Q9HCN6 (GPVI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Platelet glycoprotein VI
Short name=GPVI

Alternative name(s):
Glycoprotein 6

Gene names

Name:

GP6

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	339 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	Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma-chain, the Src kinases (likely Fyn/Lyn), the adapter protein LAT and leads to the activation of phospholipase C gamma2. Ref.2
Subunit structure	Associated with Fc receptor gamma chain. The GPVI-FcRgamma complex is associated with the Src kinase family Fyn and Lyn.
Subcellular location	Isoform 1: Cell membrane; Single-pass membrane protein. Isoform 2: Cell membrane; Single-pass membrane protein.
Tissue specificity	Megakaryocytes and platelets. Ref.2
Post-translational modification	N-linked glycosylation at Asn-92 is not required for the cell surface expression, but contributes to maximal adhesion to type I collagen, collagen-related peptide (CRP), and, to a lesser extent, to the snake venom C-type lectin convulxin (CVX).
Involvement in disease	Bleeding disorder, platelet-type 11 (BDPLT11) [MIM:614201]: A mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11
Sequence similarities	Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Biological process	Blood coagulation Hemostasis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	enzyme linked receptor protein signaling pathway Traceable author statement PubMed 9153205. Source: ProtInc leukocyte migration Traceable author statement. Source: Reactome platelet activation Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to plasma membrane Traceable author statement PubMed 10822077. Source: ProtInc
Molecular_function	collagen binding Traceable author statement Ref.1. Source: UniProtKB transmembrane signaling receptor activity Traceable author statement PubMed 10822077. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LYN	P07948	2	EBI-515278,EBI-79452

Alternative products

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

Isoform 1 (identifier: Q9HCN6-1)

Also known as: VI-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: Q9HCN6-2)

Also known as: VI-2;

The sequence of this isoform differs from the canonical sequence as follows:
     204-221: Missing.

Isoform 3 (identifier: Q9HCN6-3)

Also known as: VI-3;

The sequence of this isoform differs from the canonical sequence as follows:
     260-339: PARQYYTKGN...QDVHSRGLCS → ESCPPVLHQG...TGMNMSITLI

Note: Has no transmembrane domain. Does not interact with Fc receptor gamma chain. Does not bind to collagen-like peptides.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 339

319

Platelet glycoprotein VI

PRO_0000232383

Regions

Topological domain

21 – 267

247

Extracellular Potential

Transmembrane

268 – 288

21

Helical; Potential

Topological domain

289 – 339

51

Cytoplasmic Potential

Domain

26 – 104

79

Ig-like C2-type 1

Domain

114 – 196

83

Ig-like C2-type 2

Amino acid modifications

Glycosylation

92

1

N-linked (GlcNAc...) Ref.7

Disulfide bond

48 ↔ 88

Ref.9

Disulfide bond

134 ↔ 180

Ref.9

Natural variations

Alternative sequence

204 – 221

18

Missing in isoform 2.

VSP_017879

Alternative sequence

260 – 339

80

PARQY…RGLCS → ESCPPVLHQGQPGPDMPRGC DPNNPGGVSGRGLAQPEEAP AAQGQGCAEAASAPPAPPAD PEIKRGSGWRPTGCSQPRVM FMTAEPQARSYPREGSWHGR RLKDWRVWSVEAGGQRLQLW KRGHAASSWCSIREPFGQCL SVCLPLCLRAPSIWDGRNLW RPHPPPCTLWMTWYPGWTTY WPLSSTSLIWAPDGSLRFPA LRVDSVPSSVQNPPVLPFGP LCSCLVFPRNSHPHSISHCG LTNLLSSLRTGLAGSLGMSF IFLSVKLARCPLPFTLENKI SLCNMVKPHLYQQNKKTQKL ARCGGASLYSQQLRGLRWEN GLSLGGRGCSELRSHHCTLA RVTKPDFVSKNTGMNMSITL I in isoform 3.

VSP_017880

Natural variant

58

1

R → C in BDPLT11; results in abnormal protein migration and a loss of collagen binding. Ref.10

VAR_066590

Natural variant

175

1

S → N in BDPLT11; shows strongly reduced membrane expression and decreased interaction with the snake toxin convulxin. Ref.11

VAR_066591

Natural variant

219

1

P → S. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1613662 [ dbSNP | Ensembl ].

VAR_060352

Natural variant

237

1

E → K. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1654416 [ dbSNP | Ensembl ].

VAR_060353

Natural variant

249

1

A → T. Ref.1 Ref.3 Ref.5
Corresponds to variant rs2304167 [ dbSNP | Ensembl ].

VAR_060354

Natural variant

317

1

L → Q. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1654413 [ dbSNP | Ensembl ].

VAR_059389

Natural variant

322

1

N → H. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1671152 [ dbSNP | Ensembl ].

VAR_059390

Natural variant

335

1

R → G.
Corresponds to variant rs1654412 [ dbSNP | Ensembl ].

VAR_060355

Experimental info

Mutagenesis

61

1

K → A: Increases collagen binding. Ref.8

Mutagenesis

79

1

K → E: Dramatically reduces collagen binding. Ref.8

Mutagenesis

80

1

R → A: Reduces collagen binding. Ref.8

Mutagenesis

92

1

N → A: Reduces collagen binding (65 to 70%). Ref.7

Mutagenesis

94

1

S → A: Reduces collagen binding (65 to 70%). Ref.7

Mutagenesis

95

1

L → H: No effect on collagen binding. Ref.7

Mutagenesis

186

1

R → A: Reduces collagen binding. Ref.8

Isoform 3:

Sequence conflict

314

1

P → A in BAB12247. Ref.1

Sequence conflict

323

1

K → T in BAB12247. Ref.1

Sequence conflict

573

1

R → G in BAB12247. Ref.1

Sequence conflict

606

1

F → L in BAB12247. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

339

Helix Strand Turn

Details...

Beta strand

29 – 34

6

Beta strand

36 – 39

4

Beta strand

44 – 49

6

Beta strand

55 – 61

7

Turn

62 – 64

3

Beta strand

67 – 77

11

Helix

80 – 82

3

Beta strand

84 – 92

9

Beta strand

95 – 97

3

Beta strand

103 – 111

9

Beta strand

115 – 119

5

Beta strand

130 – 135

6

Beta strand

142 – 147

6

Beta strand

159 – 170

12

Beta strand

175 – 183

9

Beta strand

198 – 202

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (VI-1) [UniParc]. Last modified April 5, 2011. Version 4. Checksum: 3EFE2DD0E1676BA8	FASTA	339	36,866
	10 20 30 40 50 60 MSPSPTALFC LGLCLGRVPA QSGPLPKPSL QALPSSLVPL EKPVTLRCQG PPGVDLYRLE 70 80 90 100 110 120 KLSSSRYQDQ AVLFIPAMKR SLAGRYRCSY QNGSLWSLPS DQLELVATGV FAKPSLSAQP 130 140 150 160 170 180 GPAVSSGGDV TLQCQTRYGF DQFALYKEGD PAPYKNPERW YRASFPIITV TAAHSGTYRC 190 200 210 220 230 240 YSFSSRDPYL WSAPSDPLEL VVTGTSVTPS RLPTEPPSPV AEFSEATAEL TVSFTNEVFT 250 260 270 280 290 300 TETSRSITAS PKESDSPAGP ARQYYTKGNL VRICLGAVIL IILAGFLAED WHSRRKRLRH 310 320 330 RGRAVQRPLP PLPPLPLTRK SNGGQDGGRQ DVHSRGLCS
	Isoform 2 (VI-2) [UniParc]. Checksum: EEE281373112DB21	FASTA	321	35,091
	10 20 30 40 50 60 MSPSPTALFC LGLCLGRVPA QSGPLPKPSL QALPSSLVPL EKPVTLRCQG PPGVDLYRLE 70 80 90 100 110 120 KLSSSRYQDQ AVLFIPAMKR SLAGRYRCSY QNGSLWSLPS DQLELVATGV FAKPSLSAQP 130 140 150 160 170 180 GPAVSSGGDV TLQCQTRYGF DQFALYKEGD PAPYKNPERW YRASFPIITV TAAHSGTYRC 190 200 210 220 230 240 YSFSSRDPYL WSAPSDPLEL VVTEFSEATA ELTVSFTNEV FTTETSRSIT ASPKESDSPA 250 260 270 280 290 300 GPARQYYTKG NLVRICLGAV ILIILAGFLA EDWHSRRKRL RHRGRAVQRP LPPLPPLPLT 310 320 RKSNGGQDGG RQDVHSRGLC S
	Isoform 3 (VI-3) [UniParc]. Checksum: F6DBAE2547664D7A	FASTA	620	67,476
	10 20 30 40 50 60 MSPSPTALFC LGLCLGRVPA QSGPLPKPSL QALPSSLVPL EKPVTLRCQG PPGVDLYRLE 70 80 90 100 110 120 KLSSSRYQDQ AVLFIPAMKR SLAGRYRCSY QNGSLWSLPS DQLELVATGV FAKPSLSAQP 130 140 150 160 170 180 GPAVSSGGDV TLQCQTRYGF DQFALYKEGD PAPYKNPERW YRASFPIITV TAAHSGTYRC 190 200 210 220 230 240 YSFSSRDPYL WSAPSDPLEL VVTGTSVTPS RLPTEPPSPV AEFSEATAEL TVSFTNEVFT 250 260 270 280 290 300 TETSRSITAS PKESDSPAGE SCPPVLHQGQ PGPDMPRGCD PNNPGGVSGR GLAQPEEAPA 310 320 330 340 350 360 AQGQGCAEAA SAPPAPPADP EIKRGSGWRP TGCSQPRVMF MTAEPQARSY PREGSWHGRR 370 380 390 400 410 420 LKDWRVWSVE AGGQRLQLWK RGHAASSWCS IREPFGQCLS VCLPLCLRAP SIWDGRNLWR 430 440 450 460 470 480 PHPPPCTLWM TWYPGWTTYW PLSSTSLIWA PDGSLRFPAL RVDSVPSSVQ NPPVLPFGPL 490 500 510 520 530 540 CSCLVFPRNS HPHSISHCGL TNLLSSLRTG LAGSLGMSFI FLSVKLARCP LPFTLENKIS 550 560 570 580 590 600 LCNMVKPHLY QQNKKTQKLA RCGGASLYSQ QLRGLRWENG LSLGGRGCSE LRSHHCTLAR 610 620 VTKPDFVSKN TGMNMSITLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, genomic structure, chromosomal localization, and alternative splice forms of the platelet collagen receptor glycoprotein VI." Ezumi Y., Uchiyama T., Takayama H. Biochem. Biophys. Res. Commun. 277:27-36(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), PROTEIN SEQUENCE OF 28-41; 62-79 AND 114-142, VARIANTS SER-219; LYS-237; THR-249; GLN-317 AND HIS-322.
[2]	"Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily." Jandrot-Perrus M., Busfield S., Lagrue A.-H., Xiong X., Debili N., Chickering T., Le Couedic J.-P., Goodearl A., Dussault B., Fraser C., Vainchenker W., Villeval J.-L. Blood 96:1798-1807(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH FC RECEPTOR GAMMA CHAIN, TISSUE SPECIFICITY. Tissue: Megakaryocyte.
[3]	"Platelet glycoprotein VI." Miura Y. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS SER-219; LYS-237; THR-249; GLN-317 AND HIS-322.
[4]	"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].
[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] (ISOFORM 1), VARIANTS SER-219; LYS-237; THR-249; GLN-317 AND HIS-322.
[6]	"A novel association of Fc receptor gamma-chain with glycoprotein VI and their co-expression as a collagen receptor in human platelets." Tsuji M., Ezumi Y., Arai M., Takayama H. J. Biol. Chem. 272:23528-23531(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FC RECEPTOR GAMMA CHAIN.
[7]	"The influence of N-linked glycosylation on the function of platelet glycoprotein VI." Kunicki T.J., Cheli Y., Moroi M., Furihata K. Blood 106:2744-2749(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-92, MUTAGENESIS OF ASN-92; SER-94 AND LEU-95.
[8]	"Gain- and loss-of-function mutants confirm the importance of apical residues to the primary interaction of human glycoprotein VI with collagen." O'connor M.N., Smethurst P.A., Farndale R.W., Ouwehand W.H. J. Thromb. Haemost. 4:869-873(2006) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-61; LYS-79; ARG-80 AND ARG-186.
[9]	"Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI." Horii K., Kahn M.L., Herr A.B. Blood 108:936-942(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 21-203, DISULFIDE BONDS.
[10]	"Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations." Dumont B., Lasne D., Rothschild C., Bouabdelli M., Ollivier V., Oudin C., Ajzenberg N., Grandchamp B., Jandrot-Perrus M. Blood 114:1900-1903(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BDPLT11 CYS-58, CHARACTERIZATION OF VARIANT BDPLT11 CYS-58.
[11]	"A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder." Hermans C., Wittevrongel C., Thys C., Smethurst P.A., Van Geet C., Freson K. J. Thromb. Haemost. 7:1356-1363(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BDPLT11 ASN-175, CHARACTERIZATION OF VARIANT BDPLT11 ASN-175.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB043819 mRNA. Translation: BAB12245.1.
AB043820 mRNA. Translation: BAB12246.1.
AB043821 mRNA. Translation: BAB12247.1.
AB035073 mRNA. Translation: BAA89353.1.
AC011476 Genomic DNA. No translation available.
BC104832 mRNA. Translation: AAI04833.1.
BC111963 mRNA. Translation: AAI11964.1.

IPI

IPI00102300.
IPI00163074.
IPI00737479.

PIR

JC7509.

RefSeq

NP_001242946.1. NM_001256017.1.
NP_057447.4. NM_016363.4.

UniGene

Hs.661752.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GI7	X-ray	2.40	A/B	21-203	[»]

ProteinModelPortal

Q9HCN6.

SMR

Q9HCN6. Positions 22-261.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33875N.

IntAct

Q9HCN6. 4 interactions.

MINT

MINT-258007.

STRING

9606.ENSP00000308782.

Protein family/group databases

MEROPS

I43.001.

PTM databases

PhosphoSite

Q9HCN6.

Polymorphism databases

DMDM

91206792.

Proteomic databases

PaxDb

Q9HCN6.

PRIDE

Q9HCN6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000310373; ENSP00000308782; ENSG00000088053.
ENST00000333884; ENSP00000334552; ENSG00000088053.
ENST00000417454; ENSP00000394922; ENSG00000088053.
ENST00000570488; ENSP00000461307; ENSG00000262239.
ENST00000570691; ENSP00000459479; ENSG00000262069.
ENST00000571038; ENSP00000460456; ENSG00000262729.
ENST00000571040; ENSP00000459136; ENSG00000262797.
ENST00000571499; ENSP00000461350; ENSG00000262069.
ENST00000571588; ENSP00000459854; ENSG00000261961.
ENST00000571788; ENSP00000460120; ENSG00000262729.
ENST00000571871; ENSP00000458353; ENSG00000262239.
ENST00000572462; ENSP00000461591; ENSG00000262867.
ENST00000572481; ENSP00000458990; ENSG00000261961.
ENST00000572667; ENSP00000461472; ENSG00000262131.
ENST00000572758; ENSP00000461769; ENSG00000263239.
ENST00000572791; ENSP00000461893; ENSG00000262797.
ENST00000573240; ENSP00000459929; ENSG00000262729.
ENST00000573444; ENSP00000459377; ENSG00000263239.
ENST00000573560; ENSP00000458588; ENSG00000261961.
ENST00000573764; ENSP00000460988; ENSG00000262069.
ENST00000573811; ENSP00000461262; ENSG00000262797.
ENST00000574117; ENSP00000461858; ENSG00000262131.
ENST00000574603; ENSP00000460778; ENSG00000263239.
ENST00000575496; ENSP00000458876; ENSG00000262239.
ENST00000575642; ENSP00000458153; ENSG00000262131.
ENST00000575740; ENSP00000458526; ENSG00000262867.
ENST00000576196; ENSP00000459588; ENSG00000262867.

GeneID

51206.

KEGG

hsa:51206.

UCSC

uc002qik.3. human.
uc002qil.3. human.
uc010esq.3. human.

Organism-specific databases

CTD

51206.

GeneCards

GC19M055525.

HGNC

HGNC:14388. GP6.

MIM

605546. gene.
614201. phenotype.

neXtProt

NX_Q9HCN6.

Orphanet

98885. Bleeding diathesis due to glycoprotein VI deficiency.

PharmGKB

PA28824.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG79029.

HOGENOM

HOG000234395.

HOVERGEN

HBG074353.

KO

K06264.

OMA

YPGWTTY.

Enzyme and pathway databases

Reactome

REACT_604. Hemostasis.

Gene expression databases

Bgee

Q9HCN6.

CleanEx

HS_GP6.

Genevestigator

Q9HCN6.

GermOnline

ENSG00000088053. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 2 hits.

InterPro

IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]

SMART

SM00409. IG. 2 hits.
[Graphical view]

PROSITE

PS50835. IG_LIKE. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9HCN6.

GenomeRNAi

51206.

NextBio

54258.

SOURCE

Search...

Entry information

Entry name

GPVI_HUMAN

Accession

Primary (citable) accession number: Q9HCN6
Secondary accession number(s): Q9HCN7, Q9UIF2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 4, 2006
Last sequence update:	April 5, 2011
Last modified:	May 1, 2013
This is version 101 of the entry and version 4 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.