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Q13443 (ADAM9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 123. 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·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)
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.

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

Defects in ADAM9 are the cause of cone-rod dystrophy type 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. Ref.12

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
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological processPMA-inducible membrane protein ectodomain proteolysis

Traceable author statement. Source: BHF-UCL

activation of MAPKK activity

Inferred from direct assay. Source: BHF-UCL

cell-cell adhesion mediated by integrin

Inferred from expression pattern. Source: BHF-UCL

cell-matrix adhesion

Inferred from mutant phenotype. Source: BHF-UCL

integrin-mediated signaling pathway

Inferred by curator. Source: BHF-UCL

keratinocyte differentiation

Inferred from expression pattern. Source: BHF-UCL

monocyte activation

Inferred from mutant phenotype. Source: BHF-UCL

positive regulation of cell adhesion mediated by integrin

Inferred from mutant phenotype. Source: BHF-UCL

positive regulation of keratinocyte migration

Inferred from mutant phenotype. Source: BHF-UCL

positive regulation of macrophage fusion

Inferred from mutant phenotype. 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. Source: BHF-UCL

response to calcium ion

Inferred from mutant phenotype. Source: BHF-UCL

response to glucocorticoid stimulus

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

response to hydrogen peroxide

Inferred from mutant phenotype. Source: BHF-UCL

response to manganese ion

Inferred from mutant phenotype. Source: BHF-UCL

response to tumor necrosis factor

Inferred from direct assay. Source: BHF-UCL

transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype. Source: BHF-UCL

   Cellular componentextracellular space

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

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intrinsic to external side of plasma membrane

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

   Molecular functionSH3 domain binding

Inferred from physical interaction. Source: BHF-UCL

collagen binding

Inferred from mutant phenotype. Source: BHF-UCL

integrin binding

Inferred from direct assay. Source: BHF-UCL

laminin binding

Inferred from mutant phenotype. Source: BHF-UCL

metalloendopeptidase activity

Inferred from direct assay. Source: BHF-UCL

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

Modified residue7581Phosphoserine Ref.9 Ref.11
Modified residue7611Phosphothreonine Ref.9 Ref.11
Modified residue8151Phosphotyrosine Ref.10 Ref.13
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: 8647900] [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: 8809033] [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: 12054541] [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: 7584026] [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: 15489334] [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: 9016778] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-758 AND THR-761, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[10]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-815, MASS SPECTROMETRY.
Tissue: Lung carcinoma.
[11]"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: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-758 AND THR-761, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[12]"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: 19409519] [Abstract]
Cited for: INVOLVEMENT IN CORD9.
[13]"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells."
Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J.
J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-815, MASS SPECTROMETRY.
Tissue: Mammary epithelium.
[14]"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.
IPIIPI00440932.
IPI00440933.
PIRJC7850.
S71949.
RefSeqNP_003807.1. NM_003816.2.
UniGeneHs.591852.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M1Vmodel-A208-404[»]
ProteinModelPortalQ13443.
SMRQ13443. Positions 207-679.
ModBaseSearch...

Protein-protein interaction databases

IntActQ13443. 3 interactions.
MINTMINT-108373.
STRINGQ13443.

Protein family/group databases

MEROPSM12.209.

PTM databases

PhosphoSiteQ13443.

Polymorphism databases

DMDM24211441.

Proteomic databases

PRIDEQ13443.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302458; ENSP00000305538; ENSG00000168615.
GeneID8754.
KEGGhsa:8754.
UCSCuc003xmq.1. human.
uc003xmr.1. human.

Organism-specific databases

CTD8754.
GeneCardsGC08P038871.
H-InvDBHIX0021419.
HGNCHGNC:216. ADAM9.
HPAHPA004000.
MIM602713. gene.
612775. phenotype.
neXtProtNX_Q13443.
Orphanet1872. Cone rod dystrophy.
PharmGKBPA24534.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

GeneTreeENSGT00590000082741.
HOGENOMHBG507118.
HOVERGENHBG006978.
InParanoidQ13443.
OMAHDDGRDC.
PhylomeDBQ13443.

Gene expression databases

ArrayExpressQ13443.
BgeeQ13443.
CleanExHS_ADAM9.
GenevestigatorQ13443.

Family and domain databases

InterProIPR006586. ADAM_Cys-rich.
IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000742. EGF_3.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]
Gene3DG3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.
G3DSA:3.40.390.10. G3DSA:3.40.390.10. 1 hit.
KOK06834.
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. Disintegrin. 1 hit.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00022. EGF_1. False negative.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio32845.
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: January 25, 2012
This is version 123 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

Peptidase families

Classification of peptidase families and list of entries

Human chromosome 8

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

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families