Q9UNA0 (ATS5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	930 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 By similarity.
Subcellular location	Secreted › extracellular space › extracellular 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 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
Sequence similarities	Contains 1 disintegrin domain. Contains 1 peptidase M12B domain. Contains 2 TSP type-1 domains.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA proteinaceous extracellular matrix Traceable author statement Ref.1. Source: ProtInc
Molecular_function	integrin binding Traceable author statement Ref.1. Source: ProtInc metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro metallopeptidase activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACAN	P13608	2	EBI-2808663,EBI-6259246	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Potential

Propeptide

17 – 261

245

Potential

PRO_0000029170

Chain

262 – 930

669

A disintegrin and metalloproteinase with thrombospondin motifs 5

PRO_0000029171

Regions

Domain

267 – 476

210

Peptidase M12B

Domain

485 – 566

82

Disintegrin

Domain

567 – 622

56

TSP type-1 1

Domain

875 – 929

55

TSP type-1 2

Region

732 – 874

143

Spacer

Motif

207 – 214

8

Cysteine switch By similarity

Compositional bias

37 – 41

5

Poly-Ala

Compositional bias

257 – 261

5

Poly-Arg

Compositional bias

624 – 731

108

Cys-rich

Sites

Active site

411

1

By similarity

Metal binding

209

1

Zinc; in inhibited form By similarity

Metal binding

410

1

Zinc; catalytic By similarity

Metal binding

414

1

Zinc; catalytic By similarity

Metal binding

420

1

Zinc; catalytic By similarity

Amino acid modifications

Glycosylation

498

1

N-linked (GlcNAc...) Potential

Glycosylation

570

1

C-linked (Man) Ref.5

Glycosylation

573

1

C-linked (Man) Ref.5

Glycosylation

582

1

O-linked (Fuc...) Ref.5

Glycosylation

728

1

N-linked (GlcNAc...) Potential

Glycosylation

802

1

N-linked (GlcNAc...) Potential

Glycosylation

807

1

N-linked (GlcNAc...) Potential

Disulfide bond

388 ↔ 471

By similarity

Disulfide bond

426 ↔ 455

By similarity

Disulfide bond

579 ↔ 616

By similarity

Disulfide bond

583 ↔ 621

By similarity

Disulfide bond

594 ↔ 606

By similarity

Natural variations

Natural variant

138

1

G → A. Ref.1 Ref.3
Corresponds to variant rs457947 [ dbSNP | Ensembl ].

VAR_028199

Natural variant

614

1

R → H. Ref.4
Corresponds to variant rs2830585 [ dbSNP | Ensembl ].

VAR_021849

Natural variant

692

1

L → P. Ref.1 Ref.3 Ref.4
Corresponds to variant rs226794 [ dbSNP | Ensembl ].

VAR_028200

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

930

Helix Strand Turn

Details...

Beta strand

267 – 275

9

Helix

277 – 283

7

Helix

284 – 286

3

Helix

287 – 302

16

Helix

305 – 307

3

Beta strand

311 – 320

10

Turn

323 – 326

4

Helix

334 – 348

15

Beta strand

353 – 356

4

Beta strand

360 – 368

9

Beta strand

380 – 382

3

Helix

390 – 392

3

Beta strand

394 – 398

5

Beta strand

401 – 403

3

Helix

404 – 415

12

Helix

424 – 430

7

Beta strand

435 – 437

3

Beta strand

440 – 442

3

Helix

443 – 445

3

Helix

454 – 465

12

Turn

466 – 469

4

Helix

470 – 472

3

Helix

487 – 490

4

Helix

493 – 501

9

Beta strand

509 – 511

3

Turn

513 – 515

3

Beta strand

519 – 523

5

Beta strand

526 – 530

5

Beta strand

543 – 545

3

Beta strand

547 – 549

3

Beta strand

552 – 554

3

Sequences

	Sequence		Length	Mass (Da)
	Q9UNA0 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: 8CCE448A15A29CE8	FASTA	930	101,718
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY.
+	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.

IPI

IPI00009143.

RefSeq

NP_008969.2. NM_007038.3.

UniGene

Hs.58324.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RJQ	X-ray	2.60	A	262-628	[»]
3B8Z	X-ray	1.40	A/B	264-480	[»]
3HY7	X-ray	1.69	A/B	262-480	[»]
3HY9	X-ray	2.02	A/B	262-480	[»]
3HYG	X-ray	1.40	A/B	262-480	[»]
3LJT	X-ray	1.60	A	264-480	[»]

ProteinModelPortal

Q9UNA0.

SMR

Q9UNA0. Positions 259-854.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UNA0. 3 interactions.

STRING

9606.ENSP00000284987.

Protein family/group databases

MEROPS

M12.225.

PTM databases

PhosphoSite

Q9UNA0.

Polymorphism databases

DMDM

12643903.

Proteomic databases

PaxDb

Q9UNA0.

PRIDE

Q9UNA0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000284987; ENSP00000284987; ENSG00000154736.

GeneID

11096.

KEGG

hsa:11096.

UCSC

uc002ymg.3. human.

Organism-specific databases

CTD

11096.

GeneCards

GC21M028290.

H-InvDB

HIX0016044.

HGNC

HGNC:221. ADAMTS5.

HPA

CAB025996.
HPA005661.

MIM

605007. gene.

neXtProt

NX_Q9UNA0.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG302522.

HOGENOM

HOG000004799.

HOVERGEN

HBG004313.

InParanoid

Q9UNA0.

KO

K08620.

OMA

RASCETP.

OrthoDB

EOG42RD6Q.

PhylomeDB

Q9UNA0.

Gene expression databases

Bgee

Q9UNA0.

CleanEx

HS_ADAMTS5.

Genevestigator

Q9UNA0.

GermOnline

ENSG00000154736. Homo sapiens.

Family and domain databases

Gene3D

3.40.390.10. 1 hit.

InterPro

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. Thrombospondin_1_rpt.
[Graphical view]

Pfam

PF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 2 hits.
[Graphical view]

PRINTS

PR01860. ADAMTS5.
PR01857. ADAMTSFAMILY.

SMART

SM00209. TSP1. 2 hits.
[Graphical view]

SUPFAM

SSF82895. TSP1. 2 hits.

PROSITE

PS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. False negative.
PS50214. DISINTEGRIN_2. False negative.
PS50092. TSP1. 2 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9UNA0.

ChEMBL

CHEMBL2285.

EvolutionaryTrace

Q9UNA0.

GenomeRNAi

11096.

NextBio

42182.

PMAP-CutDB

Q9UNA0.

SOURCE

Search...

Entry information

Entry name

ATS5_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.