UniProtKB - O43184 (ADA12_HUMAN)
Disintegrin and metalloproteinase domain-containing protein 12
ADAM12
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 (By similarity).
By similarityCofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 179 | Zinc; in inhibited formBy similarity | 1 | |
Metal bindingi | 350 | Zinc; catalytic | 1 | |
Active sitei | 351 | 1 | ||
Metal bindingi | 354 | Zinc; catalytic | 1 | |
Metal bindingi | 360 | Zinc; catalytic | 1 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- metalloendopeptidase activity Source: InterPro
- metallopeptidase activity Source: ProtInc
- SH3 domain binding Source: BHF-UCL
GO - Biological processi
- cell adhesion Source: UniProtKB-KW
- myoblast fusion Source: ProtInc
- positive regulation of angiogenesis Source: BHF-UCL
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Biological process | Cell adhesion |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.24.B10, 2681 |
PathwayCommonsi | O43184 |
Reactomei | R-HSA-177929, Signaling by EGFR R-HSA-8941237, Invadopodia formation |
SignaLinki | O43184 |
SIGNORi | O43184 |
Protein family/group databases
MEROPSi | M12.212 |
TCDBi | 8.A.77.1.5, the sheddase (sheddase) family |
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:MLTN ORF Names:UNQ346/PRO545 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:190, ADAM12 |
MIMi | 602714, gene |
neXtProti | NX_O43184 |
VEuPathDBi | HostDB:ENSG00000148848 |
Subcellular locationi
Plasma membrane
Extracellular region or secreted
Extracellular region or secreted
- Secreted Curated
Extracellular region or secreted
- Secreted Curated
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- plasma membrane Source: BHF-UCL
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 208 – 708 | ExtracellularSequence analysisAdd BLAST | 501 | |
Transmembranei | 709 – 729 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 730 – 909 | CytoplasmicSequence analysisAdd BLAST | 180 |
Keywords - Cellular componenti
Cell membrane, Membrane, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 8038 |
OpenTargetsi | ENSG00000148848 |
PharmGKBi | PA24507 |
Miscellaneous databases
Pharosi | O43184, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5030 |
GuidetoPHARMACOLOGYi | 1660 |
Genetic variation databases
BioMutai | ADAM12 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 28 | Sequence analysisAdd BLAST | 28 | |
PropeptideiPRO_0000029078 | 29 – 207 | By similarityAdd BLAST | 179 | |
ChainiPRO_0000029079 | 208 – 909 | Disintegrin and metalloproteinase domain-containing protein 12Add BLAST | 702 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 111 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 149 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 325 ↔ 411 | By similarity | ||
Disulfide bondi | 367 ↔ 395 | By similarity | ||
Disulfide bondi | 369 ↔ 378 | By similarity | ||
Glycosylationi | 381 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 452 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 482 ↔ 502 | By similarity | ||
Glycosylationi | 651 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 660 ↔ 670 | By similarity | ||
Disulfide bondi | 664 ↔ 676 | By similarity | ||
Disulfide bondi | 678 ↔ 687 | By similarity | ||
Modified residuei | 907 | Phosphotyrosine; by SRCBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, ZymogenProteomic databases
jPOSTi | O43184 |
MassIVEi | O43184 |
MaxQBi | O43184 |
PaxDbi | O43184 |
PeptideAtlasi | O43184 |
PRIDEi | O43184 |
ProteomicsDBi | 48799 [O43184-1] 48800 [O43184-2] 48801 [O43184-3] 48802 [O43184-4] |
PTM databases
CarbonylDBi | O43184 |
GlyGeni | O43184, 5 sites |
iPTMneti | O43184 |
PhosphoSitePlusi | O43184 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000148848, Expressed in placenta and 176 other tissues |
ExpressionAtlasi | O43184, baseline and differential |
Genevisiblei | O43184, HS |
Organism-specific databases
HPAi | ENSG00000148848, Tissue enriched (placenta) |
Interactioni
Subunit structurei
Interacts with alpha-actinin-2 and with syndecans (By similarity).
Interacts with SH3PXD2A.
Interacts with FST3.
Interacts with RACK1; the interaction is required for PKC-dependent translocation of ADAM12 to the cell membrane.
By similarity4 PublicationsBinary interactionsi
O43184
With | #Exp. | IntAct |
---|---|---|
AHI1 [Q8N157] | 2 | EBI-2625825,EBI-1049056 |
HCK [P08631] | 2 | EBI-2625825,EBI-346340 |
LYN [P07948] | 2 | EBI-2625825,EBI-79452 |
SRC [P12931] | 2 | EBI-2625825,EBI-621482 |
Isoform 2 [O43184-2]
With | #Exp. | IntAct |
---|---|---|
FSTL3 [O95633] | 4 | EBI-2625865,EBI-2625790 |
Isoform 4 [O43184-4]
GO - Molecular functioni
- SH3 domain binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 113731, 39 interactors |
CORUMi | O43184 |
IntActi | O43184, 45 interactors |
MINTi | O43184 |
STRINGi | 9606.ENSP00000357668 |
Chemistry databases
BindingDBi | O43184 |
Miscellaneous databases
RNActi | O43184, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 214 – 416 | Peptidase M12BPROSITE-ProRule annotationAdd BLAST | 203 | |
Domaini | 424 – 510 | DisintegrinPROSITE-ProRule annotationAdd BLAST | 87 | |
Domaini | 656 – 688 | EGF-likePROSITE-ProRule annotationAdd BLAST | 33 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 822 – 862 | DisorderedSequence analysisAdd BLAST | 41 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 177 – 184 | Cysteine switchBy similarity | 8 | |
Motifi | 828 – 834 | SH3-binding; class IIBy similarity | 7 | |
Motifi | 834 – 841 | SH3-binding; class IBy similarity | 8 | |
Motifi | 885 – 891 | SH3-binding; class IBy similarity | 7 |
Domaini
Keywords - Domaini
EGF-like domain, SH3-binding, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3607, Eukaryota |
GeneTreei | ENSGT00940000155495 |
HOGENOMi | CLU_012714_7_0_1 |
InParanoidi | O43184 |
OMAi | VCQTHEQ |
OrthoDBi | 162519at2759 |
PhylomeDBi | O43184 |
TreeFami | TF314733 |
Family and domain databases
CDDi | cd04269, ZnMc_adamalysin_II_like, 1 hit |
Gene3Di | 3.40.390.10, 1 hit 4.10.70.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF08516, ADAM_CR, 1 hit PF00200, Disintegrin, 1 hit PF01562, Pep_M12B_propep, 1 hit PF01421, Reprolysin, 1 hit |
PRINTSi | PR00289, DISINTEGRIN |
SMARTi | View protein in SMART SM00608, ACR, 1 hit SM00050, DISIN, 1 hit |
SUPFAMi | SSF57552, SSF57552, 1 hit |
PROSITEi | View 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 |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAARPLPVSP ARALLLALAG ALLAPCEARG VSLWNQGRAD EVVSASVGSG
60 70 80 90 100
DLWIPVKSFD SKNHPEVLNI RLQRESKELI INLERNEGLI ASSFTETHYL
110 120 130 140 150
QDGTDVSLAR NYTVILGHCY YHGHVRGYSD SAVSLSTCSG LRGLIVFENE
160 170 180 190 200
SYVLEPMKSA TNRYKLFPAK KLKSVRGSCG SHHNTPNLAA KNVFPPPSQT
210 220 230 240 250
WARRHKRETL KATKYVELVI VADNREFQRQ GKDLEKVKQR LIEIANHVDK
260 270 280 290 300
FYRPLNIRIV LVGVEVWNDM DKCSVSQDPF TSLHEFLDWR KMKLLPRKSH
310 320 330 340 350
DNAQLVSGVY FQGTTIGMAP IMSMCTADQS GGIVMDHSDN PLGAAVTLAH
360 370 380 390 400
ELGHNFGMNH DTLDRGCSCQ MAVEKGGCIM NASTGYPFPM VFSSCSRKDL
410 420 430 440 450
ETSLEKGMGV CLFNLPEVRE SFGGQKCGNR FVEEGEECDC GEPEECMNRC
460 470 480 490 500
CNATTCTLKP DAVCAHGLCC EDCQLKPAGT ACRDSSNSCD LPEFCTGASP
510 520 530 540 550
HCPANVYLHD GHSCQDVDGY CYNGICQTHE QQCVTLWGPG AKPAPGICFE
560 570 580 590 600
RVNSAGDPYG NCGKVSKSSF AKCEMRDAKC GKIQCQGGAS RPVIGTNAVS
610 620 630 640 650
IETNIPLQQG GRILCRGTHV YLGDDMPDPG LVLAGTKCAD GKICLNRQCQ
660 670 680 690 700
NISVFGVHEC AMQCHGRGVC NNRKNCHCEA HWAPPFCDKF GFGGSTDSGP
710 720 730 740 750
IRQADNQGLT IGILVTILCL LAAGFVVYLK RKTLIRLLFT NKKTTIEKLR
760 770 780 790 800
CVRPSRPPRG FQPCQAHLGH LGKGLMRKPP DSYPPKDNPR RLLQCQNVDI
810 820 830 840 850
SRPLNGLNVP QPQSTQRVLP PLHRAPRAPS VPARPLPAKP ALRQAQGTCK
860 870 880 890 900
PNPPQKPLPA DPLARTTRLT HALARTPGQW ETGLRLAPLR PAPQYPHQVP
RSTHTAYIK
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketQ5JRP2 | Q5JRP2_HUMAN | Disintegrin and metalloproteinase d... | ADAM12 | 906 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_038542 | 48 | G → R4 PublicationsCorresponds to variant dbSNP:rs3740199Ensembl. | 1 | |
Natural variantiVAR_036143 | 301 | D → H in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_036144 | 479 | G → E in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1459457663Ensembl. | 1 | |
Natural variantiVAR_066310 | 712 | G → E in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_036145 | 792 | L → F in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_066311 | 893 | P → S in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs151030407Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_031001 | 114 – 116 | Missing in isoform 3 and isoform 4. 2 Publications | 3 | |
Alternative sequenceiVSP_031002 | 705 – 740 | DNQGL…RLLFT → GKEARQEAAESNRERGQGQE PVGSQEHASTASLTLI in isoform 4. 1 PublicationAdd BLAST | 36 | |
Alternative sequenceiVSP_005476 | 705 – 738 | DNQGL…LIRLL → EARQEAAESNRERGQGQEPV GSQEHASTASLTLI in isoform 2 and isoform 3. 2 PublicationsAdd BLAST | 34 | |
Alternative sequenceiVSP_005477 | 739 – 909 | Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST | 171 | |
Alternative sequenceiVSP_031003 | 741 – 909 | Missing in isoform 4. 1 PublicationAdd BLAST | 169 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF023476 mRNA Translation: AAC08702.2 AF023477 mRNA Translation: AAC08703.2 AY358878 mRNA Translation: AAQ89237.1 AC022015 Genomic DNA No translation available. AC026226 Genomic DNA No translation available. AC063963 Genomic DNA No translation available. AL589787 Genomic DNA No translation available. CH471066 Genomic DNA Translation: EAW49206.1 CH471066 Genomic DNA Translation: EAW49209.1 BC060804 mRNA Translation: AAH60804.1 |
CCDSi | CCDS7653.1 [O43184-1] CCDS7654.1 [O43184-2] |
RefSeqi | NP_001275903.1, NM_001288974.1 [O43184-4] NP_001275904.1, NM_001288975.1 [O43184-3] NP_003465.3, NM_003474.5 [O43184-1] NP_067673.2, NM_021641.4 [O43184-2] |
Genome annotation databases
Ensembli | ENST00000368676; ENSP00000357665; ENSG00000148848 [O43184-2] ENST00000368679; ENSP00000357668; ENSG00000148848 |
GeneIDi | 8038 |
KEGGi | hsa:8038 |
UCSCi | uc001ljk.4, human [O43184-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF023476 mRNA Translation: AAC08702.2 AF023477 mRNA Translation: AAC08703.2 AY358878 mRNA Translation: AAQ89237.1 AC022015 Genomic DNA No translation available. AC026226 Genomic DNA No translation available. AC063963 Genomic DNA No translation available. AL589787 Genomic DNA No translation available. CH471066 Genomic DNA Translation: EAW49206.1 CH471066 Genomic DNA Translation: EAW49209.1 BC060804 mRNA Translation: AAH60804.1 |
CCDSi | CCDS7653.1 [O43184-1] CCDS7654.1 [O43184-2] |
RefSeqi | NP_001275903.1, NM_001288974.1 [O43184-4] NP_001275904.1, NM_001288975.1 [O43184-3] NP_003465.3, NM_003474.5 [O43184-1] NP_067673.2, NM_021641.4 [O43184-2] |
3D structure databases
SMRi | O43184 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 113731, 39 interactors |
CORUMi | O43184 |
IntActi | O43184, 45 interactors |
MINTi | O43184 |
STRINGi | 9606.ENSP00000357668 |
Chemistry databases
BindingDBi | O43184 |
ChEMBLi | CHEMBL5030 |
GuidetoPHARMACOLOGYi | 1660 |
Protein family/group databases
MEROPSi | M12.212 |
TCDBi | 8.A.77.1.5, the sheddase (sheddase) family |
PTM databases
CarbonylDBi | O43184 |
GlyGeni | O43184, 5 sites |
iPTMneti | O43184 |
PhosphoSitePlusi | O43184 |
Genetic variation databases
BioMutai | ADAM12 |
Proteomic databases
jPOSTi | O43184 |
MassIVEi | O43184 |
MaxQBi | O43184 |
PaxDbi | O43184 |
PeptideAtlasi | O43184 |
PRIDEi | O43184 |
ProteomicsDBi | 48799 [O43184-1] 48800 [O43184-2] 48801 [O43184-3] 48802 [O43184-4] |
Protocols and materials databases
Antibodypediai | 19223, 474 antibodies from 40 providers |
DNASUi | 8038 |
Genome annotation databases
Ensembli | ENST00000368676; ENSP00000357665; ENSG00000148848 [O43184-2] ENST00000368679; ENSP00000357668; ENSG00000148848 |
GeneIDi | 8038 |
KEGGi | hsa:8038 |
UCSCi | uc001ljk.4, human [O43184-1] |
Organism-specific databases
CTDi | 8038 |
DisGeNETi | 8038 |
GeneCardsi | ADAM12 |
HGNCi | HGNC:190, ADAM12 |
HPAi | ENSG00000148848, Tissue enriched (placenta) |
MIMi | 602714, gene |
neXtProti | NX_O43184 |
OpenTargetsi | ENSG00000148848 |
PharmGKBi | PA24507 |
VEuPathDBi | HostDB:ENSG00000148848 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3607, Eukaryota |
GeneTreei | ENSGT00940000155495 |
HOGENOMi | CLU_012714_7_0_1 |
InParanoidi | O43184 |
OMAi | VCQTHEQ |
OrthoDBi | 162519at2759 |
PhylomeDBi | O43184 |
TreeFami | TF314733 |
Enzyme and pathway databases
BRENDAi | 3.4.24.B10, 2681 |
PathwayCommonsi | O43184 |
Reactomei | R-HSA-177929, Signaling by EGFR R-HSA-8941237, Invadopodia formation |
SignaLinki | O43184 |
SIGNORi | O43184 |
Miscellaneous databases
BioGRID-ORCSi | 8038, 6 hits in 1042 CRISPR screens |
ChiTaRSi | ADAM12, human |
GeneWikii | ADAM12 |
GenomeRNAii | 8038 |
Pharosi | O43184, Tchem |
PROi | PR:O43184 |
RNActi | O43184, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000148848, Expressed in placenta and 176 other tissues |
ExpressionAtlasi | O43184, baseline and differential |
Genevisiblei | O43184, HS |
Family and domain databases
CDDi | cd04269, ZnMc_adamalysin_II_like, 1 hit |
Gene3Di | 3.40.390.10, 1 hit 4.10.70.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF08516, ADAM_CR, 1 hit PF00200, Disintegrin, 1 hit PF01562, Pep_M12B_propep, 1 hit PF01421, Reprolysin, 1 hit |
PRINTSi | PR00289, DISINTEGRIN |
SMARTi | View protein in SMART SM00608, ACR, 1 hit SM00050, DISIN, 1 hit |
SUPFAMi | SSF57552, SSF57552, 1 hit |
PROSITEi | View 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | ADA12_HUMAN | |
Accessioni | O43184Primary (citable) accession number: O43184 Secondary accession number(s): O60470 Q6UWB0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | May 5, 2009 | |
Last modified: | February 23, 2022 | |
This is version 204 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot