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Q13443 (ADAM9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Disintegrin and metalloproteinase domain-containing protein 9

Short name=ADAM 9
EC=3.4.24.-
Alternative name(s):
Cellular disintegrin-related protein
Meltrin-gamma
Metalloprotease/disintegrin/cysteine-rich protein 9
Myeloma cell metalloproteinase
Gene names
Name:ADAM9
Synonyms:KIAA0021, MCMP, MDC9, MLTNG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length819 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probable zinc protease. May mediate cell-cell or cell-matrix interactions. Isoform 2 displays alpha-secretase activity for APP. Ref.3

Cofactor

Binds 1 zinc ion per subunit Probable.

Subunit structure

Interacts with SH3GL2 and SNX9 through its cytoplasmic tail. Ref.9

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.3.

Isoform 2: Secreted Ref.3.

Tissue specificity

Widely expressed. Expressed in chondrocytes. Isoform 2 is highly expressed in liver and heart. Ref.1 Ref.3 Ref.4 Ref.8

Involvement in disease

Cone-rod dystrophy 9 (CORD9) [MIM:612775]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 EGF-like domain.

Contains 1 peptidase M12B domain.

Caution

Has sometimes been referred to as ADAM-12.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
   DiseaseCone-rod dystrophy
   DomainSignal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processPMA-inducible membrane protein ectodomain proteolysis

Inferred from direct assay Ref.3. Source: BHF-UCL

activation of MAPKK activity

Inferred from direct assay PubMed 17704059. Source: BHF-UCL

cell adhesion

Inferred from mutant phenotype PubMed 11162558PubMed 17704059. Source: BHF-UCL

cell adhesion mediated by integrin

Inferred from mutant phenotype PubMed 17704059. Source: BHF-UCL

cell-cell adhesion mediated by integrin

Inferred from expression pattern PubMed 17704059. Source: BHF-UCL

cell-matrix adhesion

Inferred from mutant phenotype PubMed 15361064. Source: BHF-UCL

cellular response to lipopolysaccharide

Inferred from mutant phenotype PubMed 22480688. Source: BHF-UCL

collagen catabolic process

Traceable author statement. Source: Reactome

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

integrin-mediated signaling pathway

Inferred by curator PubMed 11162558. Source: BHF-UCL

keratinocyte differentiation

Inferred from expression pattern PubMed 17704059. Source: BHF-UCL

membrane protein ectodomain proteolysis

Inferred from direct assay PubMed 9920899. Source: BHF-UCL

monocyte activation

Inferred from mutant phenotype PubMed 11831872. Source: BHF-UCL

positive regulation of cell adhesion mediated by integrin

Inferred from mutant phenotype PubMed 11162558. Source: BHF-UCL

positive regulation of keratinocyte migration

Inferred from mutant phenotype PubMed 17704059. Source: BHF-UCL

positive regulation of macrophage fusion

Inferred from mutant phenotype PubMed 11831872. Source: BHF-UCL

positive regulation of membrane protein ectodomain proteolysis

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

positive regulation of protein secretion

Inferred from direct assay PubMed 17704059. Source: BHF-UCL

response to calcium ion

Inferred from mutant phenotype PubMed 11162558. Source: BHF-UCL

response to glucocorticoid

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

response to hydrogen peroxide

Inferred from mutant phenotype PubMed 17018608. Source: BHF-UCL

response to laminar fluid shear stress

Inferred from electronic annotation. Source: Ensembl

response to manganese ion

Inferred from mutant phenotype PubMed 11162558. Source: BHF-UCL

response to tumor necrosis factor

Inferred from direct assay PubMed 11831872. Source: BHF-UCL

transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype PubMed 11955914. Source: BHF-UCL

   Cellular_componentbasolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

cell surface

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

cytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from direct assay Ref.3. Source: BHF-UCL

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intrinsic component of external side of plasma membrane

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

   Molecular_functionSH3 domain binding

Inferred from physical interaction Ref.9. Source: BHF-UCL

collagen binding

Inferred from mutant phenotype PubMed 15361064. Source: BHF-UCL

integrin binding

Inferred from direct assay PubMed 15361064. Source: BHF-UCL

laminin binding

Inferred from mutant phenotype PubMed 15361064. Source: BHF-UCL

metalloendopeptidase activity

Inferred from direct assay PubMed 9920899. Source: BHF-UCL

metallopeptidase activity

Inferred from mutant phenotype PubMed 12535668. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 10527948Ref.9. Source: IntAct

protein kinase C binding

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13443-1)

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.
Isoform 2 (identifier: Q13443-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 819791Disintegrin and metalloproteinase domain-containing protein 9
PRO_0000029062

Regions

Topological domain29 – 697669Extracellular Potential
Transmembrane698 – 71821Helical; Potential
Topological domain719 – 819101Cytoplasmic Potential
Domain212 – 406195Peptidase M12B
Domain414 – 50188Disintegrin
Domain644 – 69855EGF-like
Compositional bias505 – 634130Cys-rich
Compositional bias790 – 7956Poly-Pro

Sites

Active site3481 By similarity
Metal binding3471Zinc; catalytic By similarity
Metal binding3511Zinc; catalytic By similarity
Metal binding3571Zinc; catalytic By similarity

Amino acid modifications

Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Glycosylation1541N-linked (GlcNAc...) Potential
Glycosylation2311N-linked (GlcNAc...) Potential
Glycosylation3811N-linked (GlcNAc...) Potential
Glycosylation4871N-linked (GlcNAc...) Potential
Disulfide bond322 ↔ 401 By similarity
Disulfide bond363 ↔ 385 By similarity
Disulfide bond365 ↔ 370 By similarity
Disulfide bond473 ↔ 493 By similarity
Disulfide bond644 ↔ 656 By similarity
Disulfide bond650 ↔ 662 By similarity
Disulfide bond664 ↔ 673 By similarity

Natural variations

Alternative sequence6551V → K in isoform 2.
VSP_011057
Alternative sequence656 – 819164Missing in isoform 2.
VSP_011058

Experimental info

Sequence conflict1 – 118118Missing no nucleotide entry Ref.2
Sequence conflict1171R → Q in BAA03499. Ref.4
Sequence conflict119 – 13517YVEGV…SDCFG → MWREFIIHPLLLATVLD no nucleotide entry Ref.2
Sequence conflict1541N → M no nucleotide entry Ref.2
Sequence conflict5661G → GLSLKFHAPFLSTMLQEAVR QTGTYLGGSVCCMKSDCRIV TLVK no nucleotide entry Ref.2
Sequence conflict713 – 73523AIFIF…KRSQT → DYFYLHQEGSTVEKLLQKEE ITN no nucleotide entry Ref.2
Sequence conflict736 – 81984Missing no nucleotide entry Ref.2

Secondary structure

............................. 819
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: BC186641833137FF

FASTA81990,556
        10         20         30         40         50         60 
MGSGARFPSG TLRVRWLLLL GLVGPVLGAA RPGFQQTSHL SSYEIITPWR LTRERREAPR 

        70         80         90        100        110        120 
PYSKQVSYVI QAEGKEHIIH LERNKDLLPE DFVVYTYNKE GTLITDHPNI QNHCHYRGYV 

       130        140        150        160        170        180 
EGVHNSSIAL SDCFGLRGLL HLENASYGIE PLQNSSHFEH IIYRMDDVYK EPLKCGVSNK 

       190        200        210        220        230        240 
DIEKETAKDE EEEPPSMTQL LRRRRAVLPQ TRYVELFIVV DKERYDMMGR NQTAVREEMI 

       250        260        270        280        290        300 
LLANYLDSMY IMLNIRIVLV GLEIWTNGNL INIVGGAGDV LGNFVQWREK FLITRRRHDS 

       310        320        330        340        350        360 
AQLVLKKGFG GTAGMAFVGT VCSRSHAGGI NVFGQITVET FASIVAHELG HNLGMNHDDG 

       370        380        390        400        410        420 
RDCSCGAKSC IMNSGASGSR NFSSCSAEDF EKLTLNKGGN CLLNIPKPDE AYSAPSCGNK 

       430        440        450        460        470        480 
LVDAGEECDC GTPKECELDP CCEGSTCKLK SFAECAYGDC CKDCRFLPGG TLCRGKTSEC 

       490        500        510        520        530        540 
DVPEYCNGSS QFCQPDVFIQ NGYPCQNNKA YCYNGMCQYY DAQCQVIFGS KAKAAPKDCF 

       550        560        570        580        590        600 
IEVNSKGDRF GNCGFSGNEY KKCATGNALC GKLQCENVQE IPVFGIVPAI IQTPSRGTKC 

       610        620        630        640        650        660 
WGVDFQLGSD VPDPGMVNEG TKCGAGKICR NFQCVDASVL NYDCDVQKKC HGHGVCNSNK 

       670        680        690        700        710        720 
NCHCENGWAP PNCETKGYGG SVDSGPTYNE MNTALRDGLL VFFFLIVPLI VCAIFIFIKR 

       730        740        750        760        770        780 
DQLWRSYFRK KRSQTYESDG KNQANPSRQP GSVPRHVSPV TPPREVPIYA NRFAVPTYAA 

       790        800        810 
KQPQQFPSRP PPPQPKVSSQ GNLIPARPAP APPLYSSLT 

« Hide

Isoform 2 [UniParc].

Checksum: 1E99DD3A056B90B7
Show »

FASTA65572,359

References

« Hide 'large scale' references
[1]"MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains."
Weskamp G., Kraetzschmar J., Reid M.S., Blobel C.P.
J. Cell Biol. 132:717-726(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Mammary carcinoma.
[2]"Cloning of a novel membrane-linked metalloproteinase from human myeloma cells."
McKie N., Dallas D.J., Edwards T., Apperley J.F., Russell R.G.G., Croucher P.I.
Biochem. J. 318:459-462(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[3]"A secreted form of human ADAM9 has an alpha-secretase activity for APP."
Hotoda N., Koike H., Sasagawa N., Ishiura S.
Biochem. Biophys. Res. Commun. 293:800-805(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1."
Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.
DNA Res. 1:27-35(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Bone marrow.
[5]Ohara O., Nagase T., Kikuno R., Nomura N.
Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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 2).
Tissue: Lung.
[8]"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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1."
Howard L., Nelson K.K., Maciewicz R.A., Blobel C.P.
J. Biol. Chem. 274:31693-31699(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SH3GL2 AND SNX9.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and retinal degeneration in mice."
Parry D.A., Toomes C., Bida L., Danciger M., Towns K.V., McKibbin M., Jacobson S.G., Logan C.V., Ali M., Bond J., Chance R., Swendeman S., Daniele L.L., Springell K., Adams M., Johnson C.A., Booth A.P., Jafri H. expand/collapse author list , Rashid Y., Banin E., Strom T.M., Farber D.B., Sharon D., Blobel C.P., Pugh E.N. Jr., Pierce E.A., Inglehearn C.F.
Am. J. Hum. Genet. 84:683-691(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CORD9.
[12]"Exploring the substrate affinities of MMP-3, ADAM-9 and ADAM-10 using molecular modelling and dynamics simulations."
Manzetti S., McCulloch D.R., Herington A.C.
Submitted (JUN-2002) to the PDB data bank
Cited for: 3D-STRUCTURE MODELING OF 208-404.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS6112.1. [Q13443-1]
PIRJC7850.
S71949.
RefSeqNP_003807.1. NM_003816.2. [Q13443-1]
UniGeneHs.591852.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M1Vmodel-A208-404[»]
ProteinModelPortalQ13443.
SMRQ13443. Positions 212-638, 647-675.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114290. 7 interactions.
IntActQ13443. 3 interactions.
MINTMINT-108373.
STRING9606.ENSP00000305538.

Chemistry

BindingDBQ13443.
ChEMBLCHEMBL5982.

Protein family/group databases

MEROPSM12.209.

PTM databases

PhosphoSiteQ13443.

Polymorphism databases

DMDM24211441.

Proteomic databases

MaxQBQ13443.
PaxDbQ13443.
PRIDEQ13443.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379917; ENSP00000369249; ENSG00000168615. [Q13443-2]
ENST00000487273; ENSP00000419446; ENSG00000168615. [Q13443-1]
GeneID8754.
KEGGhsa:8754.
UCSCuc003xmr.3. human. [Q13443-1]

Organism-specific databases

CTD8754.
GeneCardsGC08P038871.
HGNCHGNC:216. ADAM9.
HPAHPA004000.
MIM602713. gene.
612775. phenotype.
neXtProtNX_Q13443.
Orphanet1872. Cone rod dystrophy.
PharmGKBPA24534.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG294463.
HOGENOMHOG000230883.
HOVERGENHBG006978.
InParanoidQ13443.
KOK06834.
OMAFCQPDVF.
OrthoDBEOG7F7W89.
PhylomeDBQ13443.
TreeFamTF314733.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressQ13443.
BgeeQ13443.
CleanExHS_ADAM9.
GenevestigatorQ13443.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
4.10.70.10. 1 hit.
InterProIPR006586. ADAM_Cys-rich.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
PfamPF08516. ADAM_CR. 1 hit.
PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]
SMARTSM00608. ACR. 1 hit.
SM00050. DISIN. 1 hit.
SM00181. EGF. 1 hit.
[Graphical view]
SUPFAMSSF57552. SSF57552. 1 hit.
PROSITEPS50215. 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]
ProtoNetSearch...

Other

GeneWikiADAM9.
GenomeRNAi8754.
NextBio32845.
PROQ13443.
SOURCESearch...

Entry information

Entry nameADAM9_HUMAN
AccessionPrimary (citable) accession number: Q13443
Secondary accession number(s): B7ZLN7, Q10718, Q8NFM6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 19, 2002
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM