P35226 (BMI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Polycomb complex protein BMI-1

Alternative name(s):
Polycomb group RING finger protein 4
RING finger protein 51

Gene names

Name:	BMI1
Synonyms:	PCGF4, RNF51

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

General annotation (Comments)

Function	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. In the PRC1 complex, it is required to stimulate the E3 ubiquitin-protein ligase activity of RNF2/RING2. Ref.11 Ref.14 Ref.18
Subunit structure	Component of a PRC1-like complex. Interacts with RING1 and RING2 By similarity. Interacts vwith CBX7 and CBX8. Interacts with SPOP. Part of a complex consisting of BMI1, CUL3 and SPOP. Interacts with E4F1. Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.14 Ref.15 Ref.17 Ref.18
Subcellular location	Nucleus. Cytoplasm Ref.14 Ref.17.
Post-translational modification	Monoubiquitinated By similarity. May be polyubiquitinated; which does not lead to proteasomal degradation.
Miscellaneous	The hPRC-H complex purification reported by Ref.9 probably presents a mixture of different PRC1-like complexes.
Sequence similarities	Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Repressor
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from electronic annotation. Source: Compara embryonic skeletal system morphogenesis Inferred from electronic annotation. Source: Compara hemopoiesis Inferred from expression pattern PubMed 15334543. Source: UniProtKB histone acetylation Inferred from electronic annotation. Source: Compara histone ubiquitination Inferred from electronic annotation. Source: Compara humoral immune response Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.15. Source: UniProtKB positive regulation of B cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of fibroblast proliferation Inferred from mutant phenotype PubMed 17420273. Source: BHF-UCL positive regulation of immature T cell proliferation in thymus Inferred from electronic annotation. Source: Compara positive regulation of ubiquitin-protein ligase activity Inferred from direct assay Ref.18. Source: UniProtKB rostrocaudal neural tube patterning Inferred from electronic annotation. Source: Compara segment specification Traceable author statement PubMed 7715727. Source: ProtInc somatic stem cell division Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	PRC1 complex Inferred from direct assay Ref.9Ref.15. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear body Inferred from electronic annotation. Source: Compara nucleolus Inferred from direct assay. Source: HPA ubiquitin ligase complex Inferred from direct assay Ref.18. Source: UniProtKB
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: Compara ubiquitin-protein ligase activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from direct assay Ref.18. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CBX4	O00257-3	2	EBI-2341576,EBI-4392727
CBX6	O95503	2	EBI-2341576,EBI-3951758
CBX7	O95931	5	EBI-2341576,EBI-3923843
CBX8	Q9HC52	6	EBI-2341576,EBI-712912
RING1	Q06587	9	EBI-2341576,EBI-752313
RNF2	Q99496	5	EBI-2341576,EBI-722416
VPS11	Q9H270	2	EBI-2341576,EBI-373380

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 326

326

Polycomb complex protein BMI-1

PRO_0000055987

Regions

Zinc finger

18 – 57

40

RING-type

Region

164 – 228

65

Interaction with E4F1

Motif

81 – 95

15

Nuclear localization signal Potential

Compositional bias

251 – 326

76

Pro/Ser-rich

Amino acid modifications

Modified residue

251

1

Phosphoserine Ref.16

Modified residue

253

1

Phosphoserine By similarity

Modified residue

255

1

Phosphoserine By similarity

Natural variations

Natural variant

18

1

C → Y.
Corresponds to variant rs1042059 [ dbSNP | Ensembl ].

VAR_052087

Experimental info

Sequence conflict

109

1

G → S in AAB27059. Ref.6

Sequence conflict

265

1

I → V in AAA19873. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

326

Helix Strand Turn

Details...

Beta strand

6 – 8

3

Helix

9 – 12

4

Helix

13 – 15

3

Turn

19 – 21

3

Beta strand

22 – 24

3

Beta strand

29 – 31

3

Turn

32 – 34

3

Helix

40 – 46

7

Turn

54 – 56

3

Helix

65 – 68

4

Beta strand

69 – 71

3

Helix

73 – 82

10

Helix

86 – 100

15

Sequences

	Sequence		Length	Mass (Da)
	P35226 [UniParc]. Last modified August 13, 2002. Version 2. Checksum: 030A7D396BADA543	FASTA	326	36,949
	10 20 30 40 50 60 MHRTTRIKIT ELNPHLMCVL CGGYFIDATT IIECLHSFCK TCIVRYLETS KYCPICDVQV 70 80 90 100 110 120 HKTRPLLNIR SDKTLQDIVY KLVPGLFKNE MKRRRDFYAA HPSADAANGS NEDRGEVADE 130 140 150 160 170 180 DKRIITDDEI ISLSIEFFDQ NRLDRKVNKD KEKSKEEVND KRYLRCPAAM TVMHLRKFLR 190 200 210 220 230 240 SKMDIPNTFQ IDVMYEEEPL KDYYTLMDIA YIYTWRRNGP LPLKYRVRPT CKRMKISHQR 250 260 270 280 290 300 DGLTNAGELE SDSGSDKANS PAGGIPSTSS CLPSPSTPVQ SPHPQFPHIS STMNGTSNSP 310 320 SGNHQSSFAN RPRKSSVNGS SATSSG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization and chromosomal localization of the human proto-oncogene BMI-1." Alkema M.J., Wiegand J., Raap A.K., Berns A., van Lohuizen M. Hum. Mol. Genet. 2:1597-1603(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Erythrocyte.
[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].
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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].
[5]	"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]. Tissue: Muscle.
[6]	"flvi-2, a target of retroviral insertional mutagenesis in feline thymic lymphosarcomas, encodes bmi-1." Levy L.S., Lobelle-Rich P.A., Overbaugh J. Oncogene 8:1833-1838(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-300. Tissue: Thymus.
[7]	"Identification and characterization of interactions between the vertebrate polycomb-group protein BMI1 and human homologs of polyhomeotic." Gunster M.J., Satijn D.P.E., Hamer K.M., den Blaauwen J.L., de Bruijn D., Alkema M.J., van Lohuizen M., van Driel R., Otte A.P. Mol. Cell. Biol. 17:2326-2335(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHC2.
[8]	"RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor." Satijn D.P.E., Gunster M.J., van der Vlag J., Hamer K.M., Schul W., Alkema M.J., Saurin A.J., Freemont P.S., van Driel R., Otte A.P. Mol. Cell. Biol. 17:4105-4113(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHC2.
[9]	"The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans." Levine S.S., Weiss A., Erdjument-Bromage H., Shao Z., Tempst P., Kingston R.E. Mol. Cell. Biol. 22:6070-6078(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A PRC1-LIKE HPRC-H COMPLEX WITH CBX2; CBX4; CBX8; PHC1; PHC2; PHC3; RING1 AND RNF2.
[10]	"Role of histone H2A ubiquitination in Polycomb silencing." Wang H., Wang L., Erdjument-Bromage H., Vidal M., Tempst P., Jones R.S., Zhang Y. Nature 431:873-878(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A PRC1-LIKE COMPLEX.
[11]	"Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing." Cao R., Tsukada Y., Zhang Y. Mol. Cell 20:845-854(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase." Hernandez-Munoz I., Lund A.H., van der Stoop P., Boutsma E., Muijrers I., Verhoeven E., Nusinow D.A., Panning B., Marahrens Y., van Lohuizen M. Proc. Natl. Acad. Sci. U.S.A. 102:7635-7640(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPOP, IDENTIFICATION IN A COMPLEX WITH CUL3 AND SPOP, UBIQUITINATION.
[13]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells." Chagraoui J., Niessen S.L., Lessard J., Girard S., Coulombe P., Sauvageau M., Meloche S., Sauvageau G. Genes Dev. 20:2110-2120(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH E4F1, SUBCELLULAR LOCATION.
[15]	"Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus." Maertens G.N., El Messaoudi-Aubert S., Racek T., Stock J.K., Nicholls J., Rodriguez-Niedenfuhr M., Gil J., Peters G. PLoS ONE 4:E6380-E6380(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A PRC1-LIKE COMPLEX, INTERACTION WITH CBX7 AND CBX8.
[16]	"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-251, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Interaction proteomics analysis of polycomb proteins defines distinct PRC1 Complexes in mammalian cells." Vandamme J., Volkel P., Rosnoblet C., Le Faou P., Angrand P.O. Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A PRC1-LIKE COMPLEX, SUBCELLULAR LOCATION.
[18]	"Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex." Li Z., Cao R., Wang M., Myers M.P., Zhang Y., Xu R.M. J. Biol. Chem. 281:20643-20649(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 5-101 IN COMPLEX WITH RNF2 AND ZINC IONS, FUNCTION, MASS SPECTROMETRY, SUBUNIT.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L13689 mRNA. Translation: AAA19873.1.
AK313235 mRNA. Translation: BAG36046.1.
AL158211 Genomic DNA. Translation: CAI15958.1.
CH471072 Genomic DNA. Translation: EAW86148.1.
CH471072 Genomic DNA. Translation: EAW86150.1.
CH471072 Genomic DNA. Translation: EAW86151.1.
CH471072 Genomic DNA. Translation: EAW86154.1.
BC011652 mRNA. Translation: AAH11652.1.
AH004292 mRNA. Translation: AAB27059.1.

IPI

IPI00017299.

PIR

I54339.

RefSeq

NP_001190991.1. NM_001204062.1.
NP_005171.4. NM_005180.8.

UniGene

Hs.380403.
Hs.731287.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H0D	X-ray	2.50	A	5-101	[»]
3RPG	X-ray	2.65	B	1-109	[»]

ProteinModelPortal

P35226.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41879N.

IntAct

P35226. 23 interactions.

MINT

MINT-158260.

STRING

9606.ENSP00000365851.

PTM databases

PhosphoSite

P35226.

Polymorphism databases

DMDM

22258801.

Proteomic databases

PaxDb

P35226.

PRIDE

P35226.

Protocols and materials databases

DNASU

648.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000376663; ENSP00000365851; ENSG00000168283.

GeneID

100532731.
648.

KEGG

hsa:100532731.
hsa:648.

UCSC

uc001irh.3. human.

Organism-specific databases

CTD

100532731.
648.

GeneCards

GC10P022605.

HGNC

HGNC:1066. BMI1.

HPA

CAB011120.
HPA030472.

MIM

164831. gene.

neXtProt

NX_P35226.

PharmGKB

PA25376.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG304672.

HOGENOM

HOG000231945.

HOVERGEN

HBG052826.

InParanoid

P35226.

KO

K11459.

OMA

SNHQSSF.

OrthoDB

EOG4KSPKG.

PhylomeDB

P35226.

Gene expression databases

ArrayExpress

P35226.

Bgee

P35226.

CleanEx

HS_BMI1.

Genevestigator

P35226.

GermOnline

ENSG00000168283. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Pfam

PF00097. zf-C3HC4. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P35226.

NextBio

2628.

SOURCE

Search...

Entry information

Entry name

BMI1_HUMAN

Accession

Primary (citable) accession number: P35226
Secondary accession number(s): Q16030, Q5T8Z3, Q96F37

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	August 13, 2002
Last modified:	May 29, 2013
This is version 138 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.