Q15583 (TGIF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein TGIF1

Alternative name(s):
5'-TG-3'-interacting factor 1

Gene names

Name:	TGIF1
Synonyms:	TGIF

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	401 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. Active transcriptional corepressor of SMAD2. Links the nodal signaling pathway to the bifurcation of the forebrain and the establishment of ventral midline structures. May participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha activities.
Subunit structure	Interacts with CTBP, SMAD2, SMAD3 and HDAC1.
Subcellular location	Nucleus.
Involvement in disease	Holoprosencephaly 4 (HPE4) [MIM:142946]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10
Sequence similarities	Belongs to the TALE/TGIF homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Holoprosencephaly
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	determination of left/right symmetry Inferred from electronic annotation. Source: Ensembl dorsal/ventral pattern formation Inferred from electronic annotation. Source: Ensembl gene expression Traceable author statement. Source: Reactome multicellular organismal development Traceable author statement Ref.1. Source: ProtInc negative regulation of cell proliferation Inferred from electronic annotation. Source: Ensembl negative regulation of retinoic acid receptor signaling pathway Inferred from electronic annotation. Source: Ensembl negative regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: Reactome neural tube closure Inferred from electronic annotation. Source: Ensembl nodal signaling pathway Inferred from electronic annotation. Source: Ensembl positive regulation of fibroblast proliferation Inferred from electronic annotation. Source: Ensembl positive regulation of neuron differentiation Inferred from electronic annotation. Source: Ensembl regulation of gastrulation Inferred from electronic annotation. Source: Ensembl response to drug Inferred from electronic annotation. Source: Ensembl retina development in camera-type eye Inferred from electronic annotation. Source: Ensembl transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transcription, DNA-templated Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Ensembl sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc transcription corepressor activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LGALS8	O00214	10	EBI-714215,EBI-740058
PML	P29590	3	EBI-714215,EBI-295890

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15583-1)

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: Q15583-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-129: Missing.
     130-133: LETM → MKGK

Isoform 3 (identifier: Q15583-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-115: Missing.
     116-134: PSQGAQGPAPRRRLLETMK → MTCSGKSCALARSSLTSSQ

Isoform 4 (identifier: Q15583-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-149: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 401

401

Homeobox protein TGIF1

PRO_0000049318

Regions

DNA binding

164 – 226

63

Homeobox; TALE-type

Motif

153 – 157

5

CTBP-binding motif

Compositional bias

165 – 168

4

Poly-Arg

Natural variations

Alternative sequence

1 – 149

149

Missing in isoform 4.

VSP_046848

Alternative sequence

1 – 129

129

Missing in isoform 2.

VSP_013020

Alternative sequence

1 – 115

115

Missing in isoform 3.

VSP_043108

Alternative sequence

116 – 134

19

PSQGA…LETMK → MTCSGKSCALARSSLTSSQ in isoform 3.

VSP_043109

Alternative sequence

130 – 133

4

LETM → MKGK in isoform 2.

VSP_013021

Natural variant

157

1

S → C in HPE4. Ref.9

VAR_009961

Natural variant

192

1

P → R in HPE4. Ref.9

VAR_009962

Natural variant

236

1

Q → L in HPE4. Ref.10

VAR_023803

Natural variant

280

1

T → A in HPE4. Ref.9

VAR_009963

Natural variant

289

1

P → S.
Corresponds to variant rs11571512 [ dbSNP | Ensembl ].

VAR_047363

Natural variant

291

1

S → F in HPE4. Ref.9

VAR_009964

Natural variant

292

1

P → L.
Corresponds to variant rs2229333 [ dbSNP | Ensembl ].

VAR_020151

Natural variant

292

1

P → S. Ref.2 Ref.3
Corresponds to variant rs4468717 [ dbSNP | Ensembl ].

VAR_061268

Experimental info

Sequence conflict

96

1

P → Q in AAH31268. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

401

Helix Strand Turn

Details...

Helix

173 – 185

13

Helix

188 – 190

3

Helix

194 – 203

10

Beta strand

204 – 206

3

Helix

208 – 230

23

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 3. Checksum: 4D9C76AFB37A29F0	FASTA	401	43,013
	10 20 30 40 50 60 MVLAQSRVSA GVGSPHCSGS GGGGSDSFPW PASHPGNPQC SFSTAFLASP RLSRGTLAYL 70 80 90 100 110 120 PPAPWSSLAT PSALLGSSCA PPPPPARCPQ PRALSPELGT KAGPRRPHRW ELPRSPSQGA 130 140 150 160 170 180 QGPAPRRRLL ETMKGIVAAS GSETEDEDSM DIPLDLSSSA GSGKRRRRGN LPKESVQILR 190 200 210 220 230 240 DWLYEHRYNA YPSEQEKALL SQQTHLSTLQ VCNWFINARR RLLPDMLRKD GKDPNQFTIS 250 260 270 280 290 300 RRGAKISETS SVESVMGIKN FMPALEETPF HSCTAGPNPT LGRPLSPKPS SPGSVLARPS 310 320 330 340 350 360 VICHTTVTAL KDVPFSLCQS VGVGQNTDIQ QIAAKNFTDT SLMYPEDTCK SGPSTNTQSG 370 380 390 400 LFNTPPPTPP DLNQDFSGFQ LLVDVALKRA AEMELQAKLT A
	Isoform 2 [UniParc]. Checksum: 948D1F689996E84E	FASTA	272	29,737
	10 20 30 40 50 60 MKGKKGIVAA SGSETEDEDS MDIPLDLSSS AGSGKRRRRG NLPKESVQIL RDWLYEHRYN 70 80 90 100 110 120 AYPSEQEKAL LSQQTHLSTL QVCNWFINAR RRLLPDMLRK DGKDPNQFTI SRRGAKISET 130 140 150 160 170 180 SSVESVMGIK NFMPALEETP FHSCTAGPNP TLGRPLSPKP SSPGSVLARP SVICHTTVTA 190 200 210 220 230 240 LKDVPFSLCQ SVGVGQNTDI QQIAAKNFTD TSLMYPEDTC KSGPSTNTQS GLFNTPPPTP 250 260 270 PDLNQDFSGF QLLVDVALKR AAEMELQAKL TA
	Isoform 3 [UniParc]. Checksum: 39EA173EECBFD391	FASTA	286	31,064
	10 20 30 40 50 60 MTCSGKSCAL ARSSLTSSQG IVAASGSETE DEDSMDIPLD LSSSAGSGKR RRRGNLPKES 70 80 90 100 110 120 VQILRDWLYE HRYNAYPSEQ EKALLSQQTH LSTLQVCNWF INARRRLLPD MLRKDGKDPN 130 140 150 160 170 180 QFTISRRGAK ISETSSVESV MGIKNFMPAL EETPFHSCTA GPNPTLGRPL SPKPSSPGSV 190 200 210 220 230 240 LARPSVICHT TVTALKDVPF SLCQSVGVGQ NTDIQQIAAK NFTDTSLMYP EDTCKSGPST 250 260 270 280 NTQSGLFNTP PPTPPDLNQD FSGFQLLVDV ALKRAAEMEL QAKLTA
	Isoform 4 [UniParc]. Checksum: A3426BEBB9753C87	FASTA	252	27,715
	10 20 30 40 50 60 MDIPLDLSSS AGSGKRRRRG NLPKESVQIL RDWLYEHRYN AYPSEQEKAL LSQQTHLSTL 70 80 90 100 110 120 QVCNWFINAR RRLLPDMLRK DGKDPNQFTI SRRGAKISET SSVESVMGIK NFMPALEETP 130 140 150 160 170 180 FHSCTAGPNP TLGRPLSPKP SSPGSVLARP SVICHTTVTA LKDVPFSLCQ SVGVGQNTDI 190 200 210 220 230 240 QQIAAKNFTD TSLMYPEDTC KSGPSTNTQS GLFNTPPPTP PDLNQDFSGF QLLVDVALKR 250 AAEMELQAKL TA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif." Bertolino E., Reimund B., Wildt-Perinic D., Clerc R.G. J. Biol. Chem. 270:31178-31188(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Liver.
[2]	"Three-amino acid extension loop homeodomain proteins Meis2 and TGIF differentially regulate transcription." Yang Y., Hwang C.K., D'Souza U.M., Lee S.-H., Junn E., Mouradian M.M. J. Biol. Chem. 275:20734-20741(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT SER-292. Tissue: Brain.
[3]	"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 (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT SER-292.
[4]	"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] (ISOFORM 3).
[5]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton 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].
[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] (ISOFORMS 1 AND 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-137 (ISOFORM 4). Tissue: Brain, Placenta and Rhabdomyosarcoma.
[8]	"Solution NMR structure of homeobox domain (171-248) of human homeobox protein TGIF1, northeast structural genomics consortium target hr4411b." Northeast structural genomics consortium (NESG) Submitted (OCT-2011) to the PDB data bank Cited for: STRUCTURE BY NMR OF 171-248.
[9]	"Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination." Gripp K.W., Wotton D., Edwards M.C., Roessler E., Ades L., Meinecke P., Richieri-Costa A., Zackai E.H., Massague J., Muenke M., Elledge S.J. Nat. Genet. 25:205-208(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HPE4 CYS-157; ARG-192; ALA-280 AND PHE-291.
[10]	"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations." Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., Le Duff F., Durou M.-R., Odent S., David V. Hum. Mutat. 24:43-51(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HPE4 LEU-236.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X89750 mRNA. Translation: CAA61897.1.
AF179900 mRNA. Translation: AAF81643.1.
CR450333 mRNA. Translation: CAG29329.1.
AK291112 mRNA. Translation: BAF83801.1.
AP001025 Genomic DNA. No translation available.
CH471113 Genomic DNA. Translation: EAX01672.1.
BC000814 mRNA. Translation: AAH00814.1.
BC031268 mRNA. Translation: AAH31268.1.
BE296707 mRNA. No translation available.

RefSeq

NP_001265611.1. NM_001278682.1.
NP_001265613.1. NM_001278684.1.
NP_001265615.1. NM_001278686.1.
NP_003235.1. NM_003244.3.
NP_733796.2. NM_170695.3.
NP_775299.1. NM_173207.2.
NP_775300.1. NM_173208.2.
NP_775301.1. NM_173209.2.
NP_775302.1. NM_173210.2.
NP_775303.1. NM_173211.1.
NP_777480.1. NM_174886.2.
XP_005258192.1. XM_005258135.1.

UniGene

Hs.373550.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LK2	NMR	-	A	171-248	[»]

ProteinModelPortal

Q15583.

SMR

Q15583. Positions 171-248.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

112908. 21 interactions.

IntAct

Q15583. 8 interactions.

MINT

MINT-145985.

STRING

9606.ENSP00000327959.

PTM databases

PhosphoSite

Q15583.

Polymorphism databases

DMDM

215274200.

Proteomic databases

PaxDb

Q15583.

PRIDE

Q15583.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000330513; ENSP00000327959; ENSG00000177426. [Q15583-1]
ENST00000343820; ENSP00000339631; ENSG00000177426. [Q15583-2]
ENST00000345133; ENSP00000343969; ENSG00000177426. [Q15583-4]
ENST00000400167; ENSP00000383031; ENSG00000177426. [Q15583-4]
ENST00000401449; ENSP00000385206; ENSG00000177426. [Q15583-4]
ENST00000405385; ENSP00000384970; ENSG00000177426. [Q15583-4]
ENST00000407501; ENSP00000384133; ENSG00000177426. [Q15583-2]
ENST00000472042; ENSP00000449501; ENSG00000177426. [Q15583-4]
ENST00000548489; ENSP00000447747; ENSG00000177426. [Q15583-3]
ENST00000551541; ENSP00000450025; ENSG00000177426. [Q15583-4]

GeneID

7050.

KEGG

hsa:7050.

UCSC

uc002klu.3. human. [Q15583-1]
uc002klv.3. human. [Q15583-3]
uc002klw.3. human. [Q15583-2]

Organism-specific databases

CTD

7050.

GeneCards

GC18P003412.

H-InvDB

HIX0174209.

HGNC

HGNC:11776. TGIF1.

HPA

CAB004596.

MIM

142946. phenotype.
602630. gene.

neXtProt

NX_Q15583.

Orphanet

93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.

PharmGKB

PA36489.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG308174.

HOGENOM

HOG000232039.

HOVERGEN

HBG001143.

InParanoid

Q15583.

OMA

IAANNFT.

PhylomeDB

Q15583.

TreeFam

TF318093.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_71. Gene Expression.

SignaLink

Q15583.

Gene expression databases

ArrayExpress

Q15583.

Bgee

Q15583.

CleanEx

HS_TGIF1.

Genevestigator

Q15583.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.

InterPro

IPR001356. Homeobox_dom.
IPR008422. Homeobox_KN_domain.
IPR009057. Homeodomain-like.
[Graphical view]

Pfam

PF05920. Homeobox_KN. 1 hit.
[Graphical view]

SMART

SM00389. HOX. 1 hit.
[Graphical view]

SUPFAM

SSF46689. SSF46689. 1 hit.

PROSITE

PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q15583.

GeneWiki

Homeobox_protein_TGIF1.

GenomeRNAi

7050.

NextBio

27551.

PRO

Q15583.

SOURCE

Search...

Entry information

Entry name

TGIF1_HUMAN

Accession

Primary (citable) accession number: Q15583
Secondary accession number(s): A6NE42 , A6NLU7, F8VZB6, Q6ICR0, Q8N5X9, Q9NRS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 25, 2008
Last modified:	April 16, 2014
This is version 153 of the entry and version 3 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.