| Structural highlights
Function
[STAB2_HUMAN] Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Acts also, in different species, as a primary systemic scavenger receptor for heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), nonglycosaminoglycan (GAG), acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides and advanced glycation end products (AGE). May serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidity of bodily liquids by resorption of hyaluronan. Counter receptor which plays an important role in lymphocyte recruitment in the hepatic vasculature. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. The proteolytically processed 190 kDa form also functions as an endocytosis receptor for heparin internalisation as well as HA and CS.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
Publication Abstract from PubMed
Recent research has identified a potential role of the hyaluronic acid receptor stabilin-2 (Stab2) in cancer metastasis. Stab2 belongs to a group of scavenger receptors and is responsible for the clearance of more than ten ligands, including hyaluronic acid (HA). In vivo experiments on mice have shown that the absence of Stab2, or its blocking by an antibody, effectively opposes cancer metastasis, which is accompanied by an increase in the level of circulating HA. Knowledge of ligand recognition and signal transduction by Stab2 is limited and no three-dimensional structures of any protein fragments of this receptor have been solved to date. Here, a high-resolution X-ray structure of the seventh FAS1 domain of Stab2 is reported. This structure provides the first insight into the Stab2 structure.
Crystal structure of the FAS1 domain of the hyaluronic acid receptor stabilin-2.,Twarda-Clapa A, Labuzek B, Krzemien D, Musielak B, Grudnik P, Dubin G, Holak TA Acta Crystallogr D Struct Biol. 2018 Jul 1;74(Pt 7):695-701. doi:, 10.1107/S2059798318007271. Epub 2018 Jun 27. PMID:29968679[12]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Adachi H, Tsujimoto M. FEEL-1, a novel scavenger receptor with in vitro bacteria-binding and angiogenesis-modulating activities. J Biol Chem. 2002 Sep 13;277(37):34264-70. Epub 2002 Jun 19. PMID:12077138 doi:http://dx.doi.org/10.1074/jbc.M204277200
- ↑ Tamura Y, Adachi H, Osuga J, Ohashi K, Yahagi N, Sekiya M, Okazaki H, Tomita S, Iizuka Y, Shimano H, Nagai R, Kimura S, Tsujimoto M, Ishibashi S. FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. J Biol Chem. 2003 Apr 11;278(15):12613-7. doi: 10.1074/jbc.M210211200. Epub 2002 , Dec 6. PMID:12473645 doi:http://dx.doi.org/10.1074/jbc.M210211200
- ↑ Harris EN, Weigel JA, Weigel PH. Endocytic function, glycosaminoglycan specificity, and antibody sensitivity of the recombinant human 190-kDa hyaluronan receptor for endocytosis (HARE). J Biol Chem. 2004 Aug 27;279(35):36201-9. doi: 10.1074/jbc.M405322200. Epub 2004 , Jun 18. PMID:15208308 doi:http://dx.doi.org/10.1074/jbc.M405322200
- ↑ Hansen B, Longati P, Elvevold K, Nedredal GI, Schledzewski K, Olsen R, Falkowski M, Kzhyshkowska J, Carlsson F, Johansson S, Smedsrod B, Goerdt S, Johansson S, McCourt P. Stabilin-1 and stabilin-2 are both directed into the early endocytic pathway in hepatic sinusoidal endothelium via interactions with clathrin/AP-2, independent of ligand binding. Exp Cell Res. 2005 Feb 1;303(1):160-73. doi: 10.1016/j.yexcr.2004.09.017. PMID:15572036 doi:http://dx.doi.org/10.1016/j.yexcr.2004.09.017
- ↑ Harris EN, Kyosseva SV, Weigel JA, Weigel PH. Expression, processing, and glycosaminoglycan binding activity of the recombinant human 315-kDa hyaluronic acid receptor for endocytosis (HARE). J Biol Chem. 2007 Feb 2;282(5):2785-97. doi: 10.1074/jbc.M607787200. Epub 2006, Dec 4. PMID:17145755 doi:http://dx.doi.org/10.1074/jbc.M607787200
- ↑ Jung MY, Park SY, Kim IS. Stabilin-2 is involved in lymphocyte adhesion to the hepatic sinusoidal endothelium via the interaction with alphaMbeta2 integrin. J Leukoc Biol. 2007 Nov;82(5):1156-65. doi: 10.1189/jlb.0107052. Epub 2007 Aug 3. PMID:17675564 doi:http://dx.doi.org/10.1189/jlb.0107052
- ↑ Park SY, Jung MY, Kim HJ, Lee SJ, Kim SY, Lee BH, Kwon TH, Park RW, Kim IS. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ. 2008 Jan;15(1):192-201. doi: 10.1038/sj.cdd.4402242. Epub 2007, Oct 26. PMID:17962816 doi:http://dx.doi.org/10.1038/sj.cdd.4402242
- ↑ Park SY, Kang KB, Thapa N, Kim SY, Lee SJ, Kim IS. Requirement of adaptor protein GULP during stabilin-2-mediated cell corpse engulfment. J Biol Chem. 2008 Apr 18;283(16):10593-600. doi: 10.1074/jbc.M709105200. Epub, 2008 Jan 29. PMID:18230608 doi:http://dx.doi.org/10.1074/jbc.M709105200
- ↑ Harris EN, Weigel JA, Weigel PH. The human hyaluronan receptor for endocytosis (HARE/Stabilin-2) is a systemic clearance receptor for heparin. J Biol Chem. 2008 Jun 20;283(25):17341-50. doi: 10.1074/jbc.M710360200. Epub 2008, Apr 22. PMID:18434317 doi:http://dx.doi.org/10.1074/jbc.M710360200
- ↑ Park SY, Kim SY, Jung MY, Bae DJ, Kim IS. Epidermal growth factor-like domain repeat of stabilin-2 recognizes phosphatidylserine during cell corpse clearance. Mol Cell Biol. 2008 Sep;28(17):5288-98. doi: 10.1128/MCB.01993-07. Epub 2008 Jun , 23. PMID:18573870 doi:http://dx.doi.org/10.1128/MCB.01993-07
- ↑ Harris EN, Baggenstoss BA, Weigel PH. Rat and human HARE/stabilin-2 are clearance receptors for high- and low-molecular-weight heparins. Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1191-9. doi:, 10.1152/ajpgi.90717.2008. Epub 2009 Apr 9. PMID:19359419 doi:http://dx.doi.org/10.1152/ajpgi.90717.2008
- ↑ Twarda-Clapa A, Labuzek B, Krzemien D, Musielak B, Grudnik P, Dubin G, Holak TA. Crystal structure of the FAS1 domain of the hyaluronic acid receptor stabilin-2. Acta Crystallogr D Struct Biol. 2018 Jul 1;74(Pt 7):695-701. doi:, 10.1107/S2059798318007271. Epub 2018 Jun 27. PMID:29968679 doi:http://dx.doi.org/10.1107/S2059798318007271
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