Wed . 18 Sep 2018

S100A10

s100a10 antibody, s100a10 depression
1A4P, 1BT6, 4DRW, 4FTG, 4HRE, 4HRG, 4HRH

Identifiers Aliases S100A10, 42C, ANX2L, ANX2LG, CAL1L, CLP11, Ca, GP11, P11, p10, S100 calcium binding protein A10 External IDs MGI: 1339468 HomoloGene: 2228 GeneCards: S100A10
Gene location Human
Chr Chromosome 1 human
Band 1q213 Start 151,982,915 bp
End 151,994,390 bp
RNA expression pattern
More reference expression data
Orthologs Species Human Mouse Entrez
Ensembl
UniProt
RefSeq mRNA

NM_002966

NM_009112

RefSeq protein

NP_002957

NP_033138

Location UCSC Chr 1: 15198 – 15199 Mb Chr 3: 9356 – 9356 Mb PubMed search Wikidata
Interactor Biological function of P11 Reference
Annexin 2 Regulation of endosomal functions
5-HT1B receptor Localization of 5-HT1B receptors at the cell surface
NaV18 sodium channel Increase of NaV18 channels at the plasma membrane
TASK-1 potassium channel Regulation of TASK-1 channels at the plasma membrane
ASIC-1 channels Increase of ASIC channels at the plasma membrane
TRPV5/TRPV6 channels Increase of TRPV5/TRPV6 channels at the plasma membrane
NS3 Mediation of virus release
Cytosolic phospholipase A2 Reduced arachidonic acid release
BAD Inhibition of pro-apoptotic effect
HPV16 L2 Facilitates binding and entry of human papillomavirus type 16

Regulation

Regulation of protein activity

The p11 and annexin II complex is regulated by the phosphorylation of SerII on the annexin II molecule by protein kinase C PKC This phosphorylation hinders the complex's ability to bind to certain target molecules Protein Kinase A PKA reverses the effects of PKC by activating a phosphatase, which reactivates the complex through dephosphorylation

Regulation of transcription

Current experiments on animals have shown that various factors and physiological stimuli have been successful in regulating the levels of p11 protein transcription Some of these factors are shown in the table below

Table 2

Factor Biological system Reference
Dexamethasone BEAS and HeLa cells
Transforming growth factor-α RGM-1 cells
Epidermal growth factor depolarization BEAS and HeLa cells
Nitric Oxide donors BEAS and HeLa cells
Interferon-gamma BEAS cells
Vitamin D mouse kidney
Retinoic acid BEAS cells
nerve growth factor PC12 cells, rat dorsal root ganglion
imipramine mouse frontal cortex
tranylcypromine mouse frontal cortex
Electroconvulsive treatment rat frontal cortex
Sciatic nerve lesion rat
Experimental autoimmune encephalomyelitis rat cerebellum

Clinical significance

Depression

Depression is a widespread, debilitating disease affecting persons of all ages and backgrounds Depression is characterized by a plethora of emotional and physiological symptoms including feelings of sadness, hopelessness, pessimism, guilt, a general loss of interest in life, and a sense of reduced emotional well-being or low energy Very little is known about the underlying pathophysiology of clinical depression and other related mood-disorders including anxiety, bipolar disorder, ADD, ADHD, and Schizophrenia

The p11 protein has been intimately linked to mood disorders, to be specific, depression, due to its role in serotonin systems via its interactions with serotonin 5-HT receptors Serotonin affects diverse systems including the cardiovascular, renal, immune, and gastrointestinal systems Current research focuses on the neurotransmitter's relationship with mood-regulation

Under experimentation, mice deficient in the p11 protein display depression-like behaviors Knockout experiments in which the gene coding for protein p11 was deleted from the mouse genome caused them to show signs of depression This is also observed in humans On the other hand, those with sufficient amount of p11 protein behave normally When mice that showed depressive symptoms were administered anti-depressant drugs, their levels of p11 were found to increase at the same rate, as antidepressants affected their behavioral changes In addition, post-mortem comparisons of brain tissues showed much lower levels of p11 in depressed compared to control subjects Levels of p11 have been found to be substantially lower in depressed humans and helpless mice, which suggests that altered p11 levels may be involved in the development of depression-like symptoms

Treatment

Most of the current drugs and treatments for depression and anxiety increase levels of serotonin transmission among neurons Selective Serotonin Reuptake Inhibitors SSRIs, a very successful class of drugs, are known to increase the amount of serotonin available to brain cells quite rapidly Despite this, their therapeutic effects take a period of several weeks to months Recent studies show that protein p11 increases the concentration of the serotonin 5-HT receptors at neuronal synapses, thereby rendering serotonin signaling much more efficient The interaction with the serotonin 1b receptor 5-HT1B and p11 can be summarized as follows: When p11 levels increases, the number of 5-HT1B receptors on the cell surface increase proportionately An increase in the number of 5-HT1B receptors on the surface of the neuron increase the effectiveness of serotonin communication across the synapse On the other hand, when p11 levels decrease, fewer 5-HT1B receptors migrate from inside the neuron to the cell membrane at the synaptic cleft, thus lowering the efficiency with which serotonin signaling can occur across the synapse These findings suggest that, although the serotonin levels are immediately introduced via medication, the period of time within which the medicine alleviates the patient's depression most likely relies on other regulatory proteins Thus, given protein p11's interaction with serotonin 5-HT receptors and the increasing evidence of the protein's correlation to mood disorders, this protein has been identified as a target for research in the development of future antidepressants

Treatment with antidepressants a tricyclic and monoamine oxidase inhibitor and electroconvulsive therapy ECT caused an increase in the amount of p11 in the brain of these mice - the same biochemical change The levels of the p11 protein in humans and mice with symptoms of depression were substantially lower in comparison to the levels of p11 in non-depressed animals Leading researcher Paul Greengard and his colleagues hypothesized that increasing p11 levels would result in the mice exhibiting antidepressant-like behaviors, and the opposite if p11 protein levels were reduced They used a test that is used to measure antidepressant-like activity to affirm this hypothesis In their findings, over-expressed p11 genes, compared to the control mice, had increased mobility and more 5-HT1B receptors at the cell surface, which made possible more serotonin transmission When researchers "knocked out" the p11 gene in mice, they found that the knockout mice had fewer receptors at the cell surface, reduced serotonin signaling, reduced responsiveness to sweet reward, and decreased mobility, behaviors all characteristic of depression-like behaviors Also, the 5-HT1B receptors of p11 knockout mice were less responsive to serotonin and antidepressant drugs compared to those of control mice, which further implicates p11 in the main action of antidepressant medications Antidepressant manipulations increase the p11 levels, whereas depressant manipulations reduce it Therefore, in order to achieve an anti-depression effect, antidepressant medications should focus on the main action of the p11 proteins and increase levels of the protein

Future clinical trials

At the current time, a study by the National Institutes of Health Clinical Center CC is recruiting participants for a study that will compare levels of p11 protein in people with and without Major Depressive Disorder MDD and determine whether p11 levels in patients are affected by treatment with citalopram Celexa, a serotonin reuptake inhibitor If successful, a more personalized treatment of MDD will be available in the future

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000197747 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041959 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:" 
  4. ^ "Mouse PubMed Reference:" 
  5. ^ Gerke V, Weber K Nov 1985 "The regulatory chain in the p36-kd substrate complex of viral tyrosine-specific protein kinases is related in sequence to the S-100 protein of glial cells" The EMBO Journal 4 11: 2917–20 PMC 554598  PMID 2998764 
  6. ^ Harder T, Kube E, Gerke V Apr 1992 "Cloning and characterization of the human gene encoding p11: structural similarity to other members of the S-100 gene family" Gene 113 2: 269–74 doi:101016/0378-11199290406-F PMID 1533380 
  7. ^ a b "Entrez Gene: S100A10 S100 calcium binding protein A10" 
  8. ^ a b c Rosack J 2006 "Protein Discovery May Lead To New Psychiatric Drugs" Psychiatr News 
  9. ^ Volz A, Korge BP, Compton JG, Ziegler A, Steinert PM, Mischke D Oct 1993 "Physical mapping of a functional cluster of epidermal differentiation genes on chromosome 1q21" Genomics 18 1: 92–9 doi:101006/geno19931430 PMID 8276421 
  10. ^ a b c d e Réty S, Sopkova J, Renouard M, Osterloh D, Gerke V, Tabaries S, Russo-Marie F, Lewit-Bentley A Jan 1999 "The crystal structure of a complex of p11 with the annexin II N-terminal peptide" Nature Structural Biology 6 1: 89–95 doi:101038/4965 PMID 9886297 
  11. ^ Puisieux A, Ji J, Ozturk M Jan 1996 "Annexin II up-regulates cellular levels of p11 protein by a post-translational mechanisms" The Biochemical Journal 313 313 1: 51–5 doi:101042/bj3130051 PMC 1216908  PMID 8546709 
  12. ^ a b c Rescher U, Gerke V Jan 2008 "S100A10/p11: family, friends and functions" PDF Pflügers Archiv 455 4: 575–82 doi:101007/s00424-007-0313-4 PMID 17638009 
  13. ^ a b Warner-Schmidt JL, Flajolet M, Maller A, Chen EY, Qi H, Svenningsson P, Greengard P Feb 2009 "Role of p11 in cellular and behavioral effects of 5-HT4 receptor stimulation" The Journal of Neuroscience 29 6: 1937–46 doi:101523/JNEUROSCI5343-082009 PMID 19211900 
  14. ^ a b Kwon M, MacLeod TJ, Zhang Y, Waisman DM Jan 2005 "S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors" Frontiers in Bioscience 10 1–3: 300–25 doi:102741/1529 PMID 15574370 
  15. ^ a b c van de Graaf SF, Hoenderop JG, Gkika D, Lamers D, Prenen J, Rescher U, Gerke V, Staub O, Nilius B, Bindels RJ Apr 2003 "Functional expression of the epithelial Ca2+ channels TRPV5 and TRPV6 requires association of the S100A10-annexin 2 complex" The EMBO Journal 22 7: 1478–87 doi:101093/emboj/cdg162 PMC 152906  PMID 12660155 
  16. ^ Mai J, Finley RL, Waisman DM, Sloane BF Apr 2000 "Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells" The Journal of Biological Chemistry 275 17: 12806–12 doi:101074/jbc2751712806 PMID 10777578 
  17. ^ a b Hsu SY, Kaipia A, Zhu L, Hsueh AJ Nov 1997 "Interference of BAD Bcl-xL/Bcl-2-associated death promoter-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11" Molecular Endocrinology 11 12: 1858–67 doi:101210/me11121858 PMID 9369453 
  18. ^ a b Girard C, Tinel N, Terrenoire C, Romey G, Lazdunski M, Borsotto M Sep 2002 "p11, an annexin II subunit, an auxiliary protein associated with the background K+ channel, TASK-1" The EMBO Journal 21 17: 4439–48 doi:101093/emboj/cdf469 PMC 125412  PMID 12198146 
  19. ^ a b He KL, Deora AB, Xiong H, Ling Q, Weksler BB, Niesvizky R, Hajjar KA Jul 2008 "Endothelial cell annexin A2 regulates polyubiquitination and degradation of its binding partner S100A10/p11" The Journal of Biological Chemistry 283 28: 19192–200 doi:101074/jbcM800100200 PMC 2443646  PMID 18434302 
  20. ^ a b c d e f g Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, Vaugeois JM, Nomikos GG, Greengard P Jan 2006 "Alterations in 5-HT1B receptor function by p11 in depression-like states" Science 311 5757: 77–80 doi:101126/science1117571 PMID 16400147 
  21. ^ a b Falk W, Leonard EJ May 1982 "Chemotaxis of purified human monocytes in vitro: lack of accessory cell requirement" Infection and Immunity 36 2: 591–7 doi:101016/jcoph200610001 PMC 351269  PMID 7085073 
  22. ^ a b Gladwin MT, Yao XL, Cowan M, Huang XL, Schneider R, Grant LR, Logun C, Shelhamer JH Dec 2000 "Retinoic acid reduces p11 protein levels in bronchial epithelial cells by a posttranslational mechanism" American Journal of Physiology Lung Cellular and Molecular Physiology 279 6: L1103–9 doi:101152/ajplung20002796l1103 PMID 11076800 
  23. ^ Donier E, Rugiero F, Okuse K, Wood JN Nov 2005 "Annexin II light chain p11 promotes functional expression of acid-sensing ion channel ASIC1a" The Journal of Biological Chemistry 280 46: 38666–72 doi:101074/jbcM505981200 PMID 16169854 
  24. ^ Beaton AR, Rodriguez J, Reddy YK, Roy P Oct 2002 "The membrane trafficking protein calpactin forms a complex with bluetongue virus protein NS3 and mediates virus release" Proceedings of the National Academy of Sciences of the United States of America 99 20: 13154–9 doi:101073/pnas192432299 PMC 130602  PMID 12235365 
  25. ^ Wu T, Angus CW, Yao XL, Logun C, Shelhamer JH Jul 1997 "P11, a unique member of the S100 family of calcium-binding proteins, interacts with and inhibits the activity of the 85-kDa cytosolic phospholipase A2" The Journal of Biological Chemistry 272 27: 17145–53 doi:101074/jbc2722717145 PMID 9202034 
  26. ^ Woodham AW, Da Silva DM, Skeate JG, Raff AB, Ambroso MR, Brand HE, Isas JM, Langen R, Kast WM 2012-01-01 "The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection" PLOS ONE 7 8: e43519 doi:101371/journalpone0043519 PMC 3425544  PMID 22927980 
  27. ^ Yao XL, Cowan MJ, Gladwin MT, Lawrence MM, Angus CW, Shelhamer JH Jun 1999 "Dexamethasone alters arachidonate release from human epithelial cells by induction of p11 protein synthesis and inhibition of phospholipase A2 activity" The Journal of Biological Chemistry 274 24: 17202–8 doi:101074/jbc2742417202 PMID 10358078 
  28. ^ Akiba S, Hatazawa R, Ono K, Hayama M, Matsui H, Sato T Nov 2000 "Transforming growth factor-alpha stimulates prostaglandin generation through cytosolic phospholipase A2 under the control of p11 in rat gastric epithelial cells" British Journal of Pharmacology 131 5: 1004–10 doi:101038/sjbjp0703637 PMC 1572404  PMID 11053223 
  29. ^ Huang XL, Pawliczak R, Cowan MJ, Gladwin MT, Madara P, Logun C, Shelhamer JH Oct 2002 "Epidermal growth factor induces p11 gene and protein expression and down-regulates calcium ionophore-induced arachidonic acid release in human epithelial cells" The Journal of Biological Chemistry 277 41: 38431–40 doi:101074/jbcM207406200 PMID 12163506 
  30. ^ Pawliczak R, Cowan MJ, Huang X, Nanavaty UB, Alsaaty S, Logun C, Shelhamer JH Nov 2001 "p11 expression in human bronchial epithelial cells is increased by nitric oxide in a cGMP-dependent pathway involving protein kinase G activation" The Journal of Biological Chemistry 276 48: 44613–21 doi:101074/jbcM104993200 PMID 11571284 
  31. ^ Huang XL, Pawliczak R, Yao XL, Cowan MJ, Gladwin MT, Walter MJ, Holtzman MJ, Madara P, Logun C, Shelhamer JH Mar 2003 "Interferon-gamma induces p11 gene and protein expression in human epithelial cells through interferon-gamma-activated sequences in the p11 promoter" The Journal of Biological Chemistry 278 11: 9298–308 doi:101074/jbcM212704200 PMID 12645529 
  32. ^ Okuse K, Malik-Hall M, Baker MD, Poon WY, Kong H, Chao MV, Wood JN Jun 2002 "Annexin II light chain regulates sensory neuron-specific sodium channel expression" Nature 417 6889: 653–6 doi:101038/nature00781 PMID 12050667 
  33. ^ De León M, Van Eldik LJ, Shooter EM Jun 1991 "Differential regulation of S100 beta and mRNAs coding for S100-like proteins 42A and 42C during development and after lesion of rat sciatic nerve" Journal of Neuroscience Research 29 2: 155–62 doi:101002/jnr490290204 PMID 1890696 
  34. ^ Craner MJ, Lo AC, Black JA, Baker D, Newcombe J, Cuzner ML, Waxman SG Mar 2003 "Annexin II/p11 is up-regulated in Purkinje cells in EAE and MS" NeuroReport 14 4: 555–8 doi:101097/00001756-200303240-00005 PMID 12657884 
  35. ^ Hamilton J 2006 "Study Sheds Light on How Depression Drugs Work" National Public Radio 
  36. ^ "p11 Protein Levels in Patients With Major Depressive Disorder Treated With Citalopram" ClinicalTrialsgov 

Further reading

  • Akiba S, Hatazawa R, Ono K, Hayama M, Matsui H, Sato T Nov 2000 "Transforming growth factor-alpha stimulates prostaglandin generation through cytosolic phospholipase A2 under the control of p11 in rat gastric epithelial cells" British Journal of Pharmacology 131 5: 1004–10 doi:101038/sjbjp0703637 PMC 1572404  PMID 11053223 
  • Gladwin MT, Yao XL, Cowan M, Huang XL, Schneider R, Grant LR, Logun C, Shelhamer JH Dec 2000 "Retinoic acid reduces p11 protein levels in bronchial epithelial cells by a posttranslational mechanism" American Journal of Physiology Lung Cellular and Molecular Physiology 279 6: L1103–9 doi:101152/ajplung20002796l1103 PMID 11076800 
  • Huang XL, Pawliczak R, Cowan MJ, Gladwin MT, Madara P, Logun C, Shelhamer JH Oct 2002 "Epidermal growth factor induces p11 gene and protein expression and down-regulates calcium ionophore-induced arachidonic acid release in human epithelial cells" The Journal of Biological Chemistry 277 41: 38431–40 doi:101074/jbcM207406200 PMID 12163506 
  • Huang XL, Pawliczak R, Yao XL, Cowan MJ, Gladwin MT, Walter MJ, Holtzman MJ, Madara P, Logun C, Shelhamer JH Mar 2003 "Interferon-gamma induces p11 gene and protein expression in human epithelial cells through interferon-gamma-activated sequences in the p11 promoter" The Journal of Biological Chemistry 278 11: 9298–308 doi:101074/jbcM212704200 PMID 12645529 
  • Masiakowski P, Shooter EM Feb 1988 "Nerve growth factor induces the genes for two proteins related to a family of calcium-binding proteins in PC12 cells" Proceedings of the National Academy of Sciences of the United States of America 85 4: 1277–81 doi:101073/pnas8541277 PMC 279750  PMID 3422491 
  • Yao XL, Cowan MJ, Gladwin MT, Lawrence MM, Angus CW, Shelhamer JH Jun 1999 "Dexamethasone alters arachidonate release from human epithelial cells by induction of p11 protein synthesis and inhibition of phospholipase A2 activity" The Journal of Biological Chemistry 274 24: 17202–8 doi:101074/jbc2742417202 PMID 10358078 
  • Schäfer BW, Heizmann CW Apr 1996 "The S100 family of EF-hand calcium-binding proteins: functions and pathology" Trends in Biochemical Sciences 21 4: 134–40 doi:101016/S0968-00049680167-8 PMID 8701470 
  • Dooley TP, Weiland KL, Simon M Jul 1992 "cDNA sequence of human p11 calpactin I light chain" Genomics 13 3: 866–8 doi:101016/0888-75439290171-N PMID 1386341 
  • Creutz CE, Moss S, Edwardson JM, Hide I, Gomperts B Apr 1992 "Differential recognition of secretory vesicles by annexins European Molecular Biology Organization Course "Advanced Techniques for Studying Secretion"" Biochemical and Biophysical Research Communications 184 1: 347–52 doi:101016/0006-291X9291199-Z PMID 1533123 
  • Kube E, Weber K, Gerke V Jun 1991 "Primary structure of human, chicken, and Xenopus laevis p11, a cellular ligand of the Src-kinase substrate, annexin II" Gene 102 2: 255–9 doi:101016/0378-11199190086-Q PMID 1831433 
  • Becker T, Weber K, Johnsson N Dec 1990 "Protein-protein recognition via short amphiphilic helices; a mutational analysis of the binding site of annexin II for p11" The EMBO Journal 9 13: 4207–13 PMC 552202  PMID 2148288 
  • Schäfer BW, Wicki R, Engelkamp D, Mattei MG, Heizmann CW Feb 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:101016/0888-75439580005-7 PMID 7759097 
  • Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T Dec 1994 "Construction of a human full-length cDNA bank" Gene 150 2: 243–50 doi:101016/0378-11199490433-2 PMID 7821789 
  • Engelkamp D, Schäfer BW, Mattei MG, Erne P, Heizmann CW Jul 1993 "Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E" Proceedings of the National Academy of Sciences of the United States of America 90 14: 6547–51 doi:101073/pnas90146547 PMC 46969  PMID 8341667 
  • Jost M, Gerke V Oct 1996 "Mapping of a regulatory important site for protein kinase C phosphorylation in the N-terminal domain of annexin II" Biochimica et Biophysica Acta 1313 3: 283–9 doi:101016/0167-48899600101-2 PMID 8898866 
  • Munz B, Gerke V, Gillitzer R, Werner S Mar 1997 "Differential expression of the calpactin I subunits annexin II and p11 in cultured keratinocytes and during wound repair" The Journal of Investigative Dermatology 108 3: 307–12 doi:101111/1523-1747ep12286470 PMID 9036930 
  • Kang HM, Kassam G, Jarvis SE, Fitzpatrick SL, Waisman DM Feb 1997 "Characterization of human recombinant annexin II tetramer purified from bacteria: role of N-terminal acetylation" Biochemistry 36 8: 2041–50 doi:101021/bi962569b PMID 9047302 
  • Wu T, Angus CW, Yao XL, Logun C, Shelhamer JH Jul 1997 "P11, a unique member of the S100 family of calcium-binding proteins, interacts with and inhibits the activity of the 85-kDa cytosolic phospholipase A2" The Journal of Biological Chemistry 272 27: 17145–53 doi:101074/jbc2722717145 PMID 9202034 
  • Hsu SY, Kaipia A, Zhu L, Hsueh AJ Nov 1997 "Interference of BAD Bcl-xL/Bcl-2-associated death promoter-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11" Molecular Endocrinology 11 12: 1858–67 doi:101210/me11121858 PMID 9369453 
  • Ramalingam R, Rafii S, Worgall S, Hackett NR, Crystal RG Dec 1999 "Induction of endogenous genes following infection of human endothelial cells with an E1- E4+ adenovirus gene transfer vector" Journal of Virology 73 12: 10183–90 PMC 113071  PMID 10559334 
  • Mai J, Finley RL, Waisman DM, Sloane BF Apr 2000 "Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells" The Journal of Biological Chemistry 275 17: 12806–12 doi:101074/jbc2751712806 PMID 10777578 

External links

  • Associated story on US National Public Radio

s100a10 antibody, s100a10 depression, s100a10 hypotension, s100a10 ptsd


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    29.10.2014


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