Q8TF17 (S3TC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SH3 domain and tetratricopeptide repeat-containing protein 2

Gene names

Name:	SH3TC2
Synonyms:	KIAA1985
ORF Names:	PP12494

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	1288 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Tissue specificity	Strongly expressed in brain and spinal cord. Expressed at equal level in spinal cord and sciatic nerve. Weakly expressed in striated muscle. Ref.1
Involvement in disease	Charcot-Marie-Tooth disease 4C (CMT4C) [MIM:601596]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4C is characterized by onset in childhood, early-onset scoliosis and a distinct Schwann cell pathology. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Mononeuropathy of the median nerve mild (MNMN) [MIM:613353]: A disease characterized by median nerve mononeuropathy at the wrist. The clinical presentation ranges from a mild phenotype, consistent with carpal tunnel syndrome, to a severe median nerve mononeuropathy at the wrist associated with evidence of a more widespread axonal polyneuropathy. The latter phenotype is similar to that of patients with hereditary neuropathy with liability to pressure palsies. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Contains 1 SH3 domain. Contains 8 TPR repeats.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Charcot-Marie-Tooth disease Disease mutation Neuropathy
Domain	Repeat SH3 domain TPR repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	peripheral nervous system myelin maintenance Inferred from electronic annotation. Source: Compara
Cellular_component	plasma membrane Inferred from electronic annotation. Source: Compara recycling endosome Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8TF17-1)

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: Q8TF17-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1138: Missing.
     1139-1159: LEGYEKALEFATLAARLSTVT → MSEQMMQSVGCRISLSVFQFL

Note: No experimental confirmation available.

Isoform 3 (identifier: Q8TF17-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1138: Missing.
     1139-1159: LEGYEKALEFATLAARLSTVT → MSEQMMQSVGCRISLSVFQFL
     1226-1288: DAHDATEYFL...RWLSGGGLAL → VRARLPRFPD...GGAEKTRVPR

Note: No experimental confirmation available.

Isoform 4 (identifier: Q8TF17-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-453: Missing.
     959-1049: QLQATKSLCH...TDKAAEAWLG → KYVPCCWEAI...WSPWGSFIGT
     1050-1288: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1288	1288	SH3 domain and tetratricopeptide repeat-containing protein 2		PRO_0000106356
Regions
	Domain	268 – 331	64	SH3
	Repeat	528 – 561	34	TPR 1
	Repeat	757 – 790	34	TPR 2
	Repeat	836 – 869	34	TPR 3
	Repeat	1001 – 1037	37	TPR 4
	Repeat	1084 – 1118	35	TPR 5
	Repeat	1119 – 1152	34	TPR 6
	Repeat	1166 – 1199	34	TPR 7
	Repeat	1210 – 1244	35	TPR 8
Natural variations
	Alternative sequence	1 – 1138	1138	Missing in isoform 2 and isoform 3.		VSP_009884
	Alternative sequence	1 – 453	453	Missing in isoform 4.		VSP_009881
	Alternative sequence	959 – 1049	91	QLQAT…EAWLG → KYVPCCWEAIERSVGSSFIH FLSQVISFMSLLCVQVSFRP PNPSAISTALCPQTLRHASP TMSTGWPWLSNSGTGRWKEG CWSPWGSFIGT in isoform 4.		VSP_009882
	Alternative sequence	1050 – 1288	239	Missing in isoform 4.		VSP_009883
	Alternative sequence	1139 – 1159	21	LEGYE…LSTVT → MSEQMMQSVGCRISLSVFQF L in isoform 2 and isoform 3.		VSP_009885
	Alternative sequence	1226 – 1288	63	DAHDA…GGLAL → VRARLPRFPDSHHPTILLPD SKTMRSLCGGAEKTRVPR in isoform 3.		VSP_009886
	Natural variant	169	1	Y → H in MNMN. Ref.7		VAR_064421
	Natural variant	171	1	G → E. Corresponds to variant rs17722293 [ dbSNP | Ensembl ].		VAR_052622
	Natural variant	468	1	A → S. Ref.5 Ref.6 Corresponds to variant rs6875902 [ dbSNP | Ensembl ].		VAR_018267
	Natural variant	529	1	R → Q in CMT4C; homozygous in 2 unrelated Turkish patients; also found in 1 of 320 Turkish control chromosomes. Ref.1		VAR_018268
	Natural variant	657	1	E → K in CMT4C; homozygous in a Turkish patient. Ref.1		VAR_018269
	Natural variant	658	1	R → C in CMT4C; heterozygous in one German patient with affected sibling. Ref.1		VAR_018270
	Natural variant	696	1	H → R. Corresponds to variant rs17109261 [ dbSNP | Ensembl ].		VAR_052623
Experimental info
	Sequence conflict	334	1	M → R in BAB85571. Ref.6
	Sequence conflict	1158	1	V → I in BAB85571. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 13, 2004. Version 2. Checksum: 0E7C1B87480207B4	FASTA	1,288	144,777
	10 20 30 40 50 60 MGGCFCIPRE RSLTRGPGKE TPSKDPTVSS ECIASSEYKE KCFLPQNINP DLTLSFCVKS 70 80 90 100 110 120 RSRRCVNGPL QEAARRRLWA LENEDQEVRM LFKDLSARLV SIQSQRAQFL ITFKTMEEIW 130 140 150 160 170 180 KFSTYLNLGY VSMCLEHLLF DHKYWLNCIL VEDTEIQVSV DDKHLETIYL GLLIQEGHFF 190 200 210 220 230 240 CRALCSVTPP AEKEGECLTL CKNELISVKM AEAGSELEGV SLVTGQRGLV LVSALEPLPL 250 260 270 280 290 300 PFHQWFLKNY PGSCGLSRKR DWTGSYQIGR GRCKALTGYE PGEKDELNFY QGESIEIIGF 310 320 330 340 350 360 VIPGLQWFIG KSTSSGQVGF VPTRNIDPDS YSPMSRNSAF LSDEERCSLL ALGSDKQTEC 370 380 390 400 410 420 SSFLHTLART DITSVYRLSG FESIQNPPND LSASQPEGFK EVRPGRAWEE HQAVGSRQSS 430 440 450 460 470 480 SSEDSSLEEE LLSATSDSYR LPEPDDLDDP ELLMDLSTGQ EEEAENFAPI LAFLDHEGYA 490 500 510 520 530 540 DHFKSLYDFS FSFLTSSFYS FSEEDEFVAY LEASRKWAKK SHMTWAHARL CFLLGRLSIR 550 560 570 580 590 600 KVKLSQARVY FEEAIHILNG AFEDLSLVAT LYINLAAIYL KQRLRHKGSA LLEKAGALLA 610 620 630 640 650 660 CLPDRESSAK HELDVVAYVL RQGIVVGSSP LEARACFLAI RLLLSLGRHE EVLPFAERLQ 670 680 690 700 710 720 LLSGHPPASE AVASVLSFLY DKKYLPHLAV ASVQQHGIQS AQGMSLPIWQ VHLVLQNTTK 730 740 750 760 770 780 LLGFPSPGWG EVSALACPML RQALAACEEL ADRSTQRALC LILSKVYLEH RSPDGAIHYL 790 800 810 820 830 840 SQALVLGQLL GEQESFESSL CLAWAYLLAS QAKKALDVLE PLLCSLKETE SLTQRGVIYN 850 860 870 880 890 900 LLGLALQGEG RVNRAAKSYL RALNRAQEVG DVHNQAVAMA NLGHLSLKSW AQHPARNYLL 910 920 930 940 950 960 QAVRLYCELQ ASKETDMELV QVFLWLAQVL VSGHQLTHGL LCYEMALLFG LRHRHLKSQL 970 980 990 1000 1010 1020 QATKSLCHFY SSVSPNPEAC ITYHEHWLAL AQQLRDREME GRLLESLGQL YRNLNTARSL 1030 1040 1050 1060 1070 1080 RRSLTCIKES LRIFIDLGET DKAAEAWLGA GRLHYLMQED ELVELCLQAA IQTALKSEEP 1090 1100 1110 1120 1130 1140 LLALKLYEEA GDVFFNGTRH RHHAVEYYRA GAVPLARRLK AVRTELRIFN KLTELQISLE 1150 1160 1170 1180 1190 1200 GYEKALEFAT LAARLSTVTG DQRQELVAFH RLATVYYSLH MYEMAEDCYL KTLSLCPPWL 1210 1220 1230 1240 1250 1260 QSPKEALYYA KVYYRLGRLT FCQLKDAHDA TEYFLLALAA AVLLGDEELQ DTIRSRLDNI 1270 1280 CQSPLWHSRP SGCSSERARW LSGGGLAL
	Isoform 2 [UniParc]. Checksum: 8A0BFC9B8FCCDC27	FASTA	150	17,155
	10 20 30 40 50 60 MSEQMMQSVG CRISLSVFQF LGDQRQELVA FHRLATVYYS LHMYEMAEDC YLKTLSLCPP 70 80 90 100 110 120 WLQSPKEALY YAKVYYRLGR LTFCQLKDAH DATEYFLLAL AAAVLLGDEE LQDTIRSRLD 130 140 150 NICQSPLWHS RPSGCSSERA RWLSGGGLAL
	Isoform 3 [UniParc]. Checksum: BFE110205D4C92EA	FASTA	125	14,597
	10 20 30 40 50 60 MSEQMMQSVG CRISLSVFQF LGDQRQELVA FHRLATVYYS LHMYEMAEDC YLKTLSLCPP 70 80 90 100 110 120 WLQSPKEALY YAKVYYRLGR LTFCQLKVRA RLPRFPDSHH PTILLPDSKT MRSLCGGAEK TRVPR
	Isoform 4 [UniParc]. Checksum: B50F2AA6E12879C5	FASTA	596	66,341
	10 20 30 40 50 60 MDLSTGQEEE AENFAPILAF LDHEGYADHF KSLYDFSFSF LTSSFYSFSE EDEFVAYLEA 70 80 90 100 110 120 SRKWAKKSHM TWAHARLCFL LGRLSIRKVK LSQARVYFEE AIHILNGAFE DLSLVATLYI 130 140 150 160 170 180 NLAAIYLKQR LRHKGSALLE KAGALLACLP DRESSAKHEL DVVAYVLRQG IVVGSSPLEA 190 200 210 220 230 240 RACFLAIRLL LSLGRHEEVL PFAERLQLLS GHPPASEAVA SVLSFLYDKK YLPHLAVASV 250 260 270 280 290 300 QQHGIQSAQG MSLPIWQVHL VLQNTTKLLG FPSPGWGEVS ALACPMLRQA LAACEELADR 310 320 330 340 350 360 STQRALCLIL SKVYLEHRSP DGAIHYLSQA LVLGQLLGEQ ESFESSLCLA WAYLLASQAK 370 380 390 400 410 420 KALDVLEPLL CSLKETESLT QRGVIYNLLG LALQGEGRVN RAAKSYLRAL NRAQEVGDVH 430 440 450 460 470 480 NQAVAMANLG HLSLKSWAQH PARNYLLQAV RLYCELQASK ETDMELVQVF LWLAQVLVSG 490 500 510 520 530 540 HQLTHGLLCY EMALLFGLRH RHLKSKYVPC CWEAIERSVG SSFIHFLSQV ISFMSLLCVQ 550 560 570 580 590 VSFRPPNPSA ISTALCPQTL RHASPTMSTG WPWLSNSGTG RWKEGCWSPW GSFIGT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy." Senderek J., Bergmann C., Stendel C., Kirfel J., Verpoorten N., De Jonghe P., Timmerman V., Chrast R., Verheijen M.H.G., Lemke G., Battaloglu E., Parman Y., Erdem S., Tan E., Topaloglu H., Hahn A., Mueller-Felber W., Rizzuto N. , Fabrizi G.M., Stuhrmann M., Rudnik-Schoeneborn S., Zuechner S., Schroeder J.M., Buchheim E., Straub V., Klepper J., Huehne K., Rautenstrauss B., Buettner R., Nelis E., Zerres K. Am. J. Hum. Genet. 73:1106-1119(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS CMT4C GLN-529; LYS-657 AND CYS-658. Tissue: Sciatic nerve.
[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] (ISOFORMS 2 AND 4). Tissue: Hippocampus.
[3]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[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] (ISOFORM 1), VARIANT SER-468.
[6]	"Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins." Nagase T., Kikuno R., Ohara O. DNA Res. 8:319-327(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 334-1288 (ISOFORM 1), VARIANT SER-468. Tissue: Brain.
[7]	"Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy." Lupski J.R., Reid J.G., Gonzaga-Jauregui C., Rio Deiros D., Chen D.C., Nazareth L., Bainbridge M., Dinh H., Jing C., Wheeler D.A., McGuire A.L., Zhang F., Stankiewicz P., Halperin J.J., Yang C., Gehman C., Guo D., Irikat R.K. , Tom W., Fantin N.J., Muzny D.M., Gibbs R.A. N. Engl. J. Med. 362:1181-1191(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MNMN HIS-169.
+	Additional computationally mapped references.

Web resources

Inherited peripheral neuropathies mutation db

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY341075 mRNA. Translation: AAR03497.1. AK124854 mRNA. Translation: BAG54107.1. AK127248 mRNA. Translation: BAC86899.1. AK023667 mRNA. Translation: BAB14631.1. AF370410 mRNA. Translation: AAQ15246.1. CH471062 Genomic DNA. Translation: EAW61796.1. BC113879 mRNA. Translation: AAI13880.1. AB075865 mRNA. Translation: BAB85571.1.
IPI	IPI00291798. IPI00394968. IPI00410020. IPI00922877.
RefSeq	NP_078853.2. NM_024577.3.
UniGene	Hs.483784.
3D structure databases
ProteinModelPortal	Q8TF17.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000313025.
PTM databases
PhosphoSite	Q8TF17.
Polymorphism databases
DMDM	46396469.
Proteomic databases
PaxDb	Q8TF17.
PRIDE	Q8TF17.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000502274; ENSP00000421092; ENSG00000169247. ENST00000515425; ENSP00000423660; ENSG00000169247.
GeneID	79628.
KEGG	hsa:79628.
UCSC	uc003lpt.3. human.
Organism-specific databases
CTD	79628.
GeneCards	GC05M148303.
HGNC	HGNC:29427. SH3TC2.
HPA	HPA037684.
MIM	601596. phenotype. 608206. gene. 613353. phenotype.
neXtProt	NX_Q8TF17.
Orphanet	99949. Charcot-Marie-Tooth disease type 4C.
PharmGKB	PA134951912.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0457.
HOVERGEN	HBG054553.
InParanoid	Q8TF17.
OMA	FYSSVSP.
PhylomeDB	Q8TF17.
Gene expression databases
ArrayExpress	Q8TF17.
Bgee	Q8TF17.
CleanEx	HS_SH3TC2.
Genevestigator	Q8TF17.
GermOnline	ENSG00000169247. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.10. 3 hits.
InterPro	IPR001452. SH3_domain. IPR001440. TPR-1. IPR011990. TPR-like_helical. IPR019734. TPR_repeat. [Graphical view]
Pfam	PF00018. SH3_1. 1 hit. PF00515. TPR_1. 1 hit. [Graphical view]
SMART	SM00326. SH3. 1 hit. SM00028. TPR. 3 hits. [Graphical view]
SUPFAM	SSF50044. SH3. 1 hit.
PROSITE	PS50002. SH3. 1 hit. PS50005. TPR. False negative. PS50293. TPR_REGION. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	79628.
NextBio	68717.
SOURCE	Search...

Entry information

Entry name

S3TC2_HUMAN

Accession

Primary (citable) accession number: Q8TF17
Secondary accession number(s): B3KWE5, Q14CF5, Q9H8I5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	April 13, 2004
Last modified:	May 1, 2013
This is version 108 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.