Reviewed, UniProtKB/Swiss-Prot Q13444 (ADA15_HUMAN)

Names and origin

Protein names

Recommended name:
    ADAM 15
    EC=3.4.24.-
Alternative name(s):
    A disintegrin and metalloproteinase domain 15
    Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 15
      Short name(s)=MDC-15
    Metalloprotease RGD disintegrin protein
    Metargidin

Gene names

Name:	ADAM15
Synonyms:	MDC15

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	814 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	May be involved in cell-surface proteolysis, cell adhesion or intracellular protein maturation.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Interacts with ITAGV-ITGB3 (vitronectin receptor), PACSIN3 and SNX9. PACSIN3 and SNX9 preferentially bind the precursor but not the processed form of ADAM15, suggesting that the interaction occurs in a secretory pathway compartment prior to the medial Golgi By similarity. Interacts specifically with Src family protein-tyrosine kinases (PTKs). Interacts with SH3PXD2A.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Ubiquitously expressed. Overexpressed in atherosclerotic lesions. Constitutively expressed in cultured endothelium and smooth muscle. Expressed in chondrocytes.
Domain	The cytoplasmic domain interacts with endophilin I and sorting nexin 9 By similarity. Desintegrin domain binds to integrin alphaV-beta3. 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. Phosphorylation increases association with PTKs.
Sequence similarities	Contains 1 disintegrin domain. Contains 1 EGF-like domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Cellular component	Membrane
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-matrix adhesion Ref.8 Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Non-traceable author statement. Source: UniProtKB
Molecular function	SH3 domain binding Inferred from physical interaction. Source: UniProtKB metallopeptidase activity Ref.8 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PACSIN3	Q9UKS6	1	EBI-77818,EBI-77926
SH3GL2	Q99962	1	EBI-77818,EBI-77938

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Propeptide	18 – 206	189	By similarity
	Chain	207 – 814	608	ADAM 15
Regions
	Topological domain	207 – 696	490	Extracellular Potential
	Transmembrane	697 – 717	21	Potential
	Topological domain	718 – 814	97	Cytoplasmic Potential
	Domain	213 – 414	202	Peptidase M12B
	Domain	421 – 508	88	Disintegrin
	Domain	657 – 685	29	EGF-like
	Motif	177 – 184	8	Cysteine switch By similarity
	Motif	484 – 486	3	Cell attachment site Potential
	Motif	766 – 772	7	SH3-binding Potential
	Motif	801 – 807	7	SH3-binding Potential
	Compositional bias	509 – 656	148	Cys-rich
Sites
	Active site	349	1	By similarity
	Metal binding	179	1	Zinc (in inhibited form) By similarity
	Metal binding	348	1	Zinc (catalytic) By similarity
	Metal binding	352	1	Zinc (catalytic) By similarity
	Metal binding	358	1	Zinc (catalytic) By similarity
Amino acid modifications
	Modified residue	715	1	Phosphotyrosine
	Modified residue	735	1	Phosphotyrosine
	Glycosylation	237	1	N-linked (GlcNAc...) Potential
	Glycosylation	389	1	N-linked (GlcNAc...) Potential
	Glycosylation	392	1	N-linked (GlcNAc...) Potential
	Glycosylation	606	1	N-linked (GlcNAc...) Potential
	Glycosylation	611	1	N-linked (GlcNAc...) Potential
	Disulfide bond	323 ↔ 409		By similarity
	Disulfide bond	365 ↔ 393		By similarity
	Disulfide bond	367 ↔ 376		By similarity
	Disulfide bond	480 ↔ 500		By similarity
	Disulfide bond	657 ↔ 667		By similarity
	Disulfide bond	661 ↔ 673		By similarity
	Disulfide bond	675 ↔ 684		By similarity
Experimental info
	Sequence conflict	714	1	S → G in AAC50404. Ref.1
	Sequence conflict	791	1	A → P in AAC51112. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q13444-1 [UniParc]. Last modified March 25, 2003. Version 2. Checksum: 683A8368AD30996B	FASTA	814	87,717
	10 20 30 40 50 60 MRLALLWALG LLGAGSPLPS WPLPNIGGTE EQQAESEKAP REPLEPQVLQ DDLPISLKKV 70 80 90 100 110 120 LQTSLPEPLR IKLELDGDSH ILELLQNREL VPGRPTLVWY QPDGTRVVSE GHTLENCCYQ 130 140 150 160 170 180 GRVRGYAGSW VSICTCSGLR GLVVLTPERS YTLEQGPGDL QGPPIISRIQ DLHLPGHTCA 190 200 210 220 230 240 LSWRESVHTQ TPPEHPLGQR HIRRRRDVVT ETKTVELVIV ADHSEAQKYR DFQHLLNRTL 250 260 270 280 290 300 EVALLLDTFF RPLNVRVALV GLEAWTQRDL VEISPNPAVT LENFLHWRRA HLLPRLPHDS 310 320 330 340 350 360 AQLVTGTSFS GPTVGMAIQN SICSPDFSGG VNMDHSTSIL GVASSIAHEL GHSLGLDHDL 370 380 390 400 410 420 PGNSCPCPGP APAKTCIMEA STDFLPGLNF SNCSRRALEK ALLDGMGSCL FERLPSLPPM 430 440 450 460 470 480 AAFCGNMFVE PGEQCDCGFL DDCVDPCCDS LTCQLRPGAQ CASDGPCCQN CQLRPSGWQC 490 500 510 520 530 540 RPTRGDCDLP EFCPGDSSQC PPDVSLGDGE PCAGGQAVCM HGRCASYAQQ CQSLWGPGAQ 550 560 570 580 590 600 PAAPLCLQTA NTRGNAFGSC GRNPSGSYVS CTPRDAICGQ LQCQTGRTQP LLGSIRDLLW 610 620 630 640 650 660 ETIDVNGTEL NCSWVHLDLG SDVAQPLLTL PGTACGPGLV CIDHRCQRVD LLGAQECRSK 670 680 690 700 710 720 CHGHGVCDSN RHCYCEEGWA PPDCTTQLKA TSSLTTGLLL SLLVLLVLVM LGASYWYRAR 730 740 750 760 770 780 LHQRLCQLKG PTCQYRAAQS GPSERPGPPQ RALLARGTKS QGPAKPPPPR KPLPADPQGR 790 800 810 CPSGDLPGPG AGIPPLVVPS RPAPPPPTVS SLYL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Metargidin, a membrane-anchored metalloprotease-disintegrin protein with an RGD integrin binding sequence." Kraetzschmar J., Lum L., Blobel C.P. J. Biol. Chem. 271:4593-4596(1996) [PubMed: 8617717] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary carcinoma.
[2]	"Expression of a disintegrin-like protein in cultured human vascular cells and in vivo." Herren B., Raines E.W., Ross R. FASEB J. 11:173-180(1997) [PubMed: 9039960] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Umbilical vein.
[3]	"The characterization of human ADAM15 gene structure and promoter region." Karkkainen I., Huovila A.-P.J. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Characterization of human ADAM15 gene and promoter, and evidence for alternative exon use." Karkkainen I., Ortiz R.M., Huovila A.-P.J. Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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]. Tissue: Kidney.
[7]	"Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes." McKie N., Edwards T., Dallas D.J., Houghton A., Stringer B., Graham R., Russell G., Croucher P.I. Biochem. Biophys. Res. Commun. 230:335-339(1997) [PubMed: 9016778] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Specific interaction of the recombinant disintegrin-like domain of MDC-15 (metargidin, ADAM-15) with integrin alphavbeta3." Zhang X.P., Kamata T., Yokoyama K., Puzon-McLaughlin W., Takada Y. J. Biol. Chem. 273:7345-7350(1998) [PubMed: 9516430] [Abstract] Cited for: INTERACTION WITH INTEGRIN ALPHAV-BETA3.
[9]	"Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases." Poghosyan Z., Robbins S.M., Houslay M.D., Webster A., Murphy G., Edwards D.R. J. Biol. Chem. 277:4999-5007(2002) [PubMed: 11741929] [Abstract] Cited for: PHOSPHORYLATION AT TYR-715 AND TYR-735.
[10]	"The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells." Abram C.L., Seals D.F., Pass I., Salinsky D., Maurer L., Roth T.M., Courtneidge S.A. J. Biol. Chem. 278:16844-16851(2003) [PubMed: 12615925] [Abstract] Cited for: INTERACTION WITH SH3PXD2A.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U46005 mRNA. Translation: AAC51112.1. U41767 mRNA. Translation: AAC50404.1. AF314227 Genomic DNA. Translation: AAM44189.1. AY560594 mRNA. Translation: AAS72992.1. BT009764 mRNA. Translation: AAP88766.1. BC014566 mRNA. Translation: AAH14566.1.
PIR	G02390.
RefSeq	NP_003806.3.
UniGene	Hs.312098
3D structure databases
HSSP	HSSP built from PDB template 1FVL based on UniProtKB P18619.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13444.
Protein family/group databases
MEROPS	M12.215.
PTM databases
PhosphoSite	Q13444.
Genome annotation databases
Ensembl	ENSG00000143537. Homo sapiens. [Contig view]
GeneID	8751.
KEGG	hsa:8751.
Organism-specific databases
H-InvDB	HIX0001025.
HGNC	HGNC:193. ADAM15.
HPA	HPA011633.
MIM	605548. gene.
PharmGKB	PA24510.
GenAtlas	Search...
GeneCards	Search...
GeneLynx	Search...
Phylogenomic databases
HOVERGEN	Q13444.
Gene expression databases
ArrayExpress	Q13444.
CleanEx	HS_ADAM15.
GermOnline	ENSG00000143537. Homo sapiens.
Family and domain databases
InterPro	IPR006586. ADAM_cysteine. IPR001762. Blood-coag_inhib_Disintegrin. IPR006210. EGF. IPR000742. EGF_3. IPR013111. EGF_extracell. IPR013032. EGF_like_reg_CS. IPR001818. Pept_M10A_M12B. IPR006025. Pept_M_Zn_BS. IPR001590. Peptidase_M12B. IPR002870. Peptidase_M12B_N. [Graphical view]
Gene3D	G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.
Pfam	PF08516. ADAM_CR. 1 hit. PF00200. Disintegrin. 1 hit. PF07974. EGF_2. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF01421. Reprolysin. 1 hit. [Graphical view]
ProDom	PD000664. Disintegrin. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00608. ACR. 1 hit. SM00050. DISIN. 1 hit. SM00181. EGF. 1 hit. [Graphical view]
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00546. CYSTEINE_SWITCH. False negative. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ADA15_HUMAN

Accession

Primary (citable) accession number: Q13444
Secondary accession number(s): Q13493, Q53XQ0, Q96C78

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	March 25, 2003
Last modified:	July 22, 2008
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)