Q08174 (PCDH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protocadherin-1

Alternative name(s):
Cadherin-like protein 1
Protocadherin-42
Short name=PC42

Gene names

Name:

PCDH1

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	1060 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	May be involved in cell-cell interaction processes and in cell adhesion.
Subcellular location	Cell junction. Cell membrane; Single-pass type I membrane protein Probable. Note: Found at cell-cell boundaries and probably at cell-matrix boundaries.
Tissue specificity	Highly expressed in the brain and neuro-glial cells.
Developmental stage	Highest expression in adults.
Sequence similarities	Contains 7 cadherin domains.
Caution	It is uncertain whether Met-1 or Met-23 is the initiator.
Sequence caution	The sequence AAA36419.1 differs from that shown. Reason: Chimeric cDNA. N-terminal sequence identical to a region of chromosome 8.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell signaling Traceable author statement Ref.4. Source: ProtInc homophilic cell adhesion Inferred from electronic annotation. Source: InterPro nervous system development Traceable author statement Ref.4. Source: ProtInc
Cellular_component	cell-cell junction Traceable author statement Ref.4. Source: ProtInc integral to plasma membrane Traceable author statement Ref.4. Source: ProtInc
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q08174-1)

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: Q08174-2)

Also known as: PC42-8;

The sequence of this isoform differs from the canonical sequence as follows:
     1034-1060: VGQPFQLSTPQPLPHPYHGAIWTEVWE → LPHRRVTFSA...AQTAKREIYL

Isoform 3 (identifier: Q08174-3)

The sequence of this isoform differs from the canonical sequence as follows:
     207-218: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 57	57	Potential
	Chain	58 – 1060	1003	Protocadherin-1		PRO_0000354078
Regions
	Topological domain	58 – 852	795	Extracellular Potential
	Transmembrane	853 – 873	21	Helical; Potential
	Topological domain	874 – 1060	187	Cytoplasmic Potential
	Domain	58 – 168	111	Cadherin 1
	Domain	169 – 280	112	Cadherin 2
	Domain	281 – 387	107	Cadherin 3
	Domain	396 – 506	111	Cadherin 4
	Domain	507 – 612	106	Cadherin 5
	Domain	613 – 715	103	Cadherin 6
	Domain	718 – 844	127	Cadherin 7
Amino acid modifications
	Modified residue	918	1	Phosphoserine Ref.8
	Modified residue	949	1	Phosphoserine Ref.5
	Modified residue	962	1	Phosphoserine Ref.5 Ref.8
	Modified residue	984	1	Phosphoserine Ref.8
	Glycosylation	305	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	403	1	N-linked (GlcNAc...) Potential
	Glycosylation	618	1	N-linked (GlcNAc...) Potential
	Glycosylation	662	1	N-linked (GlcNAc...) Potential
	Glycosylation	813	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	818	1	N-linked (GlcNAc...) Ref.6
Natural variations
	Alternative sequence	207 – 218	12	Missing in isoform 3.		VSP_035772
	Alternative sequence	1034 – 1060	27	VGQPF…TEVWE → LPHRRVTFSATSQAQELQDP SQHSYYDSGLEESETPSSKS SSGPRLGPLALPEDHYERTT PDGSIGEMEHPENDLRPLPD VAMTGTCTRECSEFGHSDTC WMPGQSSPSRRTKSSALKLS TFVPYQDRGGQEPAGAGSPS PPEDRNTKTAPVRLLPSYSA FSHSSHDSCKDSATLEEIPL TQTSDFPPAATPASAQTAKR EIYL in isoform 2.		VSP_000703
	Natural variant	15	1	L → F. Corresponds to variant rs12517385 [ dbSNP | Ensembl ].		VAR_047530
	Natural variant	25	1	H → P. Ref.4 Corresponds to variant rs12515587 [ dbSNP | Ensembl ].		VAR_047531
	Natural variant	514	1	A → T. Corresponds to variant rs3822357 [ dbSNP | Ensembl ].		VAR_047532
Experimental info
	Sequence conflict	147	1	G → A in AAA36419. Ref.4
	Sequence conflict	262	1	S → T in AAA36419. Ref.4
Isoform 2:
	Sequence conflict	1156	1	V → M in AAA36418. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 0F4F24F3EE607D04	FASTA	1,060	114,743
	10 20 30 40 50 60 MDSGAGGRRC PEAALLILGP PRMEHLRHSP GPGGQRLLLP SMLLALLLLL APSPGHATRV 70 80 90 100 110 120 VYKVPEEQPP NTLIGSLAAD YGFPDVGHLY KLEVGAPYLR VDGKTGDIFT TETSIDREGL 130 140 150 160 170 180 RECQNQLPGD PCILEFEVSI TDLVQNGSPR LLEGQIEVQD INDNTPNFAS PVITLAIPEN 190 200 210 220 230 240 TNIGSLFPIP LASDRDAGPN GVASYELQAG PEAQELFGLQ VAEDQEEKQP QLIVMGNLDR 250 260 270 280 290 300 ERWDSYDLTI KVQDGGSPPR ASSALLRVTV LDTNDNAPKF ERPSYEAELS ENSPIGHSVI 310 320 330 340 350 360 QVKANDSDQG ANAEIEYTFH QAPEVVRRLL RLDRNTGLIT VQGPVDREDL STLRFSVLAK 370 380 390 400 410 420 DRGTNPKSAR AQVVVTVKDM NDNAPTIEIR GIGLVTHQDG MANISEDVAE ETAVALVQVS 430 440 450 460 470 480 DRDEGENAAV TCVVAGDVPF QLRQASETGS DSKKKYFLQT TTPLDYEKVK DYTIEIVAVD 490 500 510 520 530 540 SGNPPLSSTN SLKVQVVDVN DNAPVFTQSV TEVAFPENNK PGEVIAEITA SDADSGSNAE 550 560 570 580 590 600 LVYSLEPEPA AKGLFTISPE TGEIQVKTSL DREQRESYEL KVVAADRGSP SLQGTATVLV 610 620 630 640 650 660 NVLDCNDNDP KFMLSGYNFS VMENMPALSP VGMVTVIDGD KGENAQVQLS VEQDNGDFVI 670 680 690 700 710 720 QNGTGTILSS LSFDREQQST YTFQLKAVDG GVPPRSAYVG VTINVLDEND NAPYITAPSN 730 740 750 760 770 780 TSHKLLTPQT RLGETVSQVA AEDFDSGVNA ELIYSIAGGN PYGLFQIGSH SGAITLEKEI 790 800 810 820 830 840 ERRHHGLHRL VVKVSDRGKP PRYGTALVHL YVNETLANRT LLETLLGHSL DTPLDIDIAG 850 860 870 880 890 900 DPEYERSKQR GNILFGVVAG VVAVALLIAL AVLVRYCRQR EAKSGYQAGK KETKDLYAPK 910 920 930 940 950 960 PSGKASKGNK SKGKKSKSPK PVKPVEDEDE AGLQKSLKFN LMSDAPGDSP RIHLPLNYPP 970 980 990 1000 1010 1020 GSPDLGRHYR SNSPLPSIQL QPQSPSASKK HQVVQDLPPA NTFVGTGDTT STGSEQYSDY 1030 1040 1050 1060 SYRTNPPKYP SKQVGQPFQL STPQPLPHPY HGAIWTEVWE
	Isoform 2 (PC42-8) [UniParc]. Checksum: EF5A5BFCEE84A005	FASTA	1,237	133,722
	10 20 30 40 50 60 MDSGAGGRRC PEAALLILGP PRMEHLRHSP GPGGQRLLLP SMLLALLLLL APSPGHATRV 70 80 90 100 110 120 VYKVPEEQPP NTLIGSLAAD YGFPDVGHLY KLEVGAPYLR VDGKTGDIFT TETSIDREGL 130 140 150 160 170 180 RECQNQLPGD PCILEFEVSI TDLVQNGSPR LLEGQIEVQD INDNTPNFAS PVITLAIPEN 190 200 210 220 230 240 TNIGSLFPIP LASDRDAGPN GVASYELQAG PEAQELFGLQ VAEDQEEKQP QLIVMGNLDR 250 260 270 280 290 300 ERWDSYDLTI KVQDGGSPPR ASSALLRVTV LDTNDNAPKF ERPSYEAELS ENSPIGHSVI 310 320 330 340 350 360 QVKANDSDQG ANAEIEYTFH QAPEVVRRLL RLDRNTGLIT VQGPVDREDL STLRFSVLAK 370 380 390 400 410 420 DRGTNPKSAR AQVVVTVKDM NDNAPTIEIR GIGLVTHQDG MANISEDVAE ETAVALVQVS 430 440 450 460 470 480 DRDEGENAAV TCVVAGDVPF QLRQASETGS DSKKKYFLQT TTPLDYEKVK DYTIEIVAVD 490 500 510 520 530 540 SGNPPLSSTN SLKVQVVDVN DNAPVFTQSV TEVAFPENNK PGEVIAEITA SDADSGSNAE 550 560 570 580 590 600 LVYSLEPEPA AKGLFTISPE TGEIQVKTSL DREQRESYEL KVVAADRGSP SLQGTATVLV 610 620 630 640 650 660 NVLDCNDNDP KFMLSGYNFS VMENMPALSP VGMVTVIDGD KGENAQVQLS VEQDNGDFVI 670 680 690 700 710 720 QNGTGTILSS LSFDREQQST YTFQLKAVDG GVPPRSAYVG VTINVLDEND NAPYITAPSN 730 740 750 760 770 780 TSHKLLTPQT RLGETVSQVA AEDFDSGVNA ELIYSIAGGN PYGLFQIGSH SGAITLEKEI 790 800 810 820 830 840 ERRHHGLHRL VVKVSDRGKP PRYGTALVHL YVNETLANRT LLETLLGHSL DTPLDIDIAG 850 860 870 880 890 900 DPEYERSKQR GNILFGVVAG VVAVALLIAL AVLVRYCRQR EAKSGYQAGK KETKDLYAPK 910 920 930 940 950 960 PSGKASKGNK SKGKKSKSPK PVKPVEDEDE AGLQKSLKFN LMSDAPGDSP RIHLPLNYPP 970 980 990 1000 1010 1020 GSPDLGRHYR SNSPLPSIQL QPQSPSASKK HQVVQDLPPA NTFVGTGDTT STGSEQYSDY 1030 1040 1050 1060 1070 1080 SYRTNPPKYP SKQLPHRRVT FSATSQAQEL QDPSQHSYYD SGLEESETPS SKSSSGPRLG 1090 1100 1110 1120 1130 1140 PLALPEDHYE RTTPDGSIGE MEHPENDLRP LPDVAMTGTC TRECSEFGHS DTCWMPGQSS 1150 1160 1170 1180 1190 1200 PSRRTKSSAL KLSTFVPYQD RGGQEPAGAG SPSPPEDRNT KTAPVRLLPS YSAFSHSSHD 1210 1220 1230 SCKDSATLEE IPLTQTSDFP PAATPASAQT AKREIYL
	Isoform 3 [UniParc]. Checksum: CED808AFD713D388	FASTA	1,048	113,502
	10 20 30 40 50 60 MDSGAGGRRC PEAALLILGP PRMEHLRHSP GPGGQRLLLP SMLLALLLLL APSPGHATRV 70 80 90 100 110 120 VYKVPEEQPP NTLIGSLAAD YGFPDVGHLY KLEVGAPYLR VDGKTGDIFT TETSIDREGL 130 140 150 160 170 180 RECQNQLPGD PCILEFEVSI TDLVQNGSPR LLEGQIEVQD INDNTPNFAS PVITLAIPEN 190 200 210 220 230 240 TNIGSLFPIP LASDRDAGPN GVASYELQVA EDQEEKQPQL IVMGNLDRER WDSYDLTIKV 250 260 270 280 290 300 QDGGSPPRAS SALLRVTVLD TNDNAPKFER PSYEAELSEN SPIGHSVIQV KANDSDQGAN 310 320 330 340 350 360 AEIEYTFHQA PEVVRRLLRL DRNTGLITVQ GPVDREDLST LRFSVLAKDR GTNPKSARAQ 370 380 390 400 410 420 VVVTVKDMND NAPTIEIRGI GLVTHQDGMA NISEDVAEET AVALVQVSDR DEGENAAVTC 430 440 450 460 470 480 VVAGDVPFQL RQASETGSDS KKKYFLQTTT PLDYEKVKDY TIEIVAVDSG NPPLSSTNSL 490 500 510 520 530 540 KVQVVDVNDN APVFTQSVTE VAFPENNKPG EVIAEITASD ADSGSNAELV YSLEPEPAAK 550 560 570 580 590 600 GLFTISPETG EIQVKTSLDR EQRESYELKV VAADRGSPSL QGTATVLVNV LDCNDNDPKF 610 620 630 640 650 660 MLSGYNFSVM ENMPALSPVG MVTVIDGDKG ENAQVQLSVE QDNGDFVIQN GTGTILSSLS 670 680 690 700 710 720 FDREQQSTYT FQLKAVDGGV PPRSAYVGVT INVLDENDNA PYITAPSNTS HKLLTPQTRL 730 740 750 760 770 780 GETVSQVAAE DFDSGVNAEL IYSIAGGNPY GLFQIGSHSG AITLEKEIER RHHGLHRLVV 790 800 810 820 830 840 KVSDRGKPPR YGTALVHLYV NETLANRTLL ETLLGHSLDT PLDIDIAGDP EYERSKQRGN 850 860 870 880 890 900 ILFGVVAGVV AVALLIALAV LVRYCRQREA KSGYQAGKKE TKDLYAPKPS GKASKGNKSK 910 920 930 940 950 960 GKKSKSPKPV KPVEDEDEAG LQKSLKFNLM SDAPGDSPRI HLPLNYPPGS PDLGRHYRSN 970 980 990 1000 1010 1020 SPLPSIQLQP QSPSASKKHQ VVQDLPPANT FVGTGDTTST GSEQYSDYSY RTNPPKYPSK 1030 1040 QVGQPFQLST PQPLPHPYHG AIWTEVWE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	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].
[3]	"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). Tissue: Brain.
[4]	"Protocadherins: a large family of cadherin-related molecules in central nervous system." Sano K., Tanihara H., Heimark R.L., Obata S., Davidson M., St John T., Taketani S., Suzuki S. EMBO J. 12:2249-2256(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-1060 (ISOFORM 3), NUCLEOTIDE SEQUENCE [MRNA] OF 980-1060 (ISOFORM 2), VARIANT PRO-25. Tissue: Brain.
[5]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-949 AND SER-962, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"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-305; ASN-813 AND ASN-818, MASS SPECTROMETRY. Tissue: Liver.
[7]	"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].
[8]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-918; SER-962 AND SER-984, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC094107 Genomic DNA. No translation available. CH471062 Genomic DNA. Translation: EAW61902.1. BC035812 mRNA. Translation: AAH35812.1. L11369 mRNA. Translation: AAA36418.1. L11370 mRNA. Translation: AAA36419.1. Sequence problems.
IPI	IPI00000024. IPI00872579. IPI00914969.
RefSeq	NP_002578.2. NM_002587.3. NP_115796.2. NM_032420.2.
UniGene	Hs.79769.
3D structure databases
ProteinModelPortal	Q08174.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q08174. 1 interaction.
MINT	MINT-1185829.
PTM databases
PhosphoSite	Q08174.
Polymorphism databases
DMDM	215273864.
Proteomic databases
PaxDb	Q08174.
PRIDE	Q08174.
Protocols and materials databases
DNASU	5097.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000287008; ENSP00000287008; ENSG00000156453. ENST00000394536; ENSP00000378043; ENSG00000156453. ENST00000456271; ENSP00000403497; ENSG00000156453.
GeneID	5097.
KEGG	hsa:5097.
UCSC	uc003llp.3. human. uc003llq.3. human.
Organism-specific databases
CTD	5097.
GeneCards	GC05M141232.
HGNC	HGNC:8655. PCDH1.
HPA	HPA047720. HPA050538.
MIM	603626. gene.
neXtProt	NX_Q08174.
PharmGKB	PA32994.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG118788.
HOGENOM	HOG000234535.
HOVERGEN	HBG053523.
KO	K16498.
OMA	FPDVGHL.
Gene expression databases
ArrayExpress	Q08174.
Bgee	Q08174.
CleanEx	HS_PCDH1.
Genevestigator	Q08174.
GermOnline	ENSG00000156453. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.60. 7 hits.
InterPro	IPR002126. Cadherin. IPR015919. Cadherin-like. IPR020894. Cadherin_CS. IPR013164. Cadherin_N. IPR013585. Protocadherin. [Graphical view]
Pfam	PF00028. Cadherin. 6 hits. PF08266. Cadherin_2. 1 hit. PF08374. Protocadherin. 1 hit. [Graphical view]
PRINTS	PR00205. CADHERIN.
SMART	SM00112. CA. 6 hits. [Graphical view]
SUPFAM	SSF49313. Cadherin. 6 hits.
PROSITE	PS00232. CADHERIN_1. 6 hits. PS50268. CADHERIN_2. 7 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PCDH1. human.
GenomeRNAi	5097.
NextBio	19664.
SOURCE	Search...

Entry information

Entry name

PCDH1_HUMAN

Accession

Primary (citable) accession number: Q08174
Secondary accession number(s): Q8IUP2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 19, 2002
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 114 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.