S100A11

S100 calcium-binding protein A11 (S100A11) is a protein that in humans is encoded by the S100A11 gene.[4][5]

S100A11
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1V4Z, 1V50, 2LUC
Identifiers
Aliases	S100A11, HEL-S-43, MLN70, S100C, S100 calcium binding protein A11
External IDs	OMIM: 603114 MGI: 3645720 HomoloGene: 55916 GeneCards: S100A11
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q21.3 Start 152,032,506 bp[1] End 152,047,907 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • calcium ion binding • calcium-dependent protein binding • protein homodimerization activity • metal ion binding • S100 protein binding • cadherin binding involved in cell-cell adhesion Cellular component • cell nucleus • ruffle • extracellular exosome • cytoplasm • extracellular • secretory granule lumen • extracellular region Biological process • negative regulation of cell proliferation • negative regulation of DNA replication • signal transduction • regulation of cell proliferation • cell-cell adhesion • neutrophil degranulation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6282	277089
Ensembl	ENSG00000163191	n/a
UniProt	P31949	n/a
RefSeq (mRNA)	NM_005620	n/a
RefSeq (protein)	NP_005611	n/a
Location (UCSC)	Chr 1: 152.03 – 152.05 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100A11, also known as calgizzarin or 100C, is a small acidic protein. Along with all 13 members of the S100 family, are located as a cluster on chromosome 1q21. [6] It was first found in 1989, and later isolated from chicken gizzard muscles.[7]

The protein may function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis.[5]

Its high expression has been found in many tissues including lung, pancreas, heart, placenta, kidney, and low levels in skeletal muscle, liver, and brain tissue.[8]

S100A11 is implicated in membrane and cytoskeletar dynamics, vesicular transportation and processes of endo and exocytosis. It has been shown that S100A11 interacts with many cytoskeletal structures as tubulin, actin, intermediate filaments also with annexin I and annexin II.[9][10] S100A11 is able to control reorganization of actin and it is important in forming protrusion by metastatic cells.[11]

It lacks enzymatic activity, it functions by binding to other proteins, it regulates activity of other enzymes.[12] It is associated with cell cycle, growth, survival and apoptosis. It has been identified as dual growth mediator.[13][6] Suppression of S100A11 by small interfering RNA caused cells to apoptosis, and overexpression of S100A11 has been found to inhibit apoptosis in tumor cells. [6]Furthermore, the knock-down of S100A11 via siRNA reduces the sister-chromatid exchange and the viability of cells.

S100A11 in pathologies

IL-8 and TNF-alpha induce the expression and release of S100A11 in chondrocytes in culture and exogenous S100A11 causes chondrocyte hypertrophy.[14] S100A11 could play a role in maintaining low-grade inflammation in osteoarthritis and in its progression.[15]

Its cellular localization is associated with the regulation of cell growth and proliferation. This protein is normally found strictly in the nucleus, but appears in the cytoplasm in cancer cells. S100A11 was localized in the cytoplasm of resting human keratinocytes in vitro.[16]

It has been shown to interact with the RAGE receptor, which is also a receptor for other S100 proteins.[17]

It is associated with low or high production in many different types of cancers. Its overproduction has been found, for example, in breast, pancreas or colectal carcinoma and its levels can be used as clinical marker in these diseases.[18]

It has been shown that S100A11 enhances the recombination activity of human RAD51 in vitro. A knock-down leads to diffuse distribution of RAD54B.[19]These finding suggest a potential role of S100A11 in the process of homologous recombination repair of double-strand breaks.[20]

Usually, S100A11 makes homodimeres, but it has been shown  that S100A11 heterodimerizes with S100B[21] and it also interacts with Nucleolin,[22] and RAD54B.[19]

References

1. GRCh38: Ensembl release 89: ENSG00000163191 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Wicki R, Marenholz I, Mischke D, Schäfer BW, Heizmann CW (December 1996). "Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21". Cell Calcium. 20 (6): 459–64. doi:10.1016/S0143-4160(96)90087-1. PMID 8985590.
5. "Entrez Gene: S100A11 S100 calcium binding protein A11".
6. Kanamori T, Takakura K, Mandai M, Kariya M, Fukuhara K, Sakaguchi M, et al. (October 2004). "Increased expression of calcium-binding protein S100 in human uterine smooth muscle tumours". Molecular Human Reproduction. 10 (10): 735–42. doi:10.1093/molehr/gah100. PMID 15322223.
7. Sakaguchi M, Sonegawa H, Murata H, Kitazoe M, Futami J, Kataoka K, et al. (January 2008). "S100A11, an dual mediator for growth regulation of human keratinocytes". Molecular Biology of the Cell. 19 (1): 78–85. doi:10.1091/mbc.e07-07-0682. PMC 2174196. PMID 17978094.
8. Inada H, Naka M, Tanaka T, Davey GE, Heizmann CW (September 1999). "Human S100A11 exhibits differential steady-state RNA levels in various tissues and a distinct subcellular localization". Biochemical and Biophysical Research Communications. 263 (1): 135–8. doi:10.1006/bbrc.1999.1319. PMID 10486266.
9. Sakaguchi M, Huh NH (October 2011). "S100A11, a dual growth regulator of epidermal keratinocytes". Amino Acids. 41 (4): 797–807. doi:10.1007/s00726-010-0747-4. PMID 20872027.
10. Réty S, Osterloh D, Arié JP, Tabaries S, Seeman J, Russo-Marie F, et al. (February 2000). "Structural basis of the Ca(2+)-dependent association between S100C (S100A11) and its target, the N-terminal part of annexin I". Structure. 8 (2): 175–84. doi:10.1016/s0969-2126(00)00093-9. PMID 10673436.
11. Shankar J, Messenberg A, Chan J, Underhill TM, Foster LJ, Nabi IR (May 2010). "Pseudopodial actin dynamics control epithelial-mesenchymal transition in metastatic cancer cells". Cancer Research. 70 (9): 3780–90. doi:10.1158/0008-5472.can-09-4439. PMID 20388789.
12. Zhao XQ, Naka M, Muneyuki M, Tanaka T (January 2000). "Ca(2+)-dependent inhibition of actin-activated myosin ATPase activity by S100C (S100A11), a novel member of the S100 protein family". Biochemical and Biophysical Research Communications. 267 (1): 77–9. doi:10.1006/bbrc.1999.1918. PMID 10623577.
13. He H, Li J, Weng S, Li M, Yu Y (2009). "S100A11: diverse function and pathology corresponding to different target proteins". Cell Biochemistry and Biophysics. 55 (3): 117–26. doi:10.1007/s12013-009-9061-8. PMID 19649745.
14. Cecil DL, Johnson K, Rediske J, Lotz M, Schmidt AM, Terkeltaub R (December 2005). "Inflammation-induced chondrocyte hypertrophy is driven by receptor for advanced glycation end products". Journal of Immunology. 175 (12): 8296–302. doi:10.4049/jimmunol.175.12.8296. PMID 16339570.
15. Cecil DL, Terkeltaub R (June 2008). "Transamidation by transglutaminase 2 transforms S100A11 calgranulin into a procatabolic cytokine for chondrocytes". Journal of Immunology. 180 (12): 8378–85. doi:10.4049/jimmunol.180.12.8378. PMC 2577366. PMID 18523305.
16. Sakaguchi M, Huh NH (October 2011). "S100A11, a dual growth regulator of epidermal keratinocytes". Amino Acids. 41 (4): 797–807. doi:10.1007/s00726-010-0747-4. PMID 20872027.
17. Cecil DL, Johnson K, Rediske J, Lotz M, Schmidt AM, Terkeltaub R (December 2005). "Inflammation-induced chondrocyte hypertrophy is driven by receptor for advanced glycation end products". Journal of Immunology. 175 (12): 8296–302. doi:10.4049/jimmunol.175.12.8296. PMID 16339570.
18. Sakaguchi M, Sonegawa H, Murata H, Kitazoe M, Futami J, Kataoka K, et al. (January 2008). "S100A11, an dual mediator for growth regulation of human keratinocytes". Molecular Biology of the Cell. 19 (1): 78–85. doi:10.1091/mbc.e07-07-0682. PMC 2174196. PMID 17978094.
19. Murzik U, Hemmerich P, Weidtkamp-Peters S, Ulbricht T, Bussen W, Hentschel J, et al. (July 2008). "Rad54B targeting to DNA double-strand break repair sites requires complex formation with S100A11". Molecular Biology of the Cell. 19 (7): 2926–35. doi:10.1091/mbc.e07-11-1167. PMC 2441681. PMID 18463164.
20. Foertsch F, Szambowska A, Weise A, Zielinski A, Schlott B, Kraft F, et al. (October 2016). "S100A11 plays a role in homologous recombination and genome maintenance by influencing the persistence of RAD51 in DNA repair foci". Cell Cycle. 15 (20): 2766–79. doi:10.1080/15384101.2016.1220457. PMC 5053559. PMID 27590262.
21. Deloulme JC, Assard N, Mbele GO, Mangin C, Kuwano R, Baudier J (November 2000). "S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B protein in vivo". The Journal of Biological Chemistry. 275 (45): 35302–10. doi:10.1074/jbc.M003943200. PMID 10913138.
22. Sakaguchi M, Miyazaki M, Takaishi M, Sakaguchi Y, Makino E, Kataoka N, et al. (November 2003). "S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes". The Journal of Cell Biology. 163 (4): 825–35. doi:10.1083/jcb.200304017. PMC 2173690. PMID 14623863.

Further reading

• Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J (December 1992). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis. 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID 1286667.
• Tomasetto C, Régnier C, Moog-Lutz C, Mattei MG, Chenard MP, Lidereau R, Basset P, Rio MC (August 1995). "Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17". Genomics. 28 (3): 367–76. doi:10.1006/geno.1995.1163. PMID 7490069.
• Schäfer BW, Wicki R, Engelkamp D, Mattei MG, Heizmann CW (February 1995). "Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family". Genomics. 25 (3): 638–43. doi:10.1016/0888-7543(95)80005-7. PMID 7759097.
• Tanaka M, Adzuma K, Iwami M, Yoshimoto K, Monden Y, Itakura M (March 1995). "Human calgizzarin; one colorectal cancer-related gene selected by a large scale random cDNA sequencing and northern blot analysis". Cancer Letters. 89 (2): 195–200. doi:10.1016/0304-3835(94)03687-E. PMID 7889529.
• Mailliard WS, Haigler HT, Schlaepfer DD (January 1996). "Calcium-dependent binding of S100C to the N-terminal domain of annexin I". The Journal of Biological Chemistry. 271 (2): 719–25. doi:10.1074/jbc.271.2.719. PMID 8557678.
• Seemann J, Weber K, Gerke V (August 1997). "Annexin I targets S100C to early endosomes". FEBS Letters. 413 (1): 185–90. doi:10.1016/S0014-5793(97)00911-3. PMID 9287141.
• Inada H, Naka M, Tanaka T, Davey GE, Heizmann CW (September 1999). "Human S100A11 exhibits differential steady-state RNA levels in various tissues and a distinct subcellular localization". Biochemical and Biophysical Research Communications. 263 (1): 135–8. doi:10.1006/bbrc.1999.1319. PMID 10486266.
• Réty S, Osterloh D, Arié JP, Tabaries S, Seeman J, Russo-Marie F, Gerke V, Lewit-Bentley A (February 2000). "Structural basis of the Ca(2+)-dependent association between S100C (S100A11) and its target, the N-terminal part of annexin I". Structure. 8 (2): 175–84. doi:10.1016/S0969-2126(00)00093-9. PMID 10673436.
• Sakaguchi M, Miyazaki M, Inoue Y, Tsuji T, Kouchi H, Tanaka T, Yamada H, Namba M (June 2000). "Relationship between contact inhibition and intranuclear S100C of normal human fibroblasts". The Journal of Cell Biology. 149 (6): 1193–206. doi:10.1083/jcb.149.6.1193. PMC 2175115. PMID 10851017.
• Deloulme JC, Assard N, Mbele GO, Mangin C, Kuwano R, Baudier J (November 2000). "S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B protein in vivo". The Journal of Biological Chemistry. 275 (45): 35302–10. doi:10.1074/jbc.M003943200. PMID 10913138.
• Ruse M, Lambert A, Robinson N, Ryan D, Shon KJ, Eckert RL (March 2001). "S100A7, S100A10, and S100A11 are transglutaminase substrates". Biochemistry. 40 (10): 3167–73. doi:10.1021/bi0019747. PMID 11258932.
• Kondo A, Sakaguchi M, Makino E, Namba M, Okada S, Huh NH (February 2002). "Localization of S100C immunoreactivity in various human tissues" (PDF). Acta Medica Okayama. 56 (1): 31–4. PMID 11873942.
• Bianchi R, Giambanco I, Arcuri C, Donato R (April 2003). "Subcellular localization of S100A11 (S100C) in LLC-PK1 renal cells: Calcium- and protein kinase c-dependent association of S100A11 with S100B and vimentin intermediate filaments". Microscopy Research and Technique. 60 (6): 639–51. doi:10.1002/jemt.10305. PMID 12645011.
• Broome AM, Ryan D, Eckert RL (May 2003). "S100 protein subcellular localization during epidermal differentiation and psoriasis". The Journal of Histochemistry and Cytochemistry. 51 (5): 675–85. doi:10.1177/002215540305100513. PMC 3785113. PMID 12704215.
• Sakaguchi M, Miyazaki M, Takaishi M, Sakaguchi Y, Makino E, Kataoka N, Yamada H, Namba M, Huh NH (November 2003). "S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes". The Journal of Cell Biology. 163 (4): 825–35. doi:10.1083/jcb.200304017. PMC 2173690. PMID 14623863.
• Broome AM, Eckert RL (January 2004). "Microtubule-dependent redistribution of a cytoplasmic cornified envelope precursor". The Journal of Investigative Dermatology. 122 (1): 29–38. doi:10.1046/j.0022-202X.2003.22105.x. PMID 14962086.
• Sakaguchi M, Miyazaki M, Sonegawa H, Kashiwagi M, Ohba M, Kuroki T, Namba M, Huh NH (March 2004). "PKCalpha mediates TGFbeta-induced growth inhibition of human keratinocytes via phosphorylation of S100C/A11". The Journal of Cell Biology. 164 (7): 979–84. doi:10.1083/jcb.200312041. PMC 2172059. PMID 15051732.
• Mori M, Shimada H, Gunji Y, Matsubara H, Hayashi H, Nimura Y, Kato M, Takiguchi M, Ochiai T, Seki N (June 2004). "S100A11 gene identified by in-house cDNA microarray as an accurate predictor of lymph node metastases of gastric cancer". Oncology Reports. 11 (6): 1287–93. doi:10.3892/or.11.6.1287. PMID 15138568.