Q04725 (TLE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transducin-like enhancer protein 2

Alternative name(s):
Enhancer of split groucho-like protein 2
Short name=ESG2

Gene names

Name:

TLE2

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	743 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES By similarity.
Subunit structure	Homooligomer and heterooligomer with other family members. Binds LEF1, TCF7, TCF7L1, TCF7L2, UTY, HES1 and HES5. Ref.5
Subcellular location	Nucleus.
Tissue specificity	In all tissues examined, mostly in heart, brain, and muscle.
Post-translational modification	Ubiquitinated by XIAP/BIRC4. Ref.10
Sequence similarities	Belongs to the WD repeat Groucho/TLE family. Contains 6 WD repeats.
Sequence caution	The sequence AK308137 differs from that shown. Reason: Frameshift at position 537.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Wnt signaling pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat WD repeat
Molecular function	Repressor
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Traceable author statement. Source: Reactome Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 19460168. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 19460168. Source: UniProtKB organ morphogenesis Traceable author statement PubMed 8808280. Source: ProtInc transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	transcription corepressor activity Inferred from direct assay PubMed 19460168. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DDB1	Q16531	2	EBI-1176061,EBI-350322

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q04725-1)

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: Q04725-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.
     124-190: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q04725-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MYPQGRHP → MVQSRLTATSASQDSPASGLQ
     124-124: Q → QQ
     683-743: GRWFVSTGKDNLLNAWRTPYGASIFQSKESSSVLSCDISRNNKYIVTGSGDKKATVYEVVY → VQGVVLSPEL

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 743	743	Transducin-like enhancer protein 2		PRO_0000051278
Regions
	Repeat	455 – 493	39	WD 1
	Repeat	501 – 540	40	WD 2
	Repeat	545 – 584	40	WD 3
	Repeat	587 – 626	40	WD 4
	Repeat	669 – 708	40	WD 5
	Repeat	710 – 742	33	WD 6
	Region	195 – 256	62	CCN domain
	Motif	214 – 217	4	Nuclear localization signal Potential
	Compositional bias	1 – 133	133	Gln-rich
	Compositional bias	134 – 194	61	Gly/Pro-rich
	Compositional bias	257 – 398	142	Pro/Ser-rich
Amino acid modifications
	Modified residue	228	1	Phosphoserine; by CK2 Potential
	Modified residue	249	1	Phosphoserine; by CDK1 Potential
	Modified residue	253	1	Phosphothreonine; by CDK1 Potential
	Modified residue	281	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	1 – 55	55	Missing in isoform 2.		VSP_045693
	Alternative sequence	1 – 8	8	MYPQGRHP → MVQSRLTATSASQDSPASGL Q in isoform 3.		VSP_046162
	Alternative sequence	124 – 190	67	Missing in isoform 2.		VSP_045694
	Alternative sequence	124	1	Q → QQ in isoform 3.		VSP_046163
	Alternative sequence	683 – 743	61	GRWFV…YEVVY → VQGVVLSPEL in isoform 3.		VSP_046164
	Natural variant	381	1	S → G. Ref.2 Corresponds to variant rs199788562 [ dbSNP | Ensembl ].		VAR_069063
Experimental info
	Sequence conflict	280	1	G → R in AAA61193. Ref.1
	Sequence conflict	328	1	A → L in AAA61193. Ref.1
	Sequence conflict	441	1	G → D in AAA61193. Ref.1
	Sequence conflict	495	1	A → R in AAA61193. Ref.1
	Sequence conflict	636 – 637	2	LG → PC in AAA61193. Ref.1
	Sequence conflict	660	1	R → G in AAA61193. Ref.1
	Sequence conflict	681	1	S → P in AAA61193. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2002. Version 2. Checksum: 5E3DBFAB67278219	FASTA	743	79,841
	10 20 30 40 50 60 MYPQGRHPTP LQSGQPFKFS ILEICDRIKE EFQFLQAQYH SLKLECEKLA SEKTEMQRHY 70 80 90 100 110 120 VMYYEMSYGL NIEMHKQAEI VKRLSGICAQ IIPFLTQEHQ QQVLQAVERA KQVTVGELNS 130 140 150 160 170 180 LIGQQLQPLS HHAPPVPLTP RPAGLVGGSA TGLLALSGAL AAQAQLAAAV KEDRAGVEAE 190 200 210 220 230 240 GSRVERAPSR SASPSPPESL VEEERPSGPG GGGKQRADEK EPSGPYESDE DKSDYNLVVD 250 260 270 280 290 300 EDQPSEPPSP ATTPCGKVPI CIPARRDLVD SPASLASSLG SPLPRAKELI LNDLPASTPA 310 320 330 340 350 360 SKSCDSSPPQ DASTPGPSSA SHLCQLAAKP APSTDSVALR SPLTLSSPFT TSFSLGSHST 370 380 390 400 410 420 LNGDLSVPSS YVSLHLSPQV SSSVVYGRSP VMAFESHPHL RGSSVSSSLP SIPGGKPAYS 430 440 450 460 470 480 FHVSADGQMQ PVPFPSDALV GAGIPRHARQ LHTLAHGEVV CAVTISGSTQ HVYTGGKGCV 490 500 510 520 530 540 KVWDVGQPGA KTPVAQLDCL NRDNYIRSCK LLPDGRSLIV GGEASTLSIW DLAAPTPRIK 550 560 570 580 590 600 AELTSSAPAC YALAVSPDAK VCFSCCSDGN IVVWDLQNQT MVRQFQGHTD GASCIDISDY 610 620 630 640 650 660 GTRLWTGGLD NTVRCWDLRE GRQLQQHDFS SQIFSLGHCP NQDWLAVGME SSNVEILHVR 670 680 690 700 710 720 KPEKYQLHLH ESCVLSLKFA SCGRWFVSTG KDNLLNAWRT PYGASIFQSK ESSSVLSCDI 730 740 SRNNKYIVTG SGDKKATVYE VVY
	Isoform 2 [UniParc]. Checksum: F5100FF0B0FECFBA	FASTA	621	66,678
	10 20 30 40 50 60 MQRHYVMYYE MSYGLNIEMH KQAEIVKRLS GICAQIIPFL TQEHQQQVLQ AVERAKQVTV 70 80 90 100 110 120 GELNSLIGSA SPSPPESLVE EERPSGPGGG GKQRADEKEP SGPYESDEDK SDYNLVVDED 130 140 150 160 170 180 QPSEPPSPAT TPCGKVPICI PARRDLVDSP ASLASSLGSP LPRAKELILN DLPASTPASK 190 200 210 220 230 240 SCDSSPPQDA STPGPSSASH LCQLAAKPAP STDSVALRSP LTLSSPFTTS FSLGSHSTLN 250 260 270 280 290 300 GDLSVPSSYV SLHLSPQVSS SVVYGRSPVM AFESHPHLRG SSVSSSLPSI PGGKPAYSFH 310 320 330 340 350 360 VSADGQMQPV PFPSDALVGA GIPRHARQLH TLAHGEVVCA VTISGSTQHV YTGGKGCVKV 370 380 390 400 410 420 WDVGQPGAKT PVAQLDCLNR DNYIRSCKLL PDGRSLIVGG EASTLSIWDL AAPTPRIKAE 430 440 450 460 470 480 LTSSAPACYA LAVSPDAKVC FSCCSDGNIV VWDLQNQTMV RQFQGHTDGA SCIDISDYGT 490 500 510 520 530 540 RLWTGGLDNT VRCWDLREGR QLQQHDFSSQ IFSLGHCPNQ DWLAVGMESS NVEILHVRKP 550 560 570 580 590 600 EKYQLHLHES CVLSLKFASC GRWFVSTGKD NLLNAWRTPY GASIFQSKES SSVLSCDISR 610 620 NNKYIVTGSG DKKATVYEVV Y
	Isoform 3 [UniParc]. Checksum: 71A2BA068112A6AE	FASTA	706	75,364
	10 20 30 40 50 60 MVQSRLTATS ASQDSPASGL QTPLQSGQPF KFSILEICDR IKEEFQFLQA QYHSLKLECE 70 80 90 100 110 120 KLASEKTEMQ RHYVMYYEMS YGLNIEMHKQ AEIVKRLSGI CAQIIPFLTQ EHQQQVLQAV 130 140 150 160 170 180 ERAKQVTVGE LNSLIGQQQL QPLSHHAPPV PLTPRPAGLV GGSATGLLAL SGALAAQAQL 190 200 210 220 230 240 AAAVKEDRAG VEAEGSRVER APSRSASPSP PESLVEEERP SGPGGGGKQR ADEKEPSGPY 250 260 270 280 290 300 ESDEDKSDYN LVVDEDQPSE PPSPATTPCG KVPICIPARR DLVDSPASLA SSLGSPLPRA 310 320 330 340 350 360 KELILNDLPA STPASKSCDS SPPQDASTPG PSSASHLCQL AAKPAPSTDS VALRSPLTLS 370 380 390 400 410 420 SPFTTSFSLG SHSTLNGDLS VPSSYVSLHL SPQVSSSVVY GRSPVMAFES HPHLRGSSVS 430 440 450 460 470 480 SSLPSIPGGK PAYSFHVSAD GQMQPVPFPS DALVGAGIPR HARQLHTLAH GEVVCAVTIS 490 500 510 520 530 540 GSTQHVYTGG KGCVKVWDVG QPGAKTPVAQ LDCLNRDNYI RSCKLLPDGR SLIVGGEAST 550 560 570 580 590 600 LSIWDLAAPT PRIKAELTSS APACYALAVS PDAKVCFSCC SDGNIVVWDL QNQTMVRQFQ 610 620 630 640 650 660 GHTDGASCID ISDYGTRLWT GGLDNTVRCW DLREGRQLQQ HDFSSQIFSL GHCPNQDWLA 670 680 690 700 VGMESSNVEI LHVRKPEKYQ LHLHESCVLS LKFASCVQGV VLSPEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human homologs of a Drosophila enhancer of split gene product define a novel family of nuclear proteins." Stifani S., Blaumueller C.M., Redhead N.J., Hill R.E., Artavanis-Tsakonas S. Nat. Genet. 2:119-127(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), VARIANT GLY-381. Tissue: Brain and Urinary bladder.
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 1). Tissue: Placenta.
[5]	"Transducin-like Enhancer of split 2, a mammalian homologue of Drosophila Groucho, acts as a transcriptional repressor, interacts with Hairy/Enhancer of split proteins, and is expressed during neuronal development." Grbavec D., Lo R., Liu Y., Stifani S. Eur. J. Biochem. 258:339-349(1998) [PubMed] [Europe PMC] [Abstract] Cited for: OLIGOMERIZATION, INTERACTION WITH HES1 AND HES5.
[6]	"Groucho/transducin-like enhancer of split (TLE) family members interact with the yeast transcriptional co-repressor SSN6 and mammalian SSN6-related proteins: implications for evolutionary conservation of transcription repression mechanisms." Grbavec D., Lo R., Liu Y., Greenfield A., Stifani S. Biochem. J. 337:13-17(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UTY.
[7]	"All Tcf HMG box transcription factors interact with Groucho-related co-repressors." Brantjes H., Roose J., van De Wetering M., Clevers H. Nucleic Acids Res. 29:1410-1419(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LEF1; TCF7; TCF7L1 AND TCF7L2.
[8]	"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-281, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[10]	"XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling." Hanson A.J., Wallace H.A., Freeman T.J., Beauchamp R.D., Lee L.A., Lee E. Mol. Cell 45:619-628(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY XIAP/BIRC4.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M99436 mRNA. Translation: AAA61193.1. AK293407 mRNA. Translation: BAG56914.1. AK308137 mRNA. No translation available. AC007766 Genomic DNA. Translation: AAD38075.1. AC011549 Genomic DNA. No translation available. AC093053 Genomic DNA. No translation available. BC017364 mRNA. Translation: AAH17364.1.
IPI	IPI00297659. IPI00910233. IPI00921163.
PIR	C56695.
RefSeq	NP_001138233.1. NM_001144761.1. NP_001138234.1. NM_001144762.1. NP_003251.2. NM_003260.4.
UniGene	Hs.332173.
3D structure databases
ProteinModelPortal	Q04725.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q04725. 2 interactions.
STRING	9606.ENSP00000262953.
PTM databases
PhosphoSite	Q04725.
Polymorphism databases
DMDM	20532416.
Proteomic databases
PaxDb	Q04725.
PRIDE	Q04725.
Protocols and materials databases
DNASU	7089.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262953; ENSP00000262953; ENSG00000065717. ENST00000426948; ENSP00000392869; ENSG00000065717. ENST00000443826; ENSP00000392427; ENSG00000065717. ENST00000455444; ENSP00000413107; ENSG00000065717. ENST00000591529; ENSP00000468279; ENSG00000065717.
GeneID	7089.
KEGG	hsa:7089.
UCSC	uc002lww.3. human. uc010dti.3. human. uc010xhc.2. human.
Organism-specific databases
CTD	7089.
GeneCards	GC19M002997.
HGNC	HGNC:11838. TLE2.
HPA	HPA049103.
MIM	601041. gene.
neXtProt	NX_Q04725.
PharmGKB	PA36540.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2319.
HOGENOM	HOG000293211.
HOVERGEN	HBG004689.
InParanoid	Q04725.
OMA	EEDKSDY.
OrthoDB	EOG4WQ121.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
SignaLink	Q04725.
Gene expression databases
ArrayExpress	Q04725.
Bgee	Q04725.
CleanEx	HS_TLE2.
Genevestigator	Q04725.
GermOnline	ENSG00000065717. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR005617. Groucho/TLE_N. IPR009146. Groucho_enhance. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF03920. TLE_N. 1 hit. PF00400. WD40. 5 hits. [Graphical view]
PRINTS	PR01850. GROUCHOFAMLY.
SMART	SM00320. WD40. 7 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS00678. WD_REPEATS_1. 1 hit. PS50082. WD_REPEATS_2. 3 hits. PS50294. WD_REPEATS_REGION. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7089.
NextBio	27727.
SOURCE	Search...

Entry information

Entry name

TLE2_HUMAN

Accession

Primary (citable) accession number: Q04725
Secondary accession number(s): B4DE03 , E9PEV7, F8WCH2, Q8WVY0, Q9Y6S0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	May 10, 2002
Last modified:	May 29, 2013
This is version 127 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.