P55075 (FGF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fibroblast growth factor 8
Short name=FGF-8

Alternative name(s):
Androgen-induced growth factor
Short name=AIGF
Heparin-binding growth factor 8
Short name=HBGF-8

Gene names

Name:	FGF8
Synonyms:	AIGF

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	233 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	Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. Required for normal brain, eye, ear and limb development during embryogenesis. Required for normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Ref.9 Ref.10 Ref.12
Subunit structure	Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Ref.9 Ref.10
Subcellular location	Secreted.
Developmental stage	In adults expression is restricted to the gonads.
Involvement in disease	Hypogonadotropic hypogonadism 6 with or without anosmia (HH6) [MIM:612702]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Belongs to the heparin-binding growth factors family.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Hypogonadotropic hypogonadism Kallmann syndrome
Domain	Signal
Molecular function	Developmental protein Growth factor Mitogen
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from electronic annotation. Source: Compara MAPK cascade Inferred from electronic annotation. Source: Compara aorta morphogenesis Inferred from electronic annotation. Source: Compara apoptotic process Inferred from electronic annotation. Source: Compara blood vessel remodeling Inferred from electronic annotation. Source: Compara bone development Inferred from mutant phenotype Ref.13. Source: UniProtKB branching involved in salivary gland morphogenesis Inferred from electronic annotation. Source: Compara branching involved in ureteric bud morphogenesis Inferred from electronic annotation. Source: Compara canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara cell migration involved in mesendoderm migration Inferred from electronic annotation. Source: Compara cell proliferation in forebrain Inferred from electronic annotation. Source: Compara corticotropin hormone secreting cell differentiation Inferred from electronic annotation. Source: Compara dopaminergic neuron differentiation Inferred from direct assay PubMed 15193767. Source: UniProtKB embryonic hindlimb morphogenesis Inferred from electronic annotation. Source: Compara epithelial to mesenchymal transition involved in endocardial cushion formation Inferred from sequence or structural similarity. Source: BHF-UCL fibroblast growth factor receptor signaling pathway Inferred from genetic interaction Ref.9. Source: MGI forebrain dorsal/ventral pattern formation Inferred from electronic annotation. Source: Compara forebrain morphogenesis Inferred from electronic annotation. Source: Compara gastrulation Non-traceable author statement Ref.4. Source: UniProtKB gonad development Inferred from mutant phenotype Ref.13. Source: UniProtKB heart looping Inferred from electronic annotation. Source: Compara insulin receptor signaling pathway Traceable author statement. Source: Reactome lung morphogenesis Inferred from electronic annotation. Source: Compara male genitalia development Inferred from electronic annotation. Source: Compara mesodermal cell migration Inferred from electronic annotation. Source: Compara mesonephros development Inferred from expression pattern PubMed 18437684. Source: UniProtKB metanephros development Inferred from expression pattern PubMed 18437684. Source: UniProtKB midbrain-hindbrain boundary development Inferred from electronic annotation. Source: Compara negative regulation of cardiac muscle tissue development Inferred from mutant phenotype PubMed 20702560. Source: BHF-UCL negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara neural plate morphogenesis Inferred from electronic annotation. Source: Compara neuroepithelial cell differentiation Inferred from direct assay PubMed 17309880. Source: UniProtKB odontogenesis Inferred from expression pattern PubMed 17394220. Source: UniProtKB organ induction Inferred from electronic annotation. Source: Compara otic vesicle formation Inferred from electronic annotation. Source: Compara outflow tract septum morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB pallium development Inferred from electronic annotation. Source: Compara patterning of blood vessels Inferred from electronic annotation. Source: Compara pharyngeal system development Inferred from electronic annotation. Source: Compara positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Inferred from direct assay PubMed 17265164. Source: UniProtKB positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of mitosis Inferred from electronic annotation. Source: Compara positive regulation of organ growth Inferred from electronic annotation. Source: Compara regulation of odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara signal transduction involved in regulation of gene expression Inferred from electronic annotation. Source: Compara subpallium development Inferred from electronic annotation. Source: Compara thyroid gland development Inferred from electronic annotation. Source: Compara thyroid-stimulating hormone-secreting cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	growth factor activity Inferred from direct assay Ref.2PubMed 17265164. Source: UniProtKB type 1 fibroblast growth factor receptor binding Inferred from direct assay Ref.12. Source: UniProtKB type 2 fibroblast growth factor receptor binding Inferred from direct assay Ref.12. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Note: Additional isoforms seem to exist.

Isoform FGF-8E (identifier: P55075-1)

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 FGF-8A (identifier: P55075-2)

The sequence of this isoform differs from the canonical sequence as follows:
     24-52: Missing.

Isoform FGF-8B (identifier: P55075-3)

The sequence of this isoform differs from the canonical sequence as follows:
     24-51: EGPGRGPALGRELASLFRAGREPQGVSQ → VTVQSSPNFT

Isoform FGF-8F (identifier: P55075-4)

The sequence of this isoform differs from the canonical sequence as follows:
     52-52: Q → QVTVQSSPNFTQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 233

211

Fibroblast growth factor 8

PRO_0000008970

Amino acid modifications

Glycosylation

155

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

24 – 52

29

Missing in isoform FGF-8A.

VSP_001525

Alternative sequence

24 – 51

28

EGPGR…QGVSQ → VTVQSSPNFT in isoform FGF-8B.

VSP_001524

Alternative sequence

52

1

Q → QVTVQSSPNFTQ in isoform FGF-8F.

VSP_001526

Natural variant

14

1

H → N in HH6; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism. Ref.13

VAR_057962

Natural variant

26

1

P → L in HH6; phenotype consistent with Kallmann syndrome. Ref.13

VAR_057963

Natural variant

40

1

F → L in HH6; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism. Ref.13

VAR_057964

Natural variant

89

1

K → E in HH6; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism. Ref.13

VAR_057965

Natural variant

116

1

R → G in HH6; phenotype consistent with Kallmann syndrome. Ref.13

VAR_057966

Natural variant

218

1

T → M in HH6; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism. Ref.13

VAR_057967

Secondary structure

1

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233

Helix Strand Turn

Details...

Helix

52 – 57

6

Beta strand

63 – 65

3

Beta strand

69 – 76

8

Turn

77 – 79

3

Beta strand

80 – 85

6

Beta strand

91 – 95

5

Helix

100 – 102

3

Beta strand

104 – 110

7

Turn

111 – 113

3

Beta strand

114 – 119

6

Turn

120 – 122

3

Beta strand

125 – 128

4

Beta strand

134 – 138

5

Helix

143 – 145

3

Beta strand

146 – 151

6

Beta strand

157 – 164

8

Helix

180 – 182

3

Helix

188 – 190

3

Beta strand

192 – 195

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform FGF-8E [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 4C1EAF932A3A211D	FASTA	233	26,525
	10 20 30 40 50 60 MGSPRSALSC LLLHLLVLCL QAQEGPGRGP ALGRELASLF RAGREPQGVS QQHVREQSLV 70 80 90 100 110 120 TDQLSRRLIR TYQLYSRTSG KHVQVLANKR INAMAEDGDP FAKLIVETDT FGSRVRVRGA 130 140 150 160 170 180 ETGLYICMNK KGKLIAKSNG KGKDCVFTEI VLENNYTALQ NAKYEGWYMA FTRKGRPRKG 190 200 210 220 230 SKTRQHQREV HFMKRLPRGH HTTEQSLRFE FLNYPPFTRS LRGSQRTWAP EPR
	Isoform FGF-8A [UniParc]. Checksum: 9A4CAB7686A2B190	FASTA	204	23,522
	10 20 30 40 50 60 MGSPRSALSC LLLHLLVLCL QAQHVREQSL VTDQLSRRLI RTYQLYSRTS GKHVQVLANK 70 80 90 100 110 120 RINAMAEDGD PFAKLIVETD TFGSRVRVRG AETGLYICMN KKGKLIAKSN GKGKDCVFTE 130 140 150 160 170 180 IVLENNYTAL QNAKYEGWYM AFTRKGRPRK GSKTRQHQRE VHFMKRLPRG HHTTEQSLRF 190 200 EFLNYPPFTR SLRGSQRTWA PEPR
	Isoform FGF-8B [UniParc]. Checksum: A39424271EF7CBFF	FASTA	215	24,711
	10 20 30 40 50 60 MGSPRSALSC LLLHLLVLCL QAQVTVQSSP NFTQHVREQS LVTDQLSRRL IRTYQLYSRT 70 80 90 100 110 120 SGKHVQVLAN KRINAMAEDG DPFAKLIVET DTFGSRVRVR GAETGLYICM NKKGKLIAKS 130 140 150 160 170 180 NGKGKDCVFT EIVLENNYTA LQNAKYEGWY MAFTRKGRPR KGSKTRQHQR EVHFMKRLPR 190 200 210 GHHTTEQSLR FEFLNYPPFT RSLRGSQRTW APEPR
	Isoform FGF-8F [UniParc]. Checksum: 73DA5874CA918E6A	FASTA	244	27,715
	10 20 30 40 50 60 MGSPRSALSC LLLHLLVLCL QAQEGPGRGP ALGRELASLF RAGREPQGVS QQVTVQSSPN 70 80 90 100 110 120 FTQHVREQSL VTDQLSRRLI RTYQLYSRTS GKHVQVLANK RINAMAEDGD PFAKLIVETD 130 140 150 160 170 180 TFGSRVRVRG AETGLYICMN KKGKLIAKSN GKGKDCVFTE IVLENNYTAL QNAKYEGWYM 190 200 210 220 230 240 AFTRKGRPRK GSKTRQHQRE VHFMKRLPRG HHTTEQSLRF EFLNYPPFTR SLRGSQRTWA PEPR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human androgen-induced growth factor in prostate and breast cancer cells: its molecular cloning and growth properties." Tanaka A., Miyamoto K., Matsuo H., Matsumoto K., Yoshida H. FEBS Lett. 363:226-230(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM FGF-8A).
[2]	"Molecular cloning and characterization of human FGF8 alternative messenger RNA forms." Ghosh A.K., Shankar D.B., Shackleford G.M., Wu K., T'Ang A., Miller G.J., Zheng J., Roy-Burman P. Cell Growth Differ. 7:1425-1434(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS FGF-8A; FGF-8B AND FGF-8E). Tissue: Prostate.
[3]	"Structure and sequence of human FGF8." Gemel J., Gorry M., Ehrlich G.D., Macarthur C.A. Genomics 35:253-257(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS FGF-8B; FGF-8E AND FGF-8F). Tissue: Placenta.
[4]	"The human FGF-8 gene localizes on chromosome 10q24 and is subjected to induction by androgen in breast cancer cells." Payson R.A., Wu J., Liu Y., Chiu I.-M. Oncogene 13:47-53(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS FGF-8A AND FGF-8F).
[5]	"A novel isoform of human fibroblast growth factor 8 is induced by androgens and associated with progression of esophageal carcinoma." Tanaka S., Ueo H., Mafune K., Mori M., Wands J.R., Sugimachi K. Dig. Dis. Sci. 46:1016-1021(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM FGF-8F). Tissue: Esophageal carcinoma.
[6]	NIEHS SNPs program Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM FGF-8F).
[7]	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].
[8]	"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 FGF-8A).
[9]	"Receptor specificity of the fibroblast growth factor family." Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F., Gao G., Goldfarb M. J. Biol. Chem. 271:15292-15297(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FGFR3 AND FGFR4, FUNCTION IN CELL PROLIFERATION.
[10]	"Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family." Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M. J. Biol. Chem. 281:15694-15700(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FGFR1; FGFR2; FGFR3 AND FGFR4, FUNCTION IN STIMULATION OF CELL PROLIFERATION.
[11]	"Fibroblast growth factor signalling: from development to cancer." Turner N., Grose R. Nat. Rev. Cancer 10:116-129(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain." Olsen S.K., Li J.Y.H., Bromleigh C., Eliseenkova A.V., Ibrahimi O.A., Lao Z., Zhang F., Linhardt R.J., Joyner A.L., Mohammadi M. Genes Dev. 20:185-198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 52-204 IN COMPLEX WITH FGFR2, FUNCTION.
[13]	"Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice." Falardeau J., Chung W.C.J., Beenken A., Raivio T., Plummer L., Sidis Y., Jacobson-Dickman E.E., Eliseenkova A.V., Ma J., Dwyer A., Quinton R., Na S., Hall J.E., Huot C., Alois N., Pearce S.H., Cole L.W., Hughes V. , Mohammadi M., Tsai P., Pitteloud N. J. Clin. Invest. 118:2822-2831(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HH6 ASN-14; LEU-26; LEU-40; GLU-89; GLY-116 AND MET-218.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S78466 , S78462, S78463, S78464, S78465 Genomic DNA. Translation: AAB34255.1.
D38752 Genomic DNA. Translation: BAA22527.1.
U46213 mRNA. Translation: AAB40955.1.
U46212 mRNA. Translation: AAB40954.1.
U46211 mRNA. Translation: AAB40953.1.
U47011, U47009, U47010 Genomic DNA. Translation: AAC50784.1.
U47011, U47009, U47010 Genomic DNA. Translation: AAC50785.1.
U47011, U47009, U47010 Genomic DNA. Translation: AAC50782.1.
U36223 mRNA. Translation: AAB17893.1.
U36228 , U36225, U36226, U36227 Genomic DNA. Translation: AAB17894.1.
U47011, U47009, U47010 Genomic DNA. Translation: AAC50783.1.
U56978 mRNA. Translation: AAB03787.1.
AB014615 mRNA. Translation: BAA28605.1.
AF520763 Genomic DNA. Translation: AAM55238.1.
CH471066 Genomic DNA. Translation: EAW49746.1.
BC128235 mRNA. Translation: AAI28236.1.

IPI

IPI00183471.
IPI00218332.
IPI00218333.
IPI00219933.

RefSeq

NP_006110.1. NM_006119.4.
NP_149353.1. NM_033163.3.
NP_149354.1. NM_033164.3.
NP_149355.1. NM_033165.3.

UniGene

Hs.57710.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FDB	X-ray	2.28	M/N	52-204	[»]

ProteinModelPortal

P55075.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59630N.

STRING

9606.ENSP00000321797.

PTM databases

PhosphoSite

P55075.

Polymorphism databases

DMDM

1706791.

Proteomic databases

PaxDb

P55075.

PRIDE

P55075.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000320185; ENSP00000321797; ENSG00000107831.
ENST00000344255; ENSP00000340039; ENSG00000107831.
ENST00000346714; ENSP00000344306; ENSG00000107831.
ENST00000347978; ENSP00000321945; ENSG00000107831.

GeneID

2253.

KEGG

hsa:2253.

UCSC

uc001ktp.2. human.
uc001ktq.2. human.
uc001ktr.2. human.
uc001kts.2. human.

Organism-specific databases

CTD

2253.

GeneCards

GC10M103519.

HGNC

HGNC:3686. FGF8.

MIM

600483. gene.
612702. phenotype.

neXtProt

NX_P55075.

Orphanet

93925. Alobar holoprosencephaly.
478. Kallmann syndrome.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
432. Normosmic congenital hypogonadotropic hypogonadism.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.

PharmGKB

PA28125.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG327940.

HOGENOM

HOG000115986.

HOVERGEN

HBG005659.

KO

K04358.

OMA

INYPFNR.

Enzyme and pathway databases

Pathway_Interaction_DB

fgf_pathway. FGF signaling pathway.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.

Gene expression databases

Bgee

P55075.

CleanEx

HS_FGF8.

Genevestigator

P55075.

GermOnline

ENSG00000107831. Homo sapiens.

Family and domain databases

InterPro

IPR008996. Cytokine_IL1-like.
IPR002348. IL1_HBGF.
[Graphical view]

PANTHER

PTHR11486. PTHR11486. 1 hit.

Pfam

PF00167. FGF. 1 hit.
[Graphical view]

PRINTS

PR00262. IL1HBGF.

SMART

SM00442. FGF. 1 hit.
[Graphical view]

SUPFAM

SSF50353. Cytok_IL1_like. 1 hit.

PROSITE

PS00247. HBGF_FGF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P55075.

GenomeRNAi

2253.

NextBio

9121.

SOURCE

Search...

Entry information

Entry name

FGF8_HUMAN

Accession

Primary (citable) accession number: P55075
Secondary accession number(s): A1A514, Q14915, Q15766

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 120 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.