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Protein

Disintegrin and metalloproteinase domain-containing protein 15

Gene

Adam15

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Active metalloproteinase with gelatinolytic and collagenolytic activity. Plays a role in the wound healing process. Mediates both heterotypic intraepithelial cell/T-cell interactions and homotypic T-cell aggregation. Inhibits beta-1 integrin-mediated cell adhesion and migration of airway smooth muscle cells. Suppresses cell motility on or towards fibronectin possibly by driving alpha-v/beta-1 integrin (ITAGV-ITGB1) cell surface expression via ERK1/2 inactivation. Cleaves E-cadherin in response to growth factor deprivation. Plays a role in glomerular cell migration. Plays a role in pathological neovascularization. May play a role in cartilage remodeling. May be proteolytically processed, during sperm epididymal maturation and the acrosome reaction. May play a role in sperm-egg binding through its disintegrin domain (By similarity).By similarity

Cofactori

Zn2+CuratedNote: Binds 1 zinc ion per subunit.Curated

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi180 – 1801Zinc; in inhibited formBy similarity
Metal bindingi350 – 3501Zinc; catalyticSequence analysis
Active sitei351 – 3511PROSITE-ProRule annotation
Metal bindingi354 – 3541Zinc; catalyticSequence analysis
Metal bindingi360 – 3601Zinc; catalyticSequence analysis

GO - Molecular functioni

  • metalloendopeptidase activity Source: RGD
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Angiogenesis, Cell adhesion, Collagen degradation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-1474228. Degradation of the extracellular matrix.

Protein family/group databases

MEROPSiM12.215.

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 15 (EC:3.4.24.-)
Short name:
ADAM 15
Alternative name(s):
CRII-7
Metalloprotease RGD disintegrin protein
Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 15
Short name:
MDC-15
Metargidin
Gene namesi
Name:Adam15
Synonyms:Mdc15
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi620402. Adam15.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini209 – 698490ExtracellularSequence analysisAdd
BLAST
Transmembranei699 – 71921HelicalSequence analysisAdd
BLAST
Topological domaini720 – 864145CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasmic vesicle, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Propeptidei18 – 208191By similarityPRO_0000029086Add
BLAST
Chaini209 – 864656Disintegrin and metalloproteinase domain-containing protein 15PRO_0000029087Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi57 – 571N-linked (GlcNAc...)Sequence analysis
Glycosylationi239 – 2391N-linked (GlcNAc...)Sequence analysis
Disulfide bondi325 ↔ 411By similarity
Disulfide bondi367 ↔ 395By similarity
Disulfide bondi369 ↔ 378By similarity
Glycosylationi391 – 3911N-linked (GlcNAc...)Sequence analysis
Glycosylationi394 – 3941N-linked (GlcNAc...)Sequence analysis
Disulfide bondi482 ↔ 502By similarity
Glycosylationi608 – 6081N-linked (GlcNAc...)Sequence analysis
Glycosylationi613 – 6131N-linked (GlcNAc...)Sequence analysis
Disulfide bondi659 ↔ 669By similarity
Disulfide bondi663 ↔ 675By similarity
Disulfide bondi677 ↔ 686By similarity
Modified residuei717 – 7171Phosphotyrosine; by HCK and LCKBy similarity
Modified residuei737 – 7371Phosphotyrosine; by HCK and LCKBy similarity

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity
Phosphorylation increases association with PTKs.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiQ9QYV0.

Expressioni

Tissue specificityi

Predominantly expressed in brain, spinal cord, sciatic nerve and lung. Expressed at lower levels in all other tissues. In the peripheral nervous system, expressed predominantly by Schwann cells. In the central nervous system, preferentially expressed by neuronal cells.

Inductioni

In response to sciatic nerve injury.

Gene expression databases

GenevisibleiQ9QYV0. RN.

Interactioni

Subunit structurei

Interacts with ITAGV-ITGB3 (vitronectin receptor). Interacts with SH3GL2 and SNX9; this interaction occurs preferentially with ADAM15 precursor, rather than the processed form, suggesting it occurs in a secretory pathway compartment prior to the medial Golgi (By similarity). Interacts with ITAG9-ITGB1. Interacts specifically with Src family protein-tyrosine kinases (PTKs). Interacts with SH3PXD2A. Interacts with ITAGV-ITGB1. Interacts with GRB2, HCK, ITSN1, ITSN2, LYN, MAPK1, MAPK3, NCF1, NCK1, nephrocystin, PTK6, SNX33, LCK and SRC (By similarity).By similarity

Protein-protein interaction databases

BioGridi248604. 1 interaction.
STRINGi10116.ENSRNOP00000039351.

Structurei

3D structure databases

ProteinModelPortaliQ9QYV0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini215 – 416202Peptidase M12BPROSITE-ProRule annotationAdd
BLAST
Domaini423 – 51088DisintegrinPROSITE-ProRule annotationAdd
BLAST
Domaini659 – 68729EGF-likePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi178 – 1858Cysteine switchBy similarity
Motifi816 – 8227SH3-bindingSequence analysis
Motifi851 – 8577SH3-bindingSequence analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi511 – 658148Cys-richAdd
BLAST
Compositional biasi700 – 71314Poly-LeuAdd
BLAST

Domaini

The cytoplasmic domain is required for SH3GL2- and SNX9-binding.By similarity
Disintegrin domain binds to integrin alphaV-beta3.By similarity
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.
HOGENOMiHOG000230884.
HOVERGENiHBG006978.
InParanoidiQ9QYV0.
KOiK06836.
OMAiHGVCDSN.
OrthoDBiEOG7F7W89.
PhylomeDBiQ9QYV0.
TreeFamiTF314733.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR033605. ADAM15.
IPR006586. ADAM_Cys-rich.
IPR001762. Disintegrin_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERiPTHR11905:SF130. PTHR11905:SF130. 2 hits.
PfamiPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
SMARTiSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9QYV0-1) [UniParc]FASTAAdd to basket

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
MRLALLWALG LLGAGSPRPS PPLPNIGGTE EEQQASPERT QSRSLENQVV
60 70 80 90 100
QDSPPINLTE VLQTGLPETL RIGLELDGEN HILELQQNRD LVPGRPTLVW
110 120 130 140 150
YQPDGTRMVS EGHSLENCCY RGRVQGRPSS WVSLCACSGI RGLVVLSPER
160 170 180 190 200
SYTLELGPGD LQRPLIVSRI QDLLLPGHTC APSWHAFVPT EAAPDLLLEQ
210 220 230 240 250
HHLRRLKRDV VTETKIVELV IVADNSEVRK YPDFQQLLNR TLEVALLLDT
260 270 280 290 300
FFQPLNVRVA LVGLEAWTQR DLIEMSSNPA VLLDNFLRWR RTDLLPRLPH
310 320 330 340 350
DSAQLVTVTS FSGPMVGMAI QNSICSPDFS GGVNMDHSTS ILGVASSIAH
360 370 380 390 400
ELGHSLGLDH DSPGNSCPCP GPAPAKSCIM EASTDFLPGL NFSNCSRWAL
410 420 430 440 450
EKALLDGMGS CLFEWPPSRA PMSSLCGNMF VDPGEQCDCG FPDECTDPCC
460 470 480 490 500
DYFTCQLRPG AQCASDGPCC QNCKLQPAGW QCRLPTDDCD LPEFCLGDSS
510 520 530 540 550
QCPPDIRLGD GEPCASGEAV CMHGRCASYT RQCQSLWGPG AQPAAPLCLQ
560 570 580 590 600
TANTRGNAFG SCGRSPSGSY MPCNLRDAIC GQLQCQWGRN QPLLGSVQDQ
610 620 630 640 650
LSEVLEANGT QLNCSWVDLD LGNDVAQPLL ALPGTACGPG LVCIGHRCQP
660 670 680 690 700
VDLLGAQECR SKCHGHGVCD SSRHCHCDEG WAPPDCMTQL RATSSLTTGL
710 720 730 740 750
LLSLLLLLVL VLLGASYWYR ARLHQRLCQL KGSSCQYRAA QSGPPERPGP
760 770 780 790 800
PQRAQQMPGT KQANVSFPVP PSRPLPPNPV PKKLQAELAD RSNPPTRPLP
810 820 830 840 850
ADPVVWRPKP QGPTKPPPPR KPLPANPQGR PPLGDLPGPG DGSLQLVVPS
860
RPAPPPPAAS SLYL
Length:864
Mass (Da):93,308
Last modified:July 13, 2010 - v2
Checksum:i5D46466922A89196
GO
Isoform 2 (identifier: Q9QYV0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     762-809: Missing.

Show »
Length:816
Mass (Da):88,052
Checksum:iB9D2CE023266FC27
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti202 – 2021H → R in AAH61796 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei762 – 80948Missing in isoform 2. 1 PublicationVSP_039534Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ251198 mRNA. Translation: CAB61762.1.
BC061796 mRNA. Translation: AAH61796.1.
RefSeqiNP_064704.1. NM_020308.1. [Q9QYV0-2]
XP_006232804.1. XM_006232742.2. [Q9QYV0-1]
UniGeneiRn.162607.

Genome annotation databases

EnsembliENSRNOT00000027970; ENSRNOP00000027970; ENSRNOG00000020590. [Q9QYV0-2]
ENSRNOT00000050868; ENSRNOP00000039351; ENSRNOG00000020590. [Q9QYV0-1]
GeneIDi57025.
KEGGirno:57025.
UCSCiRGD:620402. rat. [Q9QYV0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ251198 mRNA. Translation: CAB61762.1.
BC061796 mRNA. Translation: AAH61796.1.
RefSeqiNP_064704.1. NM_020308.1. [Q9QYV0-2]
XP_006232804.1. XM_006232742.2. [Q9QYV0-1]
UniGeneiRn.162607.

3D structure databases

ProteinModelPortaliQ9QYV0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248604. 1 interaction.
STRINGi10116.ENSRNOP00000039351.

Protein family/group databases

MEROPSiM12.215.

Proteomic databases

PaxDbiQ9QYV0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000027970; ENSRNOP00000027970; ENSRNOG00000020590. [Q9QYV0-2]
ENSRNOT00000050868; ENSRNOP00000039351; ENSRNOG00000020590. [Q9QYV0-1]
GeneIDi57025.
KEGGirno:57025.
UCSCiRGD:620402. rat. [Q9QYV0-1]

Organism-specific databases

CTDi8751.
RGDi620402. Adam15.

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230884.
HOVERGENiHBG006978.
InParanoidiQ9QYV0.
KOiK06836.
OMAiHGVCDSN.
OrthoDBiEOG7F7W89.
PhylomeDBiQ9QYV0.
TreeFamiTF314733.

Enzyme and pathway databases

ReactomeiR-RNO-1474228. Degradation of the extracellular matrix.

Miscellaneous databases

PROiQ9QYV0.

Gene expression databases

GenevisibleiQ9QYV0. RN.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProiIPR033605. ADAM15.
IPR006586. ADAM_Cys-rich.
IPR001762. Disintegrin_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PANTHERiPTHR11905:SF130. PTHR11905:SF130. 2 hits.
PfamiPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
SMARTiSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
[Graphical view]
SUPFAMiSSF57552. SSF57552. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cellular localization of the disintegrin CRII-7/rMDC15 mRNA in rat PNS and CNS and regulated expression in postnatal development and after nerve injury."
    Bosse F., Petzold G., Greiner-Petter R., Pippirs U., Gillen C., Mueller H.-W.
    Glia 32:313-327(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Sciatic nerve.
  2. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Prostate.

Entry informationi

Entry nameiADA15_RAT
AccessioniPrimary (citable) accession number: Q9QYV0
Secondary accession number(s): Q6P779
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: July 13, 2010
Last modified: July 6, 2016
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.