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Protein

Disintegrin and metalloproteinase domain-containing protein 12

Gene

ADAM12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 (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

GO - Biological processi

  • cell adhesion Source: UniProtKB-KW
  • myoblast fusion Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000148848-MONOMER.
BRENDAi3.4.24.B10. 2681.
ReactomeiR-HSA-177929. Signaling by EGFR.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:190. ADAM12.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini208 – 708ExtracellularSequence analysisAdd BLAST501
Transmembranei709 – 729HelicalSequence analysisAdd BLAST21
Topological domaini730 – 909CytoplasmicSequence analysisAdd BLAST180

GO - Cellular componenti

Complete GO annotation...

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...)Sequence analysis1
Glycosylationi149N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi325 ↔ 411By similarity
Disulfide bondi367 ↔ 395By similarity
Disulfide bondi369 ↔ 378By similarity
Glycosylationi381N-linked (GlcNAc...)Sequence analysis1
Glycosylationi452N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi482 ↔ 502By similarity
Glycosylationi651N-linked (GlcNAc...)Sequence 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.

PTM databases

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.
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

WithEntry#Exp.IntActNotes
FSTL3O956334EBI-2625865,EBI-2625790

GO - Molecular functioni

  • SH3 domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi113731. 5 interactors.
IntActiO43184. 10 interactors.
MINTiMINT-246189.
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.

Sequence similaritiesi

Contains 1 disintegrin domain.PROSITE-ProRule annotation
Contains 1 EGF-like domain.PROSITE-ProRule annotation
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiO43184.
KOiK06835.
OMAiPPFCDKF.
OrthoDBiEOG091G01NX.
PhylomeDBiO43184.
TreeFamiTF314733.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
IPR000742. EGF-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]

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

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03854248G → R.4 PublicationsCorresponds to variant rs3740199dbSNPEnsembl.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 rs151030407dbSNPEnsembl.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.
AL589787
, AC022015, AC026226, AC063963 Genomic DNA. Translation: CAI40682.1.
AL589787
, AC022015, AC026226, AC063963 Genomic DNA. Translation: CAI40683.1.
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

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.
AL589787
, AC022015, AC026226, AC063963 Genomic DNA. Translation: CAI40682.1.
AL589787
, AC022015, AC026226, AC063963 Genomic DNA. Translation: CAI40683.1.
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.
IntActiO43184. 10 interactors.
MINTiMINT-246189.
STRINGi9606.ENSP00000357668.

Chemistry databases

BindingDBiO43184.
ChEMBLiCHEMBL5030.
GuidetoPHARMACOLOGYi1660.

Protein family/group databases

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

PTM databases

iPTMnetiO43184.
PhosphoSitePlusiO43184.

Polymorphism and mutation databases

BioMutaiADAM12.

Proteomic databases

MaxQBiO43184.
PaxDbiO43184.
PeptideAtlasiO43184.
PRIDEiO43184.

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.
GeneCardsiADAM12.
H-InvDBHIX0009299.
HGNCiHGNC:190. ADAM12.
HPAiHPA030866.
HPA030867.
HPA030868.
MIMi602714. gene.
neXtProtiNX_O43184.
OpenTargetsiENSG00000148848.
PharmGKBiPA24507.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiO43184.
KOiK06835.
OMAiPPFCDKF.
OrthoDBiEOG091G01NX.
PhylomeDBiO43184.
TreeFamiTF314733.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000148848-MONOMER.
BRENDAi3.4.24.B10. 2681.
ReactomeiR-HSA-177929. Signaling by EGFR.
SIGNORiO43184.

Miscellaneous databases

ChiTaRSiADAM12. human.
GeneWikiiADAM12.
GenomeRNAii8038.
PROiO43184.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000148848.
CleanExiHS_ADAM12.
ExpressionAtlasiO43184. baseline and differential.
GenevisibleiO43184. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR018358. Disintegrin_CS.
IPR001762. Disintegrin_dom.
IPR000742. EGF-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]
ProtoNetiSearch...

Entry informationi

Entry nameiADA12_HUMAN
AccessioniPrimary (citable) accession number: O43184
Secondary accession number(s): O60470
, Q5JRP0, Q5JRP1, Q6P9E3, Q6UWB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 5, 2009
Last modified: November 30, 2016
This is version 168 of the entry and version 3 of the sequence. [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 chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.