Q9NRD8 (DUOX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual oxidase 2
EC=1.11.1.-
EC=1.6.3.1

Alternative name(s):
Large NOX 2
Long NOX 2
NADH/NADPH thyroid oxidase p138-tox
NADPH oxidase/peroxidase DUOX2
NADPH thyroid oxidase 2
Thyroid oxidase 2
p138 thyroid oxidase

Gene names

Name:	DUOX2
Synonyms:	LNOX2, THOX2

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	1548 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	Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. Ref.7
Catalytic activity	NAD(P)H + O2 = NAD(P)+ + H2O2. Ref.11
Enzyme regulation	Peroxidase activity is inhibited by aminobenzohydrazide By similarity. The NADPH oxidase activity is calcium-dependent. Ref.11
Pathway	Hormone biosynthesis; thyroid hormone biosynthesis.
Subunit structure	Interacts with TXNDC11, TPO and CYBA. Ref.10
Subcellular location	Apical cell membrane; Multi-pass membrane protein. Note: Localizes to the apical membrane of epithelial cells. Ref.9
Tissue specificity	Expressed in colon, small intestine, duodenum and tracheal surface epithelial cells (at protein level). Expressed in thyrocytes. Also detected in kidney, liver, lung, pancreas, prostate, salivary glands, rectum and testis. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9
Developmental stage	Widely expressed in fetal tissues. Ref.2
Induction	By forskolin, thyrotropin and the Th1-specific cytokine IFNG/IFN-gamma. Ref.1 Ref.11
Post-translational modification	N-glycosylated. Ref.5
Involvement in disease	Thyroid dyshormonogenesis 6 (TDH6) [MIM:607200]: A disorder due to a defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.12 Ref.13 Ref.14
Sequence similarities	In the N-terminal section; belongs to the peroxidase family. Contains 3 EF-hand domains. Contains 1 FAD-binding FR-type domain. Contains 1 ferric oxidoreductase domain.

Ontologies

Keywords
Biological process	Hydrogen peroxide Thyroid hormones biosynthesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Congenital hypothyroidism Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium FAD Metal-binding NADP
Molecular function	Oxidoreductase Peroxidase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenohypophysis morphogenesis Inferred from electronic annotation. Source: Compara bone mineralization Inferred from electronic annotation. Source: Compara cuticle development Inferred from sequence or structural similarity. Source: UniProtKB cytokine-mediated signaling pathway Inferred from direct assay PubMed 16111680. Source: UniProtKB fertilization Inferred from electronic annotation. Source: Compara hormone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW hydrogen peroxide catabolic process Inferred from electronic annotation. Source: UniProtKB-KW inner ear development Inferred from electronic annotation. Source: Compara multicellular organism growth Inferred from electronic annotation. Source: Compara response to cAMP Inferred from direct assay PubMed 15062544. Source: UniProtKB response to virus Inferred from direct assay PubMed 16111680. Source: UniProtKB thyroid gland development Inferred from electronic annotation. Source: Compara thyroid hormone generation Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	NAD(P)H oxidase activity Inferred from direct assay Ref.11. Source: UniProtKB calcium ion binding Inferred from direct assay Ref.11. Source: UniProtKB heme binding Inferred from electronic annotation. Source: InterPro peroxidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 1548	1523	Dual oxidase 2		PRO_0000223349
Regions
	Topological domain	26 – 601	576	Extracellular Potential
	Transmembrane	602 – 622	21	Helical; Potential
	Topological domain	623 – 1041	419	Cytoplasmic Potential
	Transmembrane	1042 – 1062	21	Helical; Potential
	Topological domain	1063 – 1076	14	Extracellular Potential
	Transmembrane	1077 – 1097	21	Helical; Potential
	Topological domain	1098 – 1148	51	Cytoplasmic Potential
	Transmembrane	1149 – 1169	21	Helical; Potential
	Topological domain	1170 – 1185	16	Extracellular Potential
	Transmembrane	1186 – 1206	21	Helical; Potential
	Topological domain	1207 – 1223	17	Cytoplasmic Potential
	Transmembrane	1224 – 1244	21	Helical; Potential
	Transmembrane	1245 – 1265	21	Helical; Potential
	Topological domain	1266 – 1548	283	Cytoplasmic Potential
	Domain	819 – 854	36	EF-hand 1
	Domain	855 – 890	36	EF-hand 2
	Domain	899 – 934	36	EF-hand 3
	Domain	1084 – 1266	183	Ferric oxidoreductase
	Domain	1267 – 1373	107	FAD-binding FR-type
	Calcium binding	832 – 843	12	1 Potential
	Calcium binding	868 – 879	12	2 Potential
	Region	30 – 596	567	Peroxidase-like; mediates peroxidase activity By similarity
	Region	960 – 1245	286	Interaction with TXNDC11 By similarity
Amino acid modifications
	Glycosylation	100	1	N-linked (GlcNAc...) Potential
	Glycosylation	348	1	N-linked (GlcNAc...) Potential
	Glycosylation	382	1	N-linked (GlcNAc...) Potential
	Glycosylation	455	1	N-linked (GlcNAc...) Potential
	Glycosylation	537	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	36	1	Q → H in TDH6. Ref.13		VAR_025323
	Natural variant	138	1	P → L. Ref.2 Corresponds to variant rs2001616 [ dbSNP | Ensembl ].		VAR_025324
	Natural variant	376	1	R → W in TDH6. Ref.12		VAR_025325
	Natural variant	678	1	H → R. Corresponds to variant rs57659670 [ dbSNP | Ensembl ].		VAR_061177
	Natural variant	1067	1	S → L. Ref.1 Ref.2 Ref.4 Corresponds to variant rs269868 [ dbSNP | Ensembl ].		VAR_047075
	Natural variant	1518	1	G → S in TDH6; the enzyme is non-functional; expressed at the cell surface of cells albeit at low level. Ref.14		VAR_064619
Experimental info
	Sequence conflict	25	1	N → S in AAF73922. Ref.1
	Sequence conflict	25	1	N → S in AAF78954. Ref.2
	Sequence conflict	984	1	A → V in AAF78954. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9NRD8 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 7BAA2350EC0A2A7E	FASTA	1,548	175,364
	10 20 30 40 50 60 MLRARPEALM LLGALLTGSL GPSGNQDALS LPWEVQRYDG WFNNLRHHER GAVGCRLQRR 70 80 90 100 110 120 VPANYADGVY QALEEPQLPN PRRLSNAATR GIAGLPSLHN RTVLGVFFGY HVLSDVVSVE 130 140 150 160 170 180 TPGCPAEFLN IRIPPGDPVF DPDQRGDVVL PFQRSRWDPE TGRSPSNPRD LANQVTGWLD 190 200 210 220 230 240 GSAIYGSSHS WSDALRSFSG GQLASGPDPA FPRDSQNPLL MWAAPDPATG QNGPRGLYAF 250 260 270 280 290 300 GAERGNREPF LQALGLLWFR YHNLWAQRLA RQHPDWEDEE LFQHARKRVI ATYQNIAVYE 310 320 330 340 350 360 WLPSFLQKTL PEYTGYRPFL DPSISPEFVV ASEQFFSTMV PPGVYMRNAS CHFRKVLNKG 370 380 390 400 410 420 FQSSQALRVC NNYWIRENPN LNSTQEVNEL LLGMASQISE LEDNIVVEDL RDYWPGPGKF 430 440 450 460 470 480 SRTDYVASSI QRGRDMGLPS YSQALLAFGL DIPRNWSDLN PNVDPQVLEA TAALYNQDLS 490 500 510 520 530 540 QLELLLGGLL ESHGDPGPLF SAIVLDQFVR LRDGDRYWFE NTRNGLFSKK EIEDIRNTTL 550 560 570 580 590 600 RDVLVAVINI DPSALQPNVF VWHKGAPCPQ PKQLTTDGLP QCAPLTVLDF FEGSSPGFAI 610 620 630 640 650 660 TIIALCCLPL VSLLLSGVVA YFRGREHKKL QKKLKESVKK EAAKDGVPAM EWPGPKERSS 670 680 690 700 710 720 PIIIQLLSDR CLQVLNRHLT VLRVVQLQPL QQVNLILSNN RGCRTLLLKI PKEYDLVLLF 730 740 750 760 770 780 SSEEERGAFV QQLWDFCVRW ALGLHVAEMS EKELFRKAVT KQQRERILEI FFRHLFAQVL 790 800 810 820 830 840 DINQADAGTL PLDSSQKVRE ALTCELSRAE FAESLGLKPQ DMFVESMFSL ADKDGNGYLS 850 860 870 880 890 900 FREFLDILVV FMKGSPEDKS RLMFTMYDLD ENGFLSKDEF FTMMRSFIEI SNNCLSKAQL 910 920 930 940 950 960 AEVVESMFRE SGFQDKEELT WEDFHFMLRD HDSELRFTQL CVKGGGGGGN GIRDIFKQNI 970 980 990 1000 1010 1020 SCRVSFITRT PGERSHPQGL GPPAPEAPEL GGPGLKKRFG KKAAVPTPRL YTEALQEKMQ 1030 1040 1050 1060 1070 1080 RGFLAQKLQQ YKRFVENYRR HIVCVAIFSA ICVGVFADRA YYYGFASPPS DIAQTTLVGI 1090 1100 1110 1120 1130 1140 ILSRGTAASV SFMFSYILLT MCRNLITFLR ETFLNRYVPF DAAVDFHRWI AMAAVVLAIL 1150 1160 1170 1180 1190 1200 HSAGHAVNVY IFSVSPLSLL ACIFPNVFVN DGSKLPQKFY WWFFQTVPGM TGVLLLLVLA 1210 1220 1230 1240 1250 1260 IMYVFASHHF RRRSFRGFWL THHLYILLYA LLIIHGSYAL IQLPTFHIYF LVPAIIYGGD 1270 1280 1290 1300 1310 1320 KLVSLSRKKV EISVVKAELL PSGVTYLQFQ RPQGFEYKSG QWVRIACLAL GTTEYHPFTL 1330 1340 1350 1360 1370 1380 TSAPHEDTLS LHIRAVGPWT TRLREIYSSP KGNGCAGYPK LYLDGPFGEG HQEWHKFEVS 1390 1400 1410 1420 1430 1440 VLVGGGIGVT PFASILKDLV FKSSLGSQML CKKIYFIWVT RTQRQFEWLA DIIQEVEEND 1450 1460 1470 1480 1490 1500 HQDLVSVHIY VTQLAEKFDL RTTMLYICER HFQKVLNRSL FTGLRSITHF GRPPFEPFFN 1510 1520 1530 1540 SLQEVHPQVR KIGVFSCGPP GMTKNVEKAC QLVNRQDRAH FMHHYENF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family." De Deken X., Wang D., Many M.-C., Costagliola S., Libert F., Vassart G., Dumont J.E., Miot F. J. Biol. Chem. 275:23227-23233(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, TISSUE SPECIFICITY, VARIANT LEU-1067. Tissue: Thyroid.
[2]	"Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox." Edens W.A., Sharling L., Cheng G., Shapira R., Kinkade J.M., Lee T., Edens H.A., Tang X., Sullards C., Flaherty D.B., Benian G.M., Lambeth J.D. J. Cell Biol. 154:879-891(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-138 AND LEU-1067, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY. Tissue: Pancreas and Thyroid.
[3]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cDNAs." Dupuy C., Ohayon R., Valent A., Noel-Hudson M.-S., Deme D., Virion A. J. Biol. Chem. 274:37265-37269(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 339-1548, VARIANT LEU-1067. Tissue: Thyroid.
[5]	"Characterization of ThOX proteins as components of the thyroid H(2)O(2)-generating system." De Deken X., Wang D., Dumont J.E., Miot F. Exp. Cell Res. 273:187-196(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION.
[6]	"Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism." Moreno J.C., Bikker H., Kempers M.J.E., van Trotsenburg A.S., Baas F., de Vijlder J.J.M., Vulsma T., Ris-Stalpers C. N. Engl. J. Med. 347:95-102(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN TDH6.
[7]	"Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense." Geiszt M., Witta J., Baffi J., Lekstrom K., Leto T.L. FASEB J. 17:1502-1504(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]	"NADPH oxidase-dependent acid production in airway epithelial cells." Schwarzer C., Machen T.E., Illek B., Fischer H. J. Biol. Chem. 279:36454-36461(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Dual oxidase2 is expressed all along the digestive tract." Ameziane-El-Hassani R., Benfares N., Caillou B., Talbot M., Sabourin J.-C., Belotte V., Morand S., Gnidehou S., Agnandji D., Ohayon R., Kaniewski J., Noel-Hudson M.-S., Bidart J.-M., Schlumberger M., Virion A., Dupuy C. Am. J. Physiol. 288:G933-G942(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]	"Identification of a novel partner of duox: EFP1, a thioredoxin-related protein." Wang D., De Deken X., Milenkovic M., Song Y., Pirson I., Dumont J.E., Miot F. J. Biol. Chem. 280:3096-3103(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TXNDC11; TPO AND CYBA.
[11]	"Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity." Ameziane-El-Hassani R., Morand S., Boucher J.L., Frapart Y.-M., Apostolou D., Agnandji D., Gnidehou S., Ohayon R., Noel-Hudson M.-S., Francon J., Lalaoui K., Virion A., Dupuy C. J. Biol. Chem. 280:30046-30054(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION.
[12]	"Persistent mild hypothyroidism associated with novel sequence variants of the DUOX2 gene in two siblings." Vigone M.C., Fugazzola L., Zamproni I., Passoni A., Di Candia S., Chiumello G., Persani L., Weber G. Hum. Mutat. 26:395-395(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TDH6 TRP-376.
[13]	"Three mutations (p.Q36H, p.G418fsX482, and g.IVS19-2A-->C) in the dual oxidase 2 gene responsible for congenital goiter and iodide organification defect." Varela V., Rivolta C.M., Esperante S.A., Gruneiro-Papendieck L., Chiesa A., Targovnik H.M. Clin. Chem. 52:182-191(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TDH6 HIS-36.
[14]	"Compound heterozygosity for a novel hemizygous missense mutation and a partial deletion affecting the catalytic core of the H2O2-generating enzyme DUOX2 associated with transient congenital hypothyroidism." Hoste C., Rigutto S., Van Vliet G., Miot F., De Deken X. Hum. Mutat. 31:E1304-E1319(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TDH6 SER-1518, CHARACTERIZATION OF VARIANT TDH6 SER-1518.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF230496 mRNA. Translation: AAF73922.1. AF267981 mRNA. Translation: AAF78954.1. AC091117 Genomic DNA. No translation available. AF181972 mRNA. Translation: AAF20055.1.
IPI	IPI00299627.
RefSeq	NP_054799.4. NM_014080.4.
UniGene	Hs.71377.
3D structure databases
ProteinModelPortal	Q9NRD8.
SMR	Q9NRD8. Positions 43-540, 814-928.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000267837.
Protein family/group databases
PeroxiBase	3338. HsDuOx02.
TCDB	5.B.1.2.2. phagocyte (gp91phox) NADPH oxidase family.
PTM databases
PhosphoSite	Q9NRD8.
Polymorphism databases
DMDM	296434485.
Proteomic databases
PaxDb	Q9NRD8.
PRIDE	Q9NRD8.
Protocols and materials databases
DNASU	50506.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000389039; ENSP00000373691; ENSG00000140279.
GeneID	50506.
KEGG	hsa:50506.
UCSC	uc001zun.3. human.
Organism-specific databases
CTD	50506.
GeneCards	GC15M045384.
H-InvDB	HIX0038086.
HGNC	HGNC:13273. DUOX2.
MIM	606759. gene. 607200. phenotype.
neXtProt	NX_Q9NRD8.
Orphanet	95716. Familial thyroid dyshormonogenesis. 226316. Genetic transient congenital hypothyroidism.
PharmGKB	PA27517.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG287712.
HOGENOM	HOG000231774.
HOVERGEN	HBG080428.
KO	K13411.
OMA	PNVDPQV.
PhylomeDB	Q9NRD8.
Enzyme and pathway databases
BRENDA	1.6.3.1. 2681.
SABIO-RK	Q9NRD8.
UniPathway	UPA00194.
Gene expression databases
Bgee	Q9NRD8.
CleanEx	HS_DUOX2.
Genevestigator	Q9NRD8.
GermOnline	ENSG00000140279. Homo sapiens.
Family and domain databases
Gene3D	1.10.238.10. 1 hit. 1.10.640.10. 1 hit.
InterPro	IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR002048. EF_hand_dom. IPR013112. FAD-bd_8. IPR017927. Fd_Rdtase_FAD-bd. IPR013130. Fe3_Rdtase_TM_dom. IPR013121. Fe_red_NAD-bd_6. IPR010255. Haem_peroxidase. IPR002007. Haem_peroxidase_animal. IPR019791. Haem_peroxidase_animal_subgr. IPR017938. Riboflavin_synthase-like_b-brl. [Graphical view]
Pfam	PF03098. An_peroxidase. 1 hit. PF13499. EF_hand_5. 1 hit. PF08022. FAD_binding_8. 1 hit. PF01794. Ferric_reduct. 1 hit. PF08030. NAD_binding_6. 1 hit. [Graphical view]
PRINTS	PR00457. ANPEROXIDASE.
SMART	SM00054. EFh. 2 hits. [Graphical view]
SUPFAM	SSF48113. Peroxidase_super. 1 hit. SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.
PROSITE	PS00018. EF_HAND_1. 2 hits. PS50222. EF_HAND_2. 3 hits. PS51384. FAD_FR. 1 hit. PS50292. PEROXIDASE_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL3293.
ChiTaRS	DUOX2. human.
GenomeRNAi	50506.
NextBio	53066.
SOURCE	Search...

Entry information

Entry name

DUOX2_HUMAN

Accession

Primary (citable) accession number: Q9NRD8
Secondary accession number(s): A8MQ13, Q9NR02, Q9UHF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2006
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 104 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.