Protein:ADAMTS4 |
Protein Summary |
 Gene summary |
| Gene name: ADAMTS4 | ASpdb.0 ID: 9507 | Gene | Gene symbol | ADAMTS4 | Gene ID | 9507 |
| Gene name | ADAM metallopeptidase with thrombospondin type 1 motif 4 |
| Synonyms | ADAMTS-2|ADAMTS-4|ADMP-1 |
| Cytomap | 1q23.3 |
| Type of gene | protein-coding |
| Description | A disintegrin and metalloproteinase with thrombospondin motifs 4ADAM-TS 4ADAM-TS4a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 4aggrecanase-1epididymis secretory sperm binding protein |
| Modification date | 20240331 |
| UniProtAcc | O75173 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ADAMTS4 | GO:0005615 | extracellular space | 14744861 |
| Gene | ADAMTS4 | GO:0008233 | peptidase activity | 23845380 |
| Gene | ADAMTS4 | GO:0008237 | metallopeptidase activity | 21370305 |
| Gene | ADAMTS4 | GO:0008270 | zinc ion binding | 18042673 |
| Gene | ADAMTS4 | GO:0016607 | nuclear speck | - |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| O75173-1 | O75173-1_2rjp_A.pdb | 2RJP | X-ray | 2.8 | A | 214 | 508 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| O75173 | ADAMTS4 | O75173-1 | O75173-2 | 837 | 846 | 697 | 837 | Substitution | YGYNNVVTIPAGATHILVRQQGNPGHRSIYLALKLPDGSYALNGEYTLMPSPTDVVLPGAVSLRYSGATAASETLSGHGPLAQPLTLQVLVAGNPQDTRLRYSFFVPRPTPSTPRPTPQDWLHRRAQILEILRRRPWAGRK | CGTAWGSQLALQRGHCSLRDTVRPWATGPAFDTASPSGWQPPGHTPPIQLLRAPADPFNATPHSPGLAAPKSTDSGDPSAAPLGGQEITSLSRLPFLGTGASDLAGRKRELLLLPHAKTQWGGAVGVRPAPPLCPNAQAGPALVSCPGRQ | 697 | 846 |
| Multiple sequence alignment of our canonical and alternatively spliced ADAMTS4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ADAMTS4 |
| UniProt-id | ENSG | ENST | ENSP |
| O75173-1 | ENSG00000158859.10 | ENST00000367996.6 | ENSP00000356975.4 |
| UniProt-id | NM ID | NP ID |
| O75173-1 | NM_005099.5 | NP_005090.3 |
| O75173-2 | NM_001320336.1 | NP_001307265.1 |
| Amino acid sequences of our canonical and alternatively spliced ADAMTS4 |
| accession_id | Protein sequence |
| O75173-1 | MSQTGSHPGRGLAGRWLWGAQPCLLLPIVPLSWLVWLLLLLLASLLPSARLASPLPREEEIVFPEKLNGSVLPGSGAPARLLCRLQAFGE TLLLELEQDSGVQVEGLTVQYLGQAPELLGGAEPGTYLTGTINGDPESVASLHWDGGALLGVLQYRGAELHLQPLEGGTPNSAGGPGAHI LRRKSPASGQGPMCNVKAPLGSPSPRPRRAKRFASLSRFVETLVVADDKMAAFHGAGLKRYLLTVMAAAAKAFKHPSIRNPVSLVVTRLV ILGSGEEGPQVGPSAAQTLRSFCAWQRGLNTPEDSDPDHFDTAILFTRQDLCGVSTCDTLGMADVGTVCDPARSCAIVEDDGLQSAFTAA HELGHVFNMLHDNSKPCISLNGPLSTSRHVMAPVMAHVDPEEPWSPCSARFITDFLDNGYGHCLLDKPEAPLHLPVTFPGKDYDADRQCQ LTFGPDSRHCPQLPPPCAALWCSGHLNGHAMCQTKHSPWADGTPCGPAQACMGGRCLHMDQLQDFNIPQAGGWGPWGPWGDCSRTCGGGV QFSSRDCTRPVPRNGGKYCEGRRTRFRSCNTEDCPTGSALTFREEQCAAYNHRTDLFKSFPGPMDWVPRYTGVAPQDQCKLTCQAQALGY YYVLEPRVVDGTPCSPDSSSVCVQGRCIHAGCDRIIGSKKKFDKCMVCGGDGSGCSKQSGSFRKFRYGYNNVVTIPAGATHILVRQQGNP GHRSIYLALKLPDGSYALNGEYTLMPSPTDVVLPGAVSLRYSGATAASETLSGHGPLAQPLTLQVLVAGNPQDTRLRYSFFVPRPTPSTP |
| O75173-2 | MSQTGSHPGRGLAGRWLWGAQPCLLLPIVPLSWLVWLLLLLLASLLPSARLASPLPREEEIVFPEKLNGSVLPGSGAPARLLCRLQAFGE TLLLELEQDSGVQVEGLTVQYLGQAPELLGGAEPGTYLTGTINGDPESVASLHWDGGALLGVLQYRGAELHLQPLEGGTPNSAGGPGAHI LRRKSPASGQGPMCNVKAPLGSPSPRPRRAKRFASLSRFVETLVVADDKMAAFHGAGLKRYLLTVMAAAAKAFKHPSIRNPVSLVVTRLV ILGSGEEGPQVGPSAAQTLRSFCAWQRGLNTPEDSDPDHFDTAILFTRQDLCGVSTCDTLGMADVGTVCDPARSCAIVEDDGLQSAFTAA HELGHVFNMLHDNSKPCISLNGPLSTSRHVMAPVMAHVDPEEPWSPCSARFITDFLDNGYGHCLLDKPEAPLHLPVTFPGKDYDADRQCQ LTFGPDSRHCPQLPPPCAALWCSGHLNGHAMCQTKHSPWADGTPCGPAQACMGGRCLHMDQLQDFNIPQAGGWGPWGPWGDCSRTCGGGV QFSSRDCTRPVPRNGGKYCEGRRTRFRSCNTEDCPTGSALTFREEQCAAYNHRTDLFKSFPGPMDWVPRYTGVAPQDQCKLTCQAQALGY YYVLEPRVVDGTPCSPDSSSVCVQGRCIHAGCDRIIGSKKKFDKCMVCGGDGSGCSKQSGSFRKFRCGTAWGSQLALQRGHCSLRDTVRP WATGPAFDTASPSGWQPPGHTPPIQLLRAPADPFNATPHSPGLAAPKSTDSGDPSAAPLGGQEITSLSRLPFLGTGASDLAGRKRELLLL |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ADAMTS4 (go to UniProt):O75173 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| O75173 | Region | 686 | 837 | Note=Spacer | Type=Substitution;Start=697;End=837 |
Gene Isoform Structures and Expression Levels for ADAMTS4 |
| Gene structures of our canonical and alternative spliced genes of ADAMTS4 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of O75173-1 |
| 3D view using mol* of O75173-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of O75173-1 |
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| pLDDT distribution across the protein length of O75173-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of O75173-1 |
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| Ramachandran plot of O75173-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| O75173-1 | 1.077 | 476 | 1.095 | 1036.546 | 0.434 | 0.799 | 1.09 | 1.168 | 0.996 | 1.172 | 1.224 | 192,193,194,219,244,247,248,249,250,251,252,254,25 5,256,263,264,265,266,330,331,352,353,354,356,357, 358,361,362,387,389,390,392,393,394,395,396,397,39 8,399,400,401,403,427,428,431,432,433,434,435,436, 437,438,439,441,448,451,452,470,484,485,486,487,48 8,489,490,491,492,500,501,502,503,504,505,507,509, 512,515,516,551,552,553,554,555,556,557,558 |
| O75173-2 | 1.054 | 461 | 1.068 | 1060.899 | 0.436 | 0.779 | 1.034 | 0.783 | 1.042 | 0.751 | 0.95 | 217,218,219,244,247,248,249,250,251,252,254,255,25 6,257,259,261,262,263,264,265,353,354,356,357,390, 397,398,400,401,402,403,404,405,406,409,431,432,43 3,434,435,436,437,438,439,448,470,488,489,490,491, 502,503,504,505,507,514,515,516,518,546,547,548,55 1,552,553,554,555,556,557,558 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of O75173-1_O75173-1_2rjp_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O75173-1_2rjp_A_O75173-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O75173-1_O75173-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/O75173-1_vs_O75173-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/O75173-1_vs_O75173-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to ADAMTS4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to ADAMTS4 |
| Previous studies relating to the alternative splicing of ADAMTS4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ADAMTS4 | 16723216 | An alternative spliced transcript of ADAMTS4 is present in human synovium from OA patients. | The major proteoglycan of articular cartilage aggrecan is a substrate for ADAMTS4. RT-PCR analysis of human osteoarthritic (OA) synovial co-cultures using oligonucleotide primers designed to amplify across the exon 8/9 junction of human ADAMTS4 resulted in the amplification of two products, the expected product and a smaller product missing 161 bp from the 5' end of exon 9, the result of alternative splicing in which exon 8 joins to a cryptic 3' splice site within exon 9. The protein produced would be identical to human ADAMTS4 up to Arg(696), and would have a new C-terminal domain with no commonality with the ADAMTS4 spacer domain. Changes in the C-terminal domain of ADAMTS4 may alter its substrate specificity. | D010003 | Osteoarthritis |
Clinically important variants in ADAMTS4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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