P39059 (COFA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Collagen alpha-1(XV) chain

Cleaved into the following 4 chains:

1. Restin
   Alternative name(s):
   Endostatin-XV
   Related to endostatin
   Restin-I
2. Restin-2
   Alternative name(s):
   Restin-II
3. Restin-3
   Alternative name(s):
   Restin-III
4. Restin-4
   Alternative name(s):
   Restin-IV

Gene names

Name:

COL15A1

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1388 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	Structural protein that stabilizes microvessels and muscle cells, both in heart and in skeletal muscle. Ref.8 Restin potently inhibits angiogenesis By similarity. Ref.8
Subunit structure	Trimer; disulfide-linked. Ref.7 Ref.9
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Expressed predominantly in internal organs such as adrenal gland, pancreas and kidney.
Post-translational modification	Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains. O-glycosylated; with core 1 or possibly core 8 glycans. An N-terminal peptide contains chondroitin sulfate. Ref.9 Ref.10
Sequence similarities	Belongs to the multiplexin collagen family. Contains 4 collagen-like domains. Contains 1 laminin G-like domain.
Caution	The name restin has also been used for CAP-Gly domain-containing linker protein 1 the product of the CLIP1 gene.

Ontologies

Keywords
Biological process	Angiogenesis Cell adhesion Differentiation
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Collagen Repeat Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Hydroxylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Inferred by curator Ref.2. Source: UniProtKB cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW collagen catabolic process Traceable author statement. Source: Reactome extracellular matrix disassembly Traceable author statement. Source: Reactome extracellular matrix organization Traceable author statement. Source: Reactome signal transduction Non-traceable author statement PubMed 10891348. Source: UniProtKB
Cellular_component	collagen type XV trimer Traceable author statement Ref.2. Source: UniProtKB endoplasmic reticulum lumen Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from direct assay PubMed 20551380. Source: BHF-UCL extracellular vesicular exosome Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt integral component of membrane Non-traceable author statement PubMed 10891348. Source: UniProtKB
Molecular_function	extracellular matrix structural constituent Inferred by curator Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Potential

Chain

28 – 1388

1361

Collagen alpha-1(XV) chain

PRO_0000005788

Chain

1198 – 1386

189

Restin

PRO_0000005789

Chain

1207 – 1386

180

Restin-2

PRO_0000423014

Chain

1213 – 1386

174

Restin-3

PRO_0000423015

Chain

1221 – 1386

166

Restin-4

PRO_0000423016

Regions

Domain

66 – 249

184

Laminin G-like

Repeat

358 – 408

51

1

Repeat

409 – 459

51

2

Repeat

460 – 509

50

3

Repeat

510 – 555

46

4

Domain

619 – 680

62

Collagen-like 1

Domain

681 – 731

51

Collagen-like 2

Domain

823 – 865

43

Collagen-like 3

Domain

879 – 927

49

Collagen-like 4

Region

229 – 555

327

Nonhelical region 1 (NC1)

Region

358 – 555

198

4 X tandem repeats

Region

556 – 573

18

Triple-helical region 1 (COL1)

Region

574 – 618

45

Nonhelical region 2 (NC2)

Region

619 – 732

114

Triple-helical region 2 (COL2)

Region

733 – 763

31

Nonhelical region 3 (NC3)

Region

764 – 798

35

Triple-helical region 3 (COL3)

Region

799 – 822

24

Nonhelical region 4 (NC4)

Region

823 – 867

45

Triple-helical region 4 (COL4)

Region

868 – 878

11

Nonhelical region 5 (NC5)

Region

879 – 949

71

Triple-helical region 5 (COL5)

Region

950 – 983

34

Nonhelical region 6 (NC6)

Region

984 – 1013

30

Triple-helical region 6 (COL6)

Region

1014 – 1027

14

Nonhelical region 7 (NC7)

Region

1028 – 1045

18

Triple-helical region 7 (COL7)

Region

1046 – 1052

7

Nonhelical region 8 (NC8)

Region

1053 – 1107

55

Triple-helical region 8 (COL8)

Region

1108 – 1117

10

Nonhelical region 9 (NC9)

Region

1118 – 1132

15

Triple-helical region 9 (COL9)

Region

1133 – 1388

256

Nonhelical region 10 (NC10)

Amino acid modifications

Glycosylation

265

1

O-linked (GalNAc...) Ref.10

Glycosylation

306

1

N-linked (GlcNAc...) Potential

Glycosylation

324

1

N-linked (GlcNAc...) Potential

Glycosylation

687

1

N-linked (GlcNAc...) Potential

Glycosylation

807

1

N-linked (GlcNAc...) Potential

Glycosylation

814

1

N-linked (GlcNAc...) Potential

Glycosylation

1046

1

N-linked (GlcNAc...) Potential

Disulfide bond

1237 ↔ 1377

Ref.7 Ref.9

Disulfide bond

1339 ↔ 1369

Ref.7 Ref.9

Natural variations

Natural variant

163

1

R → H.
Corresponds to variant rs2075662 [ dbSNP | Ensembl ].

VAR_033787

Natural variant

204

1

M → V. Ref.4
Corresponds to variant rs2075663 [ dbSNP | Ensembl ].

VAR_033788

Natural variant

391

1

T → M.
Corresponds to variant rs10988532 [ dbSNP | Ensembl ].

VAR_033789

Natural variant

442

1

A → T.
Corresponds to variant rs16918128 [ dbSNP | Ensembl ].

VAR_033790

Natural variant

446

1

G → R.
Corresponds to variant rs35934703 [ dbSNP | Ensembl ].

VAR_033791

Natural variant

504

1

G → V.
Corresponds to variant rs2297603 [ dbSNP | Ensembl ].

VAR_048776

Natural variant

506

1

E → D.
Corresponds to variant rs35250850 [ dbSNP | Ensembl ].

VAR_033792

Natural variant

531

1

P → R.
Corresponds to variant rs35529307 [ dbSNP | Ensembl ].

VAR_033793

Natural variant

705

1

P → L.
Corresponds to variant rs41308900 [ dbSNP | Ensembl ].

VAR_061114

Natural variant

989

1

K → R.
Corresponds to variant rs35642150 [ dbSNP | Ensembl ].

VAR_033794

Natural variant

1001

1

K → R.
Corresponds to variant rs35544077 [ dbSNP | Ensembl ].

VAR_033795

Natural variant

1332

1

V → I.
Corresponds to variant rs10519 [ dbSNP | Ensembl ].

VAR_033796

Experimental info

Sequence conflict

10

1

C → S in BAA04762. Ref.4

Sequence conflict

49

1

V → D in AAA58429. Ref.1

Sequence conflict

94 – 95

2

SV → RA in AAA58429. Ref.1

Sequence conflict

94 – 95

2

SV → RA in BAA04762. Ref.4

Sequence conflict

150

1

A → P in AAA58429. Ref.1

Sequence conflict

409

1

A → R in AAA58429. Ref.1

Sequence conflict

409

1

A → R in AAC78500. Ref.2

Sequence conflict

1134

1

L → LLGELIPIPADSPPPPALSS N in AAC78500. Ref.2

Sequence conflict

1178 – 1197

20

Missing in AAC78500. Ref.2

Sequence conflict

1227

1

F → V in AAC78500. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

1388

Helix Strand Turn

Details...

Beta strand

1135 – 1140

6

Helix

1141 – 1145

5

Helix

1146 – 1150

5

Beta strand

1155 – 1159

5

Turn

1160 – 1163

4

Beta strand

1164 – 1169

6

Beta strand

1172 – 1175

4

Sequences

	Sequence		Length	Mass (Da)
	P39059 [UniParc]. Last modified July 5, 2005. Version 2. Checksum: AF54DDCC136C3745	FASTA	1,388	141,720
	10 20 30 40 50 60 MAPRRNNGQC WCLLMLLSVS TPLPAVTQTR GATETASQGH LDLTQLIGVP LPSSVSFVTG 70 80 90 100 110 120 YGGFPAYSFG PGANVGRPAR TLIPSTFFRD FAISVVVKPS STRGGVLFAI TDAFQKVIYL 130 140 150 160 170 180 GLRLSGVEDG HQRIILYYTE PGSHVSQEAA AFSVPVMTHR WNRFAMIVQG EEVTLLVNCE 190 200 210 220 230 240 EHSRIPFQRS SQALAFESSA GIFMGNAGAT GLERFTGSLQ QLTVHPDPRT PEELCDPEES 250 260 270 280 290 300 SASGETSGLQ EADGVAEILE AVTYTQASPK EAKVEPINTP PTPSSPFEDM ELSGEPVPEG 310 320 330 340 350 360 TLETTNMSII QHSSPKQGSG EILNDTLEGV HSVDGDPITD SGSGAGAFLD IAEEKNLAAT 370 380 390 400 410 420 AAGLAEVPIS TAGEAEASSV PTGGPTLSMS TENPEEGVTP GPDNEERLAA TAAGEAEALA 430 440 450 460 470 480 SMPGEVEASG VAPGELDLSM SAQSLGEEAT VGPSSEDSLT TAAAATEVSL STFEDEEASG 490 500 510 520 530 540 VPTDGLAPLT ATMAPERAVT SGPGDEEDLA AATTEEPLIT AGGEESGSPP PDGPPLPLPT 550 560 570 580 590 600 VAPERWITPA QREHVGMKGQ AGPKGEKGDA GEELPGPPEP SGPVGPTAGA EAEGSGLGWG 610 620 630 640 650 660 SDVGSGSGDL VGSEQLLRGP PGPPGPPGLP GIPGKPGTDV FMGPPGSPGE DGPAGEPGPP 670 680 690 700 710 720 GPEGQPGVDG ATGLPGMKGE KGARGPNGSV GEKGDPGNRG LPGPPGKKGQ AGPPGVMGPP 730 740 750 760 770 780 GPPGPPGPPG PGCTMGLGFE DTEGSGSTQL LNEPKLSRPT AAIGLKGEKG DRGPKGERGM 790 800 810 820 830 840 DGASIVGPPG PRGPPGHIKV LSNSLINITH GFMNFSDIPE LVGPPGPDGL PGLPGFPGPR 850 860 870 880 890 900 GPKGDTGLPG FPGLKGEQGE KGEPGAILTE DIPLERLMGK KGEPGMHGAP GPMGPKGPPG 910 920 930 940 950 960 HKGEFGLPGR PGRPGLNGLK GTKGDPGVIM QGPPGLPGPP GPPGPPGAVI NIKGAIFPIP 970 980 990 1000 1010 1020 VRPHCKMPVD TAHPGSPELI TFHGVKGEKG SWGLPGSKGE KGDQGAQGPP GPPLDLAYLR 1030 1040 1050 1060 1070 1080 HFLNNLKGEN GDKGFKGEKG EKGDINGSFL MSGPPGLPGN PGPAGQKGET VVGPQGPPGA 1090 1100 1110 1120 1130 1140 PGLPGPPGFG RPGDPGPPGP PGPPGPPAIL GAAVALPGPP GPPGQPGLPG SRNLVTAFSN 1150 1160 1170 1180 1190 1200 MDDMLQKAHL VIEGTFIYLR DSTEFFIRVR DGWKKLQLGE LIPIPADSPP PPALSSNPHQ 1210 1220 1230 1240 1250 1260 LLPPPNPISS ANYEKPALHL AALNMPFSGD IRADFQCFKQ ARAAGLLSTY RAFLSSHLQD 1270 1280 1290 1300 1310 1320 LSTIVRKAER YSLPIVNLKG QVLFNNWDSI FSGHGGQFNM HIPIYSFDGR DIMTDPSWPQ 1330 1340 1350 1360 1370 1380 KVIWHGSSPH GVRLVDNYCE AWRTADTAVT GLASPLSTGK ILDQKAYSCA NRLIVLCIEN SFMTDARK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of the alpha 1 chain of human type XV collagen and exon-intron organization in the 3' region of the corresponding gene." Kivirikko S., Heinamaki P., Rehn M.V., Honkanen N., Myers J.C., Pihlajaniemi T. J. Biol. Chem. 269:4773-4779(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Umbilical cord.
[2]	"Complete exon-intron organization of the human gene for the alpha1 chain of type XV collagen (COL15A1) and comparison with the homologous COL18A1 gene." Haegg P.M., Muona A., Lietard J., Kivirikko S., Pihlajaniemi T. J. Biol. Chem. 273:17824-17831(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The human alpha 1(XV) collagen chain contains a large amino-terminal non-triple helical domain with a tandem repeat structure and homology to alpha 1(XVIII) collagen." Muragaki Y., Abe N., Ninomiya Y., Olsen B.R., Ooshima A. J. Biol. Chem. 269:4042-4046(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-569, VARIANT VAL-204. Tissue: Placenta.
[5]	"Identification of a previously unknown human collagen chain, alpha 1(XV), characterized by extensive interruptions in the triple-helical region." Myers J.C., Kivirikko S., Gordon M.K., Dion A.S., Pihlajaniemi T. Proc. Natl. Acad. Sci. U.S.A. 89:10144-10148(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 544-1252.
[6]	"Chromosomal assignment of a gene encoding a new collagen type (COL15A1) to 9q21 --> q22." Huebner K., Cannizzaro L.A., Jabs E.W., Kivirikko S., Manzone H., Pihlajaniemi T., Myers J.C. Genomics 14:220-224(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1105-1145, CHROMOSOMAL LOCATION. Tissue: Placenta.
[7]	"Identification and characterization of novel endogenous proteolytic forms of the human angiogenesis inhibitors restin and endostatin." John H., Radtke K., Staendker L., Forssmann W.G. Biochim. Biophys. Acta 1747:161-170(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1198-1210; 1207-1219; 1213-1225 AND 1221-1233, IDENTIFICATION OF RESTIN-RELATED PEPTIDES, DISULFIDE BOND.
[8]	"Antiangiogenic activity of restin, NC10 domain of human collagen XV: comparison to endostatin." Ramchandran R., Dhanabal M., Volk R., Waterman M.J.F., Segal M., Lu H., Knebelmann B., Sukhatme V.P. Biochem. Biophys. Res. Commun. 255:735-739(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Basement membrane zone type XV collagen is a disulfide-bonded chondroitin sulfate proteoglycan in human tissues and cultured cells." Li D., Clark C.C., Myers J.C. J. Biol. Chem. 275:22339-22347(2000) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, STRUCTURE OF CARBOHYDRATES, INTERCHAIN DISULFIDE BONDS.
[10]	"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD." Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G. Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-265, STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L25286 mRNA. Translation: AAA58429.1.
L25280 , L25281, L25282, L25283, L25284, L25285, AF052956, AF052957, AF052958, AF052959, AF052960, AF052961, AF052962, AF052963, AF052964, AF052965, AF052966, AF052967, AF052968, AF052969, AF052970, AF052971, AF052972, AF052973, AF052974, AF052975 Genomic DNA. Translation: AAC78500.1.
AL136084, AL354923 Genomic DNA. Translation: CAI17044.2.
AL354923, AL136084 Genomic DNA. Translation: CAI12548.2.
D21230 mRNA. Translation: BAA04762.1.
L01697 mRNA. No translation available.

CCDS

CCDS35081.1.

PIR

A53317.

RefSeq

NP_001846.3. NM_001855.4.

UniGene

Hs.409034.

3D structure databases

PDBe
RCSB-PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3N3F	X-ray	2.00	A/B	1133-1186	[»]

ProteinModelPortal

P39059.

SMR

P39059. Positions 1133-1186, 1215-1382.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

107702. 2 interactions.

IntAct

P39059. 2 interactions.

STRING

9606.ENSP00000364140.

Chemistry

ChEMBL

CHEMBL2364188.

PTM databases

PhosphoSite

P39059.

Polymorphism databases

DMDM

68839886.

Proteomic databases

MaxQB

P39059.

PaxDb

P39059.

PRIDE

P39059.

Protocols and materials databases

DNASU

1306.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375001; ENSP00000364140; ENSG00000204291.

GeneID

1306.

KEGG

hsa:1306.

UCSC

uc004azb.2. human.

Organism-specific databases

CTD

1306.

GeneCards

GC09P101705.

H-InvDB

HIX0008227.

HGNC

HGNC:2192. COL15A1.

HPA

HPA017913.
HPA017915.

MIM

120325. gene.

neXtProt

NX_P39059.

PharmGKB

PA26708.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG12793.

HOGENOM

HOG000231591.

HOVERGEN

HBG080337.

InParanoid

P39059.

KO

K08135.

OMA

PELITFH.

OrthoDB

EOG7NSB2B.

PhylomeDB

P39059.

TreeFam

TF315821.

Enzyme and pathway databases

Reactome

REACT_118779. Extracellular matrix organization.

Gene expression databases

Bgee

P39059.

CleanEx

HS_COL15A1.

Genevestigator

P39059.

Family and domain databases

Gene3D

3.10.100.10. 1 hit.

InterPro

IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
IPR008160. Collagen.
IPR010515. Collagenase_NC10/endostatin.
IPR008985. ConA-like_lec_gl_sf.
IPR001791. Laminin_G.
[Graphical view]

Pfam

PF01391. Collagen. 4 hits.
PF06482. Endostatin. 2 hits.
[Graphical view]

SMART

SM00282. LamG. 1 hit.
SM00210. TSPN. 1 hit.
[Graphical view]

SUPFAM

SSF49899. SSF49899. 1 hit.
SSF56436. SSF56436. 2 hits.

ProtoNet

Search...

Other

ChiTaRS

COL15A1. human.

GeneWiki

Collagen,_type_XV,_alpha_1.

GenomeRNAi

1306.

NextBio

5345.

PRO

P39059.

SOURCE

Search...

Entry information

Entry name

COFA1_HUMAN

Accession

Primary (citable) accession number: P39059
Secondary accession number(s): Q5T6J4, Q9UDC5, Q9Y4W4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	July 5, 2005
Last modified:	July 9, 2014
This is version 132 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.