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Protein

Disintegrin and metalloproteinase domain-containing protein 9

Gene

Adam9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:105376 Adam9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Glycosylationi154N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi231N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi322 ↔ 401By similarity
Disulfide bondi363 ↔ 385By similarity
Disulfide bondi365 ↔ 370By similarity
Glycosylationi381N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi473 ↔ 493By similarity
Glycosylationi487N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi636N-linked (GlcNAc...) asparagineSequence 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

  • 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

BioGridi197973, 1 interactor
IntActiQ61072, 3 interactors
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

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3607 Eukaryota
ENOG410XX2M LUCA
GeneTreeiENSGT00910000144019
HOGENOMiHOG000230883
HOVERGENiHBG006978
InParanoidiQ61072
KOiK06834
OrthoDBiEOG091G01NX
TreeFamiTF314733

Family and domain databases

CDDicd04269 ZnMc_adamalysin_II_like, 1 hit
Gene3Di3.40.390.10, 1 hit
4.10.70.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR018358 Disintegrin_CS
IPR001762 Disintegrin_dom
IPR036436 Disintegrin_dom_sf
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR034027 Reprolysin_adamalysin
PfamiView protein in Pfam
PF08516 ADAM_CR, 1 hit
PF00200 Disintegrin, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF01421 Reprolysin, 1 hit
PRINTSiPR00289 DISINTEGRIN
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00050 DISIN, 1 hit
SUPFAMiSSF57552 SSF57552, 1 hit
PROSITEiView protein in PROSITE
PS50215 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

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

Similar proteinsi

Entry informationi

Entry nameiADAM9_MOUSE
AccessioniPrimary (citable) accession number: Q61072
Secondary accession number(s): E9QPP2
, Q60618, Q61853, Q80U94
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 27, 2011
Last modified: April 25, 2018
This is version 152 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health