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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 4

Gene

ADAMTS4

Organism
Bos taurus (Bovine)
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. Cleaves aggrecan at the '392-Glu-|-Ala-393' site.

Catalytic activityi

Glutamyl endopeptidase; bonds cleaved include 370-Thr-Glu-Gly-Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian aggrecan.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi194Zinc; in inhibited formBy similarity1
Metal bindingi361Zinc; catalyticBy similarity1
Active sitei362PROSITE-ProRule annotation1
Metal bindingi365Zinc; catalyticBy similarity1
Metal bindingi371Zinc; catalyticBy similarity1

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiM12.221.

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 4 (EC:3.4.24.82)
Short name:
ADAM-TS 4
Short name:
ADAM-TS4
Short name:
ADAMTS-4
Alternative name(s):
ADMP-1
Aggrecanase-1
Gene namesi
Name:ADAMTS4
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3874.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 51Sequence analysisAdd BLAST51
PropeptideiPRO_000023980252 – 2121 PublicationAdd BLAST161
ChainiPRO_0000078209213 – 839A disintegrin and metalloproteinase with thrombospondin motifs 4Add BLAST627

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi68N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi293 ↔ 345By similarity
Disulfide bondi322 ↔ 327By similarity
Disulfide bondi339 ↔ 423By similarity
Disulfide bondi377 ↔ 407By similarity
Disulfide bondi449 ↔ 472By similarity
Disulfide bondi460 ↔ 482By similarity
Disulfide bondi467 ↔ 501By similarity
Disulfide bondi495 ↔ 506By similarity
Disulfide bondi532 ↔ 569By similarity
Disulfide bondi536 ↔ 574By similarity
Disulfide bondi547 ↔ 559By similarity

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.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

PaxDbiQ9TT93.
PRIDEiQ9TT93.

Expressioni

Inductioni

By interleukin-1.

Interactioni

Subunit structurei

Interacts with SRPX2.By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000017583.

Structurei

3D structure databases

ProteinModelPortaliQ9TT93.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini218 – 428Peptidase M12BPROSITE-ProRule annotationAdd BLAST211
Domaini437 – 519DisintegrinAdd BLAST83
Domaini520 – 575TSP type-1PROSITE-ProRule annotationAdd BLAST56

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni686 – 839SpacerBy similarityAdd BLAST154

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi192 – 199Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi247 – 252Poly-Ala6
Compositional biasi577 – 685Cys-richAdd BLAST109

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 1 TSP type-1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
HOGENOMiHOG000004799.
HOVERGENiHBG004313.
InParanoidiQ9TT93.
KOiK07764.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
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. 1 hit.
[Graphical view]
PRINTSiPR01857. ADAMTSFAMILY.
SMARTiSM00608. ACR. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9TT93-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSHMDSHPGR GLADGWLWGI QPRLLLPTVP VSGSRLVWLL LLASLLPSAW
60 70 80 90 100
PASPLPREEE IVFPEKLNGS VLPGLGAPAR LLYRLPAFGE TLLLELEKDP
110 120 130 140 150
GVQVEGLTVQ YLGRAPELLG GAEPGTYLTG TINGDPESVA SLHWDGGALL
160 170 180 190 200
GVLQYRGTEL HIQPLEGGAP NSAGGPGAHI LRRKSPVSGQ GPMCNVKAPP
210 220 230 240 250
GKPSPSPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR YLLTVMAAAA
260 270 280 290 300
KAFKHPSIRN PVSLVVTRLV VLGPGEEGPQ VGPSAAQTLR SFCAWQRGLN
310 320 330 340 350
TPDDADPGHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED
360 370 380 390 400
DGLQSAFTAA HELGHVFSML HDNSKQCTGL NGPESTSRHV MAPVMAHVDP
410 420 430 440 450
EEPWSPCSAR FITDFLDNGF GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ
460 470 480 490 500
LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA MCQTKHSPWA DGTPCGPAQA
510 520 530 540 550
CMGGRCLHVD QLQAFNVPQA GGWGPWGSWG DCSRSCGGGV QFSSRDCTRP
560 570 580 590 600
VPRNGGKYCE GRRTRFRSCN TQDCPTGSAL TFREEQCAAY NHRTDLFKNF
610 620 630 640 650
PGPMDWVPRY TGVAPRDQCK LTCQTRALGY YYVLDPRVAD GTPCSPDSSS
660 670 680 690 700
VCVQGRCIHA GCDRVIGSKK KFDKCMVCGG DGSSCSKQSG SFKKFRYGYN
710 720 730 740 750
NVVTIPAGAT HILVRQQGSP SVRSLYLALK LPDGSYALNG EYTLIPSPTD
760 770 780 790 800
VVLPGAVSLR YSGATAASET LSGHGPLAEP LTLQVLVAGN PQNARLRYSF
810 820 830
FVPRPRPVPS TPRPTPQDWL RRKSQILEIL RRRSWAGRK
Length:839
Mass (Da):90,280
Last modified:June 13, 2006 - v3
Checksum:i1B488A27DF5B96B1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF516915 mRNA. Translation: AAP47196.1.
BC148059 mRNA. Translation: AAI48060.1.
AF192770 mRNA. Translation: AAF07176.1.
RefSeqiNP_858053.1. NM_181667.1.
UniGeneiBt.15675.

Genome annotation databases

GeneIDi286806.
KEGGibta:286806.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF516915 mRNA. Translation: AAP47196.1.
BC148059 mRNA. Translation: AAI48060.1.
AF192770 mRNA. Translation: AAF07176.1.
RefSeqiNP_858053.1. NM_181667.1.
UniGeneiBt.15675.

3D structure databases

ProteinModelPortaliQ9TT93.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000017583.

Chemistry databases

ChEMBLiCHEMBL3874.

Protein family/group databases

MEROPSiM12.221.

Proteomic databases

PaxDbiQ9TT93.
PRIDEiQ9TT93.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi286806.
KEGGibta:286806.

Organism-specific databases

CTDi9507.

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
HOGENOMiHOG000004799.
HOVERGENiHBG004313.
InParanoidiQ9TT93.
KOiK07764.

Miscellaneous databases

PROiQ9TT93.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
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. 1 hit.
[Graphical view]
PRINTSiPR01857. ADAMTSFAMILY.
SMARTiSM00608. ACR. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 1 hit.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATS4_BOVIN
AccessioniPrimary (citable) accession number: Q9TT93
Secondary accession number(s): A6QLR5, Q7YS95
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: June 13, 2006
Last modified: October 5, 2016
This is version 118 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Has sometimes been referred to as ADAMTS2.Curated

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.