Q07699 (SCN1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium channel subunit beta-1

Gene names

Name:

SCN1B

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	218 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	Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons. Ref.4 Ref.11 Isoform 2: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth. Ref.4 Ref.11
Subunit structure	The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more beta-1, beta-2 and beta-3. Beta-1 and beta-3 are non-covalently associated with alpha, while beta-2 is covalently linked by disulfide bonds. Beta-1 or beta-3 subunits associate with neurofascin. Associates with SCN10A By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein Ref.11. Isoform 2: Secreted Ref.11.
Tissue specificity	The overall expression of isoforms 1 and 2 is very similar. Isoform 1 is abundantly expressed in skeletal muscle, heart and brain. Isoform 2 is highly expressed in brain and skeletal muscle and present at a very low level in heart, placenta, lung, liver, kidney and pancreas. In brain, isoform 2 is most abundant in the cerebellum, followed by the cerebral cortex and occipital lobe, while isoform 1 levels are higher in the cortex compared to the cerebellum. Isoform 2 is expressed in many regions of the brain, including cerebellar Purkinje cells, cortex pyramidal neurons and many of the neuronal fibers throughout the brain (at protein level). Also detected in dorsal root ganglion, in fibers of the spinal nerve and in cortical neurons and their processes (at protein level). Ref.4
Involvement in disease	Generalized epilepsy with febrile seizures plus 1 (GEFS+1) [MIM:604233]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.14 Brugada syndrome 5 (BRGDA5) [MIM:612838]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Belongs to the sodium channel auxiliary subunit SCN1B (TC 8.A.17) family. [View classification] Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Cell adhesion Ion transport Sodium transport Transport
Cellular component	Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Brugada syndrome Disease mutation Epilepsy
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Ligand	Sodium
Molecular function	Ion channel Sodium channel Voltage-gated channel
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle contraction Inferred from mutant phenotype PubMed 19808477. Source: BHF-UCL cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW corticospinal neuron axon guidance Inferred from sequence or structural similarity. Source: BHF-UCL neuronal action potential propagation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of neuron projection development Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of sodium ion transport Inferred from direct assay PubMed 19808477. Source: BHF-UCL regulation of atrial cardiac muscle cell membrane depolarization Inferred from mutant phenotype PubMed 19808477PubMed 22247482. Source: BHF-UCL regulation of cardiac muscle cell action potential involved in contraction Inferred from mutant phenotype PubMed 19808477. Source: BHF-UCL regulation of heart rate by cardiac conduction Inferred from mutant phenotype PubMed 19808477. Source: BHF-UCL regulation of sodium ion transmembrane transporter activity Inferred from direct assay PubMed 19808477. Source: BHF-UCL regulation of ventricular cardiac muscle cell membrane repolarization Inferred from sequence or structural similarity PubMed 17884088. Source: BHF-UCL response to pyrethroid Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement Ref.12. Source: ProtInc
Cellular_component	T-tubule Inferred from sequence or structural similarity. Source: BHF-UCL extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell intercalated disc Inferred from sequence or structural similarity. Source: BHF-UCL node of Ranvier Inferred from sequence or structural similarity. Source: BHF-UCL voltage-gated sodium channel complex Inferred from direct assay PubMed 19808477PubMed 21051419. Source: BHF-UCL
Molecular_function	sodium channel inhibitor activity Inferred from sequence or structural similarity PubMed 17884088. Source: BHF-UCL voltage-gated sodium channel activity Inferred from direct assay Ref.4. Source: BHF-UCL voltage-gated sodium channel activity involved in regulation of Purkinje myocyte action potential Inferred from mutant phenotype Ref.10. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q07699-1)

Also known as: Beta-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: Q07699-2)

Also known as: Beta-1B; beta1A; beta1B;

The sequence of this isoform differs from the canonical sequence as follows:
     150-218: ANRDMASIVS...ENCTGVQVAE → GESGAACPFT...IIRCVSRGVV

Note: Due to intron 3 retention.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 218	200	Sodium channel subunit beta-1		PRO_0000014926
Regions
	Topological domain	19 – 160	142	Extracellular Potential
	Transmembrane	161 – 182	22	Helical; Potential
	Topological domain	183 – 218	36	Cytoplasmic Potential
	Domain	22 – 150	129	Ig-like C2-type
Amino acid modifications
	Glycosylation	93	1	N-linked (GlcNAc...) Potential
	Glycosylation	110	1	N-linked (GlcNAc...) Potential
	Glycosylation	114	1	N-linked (GlcNAc...) Potential
	Glycosylation	135	1	N-linked (GlcNAc...) Potential
	Disulfide bond	40 ↔ 121		By similarity
Natural variations
	Alternative sequence	150 – 218	69	ANRDM…VQVAE → GESGAACPFTVTHRRARWRD RWQAVDRTGWLCAWPANRPQ QRAEGEGSSPSCPLQLWPLF LSSPRRGQSMPVPHRRSGYR TQLCHLCCMTSGRCLLSLSQ RVVLGLPGIIIRCVSRGVV in isoform 2.		VSP_041982
	Natural variant	25	1	D → N in a patient with idiopathic epilepsy. Ref.13		VAR_062523
	Natural variant	87	1	E → Q in a patient presenting with palpitations and complete left bundle branch block on electrocardiogram. Ref.10		VAR_062524
	Natural variant	121	1	C → W in GEFS+1. Ref.12		VAR_010165
	Natural variant	125	1	R → L in GEFS+1. Ref.14		VAR_067341
	Natural variant	138	1	V → I. Ref.13		VAR_062525
	Natural variant	208	1	K → I. Ref.13		VAR_062526
	Natural variant	211	1	C → Y. Ref.13		VAR_062527
	Natural variant	213	1	G → D. Ref.13		VAR_062528

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Beta-1) [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 09B812FA3F9E9018	FASTA	218	24,707
	10 20 30 40 50 60 MGRLLALVVG AALVSSACGG CVEVDSETEA VYGMTFKILC ISCKRRSETN AETFTEWTFR 70 80 90 100 110 120 QKGTEEFVKI LRYENEVLQL EEDERFEGRV VWNGSRGTKD LQDLSIFITN VTYNHSGDYE 130 140 150 160 170 180 CHVYRLLFFE NYEHNTSVVK KIHIEVVDKA NRDMASIVSE IMMYVLIVVL TIWLVAEMIY 190 200 210 CYKKIAAATE TAAQENASEY LAITSESKEN CTGVQVAE
	Isoform 2 (Beta-1B) (beta1A) (beta1B) [UniParc]. Checksum: D9A001E676C0FAD1	FASTA	268	30,440
	10 20 30 40 50 60 MGRLLALVVG AALVSSACGG CVEVDSETEA VYGMTFKILC ISCKRRSETN AETFTEWTFR 70 80 90 100 110 120 QKGTEEFVKI LRYENEVLQL EEDERFEGRV VWNGSRGTKD LQDLSIFITN VTYNHSGDYE 130 140 150 160 170 180 CHVYRLLFFE NYEHNTSVVK KIHIEVVDKG ESGAACPFTV THRRARWRDR WQAVDRTGWL 190 200 210 220 230 240 CAWPANRPQQ RAEGEGSSPS CPLQLWPLFL SSPRRGQSMP VPHRRSGYRT QLCHLCCMTS 250 260 GRCLLSLSQR VVLGLPGIII RCVSRGVV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The cloning and expression of a sodium channel beta 1-subunit cDNA from human brain." McClatchey A.I., Cannon S.C., Slaugenhaupt S.A., Gusella J.F. Hum. Mol. Genet. 2:745-749(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Voltage-gated Na+ channel beta 1 subunit mRNA expressed in adult human skeletal muscle, heart, and brain is encoded by a single gene." Makita N., Bennett P.B. Jr., George A.L. Jr. J. Biol. Chem. 269:7571-7578(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart and Skeletal muscle.
[3]	"Genomic organization and chromosomal assignment of the human voltage-gated Na+ channel beta 1 subunit gene (SCN1B)." Makita N., Sloan-Brown K., Weghuis D.O., Ropers H.-H., George A.L. Jr. Genomics 23:628-634(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	"Molecular cloning and functional expression of the human sodium channel beta1B subunit, a novel splicing variant of the beta1 subunit." Qin N., D'Andrea M.R., Lubin M.L., Shafaee N., Codd E.E., Correa A.M. Eur. J. Biochem. 270:4762-4770(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY.
[5]	"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] (ISOFORM 1). Tissue: Skeletal muscle.
[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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	NHLBI resequencing and genotyping service (RS&G) Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	"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.
[10]	"Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans." Watanabe H., Koopmann T.T., Le Scouarnec S., Yang T., Ingram C.R., Schott J.J., Demolombe S., Probst V., Anselme F., Escande D., Wiesfeld A.C., Pfeufer A., Kaab S., Wichmann H.E., Hasdemir C., Aizawa Y., Wilde A.A., Roden D.M., Bezzina C.R. J. Clin. Invest. 118:2260-2268(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN BRGDA5, VARIANT GLN-87.
[11]	"Voltage-gated Na+ channel beta1B: a secreted cell adhesion molecule involved in human epilepsy." Patino G.A., Brackenbury W.J., Bao Y., Lopez-Santiago L.F., O'Malley H.A., Chen C., Calhoun J.D., Lafreniere R.G., Cossette P., Rouleau G.A., Isom L.L. J. Neurosci. 31:14577-14591(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2).
[12]	"Febrile seizures and generalized epilepsy associated with a mutation in the Na(+)-channel beta-1 subunit gene SCN1B." Wallace R.H., Wang D.W., Singh R., Scheffer I.E., George A.L. Jr., Phillips H.A., Saar K., Reis A., Johnson E.W., Sutherland G.R., Berkovic S.F., Mulley J.C. Nat. Genet. 19:366-370(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GEFS+1 TRP-121.
[13]	"Mutational analysis of the SCN1A, SCN1B and GABRG2 genes in 150 Italian patients with idiopathic childhood epilepsies." Orrico A., Galli L., Grosso S., Buoni S., Pianigiani R., Balestri P., Sorrentino V. Clin. Genet. 75:579-581(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASN-25; ILE-138; ILE-208; TYR-211 AND ASP-213.
[14]	"New mutation c.374C>T and a putative disease-associated haplotype within SCN1B gene in Tunisian families with febrile seizures." Fendri-Kriaa N., Kammoun F., Salem I.H., Kifagi C., Mkaouar-Rebai E., Hsairi I., Rebai A., Triki C., Fakhfakh F. Eur. J. Neurol. 18:695-702(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GEFS+1 LEU-125.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	L10338 mRNA. Translation: AAA60391.1. L16242 mRNA. Translation: AAA61277.1. U12193 , U12189, U12190, U12191, U12192 Genomic DNA. Translation: AAB97608.1. AY391842 mRNA. Translation: AAR25552.1. AK313279 mRNA. Translation: BAG36087.1. DQ677665 Genomic DNA. Translation: ABQ01236.1. BT019923 mRNA. Translation: AAV38726.1. AC020907 Genomic DNA. No translation available. BC067122 mRNA. Translation: AAH67122.1.
IPI	IPI00018980.
PIR	A55734.
RefSeq	NP_001028.1. NM_001037.4. NP_950238.1. NM_199037.3.
UniGene	Hs.436646.
3D structure databases
ProteinModelPortal	Q07699.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000396915.
PTM databases
PhosphoSite	Q07699.
Polymorphism databases
DMDM	1705868.
Proteomic databases
PaxDb	Q07699.
PRIDE	Q07699.
Protocols and materials databases
DNASU	6324.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262631; ENSP00000262631; ENSG00000105711. ENST00000415950; ENSP00000396915; ENSG00000105711.
GeneID	6324.
KEGG	hsa:6324.
UCSC	uc002nxp.3. human.
Organism-specific databases
CTD	6324.
GeneCards	GC19P035521.
HGNC	HGNC:10586. SCN1B.
MIM	600235. gene. 604233. phenotype. 612838. phenotype.
neXtProt	NX_Q07699.
Orphanet	130. Brugada syndrome. 33069. Dravet syndrome. 36387. Generalized epilepsy with febrile seizures-plus context.
PharmGKB	PA302.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG45207.
HOGENOM	HOG000276881.
HOVERGEN	HBG056582.
InParanoid	Q07699.
KO	K04845.
OMA	ISCKKRS.
OrthoDB	EOG4X97JG.
PhylomeDB	Q07699.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	Q07699.
Bgee	Q07699.
CleanEx	HS_SCN1B.
Genevestigator	Q07699.
GermOnline	ENSG00000105711. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR013783. Ig-like_fold. IPR013151. Immunoglobulin. IPR027098. Na_channel_b1/b3. [Graphical view]
PANTHER	PTHR10546. PTHR10546. 1 hit.
Pfam	PF00047. ig. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. False negative. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q07699.
ChEMBL	CHEMBL5487.
GenomeRNAi	6324.
NextBio	24542.
PMAP-CutDB	Q07699.
SOURCE	Search...

Entry information

Entry name

SCN1B_HUMAN

Accession

Primary (citable) accession number: Q07699
Secondary accession number(s): Q5TZZ4, Q6TN97

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 128 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.