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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 4

Gene

Adamts4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

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 bindingi190Zinc; in inhibited formBy similarity1
Metal bindingi357Zinc; catalyticBy similarity1
Active sitei358PROSITE-ProRule annotation1
Metal bindingi361Zinc; catalyticBy similarity1
Metal bindingi367Zinc; catalyticBy similarity1

GO - Molecular functioni

  • metalloendopeptidase activity Source: MGI
  • metallopeptidase activity Source: MGI
  • protease binding Source: MGI
  • zinc ion binding Source: InterPro

GO - Biological processi

  • defense response to bacterium Source: MGI
  • proteolysis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.82. 3474.

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):
Aggrecanase-1
Gene namesi
Name:Adamts4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1339949. Adamts4.

Subcellular locationi

GO - Cellular componenti

  • extracellular matrix Source: UniProtKB
  • extracellular space Source: MGI
  • proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 49Sequence analysisAdd BLAST49
PropeptideiPRO_000002916650 – 208By similarityAdd BLAST159
ChainiPRO_0000029167209 – 833A disintegrin and metalloproteinase with thrombospondin motifs 4Add BLAST625

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi63N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi289 ↔ 341By similarity
Glycosylationi299N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi318 ↔ 323By similarity
Disulfide bondi335 ↔ 419By similarity
Disulfide bondi373 ↔ 403By similarity
Disulfide bondi445 ↔ 468By similarity
Disulfide bondi456 ↔ 478By similarity
Disulfide bondi463 ↔ 497By similarity
Disulfide bondi491 ↔ 502By similarity
Disulfide bondi528 ↔ 565By similarity
Disulfide bondi532 ↔ 570By similarity
Disulfide bondi543 ↔ 555By 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

MaxQBiQ8BNJ2.
PaxDbiQ8BNJ2.
PRIDEiQ8BNJ2.

PTM databases

PhosphoSitePlusiQ8BNJ2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000006403.

Interactioni

Subunit structurei

Interacts with SRPX2.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000006570.

Structurei

3D structure databases

ProteinModelPortaliQ8BNJ2.
SMRiQ8BNJ2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini214 – 424Peptidase M12BPROSITE-ProRule annotationAdd BLAST211
Domaini433 – 515DisintegrinAdd BLAST83
Domaini516 – 571TSP type-1PROSITE-ProRule annotationAdd BLAST56

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni682 – 833SpacerAdd BLAST152

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi188 – 195Cysteine switchBy similarity8

Domaini

The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.By similarity
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.
InParanoidiQ8BNJ2.
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.

Q8BNJ2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQMGLHPRR GLTGHWLQRF QPCLPLHTVQ WRRLLLLAFL LSLAWPASPL
60 70 80 90 100
PREEEIVFPE KLNGSSILPG SGVPARLLYR LPAFGEMLLL ELEQDPGVQV
110 120 130 140 150
EGLTVQYLGQ APEMLGGAEP GTYLTGTING DPESVASLHW DGGALLGVLQ
160 170 180 190 200
YRGAELHLQP LEGGALNSAG GPGAHILRRK SPASSQGPMC TVKAPSGSPS
210 220 230 240 250
PISRRTKRFA SLSRFVETLV VADDKMAAFH GTGLKRYLLT VMAAAAKAFK
260 270 280 290 300
HPSIRNPVNL VVTRLVILGS GQEGPQVGPS AAQTLRSFCT WQRGLNTPND
310 320 330 340 350
SDPDHFDTAI LFTRQDLCGV STCDTLGMAD VGTVCDPARS CAIVEDDGLQ
360 370 380 390 400
SAFTAAHELG HVFNMLHDNS KPCTNLNGQG GSSRHVMAPV MAHVDPEEPW
410 420 430 440 450
SPCSARFITD FLDNGYGHCL LDKPEAPLHL PATFPGKDYD ADRQCQLTFG
460 470 480 490 500
PDSSHCPQLP PPCAALWCSG HLNGHAMCQT KHSPWADGTP CGSSQACMGG
510 520 530 540 550
RCLHVDQLKD FNVPQAGGWG PWGPWGDCSR TCGGGVQFSS RDCTRPVPRN
560 570 580 590 600
GGKYCEGRRT RFRSCNTENC PHGSALTFRE EQCAAYNHRT DLFKSFPGPM
610 620 630 640 650
DWVPRYTGVA PRDQCKLTCQ ARALGYYYVL EPRVADGTPC SPDTSSVCVQ
660 670 680 690 700
GRCIHAGCDR IIGSKKKFDK CMVCGGDGSR CSKQSGSFKK FRYGYSDVVT
710 720 730 740 750
IPAGATHILV RQQGGSGLKS IYLALKLSDG SYALNGEYTL MPSPTDVVLP
760 770 780 790 800
GAVSLRYSGA TAASETLSGH GPLAQPLTLQ VLVAGNPQNA RLRYSFFVPR
810 820 830
PVPSTPRPPP QDWLQRRAEI LKILRKRPWA GRK
Length:833
Mass (Da):90,070
Last modified:May 10, 2005 - v2
Checksum:i6512B9ED2617F3A4
GO

Sequence cautioni

The sequence BAC38944 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18Q → R in AAH27773 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK083534 mRNA. Translation: BAC38944.1. Different initiation.
BC027773 mRNA. Translation: AAH27773.1.
CCDSiCCDS15485.1.
RefSeqiNP_766433.2. NM_172845.3.
UniGeneiMm.491147.

Genome annotation databases

GeneIDi240913.
KEGGimmu:240913.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK083534 mRNA. Translation: BAC38944.1. Different initiation.
BC027773 mRNA. Translation: AAH27773.1.
CCDSiCCDS15485.1.
RefSeqiNP_766433.2. NM_172845.3.
UniGeneiMm.491147.

3D structure databases

ProteinModelPortaliQ8BNJ2.
SMRiQ8BNJ2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000006570.

Protein family/group databases

MEROPSiM12.221.

PTM databases

PhosphoSitePlusiQ8BNJ2.

Proteomic databases

MaxQBiQ8BNJ2.
PaxDbiQ8BNJ2.
PRIDEiQ8BNJ2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi240913.
KEGGimmu:240913.

Organism-specific databases

CTDi9507.
MGIiMGI:1339949. Adamts4.

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
HOGENOMiHOG000004799.
HOVERGENiHBG004313.
InParanoidiQ8BNJ2.
KOiK07764.

Enzyme and pathway databases

BRENDAi3.4.24.82. 3474.

Miscellaneous databases

PROiQ8BNJ2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000006403.

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_MOUSE
AccessioniPrimary (citable) accession number: Q8BNJ2
Secondary accession number(s): Q8K384
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: May 10, 2005
Last modified: November 2, 2016
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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.