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Q9UNA0 (ATS5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 5

Short name=ADAM-TS 5
Short name=ADAM-TS5
Short name=ADAMTS-5
EC=3.4.24.-
Alternative name(s):
A disintegrin and metalloproteinase with thrombospondin motifs 11
Short name=ADAM-TS 11
Short name=ADAMTS-11
ADMP-2
Aggrecanase-2
Gene names
Name:ADAMTS5
Synonyms:ADAMTS11, ADMP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length930 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. May play a role in proteolytic processing mostly during the peri-implantation period.

Catalytic activity

Cleaves aggrecan at the 392-Glu-|-Ala-393 site.

Cofactor

Binds 1 zinc ion per subunit. Ref.6

Subcellular location

Secretedextracellular spaceextracellular matrix By similarity.

Tissue specificity

Expressed at low level in placenta primarily but also detected in heart and brain, cervix, uterus, bladder, esophagus, rib cartilage, chondroblastoma, fibrous tissue and a joint capsule from an arthritic patient.

Domain

The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.

The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Post-translational modification

The precursor is cleaved by a furin endopeptidase By similarity.

C- and O-glycosylated. O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation can mediate the efficient secretion of ADAMTS family members. Can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion By similarity. Ref.5 Ref.6

Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion By similarity. Ref.5 Ref.6

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 peptidase M12B domain.

Contains 2 TSP type-1 domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ACANP136082EBI-2808663,EBI-6259246From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Potential
Propeptide17 – 261245 Potential
PRO_0000029170
Chain262 – 930669A disintegrin and metalloproteinase with thrombospondin motifs 5
PRO_0000029171

Regions

Domain267 – 476210Peptidase M12B
Domain485 – 56682Disintegrin
Domain567 – 62256TSP type-1 1
Domain875 – 92955TSP type-1 2
Region732 – 874143Spacer
Motif207 – 2148Cysteine switch By similarity
Compositional bias37 – 415Poly-Ala
Compositional bias257 – 2615Poly-Arg
Compositional bias624 – 731108Cys-rich

Sites

Active site4111 Ref.6
Metal binding2091Zinc; in inhibited form By similarity
Metal binding4101Zinc; catalytic
Metal binding4141Zinc; catalytic
Metal binding4201Zinc; catalytic

Amino acid modifications

Glycosylation4981N-linked (GlcNAc...) Ref.6
Glycosylation5701C-linked (Man) Ref.5
Glycosylation5731C-linked (Man) Ref.5
Glycosylation5821O-linked (Fuc...) Ref.5
Glycosylation7281N-linked (GlcNAc...) Potential
Glycosylation8021N-linked (GlcNAc...) Potential
Glycosylation8071N-linked (GlcNAc...) Potential
Disulfide bond342 ↔ 394 Ref.6
Disulfide bond371 ↔ 376 Ref.6
Disulfide bond388 ↔ 471 Ref.6
Disulfide bond426 ↔ 455 Ref.6
Disulfide bond497 ↔ 519 Ref.6
Disulfide bond508 ↔ 529 Ref.6
Disulfide bond514 ↔ 548 Ref.6
Disulfide bond542 ↔ 553 Ref.6
Disulfide bond579 ↔ 616 By similarity
Disulfide bond583 ↔ 621 By similarity
Disulfide bond594 ↔ 606 By similarity

Natural variations

Natural variant1381G → A. Ref.1 Ref.3
Corresponds to variant rs457947 [ dbSNP | Ensembl ].
VAR_028199
Natural variant6141R → H. Ref.4
Corresponds to variant rs2830585 [ dbSNP | Ensembl ].
VAR_021849
Natural variant6921L → P. Ref.1 Ref.3 Ref.4
Corresponds to variant rs226794 [ dbSNP | Ensembl ].
VAR_028200

Secondary structure

......................................................... 930
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UNA0 [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: 8CCE448A15A29CE8

FASTA930101,718
        10         20         30         40         50         60 
MLLGWASLLL CAFRLPLAAV GPAATPAQDK AGQPPTAAAA AQPRRRQGEE VQERAEPPGH 

        70         80         90        100        110        120 
PHPLAQRRRS KGLVQNIDQL YSGGGKVGYL VYAGGRRFLL DLERDGSVGI AGFVPAGGGT 

       130        140        150        160        170        180 
SAPWRHRSHC FYRGTVDGSP RSLAVFDLCG GLDGFFAVKH ARYTLKPLLR GPWAEEEKGR 

       190        200        210        220        230        240 
VYGDGSARIL HVYTREGFSF EALPPRASCE TPASTPEAHE HAPAHSNPSG RAALASQLLD 

       250        260        270        280        290        300 
QSALSPAGGS GPQTWWRRRR RSISRARQVE LLLVADASMA RLYGRGLQHY LLTLASIANR 

       310        320        330        340        350        360 
LYSHASIENH IRLAVVKVVV LGDKDKSLEV SKNAATTLKN FCKWQHQHNQ LGDDHEEHYD 

       370        380        390        400        410        420 
AAILFTREDL CGHHSCDTLG MADVGTICSP ERSCAVIEDD GLHAAFTVAH EIGHLLGLSH 

       430        440        450        460        470        480 
DDSKFCEETF GSTEDKRLMS SILTSIDASK PWSKCTSATI TEFLDDGHGN CLLDLPRKQI 

       490        500        510        520        530        540 
LGPEELPGQT YDATQQCNLT FGPEYSVCPG MDVCARLWCA VVRQGQMVCL TKKLPAVEGT 

       550        560        570        580        590        600 
PCGKGRICLQ GKCVDKTKKK YYSTSSHGNW GSWGSWGQCS RSCGGGVQFA YRHCNNPAPR 

       610        620        630        640        650        660 
NNGRYCTGKR AIYRSCSLMP CPPNGKSFRH EQCEAKNGYQ SDAKGVKTFV EWVPKYAGVL 

       670        680        690        700        710        720 
PADVCKLTCR AKGTGYYVVF SPKVTDGTEC RLYSNSVCVR GKCVRTGCDG IIGSKLQYDK 

       730        740        750        760        770        780 
CGVCGGDNSS CTKIVGTFNK KSKGYTDVVR IPEGATHIKV RQFKAKDQTR FTAYLALKKK 

       790        800        810        820        830        840 
NGEYLINGKY MISTSETIID INGTVMNYSG WSHRDDFLHG MGYSATKEIL IVQILATDPT 

       850        860        870        880        890        900 
KPLDVRYSFF VPKKSTPKVN SVTSHGSNKV GSHTSQPQWV TGPWLACSRT CDTGWHTRTV 

       910        920        930 
QCQDGNRKLA KGCPLSQRPS AFKQCLLKKC 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family."
Abbaszade I., Liu R.-Q., Yang F., Rosenfeld S.A., Ross O.H., Link J.R., Ellis D.M., Tortorella M.D., Pratta M.A., Hollis J.M., Wynn R., Duke J.L., George H.J., Hillman M.C. Jr., Murphy K., Wiswall B.H., Copeland R.A., Decicco C.P. expand/collapse author list , Bruckner R., Nagase H., Ito Y., Newton R.C., Magolda R.L., Trzaskos J.M., Hollis G.F., Arner E.C., Burn T.C.
J. Biol. Chem. 274:23443-23450(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-138 AND PRO-692.
Tissue: Liver.
[2]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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], VARIANTS ALA-138 AND PRO-692.
Tissue: Colon.
[4]"ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases."
Hurskainen T.L., Hirohata S., Seldin M.F., Apte S.S.
J. Biol. Chem. 274:25555-25563(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 413-930, VARIANTS HIS-614 AND PRO-692.
Tissue: Fetal brain.
[5]"Post-translational modification of thrombospondin type-1 repeats in ADAMTS-like 1/punctin-1 by C-mannosylation of tryptophan."
Wang L.W., Leonhard-Melief C., Haltiwanger R.S., Apte S.S.
J. Biol. Chem. 284:30004-30015(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT TRP-570; TRP-573 AND SER-582, IDENTIFICATION BY MASS SPECTROMETRY.
[6]"Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5."
Mosyak L., Georgiadis K., Shane T., Svenson K., Hebert T., McDonagh T., Mackie S., Olland S., Lin L., Zhong X., Kriz R., Reifenberg E.L., Collins-Racie L.A., Corcoran C., Freeman B., Zollner R., Marvell T., Vera M. expand/collapse author list , Sum P.E., Lavallie E.R., Stahl M., Somers W.
Protein Sci. 17:16-21(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 262-628 IN COMPLEX WITH INHIBITOR, ACTIVE SITE, COFACTOR, ZINC-BINDING SITES, DISULFIDE BONDS, GLYCOSYLATION AT ASN-498.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF142099 mRNA. Translation: AAD49577.1.
AP001698 Genomic DNA. Translation: BAA95504.1.
AP001697 Genomic DNA. Translation: BAA95503.1.
BC093775 mRNA. Translation: AAH93775.1.
BC093777 mRNA. Translation: AAH93777.1.
AF141293 mRNA. Translation: AAF02493.1.
CCDSCCDS13579.1.
RefSeqNP_008969.2. NM_007038.3.
UniGeneHs.58324.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2RJQX-ray2.60A262-628[»]
3B8ZX-ray1.40A/B264-480[»]
3HY7X-ray1.69A/B262-480[»]
3HY9X-ray2.02A/B262-480[»]
3HYGX-ray1.40A/B262-480[»]
3LJTX-ray1.60A264-480[»]
ProteinModelPortalQ9UNA0.
SMRQ9UNA0. Positions 259-797.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116277. 1 interaction.
IntActQ9UNA0. 3 interactions.
STRING9606.ENSP00000284987.

Chemistry

BindingDBQ9UNA0.
ChEMBLCHEMBL2285.

Protein family/group databases

MEROPSM12.225.

PTM databases

PhosphoSiteQ9UNA0.

Polymorphism databases

DMDM317373326.

Proteomic databases

PaxDbQ9UNA0.
PRIDEQ9UNA0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000284987; ENSP00000284987; ENSG00000154736.
GeneID11096.
KEGGhsa:11096.
UCSCuc002ymg.3. human.

Organism-specific databases

CTD11096.
GeneCardsGC21M028290.
H-InvDBHIX0016044.
HGNCHGNC:221. ADAMTS5.
HPACAB025996.
HPA005661.
MIM605007. gene.
neXtProtNX_Q9UNA0.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG302522.
HOGENOMHOG000004799.
HOVERGENHBG004313.
InParanoidQ9UNA0.
KOK08620.
OMARASCETP.
OrthoDBEOG7WDN1M.
PhylomeDBQ9UNA0.
TreeFamTF331949.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.
REACT_17015. Metabolism of proteins.
REACT_223425. Extracellular matrix organization.

Gene expression databases

BgeeQ9UNA0.
CleanExHS_ADAMTS5.
GenevestigatorQ9UNA0.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
InterProIPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR013276. Pept_M12B_ADAM-TS5.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 2 hits.
[Graphical view]
PRINTSPR01860. ADAMTS5.
PR01857. ADAMTSFAMILY.
SMARTSM00209. TSP1. 2 hits.
[Graphical view]
SUPFAMSSF82895. SSF82895. 2 hits.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 2 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9UNA0.
GeneWikiADAMTS5.
GenomeRNAi11096.
NextBio42182.
PMAP-CutDBQ9UNA0.
PROQ9UNA0.
SOURCESearch...

Entry information

Entry nameATS5_HUMAN
AccessionPrimary (citable) accession number: Q9UNA0
Secondary accession number(s): Q52LV4, Q9UKP2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 144 of the entry and version 2 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM