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Protein

Disintegrin and metalloproteinase domain-containing protein 9

Gene

ADAM9

Organism
Homo sapiens (Human)
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. May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins.By similarity
Isoform 2: May act as alpha-secretase for amyloid precursor protein (APP).1 Publication

Caution

Has sometimes been referred to as ADAM-12.Curated

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. Inhibited by hydroxamic acid-based inhibitors.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi347Zinc; catalyticBy similarity1
Active sitei348PROSITE-ProRule annotation1
Metal bindingi351Zinc; catalyticBy similarity1
Metal bindingi357Zinc; catalyticBy similarity1

GO - Molecular functioni

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

GO - Biological processi

  • activation of MAPKK activity Source: BHF-UCL
  • cell adhesion Source: BHF-UCL
  • cell adhesion mediated by integrin Source: BHF-UCL
  • cell-cell adhesion mediated by integrin Source: BHF-UCL
  • cell-matrix adhesion Source: BHF-UCL
  • cell migration Source: UniProtKB
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • integrin-mediated signaling pathway Source: BHF-UCL
  • keratinocyte differentiation Source: BHF-UCL
  • membrane protein ectodomain proteolysis Source: BHF-UCL
  • monocyte activation Source: BHF-UCL
  • PMA-inducible membrane protein ectodomain proteolysis Source: BHF-UCL
  • positive regulation of cell adhesion mediated by integrin Source: BHF-UCL
  • positive regulation of keratinocyte migration Source: BHF-UCL
  • positive regulation of macrophage fusion Source: BHF-UCL
  • positive regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
  • positive regulation of protein secretion Source: BHF-UCL
  • response to calcium ion Source: BHF-UCL
  • response to glucocorticoid Source: BHF-UCL
  • response to hydrogen peroxide Source: BHF-UCL
  • response to laminar fluid shear stress Source: Ensembl
  • response to manganese ion Source: BHF-UCL
  • response to tumor necrosis factor Source: BHF-UCL
  • transforming growth factor beta receptor signaling pathway Source: BHF-UCL

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.B9 2681
ReactomeiR-HSA-1442490 Collagen degradation

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):
Cellular disintegrin-related protein
Meltrin-gamma
Metalloprotease/disintegrin/cysteine-rich protein 9
Myeloma cell metalloproteinase
Gene namesi
Name:ADAM9
Synonyms:KIAA0021, MCMP, MDC9, MLTNG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000168615.11
HGNCiHGNC:216 ADAM9
MIMi602713 gene
neXtProtiNX_Q13443

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 domaini29 – 697ExtracellularSequence analysisAdd BLAST669
Transmembranei698 – 718HelicalSequence analysisAdd BLAST21
Topological domaini719 – 819CytoplasmicSequence analysisAdd BLAST101

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Cone-rod dystrophy 9 (CORD9)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.
See also OMIM:612775

Keywords - Diseasei

Cone-rod dystrophy

Organism-specific databases

DisGeNETi8754
MalaCardsiADAM9
MIMi612775 phenotype
OpenTargetsiENSG00000168615
Orphaneti1872 Cone rod dystrophy
PharmGKBiPA24534

Chemistry databases

ChEMBLiCHEMBL5982
DrugBankiDB05033 INCB7839
GuidetoPHARMACOLOGYi1657

Polymorphism and mutation databases

BioMutaiADAM9
DMDMi24211441

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000002906229 – 819Disintegrin and metalloproteinase domain-containing protein 9Add BLAST791

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi125N-linked (GlcNAc...) asparagineSequence analysis1
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
Disulfide bondi644 ↔ 656By similarity
Disulfide bondi650 ↔ 662By similarity
Disulfide bondi664 ↔ 673By similarity
Modified residuei758PhosphoserineCombined sources1
Modified residuei761PhosphothreonineCombined sources1

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.By similarity
Phosphorylation is induced in vitro by phorbol-12-myristate-13-acetate (PMA).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei56 – 57CleavageBy similarity2
Sitei205 – 206Cleavage; by furin-like proteaseBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ13443
MaxQBiQ13443
PaxDbiQ13443
PeptideAtlasiQ13443
PRIDEiQ13443
ProteomicsDBi59440
59441 [Q13443-2]

PTM databases

iPTMnetiQ13443
PhosphoSitePlusiQ13443

Expressioni

Tissue specificityi

Widely expressed. Expressed in chondrocytes. Isoform 2 is highly expressed in liver and heart.4 Publications

Gene expression databases

BgeeiENSG00000168615
CleanExiHS_ADAM9
ExpressionAtlasiQ13443 baseline and differential
GenevisibleiQ13443 HS

Organism-specific databases

HPAiHPA004000

Interactioni

Subunit structurei

Interacts with SH3GL2 and SNX9 through its cytoplasmic tail (PubMed:10531379). Interacts with ITGA6.By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi114290, 28 interactors
CORUMiQ13443
IntActiQ13443, 12 interactors
MINTiQ13443
STRINGi9606.ENSP00000419446

Chemistry databases

BindingDBiQ13443

Structurei

3D structure databases

ProteinModelPortaliQ13443
SMRiQ13443
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
Compositional biasi790 – 795Poly-Pro6

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3607 Eukaryota
ENOG410XX2M LUCA
GeneTreeiENSGT00910000144019
HOGENOMiHOG000230883
HOVERGENiHBG006978
InParanoidiQ13443
KOiK06834
OMAiSSQFCQP
OrthoDBiEOG091G01NX
PhylomeDBiQ13443
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
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

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: Q13443-1) [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
MGSGARFPSG TLRVRWLLLL GLVGPVLGAA RPGFQQTSHL SSYEIITPWR
60 70 80 90 100
LTRERREAPR PYSKQVSYVI QAEGKEHIIH LERNKDLLPE DFVVYTYNKE
110 120 130 140 150
GTLITDHPNI QNHCHYRGYV EGVHNSSIAL SDCFGLRGLL HLENASYGIE
160 170 180 190 200
PLQNSSHFEH IIYRMDDVYK EPLKCGVSNK DIEKETAKDE EEEPPSMTQL
210 220 230 240 250
LRRRRAVLPQ TRYVELFIVV DKERYDMMGR NQTAVREEMI LLANYLDSMY
260 270 280 290 300
IMLNIRIVLV GLEIWTNGNL INIVGGAGDV LGNFVQWREK FLITRRRHDS
310 320 330 340 350
AQLVLKKGFG GTAGMAFVGT VCSRSHAGGI NVFGQITVET FASIVAHELG
360 370 380 390 400
HNLGMNHDDG RDCSCGAKSC IMNSGASGSR NFSSCSAEDF EKLTLNKGGN
410 420 430 440 450
CLLNIPKPDE AYSAPSCGNK LVDAGEECDC GTPKECELDP CCEGSTCKLK
460 470 480 490 500
SFAECAYGDC CKDCRFLPGG TLCRGKTSEC DVPEYCNGSS QFCQPDVFIQ
510 520 530 540 550
NGYPCQNNKA YCYNGMCQYY DAQCQVIFGS KAKAAPKDCF IEVNSKGDRF
560 570 580 590 600
GNCGFSGNEY KKCATGNALC GKLQCENVQE IPVFGIVPAI IQTPSRGTKC
610 620 630 640 650
WGVDFQLGSD VPDPGMVNEG TKCGAGKICR NFQCVDASVL NYDCDVQKKC
660 670 680 690 700
HGHGVCNSNK NCHCENGWAP PNCETKGYGG SVDSGPTYNE MNTALRDGLL
710 720 730 740 750
VFFFLIVPLI VCAIFIFIKR DQLWRSYFRK KRSQTYESDG KNQANPSRQP
760 770 780 790 800
GSVPRHVSPV TPPREVPIYA NRFAVPTYAA KQPQQFPSRP PPPQPKVSSQ
810
GNLIPARPAP APPLYSSLT
Length:819
Mass (Da):90,556
Last modified:November 1, 1996 - v1
Checksum:iBC186641833137FF
GO
Isoform 2 (identifier: Q13443-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     655-655: V → K
     656-819: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:655
Mass (Da):72,359
Checksum:i1E99DD3A056B90B7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 118Missing no nucleotide entry (PubMed:8809033).CuratedAdd BLAST118
Sequence conflicti117R → Q in BAA03499 (PubMed:7584026).Curated1
Sequence conflicti119 – 135YVEGV…SDCFG → MWREFIIHPLLLATVLD no nucleotide entry (PubMed:8809033).CuratedAdd BLAST17
Sequence conflicti154N → M no nucleotide entry (PubMed:8809033).Curated1
Sequence conflicti566G → GLSLKFHAPFLSTMLQEAVR QTGTYLGGSVCCMKSDCRIV TLVK no nucleotide entry (PubMed:8809033).Curated1
Sequence conflicti713 – 735AIFIF…KRSQT → DYFYLHQEGSTVEKLLQKEE ITN no nucleotide entry (PubMed:8809033).CuratedAdd BLAST23
Sequence conflicti736 – 819Missing no nucleotide entry (PubMed:8809033).CuratedAdd BLAST84

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011057655V → K in isoform 2. 2 Publications1
Alternative sequenceiVSP_011058656 – 819Missing in isoform 2. 2 PublicationsAdd BLAST164

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U41766 mRNA Translation: AAC50403.1
AF495383 mRNA Translation: AAM49575.1
D14665 mRNA Translation: BAA03499.2
CH471080 Genomic DNA Translation: EAW63284.1
BC143923 mRNA Translation: AAI43924.1
CCDSiCCDS6112.1 [Q13443-1]
PIRiJC7850
S71949
RefSeqiNP_003807.1, NM_003816.2 [Q13443-1]
UniGeneiHs.591852

Genome annotation databases

EnsembliENST00000379917; ENSP00000369249; ENSG00000168615 [Q13443-2]
ENST00000487273; ENSP00000419446; ENSG00000168615 [Q13443-1]
GeneIDi8754
KEGGihsa:8754
UCSCiuc003xmr.4 human [Q13443-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiADAM9_HUMAN
AccessioniPrimary (citable) accession number: Q13443
Secondary accession number(s): B7ZLN7, Q10718, Q8NFM6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: November 1, 1996
Last modified: June 20, 2018
This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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