P60228 (EIF3E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic translation initiation factor 3 subunit E
Short name=eIF3e

Alternative name(s):
Eukaryotic translation initiation factor 3 subunit 6
Viral integration site protein INT-6 homolog
eIF-3 p48

Gene names

Name:	EIF3E
Synonyms:	EIF3S6, INT6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	445 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S preinitiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway. May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins. Ref.18 Ref.19 Ref.22
Subunit structure	Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with COPS3, COPS6, COPS7 (COPS7A or COPS7B), EIF4G1, EPAS1, MCM7, NCBP1, PSMC6, TRIM27 and UPF2. Interacts with the HTLV-1 protein Tax-1. Interacts with IFIT1 and IFIT2. Ref.1 Ref.3 Ref.4 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.21 Ref.22 Ref.25
Subcellular location	Cytoplasm. Nucleus › PML body Ref.3 Ref.4 Ref.9 Ref.20.
Tissue specificity	Ubiquitously expressed. Expressed at highest levels in appendix, lymph, pancreas, skeletal muscle, spleen and thymus. Ref.1 Ref.3
Sequence similarities	Belongs to the eIF-3 subunit E family. Contains 1 PCI domain.
Mass spectrometry	Molecular mass is 52131.8 Da from positions 1 - 445. Ref.21 Molecular mass is 52133.4±0.2 Da from positions 1 - 445. Determined by MALDI. Ref.25

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Molecular function	Initiation factor
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of translational initiation Non-traceable author statement Ref.9. Source: UniProtKB nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Inferred from mutant phenotype Ref.18. Source: UniProtKB
Cellular_component	PML body Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome eukaryotic translation initiation factor 3 complex Inferred from direct assay Ref.21Ref.17Ref.25Ref.1. Source: UniProtKB nucleoplasm Non-traceable author statement Ref.18. Source: UniProtKB
Molecular_function	translation initiation factor activity Inferred by curator Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EPAS1	Q99814	10	EBI-347740,EBI-447470
ORF	Q9Q2G4	5	EBI-347740,EBI-6248094	From a different organism.
TRIM27	P14373	7	EBI-347740,EBI-719493

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.8 Ref.21
	Chain	2 – 445	444	Eukaryotic translation initiation factor 3 subunit E HAMAP-Rule MF_03004		PRO_0000123515
Regions
	Domain	290 – 395	106	PCI
	Region	4 – 128	125	Sufficient for interaction with EPAS1 HAMAP-Rule MF_03004
	Region	9 – 195	187	Sufficient for interaction with TRIM27 HAMAP-Rule MF_03004
	Region	351 – 445	95	Sufficient for interaction with MCM7 HAMAP-Rule MF_03004
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.8 Ref.21
	Modified residue	399	1	Phosphoserine Ref.24 Ref.26
	Modified residue	439	1	Phosphothreonine By similarity
Natural variations
	Natural variant	185	1	A → V. Ref.7 Corresponds to variant rs17856554 [ dbSNP | Ensembl ].		VAR_046480
Experimental info
	Mutagenesis	312	1	L → D: Promotes nuclear accumulation. Ref.20

Sequences

	Sequence		Length	Mass (Da)
	P60228 [UniParc]. Last modified January 16, 2004. Version 1. Checksum: A5368651DD0DDD0C	FASTA	445	52,221
	10 20 30 40 50 60 MAEYDLTTRI AHFLDRHLVF PLLEFLSVKE IYNEKELLQG KLDLLSDTNM VDFAMDVYKN 70 80 90 100 110 120 LYSDDIPHAL REKRTTVVAQ LKQLQAETEP IVKMFEDPET TRQMQSTRDG RMLFDYLADK 130 140 150 160 170 180 HGFRQEYLDT LYRYAKFQYE CGNYSGAAEY LYFFRVLVPA TDRNALSSLW GKLASEILMQ 190 200 210 220 230 240 NWDAAMEDLT RLKETIDNNS VSSPLQSLQQ RTWLIHWSLF VFFNHPKGRD NIIDLFLYQP 250 260 270 280 290 300 QYLNAIQTMC PHILRYLTTA VITNKDVRKR RQVLKDLVKV IQQESYTYKD PITEFVECLY 310 320 330 340 350 360 VNFDFDGAQK KLRECESVLV NDFFLVACLE DFIENARLFI FETFCRIHQC ISINMLADKL 370 380 390 400 410 420 NMTPEEAERW IVNLIRNARL DAKIDSKLGH VVMGNNAVSP YQQVIEKTKS LSFRSQMLAM 430 440 NIEKKLNQNS RSEAPNWATQ DSGFY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The translation initiation factor eIF3-p48 subunit is encoded by int-6, a site of frequent integration by the mouse mammary tumor virus genome." Asano K., Merrick W.C., Hershey J.W.B. J. Biol. Chem. 272:23477-23480(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 280-289 AND 427-436, INTERACTION WITH EIF3A, IDENTIFICATION IN THE EIF-3 COMPLEX, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"The chromosome location of the human homolog of the mouse mammary tumor-associated gene INT6 and its status in human breast carcinomas." Miyazaki S., Imatani A., Ballard L., Marchetti A., Buttitta F., Albertsen H., Nevanlinna H.A., Gallahan D., Callahan R. Genomics 46:155-158(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Lung.
[3]	"Exclusion of Int-6 from PML nuclear bodies by binding to the HTLV-I Tax oncoprotein." Desbois C., Rousset R., Bantignies F., Jalinot P. Science 273:951-953(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TAX-1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"Divergent subcellular locations of HTLV-I Tax and Int-6: a contrast between in vitro protein-protein binding and intracellular protein colocalization." Neuvert C., Jin D.-Y., Semmes O.J., Diella F., Callahan R., Jeang K.-T. J. Biomed. Sci. 4:229-234(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TAX-1, SUBCELLULAR LOCATION.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-185. Tissue: Bone marrow, Brain, Lung and Muscle.
[8]	Bienvenut W.V., Heiserich L., Gottlieb E., Matallanas D., Cooper W.N., Kolch W. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-9; 60-71; 164-172; 256-265 AND 370-376, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Colon carcinoma and Mammary carcinoma.
[9]	"Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies." Morris-Desbois C., Bochard V., Reynaud C., Jalinot P. J. Cell Sci. 112:3331-3342(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF3C AND TRIM27, SUBCELLULAR LOCATION.
[10]	"Saccharomyces cerevisiae protein Pci8p and human protein eIF3e/Int-6 interact with the eIF3 core complex by binding to cognate eIF3b subunits." Shalev A., Valasek L., Pise-Masison C.A., Radonovich M., Phan L., Clayton J., He H., Brady J.N., Hinnebusch A.G., Asano K. J. Biol. Chem. 276:34948-34957(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF3B.
[11]	"The human protein HSPC021 interacts with Int-6 and is associated with eukaryotic translation initiation factor 3." Morris-Desbois C., Rety S., Ferro M., Garin J., Jalinot P. J. Biol. Chem. 276:45988-45995(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF3L.
[12]	"Association of the mammalian proto-oncoprotein Int-6 with the three protein complexes eIF3, COP9 signalosome and 26S proteasome." Hoareau Alves K., Bochard V., Rety S., Jalinot P. FEBS Lett. 527:15-21(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH COPS3; COPS6; COPS7 AND PSMC6.
[13]	"Binding of eukaryotic initiation factor 3 to ribosomal 40S subunits and its role in ribosomal dissociation and anti-association." Kolupaeva V.G., Unbehaun A., Lomakin I.B., Hellen C.U.T., Pestova T.V. RNA 11:470-486(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE EIF-3 COMPLEX.
[14]	"Induction and mode of action of the viral stress-inducible murine proteins, P56 and P54." Terenzi F., Pal S., Sen G.C. Virology 340:116-124(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IFIT1.
[15]	"Translation initiation factor eIF4G-1 binds to eIF3 through the eIF3e subunit." LeFebvre A.K., Korneeva N.L., Trutschl M., Cvek U., Duzan R.D., Bradley C.A., Hershey J.W.B., Rhoads R.E. J. Biol. Chem. 281:22917-22932(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF4G1, IDENTIFICATION IN THE EIF-3 COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
[16]	"Distinct induction patterns and functions of two closely related interferon-inducible human genes, ISG54 and ISG56." Terenzi F., Hui D.J., Merrick W.C., Sen G.C. J. Biol. Chem. 281:34064-34071(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IFIT2.
[17]	"Reconstitution reveals the functional core of mammalian eIF3." Masutani M., Sonenberg N., Yokoyama S., Imataka H. EMBO J. 26:3373-3383(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE EIF-3 COMPLEX.
[18]	"Human INT6/eIF3e is required for nonsense-mediated mRNA decay." Morris C., Wittmann J., Jaeck H.-M., Jalinot P. EMBO Rep. 8:596-602(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EIF3A; EIF3B; EIF3C; EIF4G1; NCBP1 AND UPF2.
[19]	"Mammalian tumor suppressor Int6 specifically targets hypoxia inducible factor 2 alpha for degradation by hypoxia- and pVHL-independent regulation." Chen L., Uchida K., Endler A., Shibasaki F. J. Biol. Chem. 282:12707-12716(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EPAS1.
[20]	"Isolation of the Schizosaccharomyces pombe proteasome subunit Rpn7 and a structure-function study of the proteasome-COP9-initiation factor domain." Sha Z., Yen H.-C.S., Scheel H., Suo J., Hofmann K., Chang E.C. J. Biol. Chem. 282:32414-32423(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-312.
[21]	"Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry." Damoc E., Fraser C.S., Zhou M., Videler H., Mayeur G.L., Hershey J.W.B., Doudna J.A., Robinson C.V., Leary J.A. Mol. Cell. Proteomics 6:1135-1146(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE EIF-3 COMPLEX, CHARACTERIZATION OF THE EIF-3 COMPLEX, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY.
[22]	"Human INT6 interacts with MCM7 and regulates its stability during S phase of the cell cycle." Buchsbaum S., Morris C., Bochard V., Jalinot P. Oncogene 26:5132-5144(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MCM7.
[23]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[24]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-399, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3." Zhou M., Sandercock A.M., Fraser C.S., Ridlova G., Stephens E., Schenauer M.R., Yokoi-Fong T., Barsky D., Leary J.A., Hershey J.W.B., Doudna J.A., Robinson C.V. Proc. Natl. Acad. Sci. U.S.A. 105:18139-18144(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE EIF-3 COMPLEX, CHARACTERIZATION OF THE EIF-3 COMPLEX, MASS SPECTROMETRY, INTERACTION WITH EIF3B.
[26]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-399, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]	"Structural roles for human translation factor eIF3 in initiation of protein synthesis." Siridechadilok B., Fraser C.S., Hall R.J., Doudna J.A., Nogales E. Science 310:1513-1515(2005) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING, ELECTRON MICROSCOPY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U54562 mRNA. Translation: AAC51760.1. U94174 , U94162, U94163, U94164, U94165, U94166, U94167, U94168, U94169, U94170, U94171, U94172, U94173 Genomic DNA. Translation: AAC51917.1. U94175 mRNA. Translation: AAC51919.1. U62962 mRNA. Translation: AAB58251.1. U85947 mRNA. Translation: AAB88873.1. CR542275 mRNA. Translation: CAG47071.1. CH471060 Genomic DNA. Translation: EAW91918.1. BC000734 mRNA. Translation: AAH00734.1. BC008419 mRNA. Translation: AAH08419.1. BC016706 mRNA. Translation: AAH16706.1. BC017887 mRNA. Translation: AAH17887.1. BC021679 mRNA. Translation: AAH21679.1.
IPI	IPI00013068.
RefSeq	NP_001559.1. NM_001568.2.
UniGene	Hs.405590.
3D structure databases
ProteinModelPortal	P60228.
SMR	P60228. Positions 326-399.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32691N.
IntAct	P60228. 30 interactions.
MINT	MINT-153842.
STRING	9606.ENSP00000220849.
PTM databases
PhosphoSite	P60228.
Polymorphism databases
DMDM	41019126.
Proteomic databases
PaxDb	P60228.
PeptideAtlas	P60228.
PRIDE	P60228.
Protocols and materials databases
DNASU	3646.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000220849; ENSP00000220849; ENSG00000104408.
GeneID	3646.
KEGG	hsa:3646.
UCSC	uc003ymt.3. human.
Organism-specific databases
CTD	3646.
GeneCards	GC08M109284.
HGNC	HGNC:3277. EIF3E.
HPA	HPA023973.
MIM	602210. gene.
neXtProt	NX_P60228.
PharmGKB	PA27705.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG324642.
HOVERGEN	HBG001097.
InParanoid	P60228.
KO	K03250.
OMA	FLEHLYV.
OrthoDB	EOG4CG083.
PhylomeDB	P60228.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins. REACT_1762. 3' -UTR-mediated translational regulation. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P60228.
Bgee	P60228.
CleanEx	HS_EIF3E.
Genevestigator	P60228.
GermOnline	ENSG00000104408. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
HAMAP	MF_03004. eIF3e.
InterPro	IPR019010. eIF3_su6_N. IPR000717. PCI_dom. IPR016650. Transl_init_fac_3_su6_euk. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF09440. eIF3_N. 1 hit. PF01399. PCI. 1 hit. [Graphical view]
PIRSF	PIRSF016255. eIF3e_su6. 1 hit.
SMART	SM00088. PINT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	EIF3E. human.
GenomeRNAi	3646.
NextBio	14271.
SOURCE	Search...

Entry information

Entry name

EIF3E_HUMAN

Accession

Primary (citable) accession number: P60228
Secondary accession number(s): O43902 , Q64058, Q64059, Q64252, Q6FG33, Q8WVK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 16, 2004
Last sequence update:	January 16, 2004
Last modified:	May 1, 2013
This is version 110 of the entry and version 1 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.