Q99519 (NEUR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sialidase-1
EC=3.2.1.18

Alternative name(s):
Acetylneuraminyl hydrolase
G9 sialidase
Lysosomal sialidase
N-acetyl-alpha-neuraminidase 1

Gene names

Name:	NEU1
Synonyms:	NANH

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	415 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	Catalyzes the removal of sialic acid (N-acetylneuramic acid) moities from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.
Catalytic activity	Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.
Subunit structure	Interacts with cathepsin A (protective protein), beta-galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a multienzyme complex.
Subcellular location	Lysosome membrane; Peripheral membrane protein; Lumenal side. Lysosome lumen. Cell membrane. Cytoplasmic vesicle. Note: Localized not only on the inner side of the lysosomal membrane and in the lysosomal lumen, but also on the plasma membrane and in intracellular vesicles. Ref.9
Tissue specificity	Highly expressed in pancreas, followed by skeletal muscle, kidney, placenta, heart, lung and liver. Weakly expressed in brain.
Domain	A C-terminal internalization signal (YGTL) appears to allow the targeting of plasma membrane proteins to endosomes.
Post-translational modification	N-glycosylated. Ref.8 Phosphorylation of tyrosine within the internalization signal results in inhibition of sialidase internalization and blockage on the plasma membrane.
Involvement in disease	Sialidosis (SIALIDOSIS) [MIM:256550]: Lysosomal storage disease occurring as two types with various manifestations. Type 1 sialidosis (cherry red spot-myoclonus syndrome or normosomatic type) is late-onset and it is characterized by the formation of cherry red macular spots in childhood, progressive debilitating myoclonus, insiduous visual loss and rarely ataxia. The diagnosis can be confirmed by the screening of the urine for sialyloligosaccharides. Type 2 sialidosis (also known as dysmorphic type) occurs as several variants of increasing severity with earlier age of onset. It is characterized by the presence of abnormal somatic features including coarse facies and dysostosis multiplex, vertebral deformities, mental retardation, cherry-red spot/myoclonus, sialuria, cytoplasmic vacuolation of peripheral lymphocytes, bone marrow cells and conjunctival epithelial cells. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.3 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Sequence similarities	Belongs to the glycosyl hydrolase 33 family. Contains 4 BNR repeats.
Biophysicochemical properties	pH dependence: Optimum pH is 4.6.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasmic vesicle Lysosome Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Signal
Molecular function	Glycosidase Hydrolase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	glycosphingolipid metabolic process Traceable author statement. Source: Reactome phospholipid metabolic process Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cell junction Inferred from direct assay. Source: HPA cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal lumen Traceable author statement. Source: Reactome lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	exo-alpha-(2->3)-sialidase activity Inferred from electronic annotation. Source: EC exo-alpha-(2->6)-sialidase activity Inferred from electronic annotation. Source: EC exo-alpha-(2->8)-sialidase activity Inferred from electronic annotation. Source: EC exo-alpha-sialidase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 47	47	Ref.8
	Chain	48 – 415	368	Sialidase-1		PRO_0000012026
Regions
	Repeat	112 – 123	12	BNR 1
	Repeat	172 – 183	12	BNR 2
	Repeat	231 – 242	12	BNR 3
	Repeat	347 – 358	12	BNR 4
	Motif	77 – 80	4	FRIP motif
	Motif	412 – 415	4	Internalization signal
Sites
	Active site	103	1	Proton acceptor By similarity
	Active site	370	1	Nucleophile By similarity
	Active site	394	1	Potential
	Binding site	78	1	Substrate By similarity
	Binding site	280	1	Substrate By similarity
	Binding site	341	1	Substrate By similarity
Amino acid modifications
	Glycosylation	186	1	N-linked (GlcNAc...) Potential
	Glycosylation	343	1	N-linked (GlcNAc...) Potential
	Glycosylation	352	1	N-linked (GlcNAc...) Ref.10
Natural variations
	Natural variant	54	1	V → M in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable. Ref.13		VAR_012207
	Natural variant	68	1	G → V in SIALIDOSIS; type 2; less than 10% of activity. Ref.12 Ref.13 Ref.15		VAR_012208
	Natural variant	80	1	P → L in SIALIDOSIS; type 2; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes. Ref.16		VAR_017460
	Natural variant	88	1	G → A. Corresponds to variant rs34712643 [ dbSNP | Ensembl ].		VAR_049203
	Natural variant	91	1	L → R in SIALIDOSIS; type 2. Ref.1 Ref.13		VAR_012209
	Natural variant	182	1	S → G in SIALIDOSIS; type 1; normally processed. Ref.12 Ref.13 Ref.15		VAR_012210
	Natural variant	217	1	V → M in SIALIDOSIS; type 1; partial transport and residual transport activity. Ref.14 Corresponds to variant rs28940583 [ dbSNP | Ensembl ].		VAR_012211
	Natural variant	219	1	G → A in SIALIDOSIS; type 1; unable to reach the lysosomes. Ref.13		VAR_012212
	Natural variant	225	1	R → P in SIALIDOSIS; type 2; impaired enzyme folding. Ref.17 Corresponds to variant rs28940584 [ dbSNP | Ensembl ].		VAR_018076
	Natural variant	227	1	G → R in SIALIDOSIS; type 1 and juvenile type 2; catalytically inactive; retained in pre-lysosomal compartments. Ref.12 Ref.13 Ref.15		VAR_012213
	Natural variant	231	1	L → H in SIALIDOSIS; type 1; unable to reach the lysosomes. Ref.13		VAR_012214
	Natural variant	240	1	W → R in SIALIDOSIS; type 2; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes. Ref.15 Ref.16		VAR_012215
	Natural variant	243	1	G → R in SIALIDOSIS; type 1; no enzyme activity and no transport to the lysosome. Ref.14		VAR_012216
	Natural variant	260	1	F → Y in SIALIDOSIS; infantile type 2; catalytically inactive; rapid intralysosomal degradation. Ref.3 Ref.12 Ref.13 Ref.15		VAR_012217
	Natural variant	270	1	L → F in SIALIDOSIS; type 2; reduction in enzyme activity; rapid intralysosomal degradation. Ref.12 Ref.15		VAR_012219
	Natural variant	270	1	L → P in SIALIDOSIS. Ref.13		VAR_012218
	Natural variant	294	1	R → S in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable. Ref.13		VAR_012220
	Natural variant	298	1	A → V in SIALIDOSIS; type 2; less than 10% of activity; rapid intralysosomal degradation; impaired enzyme folding. Ref.12 Ref.13 Ref.15 Ref.17		VAR_012221
	Natural variant	316	1	P → S in SIALIDOSIS; type 1; no enzyme activity; retained in the endoplasmic reticulum / Golgi or rapidly degraded in the lysosomes. Ref.16		VAR_017461
	Natural variant	328	1	G → S in SIALIDOSIS; type 1; reduction in enzyme activity. Ref.12 Ref.13 Ref.15		VAR_012222
	Natural variant	335	1	P → Q in SIALIDOSIS; type 2; unable to reach the lysosomes. Ref.13		VAR_012223
	Natural variant	341	1	R → G in SIALIDOSIS; type 2; affects substrate binding or catalysis. Ref.17		VAR_018077
	Natural variant	363	1	L → P in SIALIDOSIS; infantile type 2; unable to reach the lysosomes. Ref.3 Ref.12 Ref.13 Ref.15		VAR_012224
	Natural variant	370	1	Y → C in SIALIDOSIS; infantile type 2; catalytically inactive. Ref.13		VAR_012225
	Natural variant	400	1	Y → YHY in SIALIDOSIS; type 1; mild mutation as residual activity is still measurable.		VAR_012226
Experimental info
	Mutagenesis	412	1	Y → A: Correct sorting to the plasma membrane but no endocytosis and internalization. Ref.9
	Mutagenesis	413	1	G → A: Correct sorting to the plasma membrane but no endocytosis and internalization. Ref.9
	Mutagenesis	415	1	L → A: Correct sorting to the plasma membrane but no endocytosis and internalization. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Q99519 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 360E60A256DEA07F	FASTA	415	45,467
	10 20 30 40 50 60 MTGERPSTAL PDRRWGPRIL GFWGGCRVWV FAAIFLLLSL AASWSKAEND FGLVQPLVTM 70 80 90 100 110 120 EQLLWVSGRQ IGSVDTFRIP LITATPRGTL LAFAEARKMS SSDEGAKFIA LRRSMDQGST 130 140 150 160 170 180 WSPTAFIVND GDVPDGLNLG AVVSDVETGV VFLFYSLCAH KAGCQVASTM LVWSKDDGVS 190 200 210 220 230 240 WSTPRNLSLD IGTEVFAPGP GSGIQKQREP RKGRLIVCGH GTLERDGVFC LLSDDHGASW 250 260 270 280 290 300 RYGSGVSGIP YGQPKQENDF NPDECQPYEL PDGSVVINAR NQNNYHCHCR IVLRSYDACD 310 320 330 340 350 360 TLRPRDVTFD PELVDPVVAA GAVVTSSGIV FFSNPAHPEF RVNLTLRWSF SNGTSWRKET 370 380 390 400 410 VQLWPGPSGY SSLATLEGSM DGEEQAPQLY VLYEKGRNHY TESISVAKIS VYGTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis." Bonten E.J., van der Spoel A., Fornerod M., Grosveld G., d'Azzo A. Genes Dev. 10:3156-3169(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYPE II SIALIDOSIS ARG-91. Tissue: Fibroblast.
[2]	"Identification of a sialidase encoded in the human major histocompatibility complex." Milner C.M., Smith S.V., Carrillo M.B., Taylor G.L., Hollinshead M., Campbell R.D. J. Biol. Chem. 272:4549-4558(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Monocyte.
[3]	"Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis." Pshezhetsky A.V., Richard C., Michaud L., Igdoura S.A., Wang S., Elsliger M.-A., Ou J., Leclerc D., Gravel R.A., Dallaire L., Potier M. Nat. Genet. 15:316-320(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SIALIDOSIS TYR-260 AND PRO-363. Tissue: Fibroblast.
[4]	"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse." Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L. Genome Res. 13:2621-2636(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region." Shiina S., Tamiya G., Oka A., Inoko H. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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]. Tissue: Brain and Kidney.
[8]	"Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation." Vinogradova M.V., Michaud L., Mezentsev A.V., Lukong K.E., El-Alfy M., Morales C.R., Potier M., Pshezhetsky A.V. Biochem. J. 330:641-650(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 48-55, GLYCOSYLATION. Tissue: Placenta.
[9]	"Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail." Lukong K.E., Seyrantepe V., Landry K., Trudel S., Ahmad A., Gahl W.A., Lefrancois S., Morales C.R., Pshezhetsky A.V. J. Biol. Chem. 276:46172-46181(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-412; GLY-413 AND LEU-415.
[10]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-352, MASS SPECTROMETRY. Tissue: Liver.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex." Lukong K.E., Elsliger M.-A., Chang Y., Richard C., Thomas G., Carey W., Tylki-Szymanska A., Czartoryska B., Buchholz T., Rodriguez Criado G., Palmeri S., Pshezhetsky A.V. Hum. Mol. Genet. 9:1075-1085(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363.
[13]	"Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis." Bonten E.J., Arts W.F., Beck M., Covanis A., Donati M.A., Parini R., Zammarchi E., d'Azzo A. Hum. Mol. Genet. 9:2715-2725(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SIALIDOSIS MET-54; VAL-68; ARG-91; GLY-182; ALA-219; ARG-227; HIS-231; TYR-260; PRO-270; SER-294; VAL-298; SER-328; GLN-335; PRO-363; CYS-370 AND HIS-TYR-400 INS.
[14]	"Molecular and structural studies of Japanese patients with sialidosis type 1." Naganawa Y., Itoh K., Shimmoto M., Takiguchi K., Doi H., Nishizawa Y., Kobayashi T., Kamei S., Lukong K.E., Pshezhetsky A.V., Sakuraba H. J. Hum. Genet. 45:241-249(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SIALIDOSIS MET-217 AND ARG-243, CHARACTERIZATION OF VARIANTS SIALIDOSIS MET-217 AND ARG-243.
[15]	"Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex." Lukong K.E., Landry K., Elsliger M.-A., Chang Y., Lefrancois S., Morales C.R., Pshezhetsky A.V. J. Biol. Chem. 276:17286-17290(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; ARG-240; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363, CHARACTERIZATION OF VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363.
[16]	"Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes." Itoh K., Naganawa Y., Matsuzawa F., Aikawa S., Doi H., Sasagasako N., Yamada T., Kira J., Kobayashi T., Pshezhetsky A.V., Sakuraba H. J. Hum. Genet. 47:29-37(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SIALIDOSIS LEU-80; ARG-240 AND SER-316.
[17]	"Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression." Pattison S., Pankarican M., Rupar C.A., Graham F.L., Igdoura S.A. Hum. Mutat. 23:32-39(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SIALIDOSIS PRO-225; VAL-298 AND GLY-341, CHARACTERIZATION OF VARIANTS SIALIDOSIS PRO-225; VAL-298 AND GLY-341.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Neuraminidase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF040958 mRNA. Translation: AAB96774.1. X78687 mRNA. Translation: CAA55356.1. U84246 mRNA. Translation: AAD09239.1. AF134726 Genomic DNA. Translation: AAD21814.1. BA000025 Genomic DNA. Translation: BAB63297.1. BT007206 mRNA. Translation: AAP35870.1. BC000722 mRNA. Translation: AAH00722.1. BC011900 mRNA. Translation: AAH11900.1.
IPI	IPI00029817.
RefSeq	NP_000425.1. NM_000434.3.
UniGene	Hs.520037.
3D structure databases
ProteinModelPortal	Q99519.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99519. 5 interactions.
MINT	MINT-1389413.
STRING	9606.ENSP00000399309.
Protein family/group databases
CAZy	GH33. Glycoside Hydrolase Family 33.
PTM databases
PhosphoSite	Q99519.
Polymorphism databases
DMDM	17368612.
Proteomic databases
PaxDb	Q99519.
PeptideAtlas	Q99519.
PRIDE	Q99519.
Protocols and materials databases
DNASU	4758.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000229725; ENSP00000229725; ENSG00000184494. ENST00000375631; ENSP00000364782; ENSG00000204386. ENST00000411774; ENSP00000399309; ENSG00000234846. ENST00000422978; ENSP00000408957; ENSG00000227129. ENST00000423382; ENSP00000401067; ENSG00000228691. ENST00000434496; ENSP00000409489; ENSG00000234343. ENST00000437432; ENSP00000403720; ENSG00000223957. ENST00000439648; ENSP00000408207; ENSG00000227315.
GeneID	4758.
KEGG	hsa:4758.
UCSC	uc003nxq.4. human.
Organism-specific databases
CTD	4758.
GeneCards	GC06M031825.
HGNC	HGNC:7758. NEU1.
HPA	HPA015634. HPA021506.
MIM	256550. phenotype. 608272. gene.
neXtProt	NX_Q99519.
Orphanet	93400. Congenital sialidosis type 2. 93399. Juvenile sialidosis type 2. 812. Sialidosis type 1.
PharmGKB	PA31560.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4409.
HOGENOM	HOG000007651.
HOVERGEN	HBG057314.
InParanoid	Q99519.
KO	K01186.
OMA	YEKGRNQ.
OrthoDB	EOG4DJJWX.
PhylomeDB	Q99519.
Enzyme and pathway databases
BRENDA	3.2.1.18. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q99519.
Bgee	Q99519.
CleanEx	HS_NEU1.
Genevestigator	Q99519.
GermOnline	ENSG00000204386. Homo sapiens.
Family and domain databases
Gene3D	2.120.10.10. 1 hit.
InterPro	IPR026942. Sialidase-1. IPR026856. Sialidase_fam. IPR011040. Sialidases. [Graphical view]
PANTHER	PTHR10628. PTHR10628. 1 hit. PTHR10628:SF9. PTHR10628:SF9. 1 hit.
SUPFAM	SSF50939. Sialidase. 1 hit.
ProtoNet	Search...
Other
BindingDB	Q99519.
ChEMBL	CHEMBL2726.
ChiTaRS	NEU1. human.
DrugBank	DB00198. Oseltamivir. DB00558. Zanamivir.
GenomeRNAi	4758.
NextBio	18328.
SOURCE	Search...

Entry information

Entry name

NEUR1_HUMAN

Accession

Primary (citable) accession number: Q99519

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 137 of the entry and version 1 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.