Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Disintegrin and metalloproteinase domain-containing protein 9

Gene

Adam9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5 (PubMed:19273593). May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins (PubMed:10825303).2 Publications

Cofactori

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

Enzyme regulationi

Synthesized as an inactive form which is proteolytically cleaved to generate an active enzyme. Processing at the upstream site is particularly important for activation of the proenzyme, whereas processing at the boundary between the pro-domain and the catalytic domain does not appear to be essential (PubMed:25795784). Inhibited by hydroxamic acid-based inhibitors (PubMed:9920899).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi347Zinc; catalyticBy similarity1
Active sitei348PROSITE-ProRule annotationBy similarity1
Metal bindingi351Zinc; catalyticBy similarity1
Metal bindingi357Zinc; catalyticBy similarity1

GO - Molecular functioni

  • collagen binding Source: MGI
  • integrin binding Source: MGI
  • laminin binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: BHF-UCL
  • metallopeptidase activity Source: MGI
  • protein kinase C binding Source: BHF-UCL
  • SH3 domain binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.B9. 3474.

Protein family/group databases

MEROPSiM12.209.

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 9 (EC:3.4.24.-)
Short name:
ADAM 9
Alternative name(s):
Meltrin-gamma
Metalloprotease/disintegrin/cysteine-rich protein 9
Myeloma cell metalloproteinase
Gene namesi
Name:Adam9Imported
Synonyms:Kiaa0021Imported, Mdc9, Mltng
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:105376. Adam9.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini30 – 697ExtracellularSequence analysisAdd BLAST668
Transmembranei698 – 718HelicalSequence analysisAdd BLAST21
Topological domaini719 – 845CytoplasmicSequence analysisAdd BLAST127

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • cytoplasm Source: MGI
  • extracellular exosome Source: MGI
  • extracellular space Source: BHF-UCL
  • focal adhesion Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • intrinsic component of external side of plasma membrane Source: BHF-UCL
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Deficient mice appear to develop normally, are viable and fertile, and do not have any major pathological phenotypes (PubMed:11839819). In adulthood, 20 months after birth, mice display progressive retinal degeneration, disorganized retinal layers and a degenerate retinal pigment epithelium (PubMed:19409519).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi53R → A: Reduces the shedding activity; when associated with A-56. Does not prevent pro-domain processing between the pro- and metalloprotease domain; when associated with A-56. 1 Publication1
Mutagenesisi56R → A: Reduces the shedding activity; when associated with A-56. Does not prevent pro-domain processing between the pro- and metalloprotease domain; when associated with A-56. 1 Publication1
Mutagenesisi202R → A: Does not affect shedding activity; when associated with A-205. 1 Publication1
Mutagenesisi205R → A: Does not affect shedding activity; when associated with A-203. 1 Publication1
Mutagenesisi348E → A: Abolishes catalytic activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
ChainiPRO_000002906330 – 845Disintegrin and metalloproteinase domain-containing protein 9Add BLAST816

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi144N-linked (GlcNAc...)Sequence analysis1
Glycosylationi154N-linked (GlcNAc...)Sequence analysis1
Glycosylationi231N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi322 ↔ 401By similarity
Disulfide bondi363 ↔ 385By similarity
Disulfide bondi365 ↔ 370By similarity
Glycosylationi381N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi473 ↔ 493By similarity
Glycosylationi487N-linked (GlcNAc...)Sequence analysis1
Glycosylationi636N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi644 ↔ 656By similarity
Disulfide bondi650 ↔ 662By similarity
Disulfide bondi664 ↔ 673By similarity

Post-translational modificationi

Proteolytically cleaved in the trans-Golgi network before it reaches the plasma membrane to generate a mature protein. The removal of the pro-domain occurs via cleavage at two different sites. Processed most likely by a pro-protein convertase such as furin, at the boundary between the pro-domain and the catalytic domain. An additional upstream cleavage pro-protein convertase site (Arg-56/Glu-57) has an important role in the activation of ADAM9.2 Publications
Phosphorylation is induced in vitro by phorbol-12-myristate-13-acetate (PMA) (PubMed:9920899).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei56 – 57Cleavage1 Publication2
Sitei205 – 206Cleavage; by furin-like protease1 Publication2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

EPDiQ61072.
MaxQBiQ61072.
PaxDbiQ61072.
PRIDEiQ61072.

PTM databases

iPTMnetiQ61072.
PhosphoSitePlusiQ61072.

Expressioni

Gene expression databases

BgeeiENSMUSG00000031555.
ExpressionAtlasiQ61072. baseline and differential.
GenevisibleiQ61072. MM.

Interactioni

Subunit structurei

Interacts with SH3GL2 and SNX9 through its cytoplasmic tail (PubMed:10531379). Interacts with ITGA6 (PubMed:10825303).2 Publications

GO - Molecular functioni

  • collagen binding Source: MGI
  • integrin binding Source: MGI
  • laminin binding Source: MGI
  • protein kinase C binding Source: BHF-UCL
  • SH3 domain binding Source: BHF-UCL

Protein-protein interaction databases

IntActiQ61072. 2 interactors.
MINTiMINT-252904.
STRINGi10090.ENSMUSP00000081048.

Structurei

3D structure databases

ProteinModelPortaliQ61072.
SMRiQ61072.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini212 – 406Peptidase M12BPROSITE-ProRule annotationAdd BLAST195
Domaini414 – 501DisintegrinPROSITE-ProRule annotationAdd BLAST88
Domaini644 – 698EGF-likePROSITE-ProRule annotationAdd BLAST55

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi505 – 634Cys-richAdd BLAST130

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, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ61072.
KOiK06834.
OrthoDBiEOG091G01NX.
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.
IPR013032. EGF-like_CS.
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.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q61072-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPRALSPLA SLRLRWLLAC GLLGPVLEAG RPDLEQTVHL SSYEIITPWR
60 70 80 90 100
LTRERREALG PSSQQISYVI QAQGKQHIIH LERNTDLLPN DFVVYTYDKE
110 120 130 140 150
GSLLSDHPNV QSHCHYRGYV EGVQNSAVAV SACFGLRGLL HLENASFGIE
160 170 180 190 200
PLHNSSHFEH IFYPMDGIHQ EPLRCGVSNR DTEKEGTQGD EEEHPSVTQL
210 220 230 240 250
LRRRRAVLPQ TRYVELFIVV DKERYDMMGR NQTAVREEMI RLANYLDSMY
260 270 280 290 300
IMLNIRIVLV GLEIWTDRNP INIIGGAGDV LGNFVQWREK FLITRWRHDS
310 320 330 340 350
AQLVLKKGFG GTAGMAFVGT VCSRSHAGGI NVFGQITVET FASIVAHELG
360 370 380 390 400
HNLGMNHDDG RECFCGAKSC IMNSGASGSR NFSSCSAEDF EKLTLNKGGS
410 420 430 440 450
CLLNIPKPDE AYSAPSCGNK LVDPGEECDC GTAKECEVDP CCEGSTCKLK
460 470 480 490 500
SFAECAYGDC CKDCQFLPGG SMCRGKTSEC DVPEYCNGSS QFCPPDVFIQ
510 520 530 540 550
NGYPCQNSKA YCYNGMCQYY DAQCQVIFGS KAKAAPRDCF IEVNSKGDRF
560 570 580 590 600
GNCGFSGSEY KKCATGNALC GKLQCENVQD MPVFGIVPAI IQTPSRGTKC
610 620 630 640 650
WGVDFQLGSD VPDPGMVNEG TKCDAGKICR NFQCVNASVL NYDCDIQGKC
660 670 680 690 700
HGHGVCNSNK NCHCEDGWAP PHCDTKGYGG SVDSGPTYNA KSTALRDGLL
710 720 730 740 750
VFFFLIVPLV AAAIFLFIKR DELRKTFRKK RSQMSDGRNQ ANVSRQPGDP
760 770 780 790 800
SISRPPGGPN VSRPPGGPGV SRPPGGPGVS RPPGGPGVSR PPPGHGNRFP
810 820 830 840
VPTYAAKQPA QFPSRPPPPQ PKISSQGNLI PARPAPAPPL YSSLT
Length:845
Mass (Da):92,079
Last modified:July 27, 2011 - v2
Checksum:i38C40F89D4A77725
GO

Sequence cautioni

The sequence BAC65470 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti296W → R in AAC52446 (PubMed:8647900).Curated1
Sequence conflicti296W → R in BAC65470 (PubMed:12693553).Curated1
Sequence conflicti296W → R in AAH47156 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U41765 mRNA. Translation: AAC52446.1.
AK122188 mRNA. Translation: BAC65470.1. Different initiation.
AC156553 Genomic DNA. No translation available.
BC047156 mRNA. Translation: AAH47156.1.
D50412 mRNA. Translation: BAA08913.1.
U06145 mRNA. Translation: AAA18424.1.
PIRiI48943.
S60259.
RefSeqiNP_031430.2. NM_007404.2.
UniGeneiMm.28908.

Genome annotation databases

EnsembliENSMUST00000084035; ENSMUSP00000081048; ENSMUSG00000031555.
GeneIDi11502.
KEGGimmu:11502.
UCSCiuc009lfk.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U41765 mRNA. Translation: AAC52446.1.
AK122188 mRNA. Translation: BAC65470.1. Different initiation.
AC156553 Genomic DNA. No translation available.
BC047156 mRNA. Translation: AAH47156.1.
D50412 mRNA. Translation: BAA08913.1.
U06145 mRNA. Translation: AAA18424.1.
PIRiI48943.
S60259.
RefSeqiNP_031430.2. NM_007404.2.
UniGeneiMm.28908.

3D structure databases

ProteinModelPortaliQ61072.
SMRiQ61072.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ61072. 2 interactors.
MINTiMINT-252904.
STRINGi10090.ENSMUSP00000081048.

Protein family/group databases

MEROPSiM12.209.

PTM databases

iPTMnetiQ61072.
PhosphoSitePlusiQ61072.

Proteomic databases

EPDiQ61072.
MaxQBiQ61072.
PaxDbiQ61072.
PRIDEiQ61072.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000084035; ENSMUSP00000081048; ENSMUSG00000031555.
GeneIDi11502.
KEGGimmu:11502.
UCSCiuc009lfk.2. mouse.

Organism-specific databases

CTDi8754.
MGIiMGI:105376. Adam9.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG3607. Eukaryota.
ENOG410XX2M. LUCA.
GeneTreeiENSGT00760000118888.
HOGENOMiHOG000230883.
HOVERGENiHBG006978.
InParanoidiQ61072.
KOiK06834.
OrthoDBiEOG091G01NX.
TreeFamiTF314733.

Enzyme and pathway databases

BRENDAi3.4.24.B9. 3474.

Miscellaneous databases

PROiQ61072.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031555.
ExpressionAtlasiQ61072. baseline and differential.
GenevisibleiQ61072. MM.

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.
IPR013032. EGF-like_CS.
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.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiADAM9_MOUSE
AccessioniPrimary (citable) accession number: Q61072
Secondary accession number(s): E9QPP2
, Q60618, Q61853, Q80U94
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 141 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, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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.