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Protein

Disintegrin and metalloproteinase domain-containing protein 12

Gene

Adam12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.

Miscellaneous

Marker of skeletal muscle regeneration.

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi177Zinc; in inhibited formBy similarity1
Metal bindingi348Zinc; catalyticBy similarity1
Active sitei349PROSITE-ProRule annotation1
Metal bindingi352Zinc; catalyticBy similarity1
Metal bindingi358Zinc; catalyticBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processCell adhesion
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.B10 3474
ReactomeiR-MMU-8941237 Invadopodia formation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:105378 Adam12

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini206 – 706ExtracellularSequence analysisAdd BLAST501
Transmembranei707 – 727HelicalSequence analysisAdd BLAST21
Topological domaini728 – 903CytoplasmicSequence analysisAdd BLAST176

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
PropeptideiPRO_000002908032 – 205By similarityAdd BLAST174
ChainiPRO_0000029081206 – 903Disintegrin and metalloproteinase domain-containing protein 12Add BLAST698

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi112N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi147N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi157N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi182N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi185N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi323 ↔ 409By similarity
Disulfide bondi365 ↔ 393By similarity
Disulfide bondi367 ↔ 376By similarity
Glycosylationi450N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi480 ↔ 500By similarity
Glycosylationi649N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi658 ↔ 668By similarity
Disulfide bondi662 ↔ 674By similarity
Disulfide bondi676 ↔ 685By similarity
Modified residuei901Phosphotyrosine; by SRC1 Publication1

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

PaxDbiQ61824
PRIDEiQ61824

PTM databases

iPTMnetiQ61824
PhosphoSitePlusiQ61824

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

BgeeiENSMUSG00000054555
ExpressionAtlasiQ61824 baseline and differential
GenevisibleiQ61824 MM

Interactioni

Subunit structurei

Interacts with alpha-actinin-2 and with syndecans. Interacts with SH3PXD2A. Interacts with FST3. Interacts with RACK1; the interaction is required for PKC-dependent translocation of ADAM12 to the cell membrane (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ACTN2P356093EBI-77785,EBI-77797From Homo sapiens.

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ61824, 1 interactor
MINTiQ61824
STRINGi10090.ENSMUSP00000065213

Structurei

3D structure databases

ProteinModelPortaliQ61824
SMRiQ61824
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini212 – 414Peptidase M12BPROSITE-ProRule annotationAdd BLAST203
Domaini422 – 508DisintegrinPROSITE-ProRule annotationAdd BLAST87
Domaini654 – 686EGF-likePROSITE-ProRule annotationAdd BLAST33

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi175 – 182Cysteine switchBy similarity8
Motifi824 – 830SH3-binding; class II7
Motifi830 – 837SH3-binding; class I8
Motifi846 – 852SH3-binding; class II7
Motifi852 – 858SH3-binding; class I7
Motifi881 – 887SH3-binding; class I7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi509 – 653Cys-richAdd BLAST145

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).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.

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG3607 Eukaryota
ENOG410XX2M LUCA
GeneTreeiENSGT00910000144014
HOGENOMiHOG000230883
HOVERGENiHBG006978
InParanoidiQ61824
KOiK06835
OMAiFTSLHEF
OrthoDBiEOG091G01NX
TreeFamiTF314733

Family and domain databases

CDDicd04269 ZnMc_adamalysin_II_like, 1 hit
Gene3Di3.40.390.10, 1 hit
4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR018358 Disintegrin_CS
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
IPR000742 EGF-like_dom
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR034027 Reprolysin_adamalysin
PfamiView protein in Pfam
PF08516 ADAM_CR, 1 hit
PF00200 Disintegrin, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF01421 Reprolysin, 1 hit
PRINTSiPR00289 DISINTEGRIN
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
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

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q61824-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAERPARRAP PARALLLALA GALLAPRAAR GMSLWDQRGT YEVARASLLS
60 70 80 90 100
KDPGIPGQSI PAKDHPDVLT VQLQLESRDL ILSLERNEGL IANGFTETHY
110 120 130 140 150
LQDGTDVSLT RNHTDHCYYH GHVQGDAASV VSLSTCSGLR GLIMFENKTY
160 170 180 190 200
SLEPMKNTTD SYKLVPAESM TNIQGLCGSQ HNKSNLTMED VSPGTSQMRA
210 220 230 240 250
RRHKRETLKM TKYVELVIVA DNREFQRQGK DLEKVKQRLI EIANHVDKFY
260 270 280 290 300
RPLNIRIVLV GVEVWNDIDK CSISQDPFTS LHEFLDWRKI KLLPRKSHDN
310 320 330 340 350
AQLISGVYFQ GTTIGMAPIM SMCTAEQSGG VVMDHSDSPL GAAVTLAHEL
360 370 380 390 400
GHNFGMNHDT LERGCSCRMA AEKGGCIMNP STGFPFPMVF SSCSRKDLEA
410 420 430 440 450
SLEKGMGMCL FNLPEVKQAF GGRKCGNGYV EEGEECDCGE PEECTNRCCN
460 470 480 490 500
ATTCTLKPDA VCAHGQCCED CQLKPPGTAC RGSSNSCDLP EFCTGTAPHC
510 520 530 540 550
PANVYLHDGH PCQGVDGYCY NGICQTHEQQ CVTLWGPGAK PAPGICFERV
560 570 580 590 600
NSAGDPYGNC GKDSKSAFAK CELRDAKCGK IQCQGGASRP VIGTNAVSIE
610 620 630 640 650
TNIPQQEGGR ILCRGTHVYL GDDMPDPGLV LAGTKCAEGK ICLNRRCQNI
660 670 680 690 700
SVFGVHKCAM QCHGRGVCNN RKNCHCEAHW APPFCDKFGF GGSTDSGPIR
710 720 730 740 750
QADNQGLTVG ILVSILCLLA AGFVVYLKRK TLMRLLFTHK KTTMEKLRCV
760 770 780 790 800
HPSRTPSGPH LGQAHHTPGK GLLMNRAPHF NTPKDRHSLK CQNMDISRPL
810 820 830 840 850
DARAVPQLQS PQRVLLPLHQ TPRAPSGPAR PLPASPAVRQ AQGIRKPSPP
860 870 880 890 900
QKPLPADPLS RTSRLTSALV RTPGQQEPGH RPAPIRPAPK HQVPRPSHNA

YIK
Length:903
Mass (Da):98,504
Last modified:October 3, 2012 - v2
Checksum:iB6A1D0816E4A73FC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti40T → A in BAA08912 (PubMed:7566181).Curated1
Sequence conflicti138G → D in BAA08912 (PubMed:7566181).Curated1
Sequence conflicti280S → R in BAA08912 (PubMed:7566181).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Entry informationi

Entry nameiADA12_MOUSE
AccessioniPrimary (citable) accession number: Q61824
Secondary accession number(s): F8VQN4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: October 3, 2012
Last modified: May 23, 2018
This is version 167 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health