Reviewed, UniProtKB/Swiss-Prot O43184 (ADA12_HUMAN)

Names and origin

Protein names

Recommended name:
    ADAM 12
    EC=3.4.24.-
Alternative name(s):
    A disintegrin and metalloproteinase domain 12
    Meltrin-alpha

Gene names

Name:	ADAM12
Synonyms:	MLTN
ORF Names:	UNQ346/PRO545

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	909 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Cofactor	Binds 1 zinc ion per subunit.
Subunit structure	Interacts with alpha-actinin-2 and with syndecans By similarity. Interacts with SH3PXD2A.
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted. Isoform 3: SecretedPotential. Isoform 4: SecretedPotential.
Tissue specificity	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.
Domain	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.
Post-translational modification	The precursor is cleaved by a furin endopeptidase By similarity.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain SH3-binding Signal Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein Zymogen
Gene Ontology (GO)
Biological process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW myoblast fusion Traceable author statement. Source: ProtInc proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: ProtInc
Molecular function	SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43184-1)

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.

Isoform 2 (identifier: O43184-2)

Also known as: 12S;

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

Isoform 3 (identifier: O43184-3)

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

Notes: No experimental confirmation available.

Isoform 4 (identifier: O43184-4)

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

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Potential
	Propeptide	29 – 207	179	By similarity		PRO_0000029078
	Chain	208 – 909	702	ADAM 12		PRO_0000029079
Regions
	Topological domain	208 – 708	501	Extracellular Potential
	Transmembrane	709 – 729	21	Potential
	Topological domain	730 – 909	180	Cytoplasmic Potential
	Domain	214 – 416	203	Peptidase M12B
	Domain	424 – 510	87	Disintegrin
	Domain	656 – 688	33	EGF-like
	Motif	177 – 184	8	Cysteine switch By similarity
	Motif	828 – 834	7	SH3-binding; class II By similarity
	Motif	834 – 841	8	SH3-binding; class I By similarity
	Motif	885 – 891	7	SH3-binding; class I By similarity
	Compositional bias	514 – 649	136	Cys-rich
Sites
	Active site	351	1
	Metal binding	179	1	Zinc; in inhibited form By similarity
	Metal binding	350	1	Zinc; catalytic
	Metal binding	354	1	Zinc; catalytic
	Metal binding	360	1	Zinc; catalytic
Amino acid modifications
	Modified residue	907	1	Phosphotyrosine; by SRC By similarity
	Glycosylation	111	1	N-linked (GlcNAc...) Potential
	Glycosylation	149	1	N-linked (GlcNAc...) Potential
	Glycosylation	381	1	N-linked (GlcNAc...) Potential
	Glycosylation	452	1	N-linked (GlcNAc...) Potential
	Glycosylation	651	1	N-linked (GlcNAc...) Potential
	Disulfide bond	325 ↔ 411		By similarity
	Disulfide bond	367 ↔ 395		By similarity
	Disulfide bond	369 ↔ 378		By similarity
	Disulfide bond	482 ↔ 502		By similarity
	Disulfide bond	660 ↔ 670		By similarity
	Disulfide bond	664 ↔ 676		By similarity
	Disulfide bond	678 ↔ 687		By similarity
Natural variations
	Alternative sequence	114 – 116	3	Missing in isoform 3 and isoform 4.		VSP_031001
	Alternative sequence	705 – 740	36	DNQGL…RLLFT → GKEARQEAAESNRERGQGQE PVGSQEHASTASLTLI in isoform 4.		VSP_031002
	Alternative sequence	705 – 738	34	DNQGL…LIRLL → EARQEAAESNRERGQGQEPV GSQEHASTASLTLI in isoform 2 and isoform 3.		VSP_005476
	Alternative sequence	739 – 909	171	Missing in isoform 2 and isoform 3.		VSP_005477
	Alternative sequence	741 – 909	169	Missing in isoform 4.		VSP_031003
	Natural variant	48	1	R → G: dbSNP rs3740199. Ref.4		VAR_038542
	Natural variant	301	1	D → H in a breast cancer sample; somatic mutation. Ref.10		VAR_036143
	Natural variant	479	1	G → E in a breast cancer sample; somatic mutation. Ref.10		VAR_036144
	Natural variant	792	1	L → F in a breast cancer sample; somatic mutation. Ref.10		VAR_036145

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (12L) [UniParc]. Last modified January 31, 2002. Version 2. Checksum: 844A2D19408E97CF	FASTA	909	99,641
	10 20 30 40 50 60 MAARPLPVSP ARALLLALAG ALLAPCEARG VSLWNQGRAD EVVSASVRSG DLWIPVKSFD 70 80 90 100 110 120 SKNHPEVLNI RLQRESKELI INLERNEGLI ASSFTETHYL QDGTDVSLAR NYTVILGHCY 130 140 150 160 170 180 YHGHVRGYSD SAVSLSTCSG LRGLIVFENE SYVLEPMKSA TNRYKLFPAK KLKSVRGSCG 190 200 210 220 230 240 SHHNTPNLAA KNVFPPPSQT WARRHKRETL KATKYVELVI VADNREFQRQ GKDLEKVKQR 250 260 270 280 290 300 LIEIANHVDK FYRPLNIRIV LVGVEVWNDM DKCSVSQDPF TSLHEFLDWR KMKLLPRKSH 310 320 330 340 350 360 DNAQLVSGVY FQGTTIGMAP IMSMCTADQS GGIVMDHSDN PLGAAVTLAH ELGHNFGMNH 370 380 390 400 410 420 DTLDRGCSCQ MAVEKGGCIM NASTGYPFPM VFSSCSRKDL ETSLEKGMGV CLFNLPEVRE 430 440 450 460 470 480 SFGGQKCGNR FVEEGEECDC GEPEECMNRC CNATTCTLKP DAVCAHGLCC EDCQLKPAGT 490 500 510 520 530 540 ACRDSSNSCD LPEFCTGASP HCPANVYLHD GHSCQDVDGY CYNGICQTHE QQCVTLWGPG 550 560 570 580 590 600 AKPAPGICFE RVNSAGDPYG NCGKVSKSSF AKCEMRDAKC GKIQCQGGAS RPVIGTNAVS 610 620 630 640 650 660 IETNIPLQQG GRILCRGTHV YLGDDMPDPG LVLAGTKCAD GKICLNRQCQ NISVFGVHEC 670 680 690 700 710 720 AMQCHGRGVC NNRKNCHCEA HWAPPFCDKF GFGGSTDSGP IRQADNQGLT IGILVTILCL 730 740 750 760 770 780 LAAGFVVYLK RKTLIRLLFT NKKTTIEKLR CVRPSRPPRG FQPCQAHLGH LGKGLMRKPP 790 800 810 820 830 840 DSYPPKDNPR RLLQCQNVDI SRPLNGLNVP QPQSTQRVLP PLHRAPRAPS VPARPLPAKP 850 860 870 880 890 900 ALRQAQGTCK PNPPQKPLPA DPLARTTRLT HALARTPGQW ETGLRLAPLR PAPQYPHQVP RSTHTAYIK
	Isoform 2 (12S). Checksum: 92EABF5315D1E527		738	80,502
	10 20 30 40 50 60 MAARPLPVSP ARALLLALAG ALLAPCEARG VSLWNQGRAD EVVSASVRSG DLWIPVKSFD 70 80 90 100 110 120 SKNHPEVLNI RLQRESKELI INLERNEGLI ASSFTETHYL QDGTDVSLAR NYTVILGHCY 130 140 150 160 170 180 YHGHVRGYSD SAVSLSTCSG LRGLIVFENE SYVLEPMKSA TNRYKLFPAK KLKSVRGSCG 190 200 210 220 230 240 SHHNTPNLAA KNVFPPPSQT WARRHKRETL KATKYVELVI VADNREFQRQ GKDLEKVKQR 250 260 270 280 290 300 LIEIANHVDK FYRPLNIRIV LVGVEVWNDM DKCSVSQDPF TSLHEFLDWR KMKLLPRKSH 310 320 330 340 350 360 DNAQLVSGVY FQGTTIGMAP IMSMCTADQS GGIVMDHSDN PLGAAVTLAH ELGHNFGMNH 370 380 390 400 410 420 DTLDRGCSCQ MAVEKGGCIM NASTGYPFPM VFSSCSRKDL ETSLEKGMGV CLFNLPEVRE 430 440 450 460 470 480 SFGGQKCGNR FVEEGEECDC GEPEECMNRC CNATTCTLKP DAVCAHGLCC EDCQLKPAGT 490 500 510 520 530 540 ACRDSSNSCD LPEFCTGASP HCPANVYLHD GHSCQDVDGY CYNGICQTHE QQCVTLWGPG 550 560 570 580 590 600 AKPAPGICFE RVNSAGDPYG NCGKVSKSSF AKCEMRDAKC GKIQCQGGAS RPVIGTNAVS 610 620 630 640 650 660 IETNIPLQQG GRILCRGTHV YLGDDMPDPG LVLAGTKCAD GKICLNRQCQ NISVFGVHEC 670 680 690 700 710 720 AMQCHGRGVC NNRKNCHCEA HWAPPFCDKF GFGGSTDSGP IRQAEARQEA AESNRERGQG 730 QEPVGSQEHA STASLTLI
	Isoform 3. Checksum: CD0A72179617AB30		735	80,177
	10 20 30 40 50 60 MAARPLPVSP ARALLLALAG ALLAPCEARG VSLWNQGRAD EVVSASVRSG DLWIPVKSFD 70 80 90 100 110 120 SKNHPEVLNI RLQRESKELI INLERNEGLI ASSFTETHYL QDGTDVSLAR NYTGHCYYHG 130 140 150 160 170 180 HVRGYSDSAV SLSTCSGLRG LIVFENESYV LEPMKSATNR YKLFPAKKLK SVRGSCGSHH 190 200 210 220 230 240 NTPNLAAKNV FPPPSQTWAR RHKRETLKAT KYVELVIVAD NREFQRQGKD LEKVKQRLIE 250 260 270 280 290 300 IANHVDKFYR PLNIRIVLVG VEVWNDMDKC SVSQDPFTSL HEFLDWRKMK LLPRKSHDNA 310 320 330 340 350 360 QLVSGVYFQG TTIGMAPIMS MCTADQSGGI VMDHSDNPLG AAVTLAHELG HNFGMNHDTL 370 380 390 400 410 420 DRGCSCQMAV EKGGCIMNAS TGYPFPMVFS SCSRKDLETS LEKGMGVCLF NLPEVRESFG 430 440 450 460 470 480 GQKCGNRFVE EGEECDCGEP EECMNRCCNA TTCTLKPDAV CAHGLCCEDC QLKPAGTACR 490 500 510 520 530 540 DSSNSCDLPE FCTGASPHCP ANVYLHDGHS CQDVDGYCYN GICQTHEQQC VTLWGPGAKP 550 560 570 580 590 600 APGICFERVN SAGDPYGNCG KVSKSSFAKC EMRDAKCGKI QCQGGASRPV IGTNAVSIET 610 620 630 640 650 660 NIPLQQGGRI LCRGTHVYLG DDMPDPGLVL AGTKCADGKI CLNRQCQNIS VFGVHECAMQ 670 680 690 700 710 720 CHGRGVCNNR KNCHCEAHWA PPFCDKFGFG GSTDSGPIRQ AEARQEAAES NRERGQGQEP 730 VGSQEHASTA SLTLI
	Isoform 4. Checksum: CB4D93668071B329		737	80,362
	10 20 30 40 50 60 MAARPLPVSP ARALLLALAG ALLAPCEARG VSLWNQGRAD EVVSASVRSG DLWIPVKSFD 70 80 90 100 110 120 SKNHPEVLNI RLQRESKELI INLERNEGLI ASSFTETHYL QDGTDVSLAR NYTGHCYYHG 130 140 150 160 170 180 HVRGYSDSAV SLSTCSGLRG LIVFENESYV LEPMKSATNR YKLFPAKKLK SVRGSCGSHH 190 200 210 220 230 240 NTPNLAAKNV FPPPSQTWAR RHKRETLKAT KYVELVIVAD NREFQRQGKD LEKVKQRLIE 250 260 270 280 290 300 IANHVDKFYR PLNIRIVLVG VEVWNDMDKC SVSQDPFTSL HEFLDWRKMK LLPRKSHDNA 310 320 330 340 350 360 QLVSGVYFQG TTIGMAPIMS MCTADQSGGI VMDHSDNPLG AAVTLAHELG HNFGMNHDTL 370 380 390 400 410 420 DRGCSCQMAV EKGGCIMNAS TGYPFPMVFS SCSRKDLETS LEKGMGVCLF NLPEVRESFG 430 440 450 460 470 480 GQKCGNRFVE EGEECDCGEP EECMNRCCNA TTCTLKPDAV CAHGLCCEDC QLKPAGTACR 490 500 510 520 530 540 DSSNSCDLPE FCTGASPHCP ANVYLHDGHS CQDVDGYCYN GICQTHEQQC VTLWGPGAKP 550 560 570 580 590 600 APGICFERVN SAGDPYGNCG KVSKSSFAKC EMRDAKCGKI QCQGGASRPV IGTNAVSIET 610 620 630 640 650 660 NIPLQQGGRI LCRGTHVYLG DDMPDPGLVL AGTKCADGKI CLNRQCQNIS VFGVHECAMQ 670 680 690 700 710 720 CHGRGVCNNR KNCHCEAHWA PPFCDKFGFG GSTDSGPIRQ AGKEARQEAA ESNRERGQGQ 730 EPVGSQEHAS TASLTLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo." Gilpin B.J., Loechel F., Mattei M.-G., Engvall E., Albrechtsen R., Wewer U.M. J. Biol. Chem. 273:157-166(1998) [PubMed: 9417060] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Placenta.
[2]	Gilpin B.J., Loechel F., Mattei M.-G., Engvall E., Albrechtsen R., Wewer U.M. Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 36.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLY-48.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Placenta.
[7]	"Human ADAM 12 (meltrin alpha) is an active metalloprotease." Loechel F., Gilpin B.J.,