O43556 (SGCE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Epsilon-sarcoglycan
Short name=Epsilon-SG

Gene names

Name:	SGCE
Synonyms:	ESG
ORF Names:	UNQ433/PRO840

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

General annotation (Comments)

Function	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
Subcellular location	Cell membrane › sarcolemma; Single-pass membrane protein Potential. Cytoplasm › cytoskeleton By similarity.
Tissue specificity	Ubiquitous.
Involvement in disease	Defects in SGCE are a cause of dystonia type 11 (DYT11) [MIM:159900]; also known as myoclonic dystonia or alcohol-responsive dystonia. DYT11 is a myoclonic dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT11 is characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Inheritance is autosomal dominant. The age of onset, pattern of body involvement, presence of myoclonus and response to alcohol are all variable. Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21
Sequence similarities	Belongs to the sarcoglycan alpha/epsilon family.
Sequence caution	The sequence AAC04368.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Disease	Disease mutation Dystonia
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell-matrix adhesion Traceable author statement. Source: ProtInc muscle organ development Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement. Source: ProtInc sarcoglycan complex Traceable author statement. Source: ProtInc sarcolemma Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 437	437	Epsilon-sarcoglycan		PRO_0000031677
Regions
	Topological domain	1 – 317	317	Extracellular Potential
	Transmembrane	318 – 338	21	Helical; Potential
	Topological domain	339 – 437	99	Cytoplasmic Potential
	Compositional bias	235 – 341	107	Cys-rich
Amino acid modifications
	Glycosylation	200	1	N-linked (GlcNAc...) Ref.12
Natural variations
	Natural variant	36	1	T → R in DYT11. Ref.18		VAR_066732
	Natural variant	49	1	N → S. Ref.8 Corresponds to variant rs11548284 [ dbSNP | Ensembl ].		VAR_058088
	Natural variant	60	1	H → P in DYT11; affects protein stability; the mutant undergoes endoplasmic reticulum-associated degradation. Ref.15 Ref.21		VAR_066733
	Natural variant	60	1	H → R in DYT11; affects protein stability; the mutant undergoes endoplasmic reticulum-associated degradation. Ref.14 Ref.21		VAR_066734
	Natural variant	92	1	M → T in DYT11; results in gain-of-glycosylation; the mutant is targeted to the plasma membrane at reduced levels compared to wild-type. Ref.16 Ref.21		VAR_066735
	Natural variant	100	1	W → G in DYT11. Ref.19		VAR_066736
	Natural variant	112	1	G → R in DYT11. Ref.17		VAR_066737
	Natural variant	115	1	Y → C in DYT11; affects protein stability; the mutant undergoes endoplasmic reticulum-associated degradation. Ref.16 Ref.19 Ref.21		VAR_066738
	Natural variant	175	1	L → S in DYT11. Ref.20		VAR_066739
	Natural variant	177	1	S → C in DYT11. Ref.20		VAR_066740
	Natural variant	184	1	L → P in DYT11; affects protein stability; the mutant undergoes endoplasmic reticulum-associated degradation. Ref.18		VAR_066741
	Natural variant	196	1	L → R in DYT11. Ref.13		VAR_026750
	Natural variant	270	1	W → R in DYT11; affects protein stability; the mutant undergoes endoplasmic reticulum-associated degradation. Ref.20 Ref.21		VAR_066742
	Natural variant	271	1	C → Y in DYT11; affects protein stability; the mutant undergoes endoplasmic reticulum-associated degradation. Ref.16 Ref.21		VAR_066743
	Natural variant	399	1	P → H. Ref.8 Corresponds to variant rs17851923 [ dbSNP | Ensembl ].		VAR_058089
Experimental info
	Sequence conflict	78	1	G → S in AAM64204. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O43556 [UniParc]. Last modified July 7, 2009. Version 6. Checksum: 0996CB18272DED44	FASTA	437	49,851
	10 20 30 40 50 60 MQLPRWWELG DPCAWTGQGR GTRRMSPATT GTFLLTVYSI FSKVHSDRNV YPSAGVLFVH 70 80 90 100 110 120 VLEREYFKGE FPPYPKPGEI SNDPITFNTN LMGYPDRPGW LRYIQRTPYS DGVLYGSPTA 130 140 150 160 170 180 ENVGKPTIIE ITAYNRRTFE TARHNLIINI MSAEDFPLPY QAEFFIKNMN VEEMLASEVL 190 200 210 220 230 240 GDFLGAVKNV WQPERLNAIN ITSALDRGGR VPLPINDLKE GVYVMVGADV PFSSCLREVE 250 260 270 280 290 300 NPQNQLRCSQ EMEPVITCDK KFRTQFYIDW CKISLVDKTK QVSTYQEVIR GEGILPDGGE 310 320 330 340 350 360 YKPPSDSLKS RDYYTDFLIT LAVPSAVALV LFLILAYIMC CRREGVEKRN MQTPDIQLVH 370 380 390 400 410 420 HSAIQKSTKE LRDMSKNREI AWPLSTLPVF HPVTGEIIPP LHTDNYDSTN MPLMQTQQNL 430 PHQTQIPQQQ TTGKWYP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human epsilon-sarcoglycan is highly related to alpha-sarcoglycan (adhalin), the limb girdle muscular dystrophy 2D gene." McNally E.M., Ly C.T., Kunkel L.M. FEBS Lett. 422:27-32(1998) [PubMed: 9475163] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[2]	Nigro V. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[3]	"Epsilon-sarcoglycan mutations in three ethnically diverse families segregating Myoclonus-Dystonia." Dagvadorj A. Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain cortex.
[6]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS SER-49 AND HIS-399. Tissue: Testis.
[9]	"Epsilon-sarcoglycan, a broadly expressed homologue of the gene mutated in limb-girdle muscular dystrophy 2D." Ettinger A.J., Feng G., Sanes J.R. J. Biol. Chem. 272:32534-32538(1997) [PubMed: 9405466] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 293-437.
[10]	Erratum Ettinger A.J., Feng G., Sanes J.R. J. Biol. Chem. 273:19922-19922(1998)
[11]	"Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome." Zimprich A., Grabowski M., Asmus F., Naumann M., Berg D., Bertram M., Scheidtmann K., Kern P., Winkelmann J., Muller-Myhsok B., Riedel L., Bauer M., Muller T., Castro M., Meitinger T., Strom T.M., Gasser T. Nat. Genet. 29:66-69(2001) [PubMed: 11528394] [Abstract] Cited for: INVOLVEMENT IN DYT11.
[12]	"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-200, MASS SPECTROMETRY. Tissue: Liver.
[13]	"Epsilon-sarcoglycan mutations found in combination with other dystonia gene mutations." Klein C., Liu L., Doheny D., Kock N., Muller B., de Carvalho Aguiar P., Leung J., de Leon D., Bressman S.B., Silverman J., Smith C., Danisi F., Morrison C., Walker R.H., Velickovic M., Schwinger E., Kramer P.L., Breakefield X.O., Brin M.F., Ozelius L.J. Ann. Neurol. 52:675-679(2002) [PubMed: 12402271] [Abstract] Cited for: VARIANT DYT11 ARG-196.
[14]	"Genetic heterogeneity in ten families with myoclonus-dystonia." Schule B., Kock N., Svetel M., Dragasevic N., Hedrich K., De Carvalho Aguiar P., Liu L., Kabakci K., Garrels J., Meyer E.M., Berisavac I., Schwinger E., Kramer P.L., Ozelius L.J., Klein C., Kostic V. J. Neurol. Neurosurg. Psych. 75:1181-1185(2004) [PubMed: 15258227] [Abstract] Cited for: VARIANT DYT11 ARG-60.
[15]	"Myoclonus-dystonia: detection of novel, recurrent, and de novo SGCE mutations." Hedrich K., Meyer E.M., Schule B., Kock N., de Carvalho Aguiar P., Wiegers K., Koelman J.H., Garrels J., Durr R., Liu L., Schwinger E., Ozelius L.J., Landwehrmeyer B., Stoessl A.J., Tijssen M.A., Klein C. Neurology 62:1229-1231(2004) [PubMed: 15079037] [Abstract] Cited for: VARIANT DYT11 PRO-60.
[16]	"Epsilon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes." Tezenas du Montcel S., Clot F., Vidailhet M., Roze E., Damier P., Jedynak C.P., Camuzat A., Lagueny A., Vercueil L., Doummar D., Guyant-Marechal L., Houeto J.L., Ponsot G., Thobois S., Cournelle M.A., Durr A., Durif F., Echenne B. , Hannequin D., Tranchant C., Brice A. J. Med. Genet. 43:394-400(2006) [PubMed: 16227522] [Abstract] Cited for: VARIANTS DYT11 THR-92; CYS-115 AND TYR-271.
[17]	"Myoclonus-dystonia syndrome: clinical presentation, disease course, and genetic features in 11 families." Nardocci N., Zorzi G., Barzaghi C., Zibordi F., Ciano C., Ghezzi D., Garavaglia B. Mov. Disord. 23:28-34(2008) [PubMed: 17853490] [Abstract] Cited for: VARIANT DYT11 ARG-112.
[18]	"Phenotypic spectrum and sex effects in eleven myoclonus-dystonia families with epsilon-sarcoglycan mutations." Raymond D., Saunders-Pullman R., de Carvalho Aguiar P., Schule B., Kock N., Friedman J., Harris J., Ford B., Frucht S., Heiman G.A., Jennings D., Doheny D., Brin M.F., de Leon Brin D., Multhaupt-Buell T., Lang A.E., Kurlan R., Klein C., Ozelius L., Bressman S. Mov. Disord. 23:588-592(2008) [PubMed: 18175340] [Abstract] Cited for: VARIANTS DYT11 ARG-36 AND PRO-184.
[19]	"Myoclonus-dystonia: clinical and electrophysiologic pattern related to SGCE mutations." Roze E., Apartis E., Clot F., Dorison N., Thobois S., Guyant-Marechal L., Tranchant C., Damier P., Doummar D., Bahi-Buisson N., Andre-Obadia N., Maltete D., Echaniz-Laguna A., Pereon Y., Beaugendre Y., Dupont S., De Greslan T., Jedynak C.P. , Ponsot G., Dussaule J.C., Brice A., Durr A., Vidailhet M. Neurology 70:1010-1016(2008) [PubMed: 18362280] [Abstract] Cited for: VARIANTS DYT11 GLY-100 AND CYS-115.
[20]	"Myoclonus-dystonia: clinical and genetic evaluation of a large cohort." Ritz K., Gerrits M.C., Foncke E.M., van Ruissen F., van der Linden C., Vergouwen M.D., Bloem B.R., Vandenberghe W., Crols R., Speelman J.D., Baas F., Tijssen M.A. J. Neurol. Neurosurg. Psych. 80:653-658(2009) [PubMed: 19066193] [Abstract] Cited for: VARIANTS DYT11 SER-175; CYS-177 AND ARG-270.
[21]	"A gain-of-glycosylation mutation associated with myoclonus-dystonia syndrome affects trafficking and processing of mouse epsilon-sarcoglycan in the late secretory pathway." Waite A., De Rosa M.C., Brancaccio A., Blake D.J. Hum. Mutat. 32:1246-1258(2011) [PubMed: 21796726] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS DYT11 ARG-60; PRO-60; THR-92; CYS-115; ARG-270 AND TYR-271.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF036364 mRNA. Translation: AAC04368.1. Different initiation. AJ000534 mRNA. Translation: CAA04167.1. AF516515 mRNA. Translation: AAM64204.1. AY359042 mRNA. Translation: AAQ89401.1. AK313438 mRNA. Translation: BAG36229.1. AC069292 Genomic DNA. Translation: AAS07485.1. CH471091 Genomic DNA. Translation: EAW76784.1. CH471091 Genomic DNA. Translation: EAW76785.1. BC021709 mRNA. Translation: AAH21709.1. AF031920 mRNA. Translation: AAC14021.1.
IPI	IPI00418183.
RefSeq	NP_001092870.1. NM_001099400.1. NP_001092871.1. NM_001099401.1. NP_003910.1. NM_003919.2.
UniGene	Hs.371199.
3D structure databases
ProteinModelPortal	O43556.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43556. 2 interactions.
MINT	MINT-1415529.
STRING	O43556.
Proteomic databases
PRIDE	O43556.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265735; ENSP00000265735; ENSG00000127990.
GeneID	8910.
KEGG	hsa:8910.
UCSC	uc003unl.2. human.
Organism-specific databases
CTD	8910.
GeneCards	GC07M094214.
H-InvDB	HIX0006856.
HGNC	HGNC:10808. SGCE.
MIM	159900. phenotype. 604149. gene.
neXtProt	NX_O43556.
Orphanet	36899. Myoclonic dystonia.
PharmGKB	PA35719.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18053.
GeneTree	ENSGT00390000005672.
HOVERGEN	HBG006891.
OrthoDB	EOG46WZ8J.
PhylomeDB	O43556.
Gene expression databases
ArrayExpress	O43556.
Bgee	O43556.
CleanEx	HS_SGCE.
Genevestigator	O43556.
GermOnline	ENSG00000127990. Homo sapiens.
Family and domain databases
InterPro	IPR006644. Cadg. IPR008908. Sarcoglycan_2. [Graphical view]
PANTHER	PTHR10132. Sarcoglycan_2. 1 hit.
Pfam	PF05510. Sarcoglycan_2. 1 hit. [Graphical view]
SMART	SM00736. CADG. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	33480.
SOURCE	Search...

Entry information

Entry name

SGCE_HUMAN

Accession

Primary (citable) accession number: O43556
Secondary accession number(s): B2R8N2 , D6W5Q8, Q75MH8, Q8NFG8, Q8WW28

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	July 7, 2009
Last modified:	January 25, 2012
This is version 98 of the entry and version 6 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.