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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 5

Gene

ADAMTS5

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

Functioni

Metalloproteinase that plays an important role in connective tissue organization, development, inflammation, arthritis, and cell migration. ADAMTS5 is an extracellular matrix (ECM) degrading enzyme that show proteolytic activity toward the hyalectan group of chondroitin sulfate proteoglycans (CSPGs) including aggrecan, versican, brevican and neurocan (PubMed:16133547, PubMed:18992360). Cleavage within the hyalectans occurs at Glu-Xaa recognition motifs. Plays a role in embryonic development, including limb and cardiac morphogenesis, and skeletal muscle development through its versican remodeling properties. Participates in development of brown adipose tissue and browning of white adipose tissue. Plays an important role for T-lymphocyte migration from draining lymph nodes following viral infection.By similarity2 Publications

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi209Zinc; in inhibited formBy similarity1
Sitei261Cleveage; by furin and PCSK71 Publication1
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

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-binding, Zinc

Enzyme and pathway databases

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
SIGNORiQ9UNA0

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

EuPathDBiHostDB:ENSG00000154736.5
HGNCiHGNC:221 ADAMTS5
MIMi605007 gene
neXtProtiNX_Q9UNA0

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

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi411E → A: Complete loss of catalytic activity. 1 Publication1

Organism-specific databases

DisGeNETi11096
OpenTargetsiENSG00000154736

Chemistry databases

ChEMBLiCHEMBL2285
DrugBankiDB03880 Batimastat
DB06945 N-hydroxy-4-({4-[4-(trifluoromethyl)phenoxy]phenyl}sulfonyl)tetrahydro-2H-pyran-4-carboxamide
GuidetoPHARMACOLOGYi1678

Polymorphism and mutation databases

BioMutaiADAMTS5
DMDMi317373326

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
PropeptideiPRO_000002917017 – 2611 PublicationAdd 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...) asparagine1 Publication1
Disulfide bondi508 ↔ 5291 Publication
Disulfide bondi514 ↔ 5481 Publication
Disulfide bondi542 ↔ 5531 Publication
Glycosylationi570C-linked (Man) tryptophan1 Publication1
Glycosylationi573C-linked (Man) tryptophan1 Publication1
Disulfide bondi579 ↔ 616By similarity
Glycosylationi582O-linked (Fuc...) serine1 Publication1
Disulfide bondi583 ↔ 621By similarity
Disulfide bondi594 ↔ 606By similarity
Glycosylationi728N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi802N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi807N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

The precursor is cleaved by furin and PCSK7 outside of the cell.1 Publication
C- and O-glycosylated. O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X2-(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-X2-(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-CutDBiQ9UNA0

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 Bos taurus.

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.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IND8 Eukaryota
ENOG410ZQPN LUCA
GeneTreeiENSGT00900000140774
HOGENOMiHOG000004799
HOVERGENiHBG004313
InParanoidiQ9UNA0
KOiK08620
OMAiNYSGWSH
OrthoDBiEOG091G00AX
PhylomeDBiQ9UNA0
TreeFamiTF331949

Family and domain databases

Gene3Di2.20.100.10, 2 hits
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR006586 ADAM_Cys-rich
IPR010294 ADAM_spacer1
IPR024079 MetalloPept_cat_dom_sf
IPR013276 Pept_M12B_ADAM-TS5
IPR001590 Peptidase_M12B
IPR002870 Peptidase_M12B_N
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
PfamiView protein in Pfam
PF05986 ADAM_spacer1, 1 hit
PF01562 Pep_M12B_propep, 1 hit
PF01421 Reprolysin, 1 hit
PF00090 TSP_1, 2 hits
PRINTSiPR01860 ADAMTS5
SMARTiView protein in SMART
SM00608 ACR, 1 hit
SM00209 TSP1, 2 hits
SUPFAMiSSF82895 SSF82895, 2 hits
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS50092 TSP1, 2 hits
PS00142 ZINC_PROTEASE, 1 hit

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 → A2 PublicationsCorresponds to variant dbSNP:rs457947Ensembl.1
Natural variantiVAR_021849614R → H1 PublicationCorresponds to variant dbSNP:rs2830585Ensembl.1
Natural variantiVAR_028200692L → P3 PublicationsCorresponds to variant dbSNP:rs226794Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiATS5_HUMAN
AccessioniPrimary (citable) accession number: Q9UNA0
Secondary accession number(s): Q52LV4, Q9UKP2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 11, 2011
Last modified: February 28, 2018
This is version 175 of the entry and version 2 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
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Main funding by: National Institutes of Health