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'''Unreleased structure'''


The entry 5ctr is ON HOLD until Paper Publication
==Crystal structure of human SART3 HAT-C domain-human USP4 DUSP-UBL domain complex==
<StructureSection load='5ctr' size='340' side='right' caption='[[5ctr]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ctr]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CTR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CTR FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ctq|5ctq]], [[5ctt|5ctt]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ctr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ctr OCA], [http://pdbe.org/5ctr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ctr RCSB], [http://www.ebi.ac.uk/pdbsum/5ctr PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/SART3_HUMAN SART3_HUMAN]] Defects in SART3 are the cause of disseminated superficial actinic porokeratosis type 1 (DSAP1) [MIM:[http://omim.org/entry/175900 175900]]. DSAP1 is an autosomal dominant disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border, developing during the third or fourth decade of life on sun-exposed areas of skin.<ref>PMID:15840095</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/SART3_HUMAN SART3_HUMAN]] Regulates Tat transactivation activity through direct interaction. May be a cellular factor for HIV-1 gene expression and viral replication.<ref>PMID:11959860</ref>  [[http://www.uniprot.org/uniprot/UBP4_HUMAN UBP4_HUMAN]] Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. Plays a role in the regulation of quality control in the ER.<ref>PMID:7784062</ref> <ref>PMID:16316627</ref> <ref>PMID:16472766</ref> <ref>PMID:16339847</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Squamous cell carcinoma antigen recognized by T-cells 3 (SART3) is a U4/U6 recycling factor as well as a targeting factor of USP4 and USP15. However, the details of how SART3 recognizes these deubiquitinases and how they get subsequently translocated into the nucleus are not known. Here, we present the crystal structures of the SART3 half-a-tetratricopeptide (HAT) repeat domain alone and in complex with the domain present in ubiquitin-specific protease (DUSP)-ubiquitin-like (UBL) domains of ubiquitin specific protease 4 (USP4). The 12 HAT repeats of SART3 are in two sub-domains (HAT-N and HAT-C) forming a dimer through HAT-C. USP4 binds SART3 at the opposite surface of the HAT-C dimer interface utilizing the beta-structured linker between the DUSP and the UBL domains. The binding affinities of USP4 and USP15 to SART3 are 0.9 muM and 0.2 muM, respectively. The complex structure of SART3 nuclear localization signal (NLS) and importin-alpha reveals bipartite binding, and removal of SART3 NLS prevents the entry of USP4 (and USP15) into the nucleus and abrogates the subsequent deubiquitinase activity of USP4.


Authors: Park, J.K., Kim, E.E.
Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3.,Park JK, Das T, Song EJ, Kim EE Nucleic Acids Res. 2016 Apr 7. pii: gkw218. PMID:27060135<ref>PMID:27060135</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Kim, E.E]]
<div class="pdbe-citations 5ctr" style="background-color:#fffaf0;"></div>
[[Category: Park, J.K]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Ubiquitinyl hydrolase 1]]
[[Category: Kim, E E]]
[[Category: Park, J K]]
[[Category: Deubiquitinase]]
[[Category: Hydrolase]]
[[Category: Immune system]]
[[Category: Nuclear complex]]
[[Category: Nuclear protein]]
[[Category: Rna binding protein]]

Revision as of 15:01, 13 May 2016

Crystal structure of human SART3 HAT-C domain-human USP4 DUSP-UBL domain complexCrystal structure of human SART3 HAT-C domain-human USP4 DUSP-UBL domain complex

Structural highlights

5ctr is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:Ubiquitinyl hydrolase 1, with EC number 3.4.19.12
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[SART3_HUMAN] Defects in SART3 are the cause of disseminated superficial actinic porokeratosis type 1 (DSAP1) [MIM:175900]. DSAP1 is an autosomal dominant disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border, developing during the third or fourth decade of life on sun-exposed areas of skin.[1]

Function

[SART3_HUMAN] Regulates Tat transactivation activity through direct interaction. May be a cellular factor for HIV-1 gene expression and viral replication.[2] [UBP4_HUMAN] Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. Plays a role in the regulation of quality control in the ER.[3] [4] [5] [6]

Publication Abstract from PubMed

Squamous cell carcinoma antigen recognized by T-cells 3 (SART3) is a U4/U6 recycling factor as well as a targeting factor of USP4 and USP15. However, the details of how SART3 recognizes these deubiquitinases and how they get subsequently translocated into the nucleus are not known. Here, we present the crystal structures of the SART3 half-a-tetratricopeptide (HAT) repeat domain alone and in complex with the domain present in ubiquitin-specific protease (DUSP)-ubiquitin-like (UBL) domains of ubiquitin specific protease 4 (USP4). The 12 HAT repeats of SART3 are in two sub-domains (HAT-N and HAT-C) forming a dimer through HAT-C. USP4 binds SART3 at the opposite surface of the HAT-C dimer interface utilizing the beta-structured linker between the DUSP and the UBL domains. The binding affinities of USP4 and USP15 to SART3 are 0.9 muM and 0.2 muM, respectively. The complex structure of SART3 nuclear localization signal (NLS) and importin-alpha reveals bipartite binding, and removal of SART3 NLS prevents the entry of USP4 (and USP15) into the nucleus and abrogates the subsequent deubiquitinase activity of USP4.

Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3.,Park JK, Das T, Song EJ, Kim EE Nucleic Acids Res. 2016 Apr 7. pii: gkw218. PMID:27060135[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Zhang ZH, Niu ZM, Yuan WT, Zhao JJ, Jiang FX, Zhang J, Chai B, Cui F, Chen W, Lian CH, Xiang LH, Xu SJ, Liu WD, Zheng ZZ, Huang W. A mutation in SART3 gene in a Chinese pedigree with disseminated superficial actinic porokeratosis. Br J Dermatol. 2005 Apr;152(4):658-63. PMID:15840095 doi:10.1111/j.1365-2133.2005.06443.x
  2. ↑ Liu Y, Li J, Kim BO, Pace BS, He JJ. HIV-1 Tat protein-mediated transactivation of the HIV-1 long terminal repeat promoter is potentiated by a novel nuclear Tat-interacting protein of 110 kDa, Tip110. J Biol Chem. 2002 Jun 28;277(26):23854-63. Epub 2002 Apr 16. PMID:11959860 doi:10.1074/jbc.M200773200
  3. ↑ Gray DA, Inazawa J, Gupta K, Wong A, Ueda R, Takahashi T. Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors. Oncogene. 1995 Jun 1;10(11):2179-83. PMID:7784062
  4. ↑ Wada K, Tanji K, Kamitani T. Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity. Biochem Biophys Res Commun. 2006 Jan 20;339(3):731-6. PMID:16316627 doi:10.1016/j.bbrc.2005.11.076
  5. ↑ Wada K, Kamitani T. UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself. Biochem Biophys Res Commun. 2006 Mar 31;342(1):253-8. Epub 2006 Feb 6. PMID:16472766 doi:10.1016/j.bbrc.2006.01.144
  6. ↑ Milojevic T, Reiterer V, Stefan E, Korkhov VM, Dorostkar MM, Ducza E, Ogris E, Boehm S, Freissmuth M, Nanoff C. The ubiquitin-specific protease Usp4 regulates the cell surface level of the A2A receptor. Mol Pharmacol. 2006 Apr;69(4):1083-94. Epub 2005 Dec 9. PMID:16339847 doi:10.1124/mol.105.015818
  7. ↑ Park JK, Das T, Song EJ, Kim EE. Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3. Nucleic Acids Res. 2016 Apr 7. pii: gkw218. PMID:27060135 doi:http://dx.doi.org/10.1093/nar/gkw218

5ctr, resolution 3.01Å

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