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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 5

Gene

ADAMTS5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

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

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi209Zinc; in inhibited formBy similarity1
Metal bindingi410Zinc; catalytic1 Publication1
Active sitei411PROSITE-ProRule annotation1 Publication1
Metal bindingi414Zinc; catalytic1 Publication1
Metal bindingi420Zinc; catalytic1 Publication1

GO - Molecular functioni

  • extracellular matrix binding Source: Ensembl
  • heparin binding Source: Ensembl
  • integrin binding Source: ProtInc
  • metalloendopeptidase activity Source: Reactome
  • metallopeptidase activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000154736-MONOMER.
BRENDAi3.4.24.B12. 2681.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Protein family/group databases

MEROPSiM12.225.

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 5 (EC:3.4.24.-)
Short name:
ADAM-TS 5
Short name:
ADAM-TS5
Short name:
ADAMTS-5
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 namesi
Name:ADAMTS5
Synonyms:ADAMTS11, ADMP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:221. ADAMTS5.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi11096.
OpenTargetsiENSG00000154736.

Chemistry databases

ChEMBLiCHEMBL2285.
GuidetoPHARMACOLOGYi1678.

Polymorphism and mutation databases

BioMutaiADAMTS5.
DMDMi317373326.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
PropeptideiPRO_000002917017 – 261Sequence analysisAdd BLAST245
ChainiPRO_0000029171262 – 930A disintegrin and metalloproteinase with thrombospondin motifs 5Add BLAST669

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi342 ↔ 3941 Publication
Disulfide bondi371 ↔ 3761 Publication
Disulfide bondi388 ↔ 4711 Publication
Disulfide bondi426 ↔ 4551 Publication
Disulfide bondi497 ↔ 5191 Publication
Glycosylationi498N-linked (GlcNAc...)1 Publication1
Disulfide bondi508 ↔ 5291 Publication
Disulfide bondi514 ↔ 5481 Publication
Disulfide bondi542 ↔ 5531 Publication
Glycosylationi570C-linked (Man)1 Publication1
Glycosylationi573C-linked (Man)1 Publication1
Disulfide bondi579 ↔ 616By similarity
Glycosylationi582O-linked (Fuc...)1 Publication1
Disulfide bondi583 ↔ 621By similarity
Disulfide bondi594 ↔ 606By similarity
Glycosylationi728N-linked (GlcNAc...)Sequence analysis1
Glycosylationi802N-linked (GlcNAc...)Sequence analysis1
Glycosylationi807N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

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).By similarity
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).By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ9UNA0.
PeptideAtlasiQ9UNA0.
PRIDEiQ9UNA0.

PTM databases

iPTMnetiQ9UNA0.
PhosphoSitePlusiQ9UNA0.

Miscellaneous databases

PMAP-CutDBQ9UNA0.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000154736.
CleanExiHS_ADAMTS5.
GenevisibleiQ9UNA0. HS.

Organism-specific databases

HPAiCAB025996.
HPA005661.
HPA030906.
HPA030908.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ACANP136082EBI-2808663,EBI-6259246From a different organism.

GO - Molecular functioni

  • integrin binding Source: ProtInc

Protein-protein interaction databases

IntActiQ9UNA0. 3 interactors.
STRINGi9606.ENSP00000284987.

Chemistry databases

BindingDBiQ9UNA0.

Structurei

Secondary structure

1930
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi267 – 275Combined sources9
Helixi277 – 283Combined sources7
Helixi284 – 286Combined sources3
Helixi287 – 302Combined sources16
Helixi305 – 307Combined sources3
Beta strandi311 – 320Combined sources10
Turni323 – 326Combined sources4
Helixi334 – 348Combined sources15
Beta strandi353 – 356Combined sources4
Beta strandi360 – 368Combined sources9
Beta strandi380 – 382Combined sources3
Helixi390 – 392Combined sources3
Beta strandi394 – 398Combined sources5
Beta strandi401 – 403Combined sources3
Helixi404 – 415Combined sources12
Helixi424 – 430Combined sources7
Beta strandi435 – 437Combined sources3
Beta strandi440 – 442Combined sources3
Helixi443 – 445Combined sources3
Helixi454 – 465Combined sources12
Turni466 – 469Combined sources4
Helixi470 – 472Combined sources3
Helixi487 – 490Combined sources4
Helixi493 – 501Combined sources9
Beta strandi509 – 511Combined sources3
Turni513 – 515Combined sources3
Beta strandi519 – 523Combined sources5
Beta strandi526 – 530Combined sources5
Beta strandi543 – 545Combined sources3
Beta strandi547 – 549Combined sources3
Beta strandi552 – 554Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ9UNA0.
SMRiQ9UNA0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UNA0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini267 – 476Peptidase M12BPROSITE-ProRule annotationAdd BLAST210
Domaini485 – 566DisintegrinAdd BLAST82
Domaini567 – 622TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini875 – 929TSP type-1 2PROSITE-ProRule annotationAdd BLAST55

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni732 – 874SpacerAdd BLAST143

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi207 – 214Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi37 – 41Poly-Ala5
Compositional biasi257 – 261Poly-Arg5
Compositional biasi624 – 731Cys-richAdd BLAST108

Domaini

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.

Sequence similaritiesi

Contains 1 disintegrin domain.Curated
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation
Contains 2 TSP type-1 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IND8. Eukaryota.
ENOG410ZQPN. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000004799.
HOVERGENiHBG004313.
InParanoidiQ9UNA0.
KOiK08620.
OMAiRASCETP.
OrthoDBiEOG091G00AX.
PhylomeDBiQ9UNA0.
TreeFamiTF331949.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR013276. Pept_M12B_ADAM-TS5.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 2 hits.
[Graphical view]
PRINTSiPR01860. ADAMTS5.
PR01857. ADAMTSFAMILY.
SMARTiSM00608. ACR. 1 hit.
SM00209. TSP1. 2 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 2 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 2 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9UNA0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLGWASLLL CAFRLPLAAV GPAATPAQDK AGQPPTAAAA AQPRRRQGEE
60 70 80 90 100
VQERAEPPGH PHPLAQRRRS KGLVQNIDQL YSGGGKVGYL VYAGGRRFLL
110 120 130 140 150
DLERDGSVGI AGFVPAGGGT SAPWRHRSHC FYRGTVDGSP RSLAVFDLCG
160 170 180 190 200
GLDGFFAVKH ARYTLKPLLR GPWAEEEKGR VYGDGSARIL HVYTREGFSF
210 220 230 240 250
EALPPRASCE TPASTPEAHE HAPAHSNPSG RAALASQLLD QSALSPAGGS
260 270 280 290 300
GPQTWWRRRR RSISRARQVE LLLVADASMA RLYGRGLQHY LLTLASIANR
310 320 330 340 350
LYSHASIENH IRLAVVKVVV LGDKDKSLEV SKNAATTLKN FCKWQHQHNQ
360 370 380 390 400
LGDDHEEHYD AAILFTREDL CGHHSCDTLG MADVGTICSP ERSCAVIEDD
410 420 430 440 450
GLHAAFTVAH EIGHLLGLSH DDSKFCEETF GSTEDKRLMS SILTSIDASK
460 470 480 490 500
PWSKCTSATI TEFLDDGHGN CLLDLPRKQI LGPEELPGQT YDATQQCNLT
510 520 530 540 550
FGPEYSVCPG MDVCARLWCA VVRQGQMVCL TKKLPAVEGT PCGKGRICLQ
560 570 580 590 600
GKCVDKTKKK YYSTSSHGNW GSWGSWGQCS RSCGGGVQFA YRHCNNPAPR
610 620 630 640 650
NNGRYCTGKR AIYRSCSLMP CPPNGKSFRH EQCEAKNGYQ SDAKGVKTFV
660 670 680 690 700
EWVPKYAGVL PADVCKLTCR AKGTGYYVVF SPKVTDGTEC RLYSNSVCVR
710 720 730 740 750
GKCVRTGCDG IIGSKLQYDK CGVCGGDNSS CTKIVGTFNK KSKGYTDVVR
760 770 780 790 800
IPEGATHIKV RQFKAKDQTR FTAYLALKKK NGEYLINGKY MISTSETIID
810 820 830 840 850
INGTVMNYSG WSHRDDFLHG MGYSATKEIL IVQILATDPT KPLDVRYSFF
860 870 880 890 900
VPKKSTPKVN SVTSHGSNKV GSHTSQPQWV TGPWLACSRT CDTGWHTRTV
910 920 930
QCQDGNRKLA KGCPLSQRPS AFKQCLLKKC
Length:930
Mass (Da):101,718
Last modified:January 11, 2011 - v2
Checksum:i8CCE448A15A29CE8
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028199138G → A.2 PublicationsCorresponds to variant rs457947dbSNPEnsembl.1
Natural variantiVAR_021849614R → H.1 PublicationCorresponds to variant rs2830585dbSNPEnsembl.1
Natural variantiVAR_028200692L → P.3 PublicationsCorresponds to variant rs226794dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13579.1.
RefSeqiNP_008969.2. NM_007038.4.
UniGeneiHs.58324.

Genome annotation databases

EnsembliENST00000284987; ENSP00000284987; ENSG00000154736.
GeneIDi11096.
KEGGihsa:11096.
UCSCiuc002ymg.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13579.1.
RefSeqiNP_008969.2. NM_007038.4.
UniGeneiHs.58324.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ9UNA0.
SMRiQ9UNA0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9UNA0. 3 interactors.
STRINGi9606.ENSP00000284987.

Chemistry databases

BindingDBiQ9UNA0.
ChEMBLiCHEMBL2285.
GuidetoPHARMACOLOGYi1678.

Protein family/group databases

MEROPSiM12.225.

PTM databases

iPTMnetiQ9UNA0.
PhosphoSitePlusiQ9UNA0.

Polymorphism and mutation databases

BioMutaiADAMTS5.
DMDMi317373326.

Proteomic databases

PaxDbiQ9UNA0.
PeptideAtlasiQ9UNA0.
PRIDEiQ9UNA0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000284987; ENSP00000284987; ENSG00000154736.
GeneIDi11096.
KEGGihsa:11096.
UCSCiuc002ymg.4. human.

Organism-specific databases

CTDi11096.
DisGeNETi11096.
GeneCardsiADAMTS5.
H-InvDBHIX0016044.
HGNCiHGNC:221. ADAMTS5.
HPAiCAB025996.
HPA005661.
HPA030906.
HPA030908.
MIMi605007. gene.
neXtProtiNX_Q9UNA0.
OpenTargetsiENSG00000154736.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IND8. Eukaryota.
ENOG410ZQPN. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000004799.
HOVERGENiHBG004313.
InParanoidiQ9UNA0.
KOiK08620.
OMAiRASCETP.
OrthoDBiEOG091G00AX.
PhylomeDBiQ9UNA0.
TreeFamiTF331949.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000154736-MONOMER.
BRENDAi3.4.24.B12. 2681.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Miscellaneous databases

ChiTaRSiADAMTS5. human.
EvolutionaryTraceiQ9UNA0.
GeneWikiiADAMTS5.
GenomeRNAii11096.
PMAP-CutDBQ9UNA0.
PROiQ9UNA0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000154736.
CleanExiHS_ADAMTS5.
GenevisibleiQ9UNA0. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR013276. Pept_M12B_ADAM-TS5.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 2 hits.
[Graphical view]
PRINTSiPR01860. ADAMTS5.
PR01857. ADAMTSFAMILY.
SMARTiSM00608. ACR. 1 hit.
SM00209. TSP1. 2 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 2 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 2 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATS5_HUMAN
AccessioniPrimary (citable) accession number: Q9UNA0
Secondary accession number(s): Q52LV4, Q9UKP2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 11, 2011
Last modified: November 2, 2016
This is version 165 of the entry and version 2 of the sequence. [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 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.