Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

A disintegrin and metalloproteinase with thrombospondin motifs 4

Gene

ADAMTS4

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed-Annotation score: Annotation score: 4 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.

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):
Aggrecanase-1
Gene namesi
Name:ADAMTS4
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
Proteomesi
  • UP000001595 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 51Sequence analysisAdd BLAST51
PropeptideiPRO_000023980352 – 212By similarityAdd BLAST161
ChainiPRO_0000239804213 – 837A disintegrin and metalloproteinase with thrombospondin motifs 4Add BLAST625

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

Interactioni

Subunit structurei

Interacts with SRPX2.By similarity

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000000708.

Structurei

3D structure databases

ProteinModelPortaliQ5RFQ8.
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 – 837SpacerBy similarityAdd BLAST152

Motif

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

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.
HOVERGENiHBG004313.
InParanoidiQ5RFQ8.

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.

Q5RFQ8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQTGSHPGR GLAGRWLWGA QPCLLLPIVP LSWLVWLLLL LLASLLPSAR
60 70 80 90 100
LASPLPREEE IVFPEKLNGS VLPGSGAPAR LLCRLQAFGE TLLLELEHDS
110 120 130 140 150
GVQVEGLTVQ YLGQAPELLG GAEPGTYLTG TINGEPESVA SLHWDGGALL
160 170 180 190 200
GVLQYRGAEL HLQPLEGGTP NSAGGPGAHI LRRKSPASGQ GPMCNVKAPL
210 220 230 240 250
GSPSPRPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR YLLTVMAAAA
260 270 280 290 300
KAFKHPSIRN PVSLVVTRLV ILGSGEEGPQ VGPSAAQTLR SFCAWQRGLN
310 320 330 340 350
TPEDSDPDHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED
360 370 380 390 400
DGLQSAYTAA HELGHVFNML HDNSKPCISL NGPLSTSRHV MAPVMAHVDP
410 420 430 440 450
EEPWSPCSAR FITDFLDNGY GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ
460 470 480 490 500
LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA MCQTKHSPWA DGTPCGPAQA
510 520 530 540 550
CMGGRCLHMD QLQDFNIPQA GGWGPWGPWG DCSRTCGGGV QFSSRDCTRP
560 570 580 590 600
VPRNGGKYCE GRRTRFRSCN TEDCPTGSVL TFREEQCAAY NHCTDLFKSF
610 620 630 640 650
PGPMDWVPRY TGVAPQDQCK LTCQARALGY YYVLEPRVVD GTPCSPDSSS
660 670 680 690 700
VCVQGRCIHA GCDRIIGSKK KFDKCMVCGG DGSGCSKQSG SFRKFRYGYN
710 720 730 740 750
NVVTIPTGAT HILVRQQGNP GHRSIYLALK LPDGSYALNG EYTLMPSPTD
760 770 780 790 800
VVLPGAISLR YSGATAASET LSGHGPLAQP LTLQVLVAGN PQDARLRYSF
810 820 830
FVPRPTPSTP HPTPQDWLHR RAQILEILRR RPWVGRK
Length:837
Mass (Da):90,262
Last modified:December 21, 2004 - v1
Checksum:i08F5E69F65CF6B4C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR857094 mRNA. Translation: CAH89399.1.
UniGeneiPab.12192.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR857094 mRNA. Translation: CAH89399.1.
UniGeneiPab.12192.

3D structure databases

ProteinModelPortaliQ5RFQ8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000000708.

Protein family/group databases

MEROPSiM12.221.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
HOVERGENiHBG004313.
InParanoidiQ5RFQ8.

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_PONAB
AccessioniPrimary (citable) accession number: Q5RFQ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: December 21, 2004
Last modified: October 5, 2016
This is version 65 of the entry and version 1 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. 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.