Q3V5L5 (MGT5B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B
EC=2.4.1.-
EC=2.4.1.155

Alternative name(s):
Alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase B
GlcNAc-T Vb
Short name=GNT-Vb
Short name=hGnTVb
Mannoside acetylglucosaminyltransferase 5B
N-acetylglucosaminyl-transferase Vb
N-acetylglucosaminyltransferase IX
Short name=GNT-IX

Gene names

Name:	MGAT5B
Synonyms:	KIAA2008

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

General annotation (Comments)

Function	Glycosyltransferase that acts on alpha-linked mannose of N-glycans and O-mannosyl glycans. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) to the beta 1-6 linkage of the mannose residue of GlcNAcbeta1,2-Manalpha on both the alpha1,3- and alpha1,6-linked mannose arms in the core structure of N-glycan. Also acts on the GlcNAcbeta1,2-Manalpha1-Ser/Thr moiety, forming a 2,6-branched structure in brain O-mannosyl glycan. Plays an active role in modulating integrin and laminin-dependent adhesion and migration of neuronal cells via its activity in the O-mannosyl glycan pathway. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9
Catalytic activity	UDP-N-acetyl-D-glucosamine + 6-(2-(N-acetyl-beta-D-glucosaminyl)-alpha-D-mannosyl)-beta-D-mannosyl-R = UDP + 6-(2,6-bis(N-acetyl-beta-D-glucosaminyl)-alpha-D-mannosyl)-beta-D-mannosyl-R. Ref.1 Ref.2
Cofactor	Divalent metal cations. According to Ref.2, divalent metal cations do not effect enzyme activity. Ref.1 Ref.2
Pathway	Protein modification; protein glycosylation.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein By similarity.
Tissue specificity	Predominantly expressed in brain. Expressed in all area of the adult and fetal brain Also expressed at much lower level in testis, spleen and thymus. Ref.1 Ref.2
Sequence similarities	Belongs to the glycosyltransferase 18 family.
Sequence caution	The sequence AAH62354.1 differs from that shown. Reason: Probable cloning artifact. The sequence AAH63862.1 differs from that shown. Reason: Probable cloning artifact. The sequence BAB71598.1 differs from that shown. Reason: Chimeric sequence. The sequence BAD02406.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAE44474.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding
Molecular function	Glycosyltransferase Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein N-linked glycosylation Inferred from electronic annotation. Source: InterPro
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Hoxa1	P09022	3	EBI-3957727,EBI-3957603	From a different organism.

Alternative products

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

Isoform 1 (identifier: Q3V5L5-1)

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: Q3V5L5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MITVNPDGKIMVRRCLVTLRPF → MHSFVKHLCSRYVVERQGTMALPALLTRLLPLR
     475-476: Missing.

Isoform 3 (identifier: Q3V5L5-5)

The sequence of this isoform differs from the canonical sequence as follows:
     475-476: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 792	792	Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B		PRO_0000288611
Regions
	Topological domain	1 – 24	24	Cytoplasmic Potential
	Transmembrane	25 – 45	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	46 – 792	747	Lumenal Potential
Amino acid modifications
	Glycosylation	127	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 22	22	MITVN…TLRPF → MHSFVKHLCSRYVVERQGTM ALPALLTRLLPLR in isoform 2.		VSP_025731
	Alternative sequence	475 – 476	2	Missing in isoform 2 and isoform 3.		VSP_025734
	Natural variant	70	1	V → I. Corresponds to variant rs571264 [ dbSNP | Ensembl ].		VAR_032452

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 29, 2007. Version 2. Checksum: C2EB9445FDBE9429	FASTA	792	89,535
	10 20 30 40 50 60 MITVNPDGKI MVRRCLVTLR PFRLFVLGIG FFTLCFLMTS LGGQFSARRL GDSPFTIRTE 70 80 90 100 110 120 VMGGPESRGV LRKMSDLLEL MVKRMDALAR LENSSELHRA GGDLHFPADR MPPGAGLMER 130 140 150 160 170 180 IQAIAQNVSD IAVKVDQILR HSLLLHSKVS EGRRDQCEAP SDPKFPDCSG KVEWMRARWT 190 200 210 220 230 240 SDPCYAFFGV DGTECSFLIY LSEVEWFCPP LPWRNQTAAQ RAPKPLPKVQ AVFRSNLSHL 250 260 270 280 290 300 LDLMGSGKES LIFMKKRTKR LTAQWALAAQ RLAQKLGATQ RDQKQILVHI GFLTEESGDV 310 320 330 340 350 360 FSPRVLKGGP LGEMVQWADI LTALYVLGHG LRVTVSLKEL QSNLGVPPGR GSCPLTMPLP 370 380 390 400 410 420 FDLIYTDYHG LQQMKRHMGL SFKKYRCRIR VIDTFGTEPA YNHEEYATLH GYRTNWGYWN 430 440 450 460 470 480 LNPKQFMTMF PHTPDNSFMG FVSEELNETE KRLIKGGKAS NMAVVYGKEA SIWKLQGKEK 490 500 510 520 530 540 FLGILNKYME IHGTVYYESQ RPPEVPAFVK NHGLLPQPEF QQLLRKAKLF IGFGFPYEGP 550 560 570 580 590 600 APLEAIANGC IFLQSRFSPP HSSLNHEFFR GKPTSREVFS QHPYAENFIG KPHVWTVDYN 610 620 630 640 650 660 NSEEFEAAIK AIMRTQVDPY LPYEYTCEGM LERIHAYIQH QDFCRAPDPA LPEAHAPQSP 670 680 690 700 710 720 FVLAPNATHL EWARNTSLAP GAWPPAHALR AWLAVPGRAC TDTCLDHGLI CEPSFFPFLN 730 740 750 760 770 780 SQDAFLKLQV PCDSTESEMN HLYPAFAQPG QECYLQKEPL LFSCAGSNTK YRRLCPCRDF 790 RKGQVALCQG CL
	Isoform 2 [UniParc]. Checksum: B5EC03A96DBFB38B	FASTA	801	90,571
	10 20 30 40 50 60 MHSFVKHLCS RYVVERQGTM ALPALLTRLL PLRRLFVLGI GFFTLCFLMT SLGGQFSARR 70 80 90 100 110 120 LGDSPFTIRT EVMGGPESRG VLRKMSDLLE LMVKRMDALA RLENSSELHR AGGDLHFPAD 130 140 150 160 170 180 RMPPGAGLME RIQAIAQNVS DIAVKVDQIL RHSLLLHSKV SEGRRDQCEA PSDPKFPDCS 190 200 210 220 230 240 GKVEWMRARW TSDPCYAFFG VDGTECSFLI YLSEVEWFCP PLPWRNQTAA QRAPKPLPKV 250 260 270 280 290 300 QAVFRSNLSH LLDLMGSGKE SLIFMKKRTK RLTAQWALAA QRLAQKLGAT QRDQKQILVH 310 320 330 340 350 360 IGFLTEESGD VFSPRVLKGG PLGEMVQWAD ILTALYVLGH GLRVTVSLKE LQSNLGVPPG 370 380 390 400 410 420 RGSCPLTMPL PFDLIYTDYH GLQQMKRHMG LSFKKYRCRI RVIDTFGTEP AYNHEEYATL 430 440 450 460 470 480 HGYRTNWGYW NLNPKQFMTM FPHTPDNSFM GFVSEELNET EKRLIKGGKA SNMAVVYGKE 490 500 510 520 530 540 ASIWKGKEKF LGILNKYMEI HGTVYYESQR PPEVPAFVKN HGLLPQPEFQ QLLRKAKLFI 550 560 570 580 590 600 GFGFPYEGPA PLEAIANGCI FLQSRFSPPH SSLNHEFFRG KPTSREVFSQ HPYAENFIGK 610 620 630 640 650 660 PHVWTVDYNN SEEFEAAIKA IMRTQVDPYL PYEYTCEGML ERIHAYIQHQ DFCRAPDPAL 670 680 690 700 710 720 PEAHAPQSPF VLAPNATHLE WARNTSLAPG AWPPAHALRA WLAVPGRACT DTCLDHGLIC 730 740 750 760 770 780 EPSFFPFLNS QDAFLKLQVP CDSTESEMNH LYPAFAQPGQ ECYLQKEPLL FSCAGSNTKY 790 800 RRLCPCRDFR KGQVALCQGC L
	Isoform 3 [UniParc]. Checksum: 22193B688EFFACFF	FASTA	790	89,294
	10 20 30 40 50 60 MITVNPDGKI MVRRCLVTLR PFRLFVLGIG FFTLCFLMTS LGGQFSARRL GDSPFTIRTE 70 80 90 100 110 120 VMGGPESRGV LRKMSDLLEL MVKRMDALAR LENSSELHRA GGDLHFPADR MPPGAGLMER 130 140 150 160 170 180 IQAIAQNVSD IAVKVDQILR HSLLLHSKVS EGRRDQCEAP SDPKFPDCSG KVEWMRARWT 190 200 210 220 230 240 SDPCYAFFGV DGTECSFLIY LSEVEWFCPP LPWRNQTAAQ RAPKPLPKVQ AVFRSNLSHL 250 260 270 280 290 300 LDLMGSGKES LIFMKKRTKR LTAQWALAAQ RLAQKLGATQ RDQKQILVHI GFLTEESGDV 310 320 330 340 350 360 FSPRVLKGGP LGEMVQWADI LTALYVLGHG LRVTVSLKEL QSNLGVPPGR GSCPLTMPLP 370 380 390 400 410 420 FDLIYTDYHG LQQMKRHMGL SFKKYRCRIR VIDTFGTEPA YNHEEYATLH GYRTNWGYWN 430 440 450 460 470 480 LNPKQFMTMF PHTPDNSFMG FVSEELNETE KRLIKGGKAS NMAVVYGKEA SIWKGKEKFL 490 500 510 520 530 540 GILNKYMEIH GTVYYESQRP PEVPAFVKNH GLLPQPEFQQ LLRKAKLFIG FGFPYEGPAP 550 560 570 580 590 600 LEAIANGCIF LQSRFSPPHS SLNHEFFRGK PTSREVFSQH PYAENFIGKP HVWTVDYNNS 610 620 630 640 650 660 EEFEAAIKAI MRTQVDPYLP YEYTCEGMLE RIHAYIQHQD FCRAPDPALP EAHAPQSPFV 670 680 690 700 710 720 LAPNATHLEW ARNTSLAPGA WPPAHALRAW LAVPGRACTD TCLDHGLICE PSFFPFLNSQ 730 740 750 760 770 780 DAFLKLQVPC DSTESEMNHL YPAFAQPGQE CYLQKEPLLF SCAGSNTKYR RLCPCRDFRK 790 GQVALCQGCL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel beta(1,6)-N-acetylglucosaminyltransferase V (GnT-VB)." Kaneko M., Alvarez-Manilla G., Kamar M., Lee I., Lee J.-K., Troupe K., Zhang W., Osawa M., Pierce M. FEBS Lett. 554:515-519(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ENZYME ACTIVITY, FUNCTION, COFACTOR, TISSUE SPECIFICITY.
[2]	"Molecular cloning and characterization of human GnT-IX, a novel beta1,6-N-acetylglucosaminyltransferase that is specifically expressed in the brain." Inamori K., Endo T., Ide Y., Fujii S., Gu J., Honke K., Taniguchi N. J. Biol. Chem. 278:43102-43109(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, FUNCTION, COFACTOR, TISSUE SPECIFICITY. Tissue: Brain.
[3]	"The nucleotide sequence of a long cDNA clone isolated from human." Nagase T., Kikuno R., Ohara O. Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[4]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [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] OF 1-341 (ISOFORMS 1/3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 616-792. Tissue: PNS and Skin.
[6]	"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] OF 100-306. Tissue: Brain.
[7]	"N-Acetylglucosaminyltransferase IX acts on the GlcNAc beta 1,2-Man alpha 1-Ser/Thr moiety, forming a 2,6-branched structure in brain O-mannosyl glycan." Inamori K., Endo T., Gu J., Matsuo I., Ito Y., Fujii S., Iwasaki H., Narimatsu H., Miyoshi E., Honke K., Taniguchi N. J. Biol. Chem. 279:2337-2340(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Integrin-dependent neuroblastoma cell adhesion and migration on laminin is regulated by expression levels of two enzymes in the O-mannosyl-linked glycosylation pathway, PomGnT1 and GnT-Vb." Abbott K.L., Troupe K., Lee I., Pierce M. Exp. Cell Res. 312:2837-2850(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"N-acetylglucosaminyltransferase VB expression enhances beta1 integrin-dependent PC12 neurite outgrowth on laminin and collagen." Lee I., Guo H.-B., Kamar M., Abbott K., Troupe K., Lee J.-K., Alvarez-Manilla G., Pierce M. J. Neurochem. 97:947-956(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB114297 mRNA. Translation: BAD02406.1. Different initiation. AB109185 mRNA. Translation: BAC84969.1. AB235153 mRNA. Translation: BAE44474.1. Different initiation. AC016168 Genomic DNA. No translation available. BC062354 mRNA. Translation: AAH62354.1. Sequence problems. BC063862 mRNA. Translation: AAH63862.1. Sequence problems. AK057861 mRNA. Translation: BAB71598.1. Sequence problems.
IPI	IPI00440497. IPI00441187. IPI00746336. IPI00848338. IPI00940587.
RefSeq	NP_001186101.1. NM_001199172.1. NP_653278.2. NM_144677.2. NP_945193.1. NM_198955.1.
UniGene	Hs.144531.
3D structure databases
ProteinModelPortal	Q3V5L5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q3V5L5. 1 interaction.
STRING	9606.ENSP00000391227.
Protein family/group databases
CAZy	GT18. Glycosyltransferase Family 18.
Polymorphism databases
DMDM	152040009.
Proteomic databases
PaxDb	Q3V5L5.
PRIDE	Q3V5L5.
Protocols and materials databases
DNASU	146664.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000301618; ENSP00000301618; ENSG00000167889. ENST00000428789; ENSP00000391227; ENSG00000167889. ENST00000569840; ENSP00000456037; ENSG00000167889.
GeneID	146664.
KEGG	hsa:146664.
UCSC	uc002jth.3. human. uc002jti.3. human. uc002jtj.3. human.
Organism-specific databases
CTD	146664.
GeneCards	GC17P074864.
HGNC	HGNC:24140. MGAT5B.
HPA	HPA017424.
MIM	612441. gene.
neXtProt	NX_Q3V5L5.
PharmGKB	PA134987427.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG270839.
HOGENOM	HOG000006557.
HOVERGEN	HBG052469.
InParanoid	Q3V5L5.
KO	K09661.
OMA	DHGLICE.
OrthoDB	EOG4VMFDR.
Enzyme and pathway databases
UniPathway	UPA00378.
Gene expression databases
ArrayExpress	Q3V5L5.
Bgee	Q3V5L5.
CleanEx	HS_MGAT5B.
Genevestigator	Q3V5L5.
Family and domain databases
InterPro	IPR026116. GlyclTrfase_18. [Graphical view]
PANTHER	PTHR15075. PTHR15075. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	MGAT5B. human.
GenomeRNAi	146664.
NextBio	85408.
SOURCE	Search...

Entry information

Entry name

MGT5B_HUMAN

Accession

Primary (citable) accession number: Q3V5L5
Secondary accession number(s): Q6P3S8 , Q6P6B3, Q766X5, Q76D04, Q96LS2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 29, 2007
Last sequence update:	May 29, 2007
Last modified:	May 1, 2013
This is version 75 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.