalloendopeptidase activity Source: InterPro
  2. protein binding Source: IntAct
  3. zinc ion binding Source: InterPro

GO - Biological processi

  1. cell adhesion Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiM12.212.

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 12 (EC:3.4.24.-)
Short name:
ADAM 12
Alternative name(s):
Meltrin-alpha
Gene namesi
Name:Adam12
Synonyms:Mltna
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:105378. Adam12.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini206 – 706501Extracellular Reviewed prediction
Add
BLAST
Transmembranei707 – 72721Helical; Reviewed prediction
Add
BLAST
Topological domaini728 – 903176Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. mitochondrion Source: Ensembl
  3. nucleus Source: Ensembl
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131 Reviewed prediction
Add
BLAST
Propeptidei32 – 205174 By similarity
PRO_0000029080Add
BLAST
Chaini206 – 903698Disintegrin and metalloproteinase domain-containing protein 12
PRO_0000029081Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi112 – 1121N-linked (GlcNAc...) Reviewed prediction
Glycosylationi147 – 1471N-linked (GlcNAc...) Reviewed prediction
Glycosylationi157 – 1571N-linked (GlcNAc...) Reviewed prediction
Glycosylationi182 – 1821N-linked (GlcNAc...) Reviewed prediction
Glycosylationi185 – 1851N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi323 ↔ 409 By similarity
Disulfide bondi365 ↔ 393 By similarity
Disulfide bondi367 ↔ 376 By similarity
Glycosylationi450 – 4501N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi480 ↔ 500 By similarity
Glycosylationi649 – 6491N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi658 ↔ 668 By similarity
Disulfide bondi662 ↔ 674 By similarity
Disulfide bondi676 ↔ 685 By similarity
Modified residuei901 – 9011Phosphotyrosine; by SRC Inferred

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

PRIDEiQ61824.

PTM databases

PhosphoSiteiQ61824.

Expressioni

Tissue specificityi

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.1 Publication

Inductioni

At the onset of myoblast fusion.

Gene expression databases

ArrayExpressiQ61824.
GenevestigatoriQ61824.

Interactioni

Subunit structurei

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ACTN2P356093EBI-77785,EBI-77797From a different organism.

Protein-protein interaction databases

IntActiQ61824. 1 interaction.
MINTiMINT-154663.

Structurei

3D structure databases

ProteinModelPortaliQ61824.
SMRiQ61824. Positions 211-688.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini212 – 414203Peptidase M12B
Add
BLAST
Domaini422 – 50887Disintegrin
Add
BLAST
Domaini654 – 68633EGF-like
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi175 – 1828Cysteine switch By similarity
Motifi824 – 8307SH3-binding; class II
Motifi830 – 8378SH3-binding; class I
Motifi846 – 8527SH3-binding; class II
Motifi852 – 8587SH3-binding; class I
Motifi881 – 8877SH3-binding; class I

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi509 – 653145Cys-rich
Add
BLAST

Domaini

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.

Sequence similaritiesi

Contains 1 disintegrin domain.
Contains 1 EGF-like domain.

Keywords - Domaini

EGF-like domain, SH3-binding, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG294463.
GeneTreeiENSGT00740000114848.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ61824.
KOiK06835.
OMAiPPFCDKF.
OrthoDBiEOG7F7W89.
TreeFamiTF314733.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR000742. EG-like_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamiPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
PRINTSiPR00289. DISINTEGRIN.
SMARTiSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS50026. EGF_3. 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.

Q61824-1 [UniParc]FASTAAdd to Basket

« Hide

MAERPARRAP PARALLLALA GALLAPRAAR GMSLWDQRGT YEVARASLLS    50
KDPGIPGQSI PAKDHPDVLT VQLQLESRDL ILSLERNEGL IANGFTETHY 100
LQDGTDVSLT RNHTDHCYYH GHVQGDAASV VSLSTCSGLR GLIMFENKTY 150
SLEPMKNTTD SYKLVPAESM TNIQGLCGSQ HNKSNLTMED VSPGTSQMRA 200
RRHKRETLKM TKYVELVIVA DNREFQRQGK DLEKVKQRLI EIANHVDKFY 250
RPLNIRIVLV GVEVWNDIDK CSISQDPFTS LHEFLDWRKI KLLPRKSHDN 300
AQLISGVYFQ GTTIGMAPIM SMCTAEQSGG VVMDHSDSPL GAAVTLAHEL 350
GHNFGMNHDT LERGCSCRMA AEKGGCIMNP STGFPFPMVF SSCSRKDLEA 400
SLEKGMGMCL FNLPEVKQAF GGRKCGNGYV EEGEECDCGE PEECTNRCCN 450
ATTCTLKPDA VCAHGQCCED CQLKPPGTAC RGSSNSCDLP EFCTGTAPHC 500
PANVYLHDGH PCQGVDGYCY NGICQTHEQQ CVTLWGPGAK PAPGICFERV 550
NSAGDPYGNC GKDSKSAFAK CELRDAKCGK IQCQGGASRP VIGTNAVSIE 600
TNIPQQEGGR ILCRGTHVYL GDDMPDPGLV LAGTKCAEGK ICLNRRCQNI 650
SVFGVHKCAM QCHGRGVCNN RKNCHCEAHW APPFCDKFGF GGSTDSGPIR 700
QADNQGLTVG ILVSILCLLA AGFVVYLKRK TLMRLLFTHK KTTMEKLRCV 750
HPSRTPSGPH LGQAHHTPGK GLLMNRAPHF NTPKDRHSLK CQNMDISRPL 800
DARAVPQLQS PQRVLLPLHQ TPRAPSGPAR PLPASPAVRQ AQGIRKPSPP 850
QKPLPADPLS RTSRLTSALV RTPGQQEPGH RPAPIRPAPK HQVPRPSHNA 900
YIK 903
Length:903
Mass (Da):98,504
Last modified:October 3, 2012 - v2
Checksum:iB6A1D0816E4A73FC
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti40 – 401T → A in BAA08912. 1 Publication
Sequence conflicti138 – 1381G → D in BAA08912. 1 Publication
Sequence conflicti280 – 2801S → R in BAA08912. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D50411 mRNA. Translation: BAA08912.1.
AC125372 Genomic DNA. No translation available.
AC126676 Genomic DNA. No translation available.
AC140055 Genomic DNA. No translation available.
CCDSiCCDS21938.1.
PIRiS60257.
RefSeqiNP_031426.2. NM_007400.2.
UniGeneiMm.439714.

Genome annotation databases

EnsembliENSMUST00000067680; ENSMUSP00000065213; ENSMUSG00000054555.
GeneIDi11489.
KEGGimmu:11489.
UCSCiuc009kdo.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D50411 mRNA. Translation: BAA08912.1 .
AC125372 Genomic DNA. No translation available.
AC126676 Genomic DNA. No translation available.
AC140055 Genomic DNA. No translation available.
CCDSi CCDS21938.1.
PIRi S60257.
RefSeqi NP_031426.2. NM_007400.2.
UniGenei Mm.439714.

3D structure databases

ProteinModelPortali Q61824.
SMRi Q61824. Positions 211-688.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q61824. 1 interaction.
MINTi MINT-154663.

Protein family/group databases

MEROPSi M12.212.

PTM databases

PhosphoSitei Q61824.

Proteomic databases

PRIDEi Q61824.

Protocols and materials databases

DNASUi 11489.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000067680 ; ENSMUSP00000065213 ; ENSMUSG00000054555 .
GeneIDi 11489.
KEGGi mmu:11489.
UCSCi uc009kdo.2. mouse.

Organism-specific databases

CTDi 8038.
MGIi MGI:105378. Adam12.

Phylogenomic databases

eggNOGi NOG294463.
GeneTreei ENSGT00740000114848.
HOGENOMi HOG000230883.
HOVERGENi HBG006978.
InParanoidi Q61824.
KOi K06835.
OMAi PPFCDKF.
OrthoDBi EOG7F7W89.
TreeFami TF314733.

Miscellaneous databases

ChiTaRSi ADAM12. mouse.
NextBioi 278856.
PROi Q61824.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q61824.
Genevestigatori Q61824.

Family and domain databases

Gene3Di 3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProi IPR006586. ADAM_Cys-rich.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR000742. EG-like_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view ]
Pfami PF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view ]
PRINTSi PR00289. DISINTEGRIN.
SMARTi SM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view ]
SUPFAMi SSF57552. SSF57552. 1 hit.
PROSITEi PS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Embryonic fibroblast.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "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] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ALPHA-ACTININ-2.
  5. "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] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-901.

Entry informationi

Entry nameiADA12_MOUSE
AccessioniPrimary (citable) accession number: Q61824
Secondary accession number(s): F8VQN4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: October 3, 2012
Last modified: September 3, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Marker of skeletal muscle regeneration.

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

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