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UniProtKB - O43184 (ADA12_HUMAN)

Protein

Disintegrin and metalloproteinase domain-containing protein 12

Gene

ADAM12

Organism
Homo sapiens (Human)
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 (By similarity).By similarity

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi179Zinc; in inhibited formBy similarity1
Metal bindingi350Zinc; catalytic1
Active sitei3511
Metal bindingi354Zinc; catalytic1
Metal bindingi360Zinc; catalytic1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: InterPro
  • metallopeptidase activity Source: ProtInc
  • SH3 domain binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cell adhesion Source: UniProtKB-KW
  • extracellular matrix organization Source: Reactome
  • myoblast fusion Source: ProtInc
  • positive regulation of angiogenesis Source: BHF-UCL
View the complete GO annotation on QuickGO ...

Keywordsi

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

Enzyme and pathway databases

BRENDAi3.4.24.B10 2681
ReactomeiR-HSA-177929 Signaling by EGFR
R-HSA-8941237 Invadopodia formation
SIGNORiO43184

Protein family/group databases

MEROPSiM12.212
TCDBi8.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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000148848.14
HGNCiHGNC:190 ADAM12
MIMi602714 gene
neXtProtiNX_O43184

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 domaini208 – 708ExtracellularSequence analysisAdd BLAST501
Transmembranei709 – 729HelicalSequence analysisAdd BLAST21
Topological domaini730 – 909CytoplasmicSequence analysisAdd BLAST180

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi8038
OpenTargetsiENSG00000148848
PharmGKBiPA24507

Chemistry databases

ChEMBLiCHEMBL5030
GuidetoPHARMACOLOGYi1660

Polymorphism and mutation databases

BioMutaiADAM12

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
PropeptideiPRO_000002907829 – 207By similarityAdd BLAST179
ChainiPRO_0000029079208 – 909Disintegrin and metalloproteinase domain-containing protein 12Add BLAST702

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi111N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi149N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi325 ↔ 411By similarity
Disulfide bondi367 ↔ 395By similarity
Disulfide bondi369 ↔ 378By similarity
Glycosylationi381N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi452N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi482 ↔ 502By similarity
Glycosylationi651N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi660 ↔ 670By similarity
Disulfide bondi664 ↔ 676By similarity
Disulfide bondi678 ↔ 687By similarity
Modified residuei907Phosphotyrosine; by SRCBy similarity1

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

MaxQBiO43184
PaxDbiO43184
PeptideAtlasiO43184
PRIDEiO43184
ProteomicsDBi48799
48800 [O43184-2]
48801 [O43184-3]
48802 [O43184-4]

PTM databases

CarbonylDBiO43184
iPTMnetiO43184
PhosphoSitePlusiO43184

Expressioni

Tissue specificityi

Isoform 1 is expressed in placenta and skeletal, cardiac, and smooth muscle. Isoform 2 seems to be expressed only in placenta or in embryo and fetus. Both forms were expressed in some tumor cells lines. Not detected in brain, lung, liver, kidney or pancreas.

Gene expression databases

BgeeiENSG00000148848 Expressed in 147 organ(s), highest expression level in placenta
CleanExiHS_ADAM12
ExpressionAtlasiO43184 baseline and differential
GenevisibleiO43184 HS

Organism-specific databases

HPAiHPA030866
HPA030867
HPA030868

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 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi113731, 5 interactors
CORUMiO43184
IntActiO43184, 30 interactors
MINTiO43184
STRINGi9606.ENSP00000357668

Chemistry databases

BindingDBiO43184

Structurei

3D structure databases

ProteinModelPortaliO43184
SMRiO43184
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini214 – 416Peptidase M12BPROSITE-ProRule annotationAdd BLAST203
Domaini424 – 510DisintegrinPROSITE-ProRule annotationAdd BLAST87
Domaini656 – 688EGF-likePROSITE-ProRule annotationAdd BLAST33

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi177 – 184Cysteine switchBy similarity8
Motifi828 – 834SH3-binding; class IIBy similarity7
Motifi834 – 841SH3-binding; class IBy similarity8
Motifi885 – 891SH3-binding; class IBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi514 – 649Cys-richAdd BLAST136

Domaini

The cysteine-rich domain supports cell adhesion through syndecans and triggers signaling events that lead to beta-1 integrin-dependent cell spreading. In carcinomas cells the binding of this domain to syndecans does not allow the integrin-mediated cell spreading.
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
InParanoidiO43184
KOiK06835
OMAiWARRHKR
OrthoDBiEOG091G01NX
PhylomeDBiO43184
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

Sequences (4+)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O43184-1) [UniParc]FASTAAdd to basket
Also known as: 12L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:909
Mass (Da):99,542
Last modified:May 5, 2009 - v3
Checksum:iE28131C64C4304AB
GO
Isoform 2 (identifier: O43184-2) [UniParc]FASTAAdd to basket
Also known as: 12S

The sequence of this isoform differs from the canonical sequence as follows:
     705-738: DNQGLTIGILVTILCLLAAGFVVYLKRKTLIRLL → EARQEAAESNRERGQGQEPVGSQEHASTASLTLI
     739-909: Missing.

Show »
Length:738
Mass (Da):80,403
Checksum:i19699D2852ED28F6
GO
Isoform 3 (identifier: O43184-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     114-116: Missing.
     705-738: DNQGLTIGILVTILCLLAAGFVVYLKRKTLIRLL → EARQEAAESNRERGQGQEPVGSQEHASTASLTLI
     739-909: Missing.

Note: No experimental confirmation available.
Show »
Length:735
Mass (Da):80,078
Checksum:i664D4EDA47F8B533
GO
Isoform 4 (identifier: O43184-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     114-116: Missing.
     705-740: DNQGLTIGILVTILCLLAAGFVVYLKRKTLIRLLFT → GKEARQEAAESNRERGQGQEPVGSQEHASTASLTLI
     741-909: Missing.

Note: No experimental confirmation available.
Show »
Length:737
Mass (Da):80,263
Checksum:iD86FE821BCBC62C6
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5JRP2Q5JRP2_HUMAN
Disintegrin and metalloproteinase d...
ADAM12
278Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03854248G → R4 PublicationsCorresponds to variant dbSNP:rs3740199Ensembl.1
Natural variantiVAR_036143301D → H in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_036144479G → E in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_066310712G → E in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_036145792L → F in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_066311893P → S in a cutaneous metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs151030407Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_031001114 – 116Missing in isoform 3 and isoform 4. 2 Publications3
Alternative sequenceiVSP_031002705 – 740DNQGL…RLLFT → GKEARQEAAESNRERGQGQE PVGSQEHASTASLTLI in isoform 4. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_005476705 – 738DNQGL…LIRLL → EARQEAAESNRERGQGQEPV GSQEHASTASLTLI in isoform 2 and isoform 3. 2 PublicationsAdd BLAST34
Alternative sequenceiVSP_005477739 – 909Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST171
Alternative sequenceiVSP_031003741 – 909Missing in isoform 4. 1 PublicationAdd BLAST169

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
CCDSiCCDS7653.1 [O43184-1]
CCDS7654.1 [O43184-2]
RefSeqiNP_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]
UniGeneiHs.594351
Hs.741333

Genome annotation databases

EnsembliENST00000368676; ENSP00000357665; ENSG00000148848 [O43184-2]
ENST00000368679; ENSP00000357668; ENSG00000148848 [O43184-1]
GeneIDi8038
KEGGihsa:8038
UCSCiuc001ljk.4 human [O43184-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS7653.1 [O43184-1]
CCDS7654.1 [O43184-2]
RefSeqiNP_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]
UniGeneiHs.594351
Hs.741333

3D structure databases

ProteinModelPortaliO43184
SMRiO43184
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113731, 5 interactors
CORUMiO43184
IntActiO43184, 30 interactors
MINTiO43184
STRINGi9606.ENSP00000357668

Chemistry databases

BindingDBiO43184
ChEMBLiCHEMBL5030
GuidetoPHARMACOLOGYi1660

Protein family/group databases

MEROPSiM12.212
TCDBi8.A.77.1.5 the sheddase (sheddase) family

PTM databases

CarbonylDBiO43184
iPTMnetiO43184
PhosphoSitePlusiO43184

Polymorphism and mutation databases

BioMutaiADAM12

Proteomic databases

MaxQBiO43184
PaxDbiO43184
PeptideAtlasiO43184
PRIDEiO43184
ProteomicsDBi48799
48800 [O43184-2]
48801 [O43184-3]
48802 [O43184-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368676; ENSP00000357665; ENSG00000148848 [O43184-2]
ENST00000368679; ENSP00000357668; ENSG00000148848 [O43184-1]
GeneIDi8038
KEGGihsa:8038
UCSCiuc001ljk.4 human [O43184-1]

Organism-specific databases

CTDi8038
DisGeNETi8038
EuPathDBiHostDB:ENSG00000148848.14
GeneCardsiADAM12
H-InvDBiHIX0009299
HGNCiHGNC:190 ADAM12
HPAiHPA030866
HPA030867
HPA030868
MIMi602714 gene
neXtProtiNX_O43184
OpenTargetsiENSG00000148848
PharmGKBiPA24507
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607 Eukaryota
ENOG410XX2M LUCA
GeneTreeiENSGT00910000144014
HOGENOMiHOG000230883
HOVERGENiHBG006978
InParanoidiO43184
KOiK06835
OMAiWARRHKR
OrthoDBiEOG091G01NX
PhylomeDBiO43184
TreeFamiTF314733

Enzyme and pathway databases

BRENDAi3.4.24.B10 2681
ReactomeiR-HSA-177929 Signaling by EGFR
R-HSA-8941237 Invadopodia formation
SIGNORiO43184

Miscellaneous databases

ChiTaRSiADAM12 human
GeneWikiiADAM12
GenomeRNAii8038
PROiPR:O43184
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000148848 Expressed in 147 organ(s), highest expression level in placenta
CleanExiHS_ADAM12
ExpressionAtlasiO43184 baseline and differential
GenevisibleiO43184 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiADA12_HUMAN
AccessioniPrimary (citable) accession number: O43184
Secondary accession number(s): O60470
, Q5JRP0, Q5JRP1, Q6P9E3, Q6UWB0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 5, 2009
Last modified: November 7, 2018
This is version 185 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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