Q9NZI2 (KCIP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kv channel-interacting protein 1
Short name=KChIP1

Alternative name(s):
A-type potassium channel modulatory protein 1
Potassium channel-interacting protein 1
Vesicle APC-binding protein

Gene names

Name:	KCNIP1
Synonyms:	KCHIP1, VABP

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	227 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Probably modulates channels density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND1/Kv4.1 and KCND2/Kv4.2 currents. Seems to be involved in KCND2 trafficking to the cell surface. Ref.1 Ref.10 Ref.11
Subunit structure	Component of heteromultimeric potassium channels. Interacts with KCND3 and the N-terminal domain of KCND2. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. Self-associates to form homodimers and homotetramers. Interacts with KCNIP2 isoform 3 in a calcium-dependent manner. Interacts with Naja atra venom CTX3. Ref.1 Ref.12 Ref.13 Ref.14 Ref.15
Subcellular location	Cell membrane; Peripheral membrane protein By similarity.
Tissue specificity	Isoform 1 and isoform 2 are expressed in brain and kidney. Isoform 1 is also expressed in liver, pancreas, skeletal muscle, small intestine and testis. Isoform 2 is also expressed in lung, pancreas, leukocytes, prostate and thymus. Ref.9
Sequence similarities	Belongs to the recoverin family. Contains 4 EF-hand domains.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	Calcium Metal-binding Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	detection of calcium ion Traceable author statement Ref.1. Source: ProtInc positive regulation of action potential Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc synaptic transmission Traceable author statement Ref.1. Source: ProtInc
Cellular_component	dendrite Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: Compara potassium channel activity Inferred from electronic annotation. Source: UniProtKB-KW potassium channel regulator activity Inferred from electronic annotation. Source: Compara voltage-gated ion channel activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KCND2	Q9NZV8	4	EBI-2120635,EBI-1646745
KCNIP2	Q9NS61-3	4	EBI-2120635,EBI-1053010

Alternative products

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

Isoform 1 (identifier: Q9NZI2-1)

Also known as: KCHIP1b;

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: Q9NZI2-2)

Also known as: KCHIP1a;

The sequence of this isoform differs from the canonical sequence as follows:
     21-31: Missing.

Isoform 3 (identifier: Q9NZI2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: Missing.

Isoform 4 (identifier: Q9NZI2-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: MGAVMGTFSSLQTKQRRPSKDIAWWYYQYQR → MSGCSKRCKLGFVKFAQTIFKLITGTLSK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 227

227

Kv channel-interacting protein 1

PRO_0000073818

Regions

Domain

38 – 94

57

EF-hand 1; degenerate

Domain

97 – 132

36

EF-hand 2

Domain

133 – 168

36

EF-hand 3

Domain

181 – 216

36

EF-hand 4

Calcium binding

146 – 157

12

1 Ref.15

Calcium binding

194 – 205

12

2 Ref.15

Region

214 – 227

14

Interaction with KCND2 By similarity

Natural variations

Alternative sequence

1 – 39

39

Missing in isoform 3.

VSP_015043

Alternative sequence

1 – 31

31

MGAVM…YQYQR → MSGCSKRCKLGFVKFAQTIF KLITGTLSK in isoform 4.

VSP_041511

Alternative sequence

21 – 31

11

Missing in isoform 2.

VSP_015044

Experimental info

Sequence conflict

116

1

S → P in BAH13550. Ref.5

Secondary structure

1

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227

Helix Strand Turn

Details...

Helix

50 – 56

7

Beta strand

57 – 59

3

Helix

61 – 74

14

Turn

76 – 78

3

Helix

82 – 90

9

Beta strand

93 – 96

4

Helix

99 – 109

11

Beta strand

112 – 116

5

Helix

119 – 131

13

Helix

134 – 145

12

Beta strand

151 – 153

3

Helix

155 – 169

15

Helix

175 – 177

3

Beta strand

179 – 181

3

Helix

182 – 193

12

Beta strand

198 – 201

4

Helix

203 – 211

9

Helix

214 – 225

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (KCHIP1b) [UniParc]. Last modified August 16, 2005. Version 2. Checksum: D39DD5F8EA13B0FD	FASTA	227	26,817
	10 20 30 40 50 60 MGAVMGTFSS LQTKQRRPSK DIAWWYYQYQ RDKIEDELEM TMVCHRPEGL EQLEAQTNFT 70 80 90 100 110 120 KRELQVLYRG FKNECPSGVV NEDTFKQIYA QFFPHGDAST YAHYLFNAFD TTQTGSVKFE 130 140 150 160 170 180 DFVTALSILL RGTVHEKLRW TFNLYDINKD GYINKEEMMD IVKAIYDMMG KYTYPVLKED 190 200 210 220 TPRQHVDVFF QKMDKNKDGI VTLDEFLESC QEDDNIMRSL QLFQNVM
	Isoform 2 (KCHIP1a) [UniParc]. Checksum: E8384AC242B6B69C	FASTA	216	25,244
	10 20 30 40 50 60 MGAVMGTFSS LQTKQRRPSK DKIEDELEMT MVCHRPEGLE QLEAQTNFTK RELQVLYRGF 70 80 90 100 110 120 KNECPSGVVN EDTFKQIYAQ FFPHGDASTY AHYLFNAFDT TQTGSVKFED FVTALSILLR 130 140 150 160 170 180 GTVHEKLRWT FNLYDINKDG YINKEEMMDI VKAIYDMMGK YTYPVLKEDT PRQHVDVFFQ 190 200 210 KMDKNKDGIV TLDEFLESCQ EDDNIMRSLQ LFQNVM
	Isoform 3 [UniParc]. Checksum: 5712C89FF2FA0176	FASTA	188	22,079
	10 20 30 40 50 60 MTMVCHRPEG LEQLEAQTNF TKRELQVLYR GFKNECPSGV VNEDTFKQIY AQFFPHGDAS 70 80 90 100 110 120 TYAHYLFNAF DTTQTGSVKF EDFVTALSIL LRGTVHEKLR WTFNLYDINK DGYINKEEMM 130 140 150 160 170 180 DIVKAIYDMM GKYTYPVLKE DTPRQHVDVF FQKMDKNKDG IVTLDEFLES CQEDDNIMRS LQLFQNVM
	Isoform 4 [UniParc]. Checksum: 15705CD8C4385B7B	FASTA	225	26,227
	10 20 30 40 50 60 MSGCSKRCKL GFVKFAQTIF KLITGTLSKD KIEDELEMTM VCHRPEGLEQ LEAQTNFTKR 70 80 90 100 110 120 ELQVLYRGFK NECPSGVVNE DTFKQIYAQF FPHGDASTYA HYLFNAFDTT QTGSVKFEDF 130 140 150 160 170 180 VTALSILLRG TVHEKLRWTF NLYDINKDGY INKEEMMDIV KAIYDMMGKY TYPVLKEDTP 190 200 210 220 RQHVDVFFQK MDKNKDGIVT LDEFLESCQE DDNIMRSLQL FQNVM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Modulation of A-type potassium channels by a family of calcium sensors." An W.F., Bowlby M.R., Betty M., Cao J., Ling H.-P., Mendoza G., Hinson J.W., Mattsson K.I., Strassle B.W., Trimmer J.S., Rhodes K.J. Nature 403:553-556(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH KCND2.
[2]	"Molecular cloning of human VABP gene." Xia K., Fang H.Y., Zhong X.Y., Xia J.H., Zhang Z.H. Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"Structure, alternative splicing, and expression of the human and mouse KCNIP gene family." Pruunsild P., Timmusk T. Genomics 86:581-593(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[4]	"Study on mutations in KCNIP1 gene." Zheng L., Jun X.X., Yue F.F., Min L.Y., Ming S.Y., Jun Y.F. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[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 4). Tissue: Testis.
[6]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton 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 2). Tissue: Brain.
[9]	"Differential modulation of Kv4 kinetics by KCHIP1 splice variants." Van Hoorick D., Raes A., Keysers W., Mayeur E., Snyders D.J. Mol. Cell. Neurosci. 24:357-366(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), TISSUE SPECIFICITY (ISOFORMS 1 AND 2).
[10]	"Different effects of the Ca(2+)-binding protein, KChIP1, on two Kv4 subfamily members, Kv4.1 and Kv4.2." Nakamura T.Y., Nandi S., Pountney D.J., Artman M., Rudy B., Coetzee W.A. FEBS Lett. 499:205-209(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"A fundamental role for KChIPs in determining the molecular properties and trafficking of Kv4.2 potassium channels." Shibata R., Misonou H., Campomanes C.R., Anderson A.E., Schrader L.A., Doliveira L.C., Carroll K.I., Sweatt J.D., Rhodes K.J., Trimmer J.S. J. Biol. Chem. 278:36445-36454(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Evidence showing an intermolecular interaction between KChIP proteins and Taiwan cobra cardiotoxins." Lin Y.-L., Lin S.-R., Wu T.T., Chang L.-S. Biochem. Biophys. Res. Commun. 319:720-724(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNAKE CTX3.
[13]	"Protein-protein interactions of KChIP proteins and Kv4.2." Lin Y.-L., Chen C.Y., Cheng C.P., Chang L.S. Biochem. Biophys. Res. Commun. 321:606-610(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KCNIP2 AND KCDN2, HOMOOLIGOMERIZATION.
[14]	"Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1." Scannevin R.H., Wang K., Jow F., Megules J., Kopsco D.C., Edris W., Carroll K.C., Lu Q., Xu W., Xu Z., Katz A.H., Olland S., Lin L., Taylor M., Stahl M., Malakian K., Somers W., Mosyak L. , Bowlby M.R., Chanda P., Rhodes K.J. Neuron 41:587-598(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) (ISOFORM 2), INTERACTION WITH KCDN2 AND KCDN3.
[15]	"Three-dimensional structure of the KChIP1-Kv4.3 T1 complex reveals a cross-shaped octamer." Pioletti M., Findeisen F., Hura G.L., Minor D.L. Jr. Nat. Struct. Mol. Biol. 13:987-995(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS) OF 48-227 IN COMPLEX WITH KCND3, SUBUNIT, CALCIUM-BINDING.
[16]	"Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits." Wang H., Yan Y., Liu Q., Huang Y., Shen Y., Chen L., Chen Y., Yang Q., Hao Q., Wang K., Chai J. Nat. Neurosci. 10:32-39(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 49-227 IN COMPLEX WITH KCND3.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF199597 mRNA. Translation: AAF33682.1.
AY170821 mRNA. Translation: AAN77491.1.
DQ148477 mRNA. Translation: AAZ77794.1.
AY780424 mRNA. Translation: AAV51968.1.
AK301775 mRNA. Translation: BAH13550.1.
AC008619 Genomic DNA. No translation available.
AC008719 Genomic DNA. No translation available.
AC027306 Genomic DNA. No translation available.
AC027312 Genomic DNA. No translation available.
AC034199 Genomic DNA. No translation available.
AC113432 Genomic DNA. No translation available.
AC134820 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61470.1.
BC050375 mRNA. Translation: AAH50375.1.

IPI

IPI00433691.
IPI00641978.
IPI00645089.
IPI00845317.

RefSeq

NP_001030009.1. NM_001034837.1.
NP_055407.1. NM_014592.2.

UniGene

Hs.484111.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S1E	X-ray	2.30	A	1-227	[»]
2I2R	X-ray	3.35	E/F/G/H/M/N/O/P	48-227	[»]
2NZ0	X-ray	3.20	A/C	49-227	[»]

ProteinModelPortal

Q9NZI2.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29246N.

IntAct

Q9NZI2. 2 interactions.

STRING

9606.ENSP00000395323.

Polymorphism databases

DMDM

73621122.

Proteomic databases

PaxDb

Q9NZI2.

PRIDE

Q9NZI2.

Protocols and materials databases

DNASU

30820.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000328939; ENSP00000329686; ENSG00000182132.
ENST00000377360; ENSP00000366577; ENSG00000182132.
ENST00000390656; ENSP00000375071; ENSG00000182132.
ENST00000411494; ENSP00000395323; ENSG00000182132.
ENST00000520740; ENSP00000431102; ENSG00000182132.

GeneID

30820.

KEGG

hsa:30820.

UCSC

uc003mas.3. human.

Organism-specific databases

CTD

30820.

GeneCards

GC05P169780.

HGNC

HGNC:15521. KCNIP1.

HPA

HPA022864.

MIM

604660. gene.

neXtProt

NX_Q9NZI2.

PharmGKB

PA30041.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5126.

HOGENOM

HOG000233019.

HOVERGEN

HBG108179.

InParanoid

Q9NZI2.

OMA

NFNKREL.

OrthoDB

EOG4N8R5P.

Gene expression databases

ArrayExpress

Q9NZI2.

Bgee

Q9NZI2.

CleanEx

HS_KCNIP1.

Genevestigator

Q9NZI2.

GermOnline

ENSG00000182132. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 3 hits.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001125. Recoverin.
[Graphical view]

Pfam

PF13499. EF_hand_5. 1 hit.
[Graphical view]

PRINTS

PR00450. RECOVERIN.

SMART

SM00054. EFh. 3 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

KCNIP1. human.

EvolutionaryTrace

Q9NZI2.

GenomeRNAi

30820.

NextBio

52920.

SOURCE

Search...

Entry information

Entry name

KCIP1_HUMAN

Accession

Primary (citable) accession number: Q9NZI2
Secondary accession number(s): B7Z7B4, Q3YAD2, Q5U822

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	August 16, 2005
Last modified:	May 1, 2013
This is version 107 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.