O15379 (HDAC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone deacetylase 3
Short name=HD3
EC=3.5.1.98

Alternative name(s):
RPD3-2
SMAP45

Gene names

Name:

HDAC3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	428 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Probably participates in the regulation of transcription through its binding to the zinc-finger transcription factor YY1; increases YY1 repression activity. Required to repress transcription of the POU1F1 transcription factor. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation By similarity. Ref.28
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Subunit structure	Interacts with HDAC7 and HDAC9. Forms a heterologous complex at least with YY1. Interacts with DAXX, HDAC10 and DACH1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY. Interacts with BTBD14B. Interacts with GLIS2. Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation By similarity. Component of the Notch corepressor complex. Interacts with CBFA2T3 and NKAP. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with and deacetylates MAPK14. Interacts with ZMYND15 By similarity. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.18 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26
Subcellular location	Nucleus.
Tissue specificity	Widely expressed.
Post-translational modification	Sumoylated in vitro. Ref.15
Sequence similarities	Belongs to the histone deacetylase family. HD type 1 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: ProtInc cellular lipid metabolic process Traceable author statement. Source: Reactome negative regulation of JNK cascade Inferred from mutant phenotype Ref.19. Source: UniProtKB negative regulation of cell cycle Traceable author statement. Source: Reactome negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.20. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome spindle assembly Inferred from mutant phenotype. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Traceable author statement. Source: UniProtKB histone deacetylase complex Traceable author statement. Source: UniProtKB spindle microtubule Inferred from direct assay. Source: UniProtKB transcriptional repressor complex Inferred from direct assay Ref.20. Source: UniProtKB
Molecular function	NAD-dependent histone deacetylase activity (H3-K14 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K9 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H4-K16 specific) Inferred from electronic annotation. Source: EC histone deacetylase activity (H3-K16 specific) Inferred from electronic annotation. Source: EC histone deacetylase binding Inferred from physical interaction. Source: BHF-UCL transcription corepressor activity Inferred from mutant phenotype Ref.20. Source: UniProtKB transcription factor binding Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MBD1	Q9UIS9	3	EBI-607682,EBI-867196
NCOR1	O75376	2	EBI-607682,EBI-347233
Nrip1	Q8CBD1	2	EBI-607682,EBI-1771626	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O15379-1)

Also known as: RPD3-2B;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O15379-2)

Also known as: RPD3-2A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MAKTVAYFYDPDVGN → MIVFKPYQASQHDMCR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 428	428	Histone deacetylase 3		PRO_0000114696
Regions
	Region	3 – 316	314	Histone deacetylase
Sites
	Active site	135	1	By similarity
Amino acid modifications
	Modified residue	424	1	Phosphoserine Ref.27
	Cross-link	44		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.25
Natural variations
	Alternative sequence	1 – 15	15	MAKTV…PDVGN → MIVFKPYQASQHDMCR in isoform 2.		VSP_002079
	Natural variant	411	1	N → S. Corresponds to variant rs34901743 [ dbSNP | Ensembl ].		VAR_033988
Experimental info
	Sequence conflict	359	1	R → L in AAC52038. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (RPD3-2B) [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 94485C1EBDCF5AD0	FASTA	428	48,848
	10 20 30 40 50 60 MAKTVAYFYD PDVGNFHYGA GHPMKPHRLA LTHSLVLHYG LYKKMIVFKP YQASQHDMCR 70 80 90 100 110 120 FHSEDYIDFL QRVSPTNMQG FTKSLNAFNV GDDCPVFPGL FEFCSRYTGA SLQGATQLNN 130 140 150 160 170 180 KICDIAINWA GGLHHAKKFE ASGFCYVNDI VIGILELLKY HPRVLYIDID IHHGDGVQEA 190 200 210 220 230 240 FYLTDRVMTV SFHKYGNYFF PGTGDMYEVG AESGRYYCLN VPLRDGIDDQ SYKHLFQPVI 250 260 270 280 290 300 NQVVDFYQPT CIVLQCGADS LGCDRLGCFN LSIRGHGECV EYVKSFNIPL LVLGGGGYTV 310 320 330 340 350 360 RNVARCWTYE TSLLVEEAIS EELPYSEYFE YFAPDFTLHP DVSTRIENQN SRQYLDQIRQ 370 380 390 400 410 420 TIFENLKMLN HAPSVQIHDV PADLLTYDRT DEADAEERGP EENYSRPEAP NEFYDGDHDN DKESDVEI
	Isoform 2 (RPD3-2A) [UniParc]. Checksum: 0B654598513D284B	FASTA	429	49,111
	10 20 30 40 50 60 MIVFKPYQAS QHDMCRFHYG AGHPMKPHRL ALTHSLVLHY GLYKKMIVFK PYQASQHDMC 70 80 90 100 110 120 RFHSEDYIDF LQRVSPTNMQ GFTKSLNAFN VGDDCPVFPG LFEFCSRYTG ASLQGATQLN 130 140 150 160 170 180 NKICDIAINW AGGLHHAKKF EASGFCYVND IVIGILELLK YHPRVLYIDI DIHHGDGVQE 190 200 210 220 230 240 AFYLTDRVMT VSFHKYGNYF FPGTGDMYEV GAESGRYYCL NVPLRDGIDD QSYKHLFQPV 250 260 270 280 290 300 INQVVDFYQP TCIVLQCGAD SLGCDRLGCF NLSIRGHGEC VEYVKSFNIP LLVLGGGGYT 310 320 330 340 350 360 VRNVARCWTY ETSLLVEEAI SEELPYSEYF EYFAPDFTLH PDVSTRIENQ NSRQYLDQIR 370 380 390 400 410 420 QTIFENLKML NHAPSVQIHD VPADLLTYDR TDEADAEERG PEENYSRPEA PNEFYDGDHD NDKESDVEI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Differential display cloning of a novel human histone deacetylase (HDAC3) cDNA from PHA-activated immune cells." Dangond F., Hafler D.A., Tong J.K., Randall J., Kojima R., Utku N., Gullans S.R. Biochem. Biophys. Res. Commun. 242:648-652(1998) [PubMed: 9464271] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). Tissue: Spleen and T-cell.
[2]	"Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family." Yang W.-M., Yao Y.-L., Sun J.-M., Davie J.R., Seto E. J. Biol. Chem. 272:28001-28007(1997) [PubMed: 9346952] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Fibroblast.
[3]	"Characterization of a human RPD3 ortholog, HDAC3." Emiliani S., Fischle W., van Lint C., Al-Abed Y., Verdin E. Proc. Natl. Acad. Sci. U.S.A. 95:2795-2800(1998) [PubMed: 9501169] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Genomic organization and chromosomal localization of the human histone deacetylase 3 gene." Mahlknecht U., Emiliani S., Najfeld V., Young S., Verdin E. Genomics 56:197-202(1999) [PubMed: 10051405] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skin.
[7]	Lynch E.D., Lee M.K., King M.-C. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-353 AND 407-428.
[8]	"Receptor-interacting protein 140 directly recruits histone deacetylases for gene silencing." Wei L.-N., Hu X., Chandra D., Seto E., Farooqui M. J. Biol. Chem. 275:40782-40787(2000) [PubMed: 11006275] [Abstract] Cited for: INTERACTION WITH NRIP1.
[9]	"Sequestration and inhibition of Daxx-mediated transcriptional repression by PML." Li H., Leo C., Zhu J., Wu X., O'Neil J., Park E.-J., Chen J.D. Mol. Cell. Biol. 20:1784-1796(2000) [PubMed: 10669754] [Abstract] Cited for: INTERACTION WITH DAXX.
[10]	"Identification of a transcriptional repressor related to the noncatalytic domain of histone deacetylases 4 and 5." Zhou X., Richon V.M., Rifkind R.A., Marks P.A. Proc. Natl. Acad. Sci. U.S.A. 97:1056-1061(2000) [PubMed: 10655483] [Abstract] Cited for: INTERACTION WITH HDAC9.
[11]	"The histone deacetylase-3 complex contains nuclear receptor corepressors." Wen Y.-D., Perissi V., Staszewski L.M., Yang W.-M., Krones A., Glass C.K., Rosenfeld M.G., Seto E. Proc. Natl. Acad. Sci. U.S.A. 97:7202-7207(2000) [PubMed: 10860984] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH NCOR1 AND NCOR2.
[12]	"Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo." Fischle W., Dequiedt F., Fillion M., Hendzel M.J., Voelter W., Verdin E. J. Biol. Chem. 276:35826-35835(2001) [PubMed: 11466315] [Abstract] Cited for: INTERACTION WITH HDAC7.
[13]	"ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain." Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W. Mol. Cell. Biol. 21:6470-6483(2001) [PubMed: 11533236] [Abstract] Cited for: INTERACTION WITH CBFA2T3.
[14]	"Identification of HDAC10, a novel class II human histone deacetylase containing a leucine-rich domain." Tong J.J., Liu J., Bertos N.R., Yang X.-J. Nucleic Acids Res. 30:1114-1123(2002) [PubMed: 11861901] [Abstract] Cited for: INTERACTION WITH HDAC10.
[15]	"The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase." Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E., Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A. EMBO J. 21:2682-2691(2002) [PubMed: 12032081] [Abstract] Cited for: SUMOYLATION.
[16]	"A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness." Guenther M.G., Lane W.S., Fischle W., Verdin E., Lazar M.A., Shiekhattar R. Genes Dev. 14:1048-1057(2000) [PubMed: 10809664] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, COMPONENT OF THE N-COR COMPLEX WITH NCOR2 AND TBL1X.
[17]	"Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3." Li J., Wang J., Wang J., Nawaz Z., Liu J.M., Qin J., Wong J. EMBO J. 19:4342-4350(2000) [PubMed: 10944117] [Abstract] Cited for: COMPONENT OF THE N-COR COMPLEX WITH NCOR2 AND HDAC3.
[18]	"BCoR, a novel corepressor involved in BCL-6 repression." Huynh K.D., Fischle W., Verdin E., Bardwell V.J. Genes Dev. 14:1810-1823(2000) [PubMed: 10898795] [Abstract] Cited for: INTERACTION WITH BCOR.
[19]	"The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2." Zhang J., Kalkum M., Chait B.T., Roeder R.G. Mol. Cell 9:611-623(2002) [PubMed: 11931768] [Abstract] Cited for: COMPONENT OF THE N-COR COMPLEX WITH NCOR1; NCOR2; GPS2; TBL1R AND TBL1X.
[20]	"Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1." Yoon H.-G., Chan D.W., Huang Z.-Q., Li J., Fondell J.D., Qin J., Wong J. EMBO J. 22:1336-1346(2003) [PubMed: 12628926] [Abstract] Cited for: COMPONENT OF THE N-COR COMPLEX WITH TBL1R; TBL1X AND CORO2A.
[21]	"Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene." Bhakat K.K., Izumi T., Yang S.H., Hazra T.K., Mitra S. EMBO J. 22:6299-6309(2003) [PubMed: 14633989] [Abstract] Cited for: INTERACTION WITH APEX1.
[22]	"DACH1 inhibits transforming growth factor-beta signaling through binding Smad4." Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K., Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G. J. Biol. Chem. 278:51673-51684(2003) [PubMed: 14525983] [Abstract] Cited for: INTERACTION WITH DACH1.
[23]	"Regulation of human SRY subcellular distribution by its acetylation/deacetylation." Thevenet L., Mejean C., Moniot B., Bonneaud N., Galeotti N., Aldrian-Herrada G., Poulat F., Berta P., Benkirane M., Boizet-Bonhoure B. EMBO J. 23:3336-3345(2004) [PubMed: 15297880] [Abstract] Cited for: INTERACTION WITH SRY.
[24]	"Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein." Gray S.G., Iglesias A.H., Lizcano F., Villanueva R., Camelo S., Jingu H., Teh B.T., Koibuchi N., Chin W.W., Kokkotou E., Dangond F. J. Biol. Chem. 280:28507-28518(2005) [PubMed: 15927959] [Abstract] Cited for: INTERACTION WITH JMJD2A.
[25]	"Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells." Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X. Proteomics 8:2885-2896(2008) [PubMed: 18655026] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-44, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[26]	"NKAP is a transcriptional repressor of notch signaling and is required for T cell development." Pajerowski A.G., Nguyen C., Aghajanian H., Shapiro M.J., Shapiro V.S. Immunity 30:696-707(2009) [PubMed: 19409814] [Abstract] Cited for: INTERACTION WITH NKAP.
[27]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-424, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[28]	"Acetylation of a conserved lysine residue in the ATP binding pocket of p38 augments its kinase activity during hypertrophy of cardiomyocytes." Pillai V.B., Sundaresan N.R., Samant S.A., Wolfgeher D., Trivedi C.M., Gupta M.P. Mol. Cell. Biol. 31:2349-2363(2011) [PubMed: 21444723] [Abstract] Cited for: FUNCTION IN DEACETYLATION OF MAPK14.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	U66914 mRNA. Translation: AAC52038.1. U75697 mRNA. Translation: AAB88241.1. U75696 mRNA. Translation: AAB88240.1. AF005482 mRNA. Translation: AAB87752.1. AF039703 mRNA. Translation: AAC98927.1. AF059650 Genomic DNA. Translation: AAC26509.1. CH471062 Genomic DNA. Translation: EAW61915.1. CH471062 Genomic DNA. Translation: EAW61916.1. BC000614 mRNA. Translation: AAH00614.1. AF053138, AF053137 Genomic DNA. Translation: AAC08351.1. AF053139 Genomic DNA. Translation: AAC08352.1.
IPI	IPI00006187. IPI00217965.
PIR	JC5834.
RefSeq	NP_003874.2. NM_003883.3.
UniGene	Hs.519632.
3D structure databases
ProteinModelPortal	O15379.
SMR	O15379. Positions 3-369.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-24253N.
IntAct	O15379. 24 interactions.
MINT	MINT-196172.
STRING	O15379.
PTM databases
PhosphoSite	O15379.
Proteomic databases
PRIDE	O15379.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000305264; ENSP00000302967; ENSG00000171720.
GeneID	8841.
KEGG	hsa:8841.
UCSC	uc003llf.2. human.
Organism-specific databases
CTD	8841.
GeneCards	GC05M140980.
H-InvDB	HIX0200752.
HGNC	HGNC:4854. HDAC3.
HPA	CAB005583.
MIM	605166. gene.
neXtProt	NX_O15379.
PharmGKB	PA29228.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11179.
HOGENOM	HBG396919.
HOVERGEN	HBG057112.
InParanoid	O15379.
OMA	NLKMCQH.
OrthoDB	EOG4MGS79.
PhylomeDB	O15379.
Enzyme and pathway databases
Pathway_Interaction_DB	retinoic_acid_pathway. Retinoic acid receptors-mediated signaling. hdac_classi_pathway. Signaling events mediated by HDAC Class I. hdac_classii_pathway. Signaling events mediated by HDAC Class II.
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction. REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	O15379.
Bgee	O15379.
CleanEx	HS_HDAC3.
Genevestigator	O15379.
GermOnline	ENSG00000171720. Homo sapiens.
Family and domain databases
InterPro	IPR000286. His_deacetylse. IPR003084. His_deacetylse_1. IPR023801. His_deacetylse_dom. [Graphical view]
Gene3D	G3DSA:3.40.800.20. His_deacetylse. 1 hit.
KO	K11404.
PANTHER	PTHR10625. His_deacetylse. 1 hit.
Pfam	PF00850. Hist_deacetyl. 1 hit. [Graphical view]
PIRSF	PIRSF037913. His_deacetylse_1. 1 hit.
PRINTS	PR01270. HDASUPER. PR01271. HISDACETLASE.
ProtoNet	Search...
Other
BindingDB	O15379.
DrugBank	DB02546. Vorinostat.
NextBio	33190.
PMAP-CutDB	O15379.
SOURCE	Search...

Entry information

Entry name

HDAC3_HUMAN

Accession

Primary (citable) accession number: O15379
Secondary accession number(s): D3DQE1 , O43268, Q9UEI5, Q9UEV0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	January 25, 2012
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.