P49759 (CLK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual specificity protein kinase CLK1
EC=2.7.12.1

Alternative name(s):
CDC-like kinase 1

Gene names

Name:	CLK1
Synonyms:	CLK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	484 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA. Ref.7 Ref.13
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Regulates splicing of its own pre-mRNA according to its kinase activity; increased expression of the catalytically active form influences splicing to generate the catalytically inactive splicing variant lacking the kinase domain. Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins By similarity.
Subunit structure	Interacts with PPIG and UBL5. Ref.8
Subcellular location	Nucleus.
Tissue specificity	Endothelial cells. Ref.13
Post-translational modification	Autophosphorylates on all three types of residues By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell proliferation Traceable author statement. Source: ProtInc regulation of RNA splicing Inferred from mutant phenotype Ref.13. Source: UniProtKB
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Traceable author statement. Source: ProtInc protein serine/threonine kinase activity Inferred from direct assay Ref.7. Source: UniProtKB protein serine/threonine/tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P49759-1)

Also known as: Long;

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: P49759-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     131-136: KSHRRK → MKLLIL
     137-484: Missing.

Note: Lacks the kinase domain. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 484

484

Dual specificity protein kinase CLK1

PRO_0000085866

Regions

Domain

161 – 477

317

Protein kinase

Nucleotide binding

167 – 175

9

ATP By similarity

Sites

Active site

288

1

Proton acceptor By similarity

Binding site

191

1

ATP By similarity

Amino acid modifications

Modified residue

37

1

Phosphoserine Ref.11

Modified residue

61

1

Phosphoserine Ref.11 Ref.14

Modified residue

138

1

Phosphothreonine Ref.10 Ref.11 Ref.12 Ref.14

Modified residue

140

1

Phosphoserine Ref.10 Ref.11 Ref.12 Ref.14

Modified residue

330

1

Phosphothreonine Ref.14

Modified residue

338

1

Phosphothreonine Ref.14

Modified residue

341

1

Phosphoserine Ref.11 Ref.14

Modified residue

342

1

Phosphothreonine Ref.11

Natural variations

Alternative sequence

131 – 136

6

KSHRRK → MKLLIL in isoform 2.

VSP_004852

Alternative sequence

137 – 484

348

Missing in isoform 2.

VSP_004853

Natural variant

61

1

S → F. Ref.15
Corresponds to variant rs55989135 [ dbSNP | Ensembl ].

VAR_040409

Natural variant

99

1

N → D.
Corresponds to variant rs6735666 [ dbSNP | Ensembl ].

VAR_046551

Natural variant

118

1

R → G. Ref.15
Corresponds to variant rs56135616 [ dbSNP | Ensembl ].

VAR_040410

Natural variant

307

1

P → S. Ref.15
Corresponds to variant rs35412475 [ dbSNP | Ensembl ].

VAR_040411

Natural variant

440

1

M → T. Ref.15
Corresponds to variant rs35393352 [ dbSNP | Ensembl ].

VAR_040412

Natural variant

459

1

E → G.
Corresponds to variant rs12709 [ dbSNP | Ensembl ].

VAR_051620

Experimental info

Sequence conflict

432

1

R → A in AAA61480. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

484

Helix Strand Turn

Details...

Turn

158 – 160

3

Beta strand

161 – 170

10

Beta strand

173 – 180

8

Turn

181 – 185

5

Beta strand

187 – 193

7

Helix

197 – 216

20

Beta strand

227 – 233

7

Beta strand

236 – 242

7

Helix

248 – 254

7

Turn

255 – 257

3

Helix

262 – 281

20

Helix

291 – 293

3

Beta strand

294 – 297

4

Beta strand

301 – 305

5

Beta strand

312 – 317

6

Beta strand

321 – 323

3

Helix

343 – 345

3

Helix

348 – 351

4

Helix

359 – 374

16

Helix

384 – 395

12

Helix

400 – 405

6

Helix

409 – 411

3

Helix

424 – 432

9

Helix

436 – 439

4

Helix

445 – 457

13

Turn

462 – 464

3

Helix

468 – 471

4

Helix

475 – 481

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified September 23, 2008. Version 2. Checksum: F34B5B44988BD118	FASTA	484	57,291
	10 20 30 40 50 60 MRHSKRTYCP DWDDKDWDYG KWRSSSSHKR RKRSHSSAQE NKRCKYNHSK MCDSHYLESR 70 80 90 100 110 120 SINEKDYHSR RYIDEYRNDY TQGCEPGHRQ RDHESRYQNH SSKSSGRSGR SSYKSKHRIH 130 140 150 160 170 180 HSTSHRRSHG KSHRRKRTRS VEDDEEGHLI CQSGDVLSAR YEIVDTLGEG AFGKVVECID 190 200 210 220 230 240 HKAGGRHVAV KIVKNVDRYC EAARSEIQVL EHLNTTDPNS TFRCVQMLEW FEHHGHICIV 250 260 270 280 290 300 FELLGLSTYD FIKENGFLPF RLDHIRKMAY QICKSVNFLH SNKLTHTDLK PENILFVQSD 310 320 330 340 350 360 YTEAYNPKIK RDERTLINPD IKVVDFGSAT YDDEHHSTLV STRHYRAPEV ILALGWSQPC 370 380 390 400 410 420 DVWSIGCILI EYYLGFTVFP THDSKEHLAM MERILGPLPK HMIQKTRKRK YFHHDRLDWD 430 440 450 460 470 480 EHSSAGRYVS RRCKPLKEFM LSQDVEHERL FDLIQKMLEY DPAKRITLRE ALKHPFFDLL KKSI
	Isoform 2 (Short) [UniParc]. Checksum: 3A1B92FD19E2A521	FASTA	136	16,570
	10 20 30 40 50 60 MRHSKRTYCP DWDDKDWDYG KWRSSSSHKR RKRSHSSAQE NKRCKYNHSK MCDSHYLESR 70 80 90 100 110 120 SINEKDYHSR RYIDEYRNDY TQGCEPGHRQ RDHESRYQNH SSKSSGRSGR SSYKSKHRIH 130 HSTSHRRSHG MKLLIL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a novel human cdc2/CDC28-like protein kinase." Johnson K.W., Smith K.A. J. Biol. Chem. 266:3402-3407(1991) [PubMed: 1704889] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases." Hanes J.J., der Kammer H., Klaudiny J.J., Scheit K.H. J. Mol. Biol. 244:665-672(1994) [PubMed: 7990150] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 1 AND 2). Tissue: Blood and Bone.
[7]	"The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B." Moeslein F.M., Myers M.P., Landreth G.E. J. Biol. Chem. 274:26697-26704(1999) [PubMed: 10480872] [Abstract] Cited for: FUNCTION.
[8]	"Beacon interacts with cdc2/cdc28-like kinases." Kantham L., Kerr-Bayles L., Godde N., Quick M., Webb R., Sunderland T., Bond J., Walder K., Augert G., Collier G. Biochem. Biophys. Res. Commun. 304:125-129(2003) [PubMed: 12705895] [Abstract] Cited for: INTERACTION WITH UBL5.
[9]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138 AND SER-140, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; SER-61; THR-138; SER-140; SER-341 AND THR-342, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-138 AND SER-140, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells." Eisenreich A., Bogdanov V.Y., Zakrzewicz A., Pries A., Antoniak S., Poller W., Schultheiss H.P., Rauch U. Circ. Res. 104:589-599(2009) [PubMed: 19168442] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[14]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61; THR-138; SER-140; THR-330; THR-338 AND SER-341, MASS SPECTROMETRY.
[15]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] PHE-61; GLY-118; SER-307 AND THR-440.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L29219 mRNA. Translation: AAA61480.1.
L29222 mRNA. Translation: AAB59459.1.
AK289365 mRNA. Translation: BAF82054.1.
AC005037 Genomic DNA. Translation: AAY14722.1.
CH471063 Genomic DNA. Translation: EAW70217.1.
BC028149 mRNA. Translation: AAH28149.1.
BC031549 mRNA. Translation: AAH31549.1.

IPI

IPI00028061.
IPI00966856.

PIR

S53641.

RefSeq

NP_004062.2. NM_004071.3.

UniGene

Hs.433732.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z57	X-ray	1.70	A	148-484	[»]
2VAG	X-ray	1.80	A	148-484	[»]

ProteinModelPortal

P49759.

SMR

P49759. Positions 148-482.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49759. 3 interactions.

MINT

MINT-1416122.

STRING

P49759.

PTM databases

PhosphoSite

P49759.

Polymorphism databases

DMDM

206729857.

Proteomic databases

PRIDE

P49759.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000321356; ENSP00000326830; ENSG00000013441.
ENST00000434813; ENSP00000394734; ENSG00000013441.

GeneID

1195.

KEGG

hsa:1195.

Organism-specific databases

CTD

1195.

GeneCards

GC02M201717.

H-InvDB

HIX0002728.

HGNC

HGNC:2068. CLK1.

HPA

CAB033141.

MIM

601951. gene.

neXtProt

NX_P49759.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19552.

GeneTree

ENSGT00580000081366.

HOVERGEN

HBG107720.

InParanoid

P49759.

OrthoDB

EOG4XD3R2.

PhylomeDB

P49759.

Enzyme and pathway databases

BRENDA

2.7.12.1. 2681.

Gene expression databases

ArrayExpress

P49759.

Bgee

P49759.

CleanEx

HS_CLK1.

Genevestigator

P49759.

GermOnline

ENSG00000013441. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

KO

K08823.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

4936.

SOURCE

Search...

Entry information

Entry name

CLK1_HUMAN

Accession

Primary (citable) accession number: P49759
Secondary accession number(s): Q0P694, Q8N5V8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	September 23, 2008
Last modified:	January 25, 2012
This is version 118 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.