T-cell surface glycoprotein CD4 precursor

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Preferred order of sections

Names and origin

Protein names

Recommended name:
T-cell surface glycoprotein CD4

Alternative name(s):
T-cell surface antigen T4/Leu-3
CD_antigen=CD4

Gene names

Name:

CD4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	458 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	Accessory protein for MHC class-II antigen/T-cell receptor interaction. May regulate T-cell activation. Induces the aggregation of lipid rafts.
Subunit structure	Associates with LCK. Binds to HIV-1 gp120 and to P4HB/PDI and upon HIV-1 binding to the cell membrane, is part of P4HB/PDI-CD4-CXCR4-gp120 complex. Interacts with HIV-1 Envelope polyprotein gp160 and protein Vpu. Interacts with Human Herpes virus 7 capsid proteins. Ref.15 Ref.18 Ref.19 Ref.21
Subcellular location	Cell membrane; Single-pass type I membrane protein. Note: Localizes to lipid rafts. Removed from plasma membrane by HIV-1 Nef protein that increases clathrin-dependent endocytosis of this antigen to target it to lysosomal degradation. Cell surface expression is also down-modulated by HIV-1 Envelope polyprotein gp160 that interacts with, and sequesters CD4 in the endoplasmic reticulum. Ref.20
Post-translational modification	Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts.
Miscellaneous	Primary receptor for HIV-1.
Sequence similarities	Contains 3 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Adaptive immunity Host-virus interaction Immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	T cell selection Inferred from direct assay. Source: UniProtKB cell adhesion Inferred from electronic annotation. Source: InterPro immune response Non-traceable author statement. Source: UniProtKB induction by virus of host cell-cell fusion Inferred from direct assay. Source: UniProtKB initiation of viral infection Inferred from Experiment. Source: Reactome maintenance of protein location in cell Inferred from direct assay. Source: MGI positive regulation of interleukin-2 biosynthetic process Non-traceable author statement. Source: UniProtKB positive regulation of protein kinase activity Inferred from direct assay. Source: UniProtKB protein amino acid palmitoleylation Inferred from direct assay. Source: MGI transmembrane receptor protein tyrosine kinase signaling pathway Non-traceable author statement. Source: UniProtKB
Cellular component	T cell receptor complex Non-traceable author statement. Source: UniProtKB early endosome Inferred from Experiment. Source: Reactome endoplasmic reticulum membrane Inferred from Experiment. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	MHC class II protein binding Non-traceable author statement. Source: UniProtKB coreceptor activity Non-traceable author statement. Source: UniProtKB extracellular matrix structural constituent Non-traceable author statement. Source: UniProtKB glycoprotein binding Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB protein kinase binding Inferred from physical interaction. Source: UniProtKB transmembrane receptor activity Traceable author statement. Source: ProtInc zinc ion binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Ref.12 Ref.13

Chain

26 – 458

433

T-cell surface glycoprotein CD4

PRO_0000014621

Regions

Topological domain

26 – 396

371

Extracellular Potential

Transmembrane

397 – 418

22

Helical; Potential

Topological domain

419 – 458

40

Cytoplasmic Potential

Domain

26 – 125

100

Ig-like V-type

Domain

126 – 203

78

Ig-like C2-type 1

Domain

204 – 317

114

Ig-like C2-type 2

Domain

318 – 374

57

Ig-like C2-type 3

Region

427 – 455

29

HIV-1 Vpu-susceptibility domain

Amino acid modifications

Lipidation

419

1

S-palmitoyl cysteine Ref.16

Lipidation

422

1

S-palmitoyl cysteine Ref.16

Glycosylation

296

1

N-linked (GlcNAc...) Ref.22

CAR_000053

Glycosylation

325

1

N-linked (GlcNAc...)

Disulfide bond

Disulfide bond

Disulfide bond

Natural variations

Natural variant

191

1

K → E. [dbSNP:rs28917504] Ref.8

VAR_023459

Natural variant

227

1

F → S. [dbSNP:rs11064419] Ref.8

VAR_023460

Natural variant

265

1

R → W in OKT4-negative populations. [dbSNP:rs28919570] Ref.8 Ref.5 Ref.14

VAR_003906

Experimental info

Mutagenesis

432

1

M → T: No effect. Ref.19 Ref.17

Mutagenesis

433

1

S → A: No effect. Ref.19 Ref.17

Mutagenesis

438 – 439

2

LL → AA: Loss of Nef-induced CD4 down-modulation. Ref.19

Mutagenesis

440

1

S → L: No effect. Ref.19 Ref.17

Mutagenesis

457 – 458

2

Missing: Abolished interaction with SPG21 and induced T-cell activation. Ref.19

Secondary structure

1

.

458

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P01730-1 [UniParc].

Last modified November 1, 1988. Version 1.
Checksum: 20ED893F9E56D236
Show »

FASTA

458

51,111

        10         20         30         40         50         60 
MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGDTVELT CTASQKKSIQ FHWKNSNQIK 

        70         80         90        100        110        120 
ILGNQGSFLT KGPSKLNDRA DSRRSLWDQG NFPLIIKNLK IEDSDTYICE VEDQKEEVQL 

       130        140        150        160        170        180 
LVFGLTANSD THLLQGQSLT LTLESPPGSS PSVQCRSPRG KNIQGGKTLS VSQLELQDSG 

       190        200        210        220        230        240 
TWTCTVLQNQ KKVEFKIDIV VLAFQKASSI VYKKEGEQVE FSFPLAFTVE KLTGSGELWW 

       250        260        270        280        290        300 
QAERASSSKS WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA 

       310        320        330        340        350        360 
LEAKTGKLHQ EVNLVVMRAT QLQKNLTCEV WGPTSPKLML SLKLENKEAK VSKREKAVWV 

       370        380        390        400        410        420 
LNPEAGMWQC LLSDSGQVLL ESNIKVLPTW STPVQPMALI VLGGVAGLLL FIGLGIFFCV 

       430        440        450 
RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family." Maddon P.J., Littman D.R., Godfrey M., Maddon D.E., Chess L., Axel R. Cell 42:93-104(1985) [PubMed: 2990730] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Corrected CD4 sequence." Littman D.R., Maddon P.J., Axel R. Cell 55:541-541(1988) [PubMed: 3263213] [Abstract] Cited for: SEQUENCE REVISION TO 26.
[3]	"A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13." Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S., Malley T., Gibbs R.A. Genome Res. 6:314-326(1996) [PubMed: 8723724] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination." Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A. Genome Res. 7:268-280(1997) [PubMed: 9074930] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Brain.
[5]	"Humans with OKT4-epitope deficiency have a single nucleotide base change in the CD4 gene, resulting in substitution of TRP240 for ARG240." Hodge T.W., Sasso D.R., McDougal J.S. Hum. Immunol. 30:99-104(1991) [PubMed: 1708753] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TRP-265.
[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]	"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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[8]	NIEHS SNPs program Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLU-191; SER-227 AND TRP-265.
[9]	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. Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[11]	"Cloning and sequences of primate CD4 molecules: diversity of the cellular receptor for simian immunodeficiency virus/human immunodeficiency virus." Fomsgaard A., Hirsch V.M., Johnson P.R. Eur. J. Immunol. 22:2973-2981(1992) [PubMed: 1425921] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-424. Tissue: Blood.
[12]	"Protein and carbohydrate structural analysis of a recombinant soluble CD4 receptor by mass spectrometry." Carr S.A., Hemling M.E., Folena-Wasserman G., Sweet R.W., Anumula K., Barr J.R., Huddleston M.J., Taylor P. J. Biol. Chem. 264:21286-21295(1989) [PubMed: 2592374] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-394, DISULFIDE BOND.
[13]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-40.
[14]	"A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4." Lederman S., DeMartino J.A., Daugherty B.L., Foeldvari I., Yellin M.J., Cleary A.M., Berkowitz N., Lowy I., Braunstein N.S., Mark G.E. Mol. Immunol. 28:1171-1181(1991) [PubMed: 1961196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 250-280, VARIANT TRP-265.
[15]	"CD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor." Crise B., Buonocore L., Rose J.K. J. Virol. 64:5585-5593(1990) [PubMed: 2214026] [Abstract] Cited for: INTERACTION WITH HIV-1 ENVELOPE POLYPROTEIN GP160.
[16]	"Identification of palmitoylation sites on CD4, the human immunodeficiency virus receptor." Crise B., Rose J.K. J. Biol. Chem. 267:13593-13597(1992) [PubMed: 1618861] [Abstract] Cited for: PALMITOYLATION AT CYS-419 AND CYS-422.
[17]	"Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain." Aiken C., Konner J., Landau N.R., Lenburg M.E., Trono D. Cell 76:853-864(1994) [PubMed: 8124721] [Abstract] Cited for: REMOVAL FROM CELL SURFACE BY HIV-1 NEF, MUTAGENESIS OF MET-432; SER-433; 438-LEU-LEU-439 AND SER-440.
[18]	"CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus." Lusso P., Secchiero P., Crowley R.W., Garzino-Demo A., Berneman Z.N., Gallo R.C. Proc. Natl. Acad. Sci. U.S.A. 91:3872-3876(1994) [PubMed: 7909607] [Abstract] Cited for: INTERACTION WITH HUMAN HERPESVIRUS 7 CAPSID PROTEINS.
[19]	"Cloning of ACP33 as a novel intracellular ligand of CD4." Zeitlmann L., Sirim P., Kremmer E., Kolanus W. J. Biol. Chem. 276:9123-9132(2001) [PubMed: 11113139] [Abstract] Cited for: INTERACTION WITH SPG21, MUTAGENESIS OF 457-PRO-ILE-458.
[20]	"Lipid raft distribution of CD4 depends on its palmitoylation and association with Lck, and evidence for CD4-induced lipid raft aggregation as an additional mechanism to enhance CD3 signaling." Fragoso R., Ren D., Zhang X., Su M.W., Burakoff S.J., Jin Y.J. J. Immunol. 170:913-921(2003) [PubMed: 12517957] [Abstract] Cited for: SUBCELLULAR LOCATION.
[21]	"Protein minimization of the gp120 binding region of human CD4." Sharma D., Balamurali M.M., Chakraborty K., Kumaran S., Jeganathan S., Rashid U., Ingallinella P., Varadarajan R. Biochemistry 44:16192-16202(2005) [PubMed: 16331979] [Abstract] Cited for: INTERACTION WITH HIV-1 SURFACE PROTEIN GP120.
[22]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-296, MASS SPECTROMETRY. Tissue: Liver.
[23]	"Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains." Wang J., Yan Y., Garrett T.P., Liu J., Rodgers D.W., Garlick R.L., Tarr G.E., Husain Y., Reinherz E.L., Harrison S.C. Nature 348:411-418(1990) [PubMed: 1701030] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 26-208.
[24]	"Crystal structure of an HIV-binding recombinant fragment of human CD4." Ryu S.-E., Kwong P.D., Truneh A., Porter T.G., Arthos J., Rosenberg M., Dai X., Xuong N.-H., Axel R., Sweet R.W., Hendrickson W.A. Nature 348:419-426(1990) [PubMed: 2247146] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 26-208.
[25]	"Dimeric association and segmental variability in the structure of human CD4." Wu H., Kwong P.D., Hendrickson W.A. Nature 387:527-530(1997) [PubMed: 9168119] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.9 ANGSTROMS) OF 26-388.
[26]	"Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody." Kwong P.D., Wyatt R., Robinson J., Sweet R.W., Sodroski J., Hendrickson W.A. Nature 393:648-659(1998) [PubMed: 9641677] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 26-208 IN COMPLEX WITH HIV SURFACE PROTEIN GP120.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

CD4 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M12807 mRNA. Translation: AAA35572.1.
U47924 Genomic DNA. Translation: AAB51309.1.
M35160 mRNA. Translation: AAA16069.1.
BT019791 mRNA. Translation: AAV38594.1.
BT019811 mRNA. Translation: AAV38614.1.
DQ012936 Genomic DNA. Translation: AAY22175.1.
AK312828 mRNA. Translation: BAG35684.1.
CH471116 Genomic DNA. Translation: EAW88738.1.
BC025782 mRNA. Translation: AAH25782.1.

IPI

IPI00003983.

PIR

RWHUT4. A90872.

RefSeq

NP_000607.1.

UniGene

Hs.631659.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CDH	X-ray	2.30	A	26-203	[»]
1CDI	X-ray	2.90	A	26-203	[»]
1CDJ	X-ray	2.50	A	26-203	[»]
1CDU	X-ray	2.70	A	26-203	[»]
1CDY	X-ray	2.00	A	26-203	[»]
1G9M	X-ray	2.20	C	26-208	[»]
1G9N	X-ray	2.90	C	26-208	[»]
1GC1	X-ray	2.50	C	26-208	[»]
1JL4	X-ray	4.30	D	26-203	[»]
1OPN	model	-	C	26-206	[»]
1OPT	model	-	C	26-206	[»]
1OPW	model	-	C	26-206	[»]
1Q68	NMR	-	A	421-458	[»]
1RZJ	X-ray	2.20	C	26-208	[»]
1RZK	X-ray	2.90	C	26-208	[»]
1WBR	NMR	-	A	428-444	[»]
1WIO	X-ray	3.90	A/B	26-388	[»]
1WIP	X-ray	4.00	A/B	26-388	[»]
1WIQ	X-ray	5.00	A/B	26-388	[»]
2B4C	X-ray	3.30	C	26-206	[»]
2JKR	X-ray	2.98	P/Q	431-441	[»]
2JKT	X-ray	3.40	P/Q	431-441	[»]
2KLU	NMR	-	A	397-458	[»]
2NXY	X-ray	2.00	B	26-208	[»]
2NXZ	X-ray	2.04	B	26-208	[»]
2NY0	X-ray	2.20	B	26-208	[»]
2NY1	X-ray	1.99	B	26-208	[»]
2NY2	X-ray	2.00	B	26-208	[»]
2NY3	X-ray	2.00	B	26-208	[»]
2NY4	X-ray	2.00	B	26-208	[»]
2NY5	X-ray	2.50	C	26-208	[»]
2NY6	X-ray	2.80	B	26-208	[»]
2QAD	X-ray	3.30	B/F	26-206	[»]
3B71	X-ray	2.82	D/E/F	428-450	[»]
3CD4	X-ray	2.20	A	26-207	[»]
3JWD	X-ray	2.61	C/D	26-208	[»]
3JWO	X-ray	3.51	C	26-208	[»]
3LQA	X-ray	3.40	C	26-207	[»]

ProteinModelPortal

P01730.

DisProt

DP00123.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-617N.

MINT

MINT-1130311.

STRING

P01730.

PTM databases

GlycoSuiteDB

P01730.

PhosphoSite

P01730.

Proteomic databases

PeptideAtlas

P01730.

PRIDE

P01730.

Genome annotation databases

Ensembl

ENST00000011653; ENSP00000011653; ENSG00000010610; Homo sapiens. [Genome view]

GeneID

920.

KEGG

hsa:920.

UCSC

uc001qqv.1. human.

Organism-specific databases

CTD

920.

GeneCards

GC12P006899.

H-InvDB

HIX0023001.

HGNC

HGNC:1678. CD4.

HPA

CAB000011.
HPA004252.
HPA004472.

MIM

186940. gene+phenotype.

PharmGKB

PA24403.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18997.

HOGENOM

HBG126620.

HOVERGEN

HBG005281.

InParanoid

P01730.

OMA

QAERMSQ.

OrthoDB

EOG9SFCS8.

PhylomeDB

P01730.

Enzyme and pathway databases

Pathway_Interaction_DB

arf_3pathway. Arf1 pathway.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
il23pathway. IL23-mediated signaling events.
tcrpathway. TCR signaling in naive CD4+ T cells.

Reactome

REACT_6185. HIV Infection.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P01730.

Bgee

P01730.

CleanEx

HS_CD4.

Genevestigator

P01730.

GermOnline

ENSG00000010610. Homo sapiens.

Family and domain databases

InterPro

IPR000973. Ag_CD4.
IPR015274. CD4-extracel.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR008424. Ig_C2-set.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR003596. Ig_V-set_sub.
IPR021963. Tcell_CD4_Cterm.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 4 hits.

Pfam

PF05790. C2-set. 2 hits.
PF09191. CD4-extracel. 1 hit.
PF12104. Tcell_CD4_Cterm. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

PRINTS

PR00692. CD4TCANTIGEN.

SMART

SM00409. IG. 2 hits.
SM00406. IGv. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

3806.

SOURCE

Search...

Entry information

Entry name

CD4_HUMAN

Accession

Primary (citable) accession number: P01730
Secondary accession number(s): B2R737

Q9UDE5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	November 1, 1988
Last modified:	August 10, 2010
This is version 137 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.