F
IPR043563

Nuclear body protein Sp110/Sp140/Sp140L-like

InterPro entry
Short nameSp110/Sp140/Sp140L-like
family relationships

Description

This entry includes a group of nuclear dot-associated proteins, including Sp110/Sp140/Sp140L and autoimmune regulator from humans. They are proteins with a constituent of nuclear domains, also known as nuclear dots (NDs). Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region)
[7]
.

Sp110 is a leukocyte-specific component of the nuclear body
[2]
. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells
[9]
. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers
[10, 11]
. Sp110 gene polymorphisms may be associated with susceptibility to tuberculosis in Chinese population
[8]
.

The function of nuclear protein Sp140 is not known, though it contains several chromatin related modules such as plant homeodomain (PHD), bromodomain (BRD) and SAND domain, which suggests a role in chromatin-mediated regulation of gene expression
[3]
. It also harbours a nuclear localisation signal and a dimerisation domain (HSR or CARD domain). The PHD finger of Sp140 presents an atypical fold which does not bind to histone H3 tails but binds to peptidylprolyl isomerase Pin1. Pin1 catalyses the isomerisation of a phospho-Threonine-Proline bond in Sp140-PHD and thus may modulate Sp140 function
[5]
.

Human Sp140 is an interferon inducible nuclear leukocyte-specific protein that may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection
[2]
. It localises to LYSP100-associated nuclear dots and is also a component of the promyelocytic leukemia nuclear body (PML-NBs)
[2, 1]
. The Sp140 locus has been identified as a lymphocytic leukemia (CLL) risk locus
[4]
.

This family also includes protein Sp140-like (SP140L)
[6]
.

References

1.LYSP100-associated nuclear domains (LANDs): description of a new class of subnuclear structures and their relationship to PML nuclear bodies. Dent AL, Yewdell J, Puvion-Dutilleul F, Koken MH, de The H, Staudt LM. Blood 88, 1423-6, (1996). PMID: 8695863

2.Identification and characterization of a leukocyte-specific component of the nuclear body. Bloch DB, de la Monte SM, Guigaouri P, Filippov A, Bloch KD. J. Biol. Chem. 271, 29198-204, (1996). View articlePMID: 8910577

3.Keeping it in the family: diverse histone recognition by conserved structural folds. Yap KL, Zhou MM. Crit. Rev. Biochem. Mol. Biol. 45, 488-505, (2010). View articlePMID: 20923397

4.A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia. Di Bernardo MC, Crowther-Swanepoel D, Broderick P, Webb E, Sellick G, Wild R, Sullivan K, Vijayakrishnan J, Wang Y, Pittman AM, Sunter NJ, Hall AG, Dyer MJ, Matutes E, Dearden C, Mainou-Fowler T, Jackson GH, Summerfield G, Harris RJ, Pettitt AR, Hillmen P, Allsup DJ, Bailey JR, Pratt G, Pepper C, Fegan C, Allan JM, Catovsky D, Houlston RS. Nat. Genet. 40, 1204-10, (2008). View articlePMID: 18758461

5.Structure of human Sp140 PHD finger: an atypical fold interacting with Pin1. Zucchelli C, Tamburri S, Quilici G, Palagano E, Berardi A, Saare M, Peterson P, Bachi A, Musco G. FEBS J. 281, 216-31, (2014). View articlePMID: 24267382

6.SP140L, an Evolutionarily Recent Member of the SP100 Family, Is an Autoantigen in Primary Biliary Cirrhosis. Saare M, Hamarik U, Venta R, Panarina M, Zucchelli C, Pihlap M, Remm A, Kisand K, Toots U, Moll K, Salupere R, Musco G, Uibo R, Peterson P. J Immunol Res 2015, 526518, (2015). View articlePMID: 26347895

7.The nuclear dot protein sp100, characterization of domains necessary for dimerization, subcellular localization, and modification by small ubiquitin-like modifiers. Sternsdorf T, Jensen K, Reich B, Will H. J. Biol. Chem. 274, 12555-66, (1999). View articlePMID: 10212234

8.Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa. Tosh K, Campbell SJ, Fielding K, Sillah J, Bah B, Gustafson P, Manneh K, Lisse I, Sirugo G, Bennett S, Aaby P, McAdam KPWJ, Bah-Sow O, Lienhardt C, Kramnik I, Hill AVS. Proc. Natl. Acad. Sci. U.S.A. 103, 10364-10368, (2006). PMID: 16803959

9.Sp110 localizes to the PML-Sp100 nuclear body and may function as a nuclear hormone receptor transcriptional coactivator. Bloch DB, Nakajima A, Gulick T, Chiche JD, Orth D, de La Monte SM, Bloch KD. Mol. Cell. Biol. 20, 6138-46, (2000). PMID: 10913195

10.Identification of proteins interacting with human SP110 during the process of viral infections. Cai L, Wang Y, Wang JF, Chou KC. Med Chem 7, 121-6, (2011). PMID: 21222611

11.Mutations in the gene encoding the PML nuclear body protein Sp110 are associated with immunodeficiency and hepatic veno-occlusive disease. Roscioli T, Cliffe ST, Bloch DB, Bell CG, Mullan G, Taylor PJ, Sarris M, Wang J, Donald JA, Kirk EP, Ziegler JB, Salzer U, McDonald GB, Wong M, Lindeman R, Buckley MF. Nat. Genet. 38, 620-2, (2006). PMID: 16648851

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