Q96NW7 (LRRC7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leucine-rich repeat-containing protein 7

Alternative name(s):
Densin-180
Protein LAP1

Gene names

Name:	LRRC7
Synonyms:	KIAA1365, LAP1

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	1537 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in the organization of synaptic cell-cell contacts. Ref.1
Subunit structure	Interacts with CAMKII, CNKSR2 and DLG4 By similarity. Interacts with CTNND2/Catenin delta-2. Forms a complex with N-cadherin through CTNND2. Ref.1
Subcellular location	Cytoplasm Ref.1.
Tissue specificity	Brain-specific. Isoform 3 is ubiquitously expressed. Ref.2
Sequence similarities	Belongs to the LAP (LRR and PDZ) protein family. Contains 17 LRR (leucine-rich) repeats. Contains 1 PDZ (DHR) domain.
Sequence caution	The sequence AAP06801.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA92603.1 differs from that shown. Reason: Frameshift at position 665. The sequence CAH70975.1 differs from that shown. Reason: Erroneous initiation. The sequence CAH73692.1 differs from that shown. Reason: Erroneous initiation. The sequence CAH74019.1 differs from that shown. Reason: Erroneous initiation. The sequence CAI22426.1 differs from that shown. Reason: Erroneous initiation. The sequence CAI23423.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Leucine-rich repeat Repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96NW7-1)

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 2 (identifier: Q96NW7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1286-1332: Missing.

Isoform 3 (identifier: Q96NW7-3)

Also known as: LRRC7;

The sequence of this isoform differs from the canonical sequence as follows:
     178-179: KS → NI
     180-1537: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1537	1537	Leucine-rich repeat-containing protein 7		PRO_0000188298
Regions
	Repeat	23 – 44	22	LRR 1
	Repeat	47 – 68	22	LRR 2
	Repeat	70 – 91	22	LRR 3
	Repeat	93 – 114	22	LRR 4
	Repeat	116 – 137	22	LRR 5
	Repeat	139 – 161	23	LRR 6
	Repeat	162 – 183	22	LRR 7
	Repeat	185 – 206	22	LRR 8
	Repeat	208 – 229	22	LRR 9
	Repeat	231 – 253	23	LRR 10
	Repeat	254 – 275	22	LRR 11
	Repeat	277 – 298	22	LRR 12
	Repeat	300 – 321	22	LRR 13
	Repeat	323 – 344	22	LRR 14
	Repeat	346 – 367	22	LRR 15
	Repeat	369 – 391	23	LRR 16
	Repeat	392 – 413	22	LRR 17
	Domain	1445 – 1535	91	PDZ
Amino acid modifications
	Modified residue	90	1	Phosphoserine By similarity
	Modified residue	850	1	Phosphoserine By similarity
	Modified residue	865	1	Phosphothreonine By similarity
	Modified residue	933	1	Phosphoserine By similarity
	Modified residue	949	1	Phosphoserine By similarity
	Modified residue	1439	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	178 – 179	2	KS → NI in isoform 3.		VSP_010795
	Alternative sequence	180 – 1537	1358	Missing in isoform 3.		VSP_010796
	Alternative sequence	1286 – 1332	47	Missing in isoform 2.		VSP_010797
	Natural variant	235	1	L → M in a breast cancer sample; somatic mutation. Ref.6		VAR_035715
	Natural variant	1054	1	H → Y. Corresponds to variant rs12069888 [ dbSNP | Ensembl ].		VAR_049727
Experimental info
	Sequence conflict	373	1	L → P Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 1EB99AF133CD2925	FASTA	1,537	172,581
	10 20 30 40 50 60 MTTKRKIIGR LVPCRCFRGE EEIISVLDYS HCSLQQVPKE VFNFERTLEE LYLDANQIEE 70 80 90 100 110 120 LPKQLFNCQA LRKLSIPDND LSNLPTTIAS LVNLKELDIS KNGVQEFPEN IKCCKCLTII 130 140 150 160 170 180 EASVNPISKL PDGFTQLLNL TQLYLNDAFL EFLPANFGRL VKLRILELRE NHLKTLPKSM 190 200 210 220 230 240 HKLAQLERLD LGNNEFGELP EVLDQIQNLR ELWMDNNALQ VLPGSIGKLK MLVYLDMSKN 250 260 270 280 290 300 RIETVDMDIS GCEALEDLLL SSNMLQQLPD SIGLLKKLTT LKVDDNQLTM LPNTIGNLSL 310 320 330 340 350 360 LEEFDCSCNE LESLPSTIGY LHSLRTLAVD ENFLPELPRE IGSCKNVTVM SLRSNKLEFL 370 380 390 400 410 420 PEEIGQMQKL RVLNLSDNRL KNLPFSFTKL KELAALWLSD NQSKALIPLQ TEAHPETKQR 430 440 450 460 470 480 VLTNYMFPQQ PRGDEDFQSD SDSFNPTLWE EQRQQRMTVA FEFEDKKEDD ENAGKVKDLS 490 500 510 520 530 540 CQAPWERGQR GITLQPARLS GDCCTPWARC DQQIQDMPVP QNDPQLAWGC ISGLQQERSM 550 560 570 580 590 600 CTPLPVAAQS TTLPSLSGRQ VEINLKRYPT PYPEDLKNMV KSVQNLVGKP SHGVRVENSN 610 620 630 640 650 660 PTANTEQTVK EKYEHKWPVA PKEITVEDSF VHPANEMRIG ELHPSLAETP LYPPKLVLLG 670 680 690 700 710 720 KDKKESTDES EVDKTHCLNN SVSSGTYSDY SPSQASSGSS NTRVKVGSLQ TTAKDAVHNS 730 740 750 760 770 780 LWGNRIAPSF PQPLDSKPLL SQREAVPPGN IPQRPDRLPM SDTFTDNWTD GSHYDNTGFV 790 800 810 820 830 840 AEETTAENAN SNPLLSSKSR STSSHGRRPL IRQDRIVGVP LELEQSTHRH TPETEVPPSN 850 860 870 880 890 900 PWQNWTRTPS PFEDRTAFPS KLETTPTTSP LPERKEHIKE STEIPSPFSP GVPWEYHDSN 910 920 930 940 950 960 PNRSLSNVFS QIHCRPESSK GVISISKSTE RLSPLMKDIK SNKFKKSQSI DEIDIGTYKV 970 980 990 1000 1010 1020 YNIPLENYAS GSDHLGSHER PDKMLGPEHG MSSMSRSQSV PMLDDEMLTY GSSKGPQQQK 1030 1040 1050 1060 1070 1080 ASMTKKVYQF DQSFNPQGSV EVKAEKRIPP PFQHNPEYVQ QASKNIAKDL ISPRAYRGYP 1090 1100 1110 1120 1130 1140 PMEQMFSFSQ PSVNEDAVVN AQFASQGARA GFLRRADSLV SATEMAMFRR VNEPHELPPT 1150 1160 1170 1180 1190 1200 DRYGRPPYRG GLDRQSSVTV TESQFLKRNG RYEDEHPSYQ EVKAQAGSFP VKNLTQRRPL 1210 1220 1230 1240 1250 1260 SARSYSTESY GASQTRPVSA RPTMAALLEK IPSDYNLGNY GDKPSDNSDL KTRPTPVKGE 1270 1280 1290 1300 1310 1320 ESCGKMPADW RQQLLRHIEA RRLDRNAAYK HNTVNLGMLP YGGISAMHAG RSMTLNLQTK 1330 1340 1350 1360 1370 1380 SKFDHQELPL QKTPSQQSNI LDNGQEDVSP SGQWNPYPLG RRDVPPDTIT KKAGSHIQTL 1390 1400 1410 1420 1430 1440 MGSQSLQHRS REQQPYEGNI NKVTIQQFQS PLPIQIPSSQ ATRGPQPGRC LIQTKGQRSM 1450 1460 1470 1480 1490 1500 DGYPEQFCVR IEKNPGLGFS ISGGISGQGN PFKPSDKGIF VTRVQPDGPA SNLLQPGDKI 1510 1520 1530 LQANGHSFVH MEHEKAVLLL KSFQNTVDLV IQRELTV
	Isoform 2 [UniParc]. Checksum: C9DFBE243559DD97	FASTA	1,490	167,386
	10 20 30 40 50 60 MTTKRKIIGR LVPCRCFRGE EEIISVLDYS HCSLQQVPKE VFNFERTLEE LYLDANQIEE 70 80 90 100 110 120 LPKQLFNCQA LRKLSIPDND LSNLPTTIAS LVNLKELDIS KNGVQEFPEN IKCCKCLTII 130 140 150 160 170 180 EASVNPISKL PDGFTQLLNL TQLYLNDAFL EFLPANFGRL VKLRILELRE NHLKTLPKSM 190 200 210 220 230 240 HKLAQLERLD LGNNEFGELP EVLDQIQNLR ELWMDNNALQ VLPGSIGKLK MLVYLDMSKN 250 260 270 280 290 300 RIETVDMDIS GCEALEDLLL SSNMLQQLPD SIGLLKKLTT LKVDDNQLTM LPNTIGNLSL 310 320 330 340 350 360 LEEFDCSCNE LESLPSTIGY LHSLRTLAVD ENFLPELPRE IGSCKNVTVM SLRSNKLEFL 370 380 390 400 410 420 PEEIGQMQKL RVLNLSDNRL KNLPFSFTKL KELAALWLSD NQSKALIPLQ TEAHPETKQR 430 440 450 460 470 480 VLTNYMFPQQ PRGDEDFQSD SDSFNPTLWE EQRQQRMTVA FEFEDKKEDD ENAGKVKDLS 490 500 510 520 530 540 CQAPWERGQR GITLQPARLS GDCCTPWARC DQQIQDMPVP QNDPQLAWGC ISGLQQERSM 550 560 570 580 590 600 CTPLPVAAQS TTLPSLSGRQ VEINLKRYPT PYPEDLKNMV KSVQNLVGKP SHGVRVENSN 610 620 630 640 650 660 PTANTEQTVK EKYEHKWPVA PKEITVEDSF VHPANEMRIG ELHPSLAETP LYPPKLVLLG 670 680 690 700 710 720 KDKKESTDES EVDKTHCLNN SVSSGTYSDY SPSQASSGSS NTRVKVGSLQ TTAKDAVHNS 730 740 750 760 770 780 LWGNRIAPSF PQPLDSKPLL SQREAVPPGN IPQRPDRLPM SDTFTDNWTD GSHYDNTGFV 790 800 810 820 830 840 AEETTAENAN SNPLLSSKSR STSSHGRRPL IRQDRIVGVP LELEQSTHRH TPETEVPPSN 850 860 870 880 890 900 PWQNWTRTPS PFEDRTAFPS KLETTPTTSP LPERKEHIKE STEIPSPFSP GVPWEYHDSN 910 920 930 940 950 960 PNRSLSNVFS QIHCRPESSK GVISISKSTE RLSPLMKDIK SNKFKKSQSI DEIDIGTYKV 970 980 990 1000 1010 1020 YNIPLENYAS GSDHLGSHER PDKMLGPEHG MSSMSRSQSV PMLDDEMLTY GSSKGPQQQK 1030 1040 1050 1060 1070 1080 ASMTKKVYQF DQSFNPQGSV EVKAEKRIPP PFQHNPEYVQ QASKNIAKDL ISPRAYRGYP 1090 1100 1110 1120 1130 1140 PMEQMFSFSQ PSVNEDAVVN AQFASQGARA GFLRRADSLV SATEMAMFRR VNEPHELPPT 1150 1160 1170 1180 1190 1200 DRYGRPPYRG GLDRQSSVTV TESQFLKRNG RYEDEHPSYQ EVKAQAGSFP VKNLTQRRPL 1210 1220 1230 1240 1250 1260 SARSYSTESY GASQTRPVSA RPTMAALLEK IPSDYNLGNY GDKPSDNSDL KTRPTPVKGE 1270 1280 1290 1300 1310 1320 ESCGKMPADW RQQLLRHIEA RRLDRTPSQQ SNILDNGQED VSPSGQWNPY PLGRRDVPPD 1330 1340 1350 1360 1370 1380 TITKKAGSHI QTLMGSQSLQ HRSREQQPYE GNINKVTIQQ FQSPLPIQIP SSQATRGPQP 1390 1400 1410 1420 1430 1440 GRCLIQTKGQ RSMDGYPEQF CVRIEKNPGL GFSISGGISG QGNPFKPSDK GIFVTRVQPD 1450 1460 1470 1480 1490 GPASNLLQPG DKILQANGHS FVHMEHEKAV LLLKSFQNTV DLVIQRELTV
	Isoform 3 (LRRC7) [UniParc]. Checksum: 4DD81D9302A9CB0E	FASTA	179	20,546
	10 20 30 40 50 60 MTTKRKIIGR LVPCRCFRGE EEIISVLDYS HCSLQQVPKE VFNFERTLEE LYLDANQIEE 70 80 90 100 110 120 LPKQLFNCQA LRKLSIPDND LSNLPTTIAS LVNLKELDIS KNGVQEFPEN IKCCKCLTII 130 140 150 160 170 EASVNPISKL PDGFTQLLNL TQLYLNDAFL EFLPANFGRL VKLRILELRE NHLKTLPNI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses." Izawa I., Nishizawa M., Ohtakara K., Inagaki M. J. Biol. Chem. 277:5345-5350(2002) [PubMed: 11729199] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CTNND2.
[2]	"Cloning and characterization of a novel splice variant of the brain-specific protein densin-180." Wang L., Xu J., Wu Q., Dai J., Ye X., Zeng L., Ji C., Gu S., Zhao R.C., Xie Y., Mao Y. Int. J. Mol. Med. 11:257-260(2003) [PubMed: 12525888] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY. Tissue: Brain.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-1537 (ISOFORM 1). Tissue: Amygdala.
[5]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed: 10718198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 641-1537 (ISOFORM 2). Tissue: Brain.
[6]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-235.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF434715 mRNA. Translation: AAL28133.1. AF498274 mRNA. Translation: AAP06801.1. Different initiation. AL158840 , AL391728, AL359412, AL157948 Genomic DNA. Translation: CAH70974.1. AL158840 , AL117353, AL157948, AL359412, AL391728 Genomic DNA. Translation: CAH70975.1. Different initiation. AL391728 , AL157948, AL359412, AL158840 Genomic DNA. Translation: CAH73691.1. AL391728 , AL117353, AL157948, AL158840, AL359412 Genomic DNA. Translation: CAH73692.1. Different initiation. AL359412 , AL158840, AL157948, AL391728 Genomic DNA. Translation: CAH74018.1. AL359412 , AL117353, AL157948, AL158840, AL391728 Genomic DNA. Translation: CAH74019.1. Different initiation. AL157948 , AL158840, AL391728, AL359412 Genomic DNA. Translation: CAI22425.1. AL157948 , AL117353, AL158840, AL359412, AL391728 Genomic DNA. Translation: CAI22426.1. Different initiation. AL117353 , AL157948, AL158840, AL359412, AL391728 Genomic DNA. Translation: CAI23423.1. Different initiation. CR749629 mRNA. Translation: CAH18423.1. AB037786 mRNA. Translation: BAA92603.1. Frameshift.
IPI	IPI00384313. IPI00426267. IPI00426269.
RefSeq	NP_065845.1. NM_020794.2.
UniGene	Hs.479658.
3D structure databases
ProteinModelPortal	Q96NW7.
SMR	Q96NW7. Positions 14-410, 1368-1535.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96NW7. 1 interaction.
MINT	MINT-223197.
STRING	Q96NW7.
PTM databases
PhosphoSite	Q96NW7.
Polymorphism databases
DMDM	50401129.
Proteomic databases
PRIDE	Q96NW7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000035383; ENSP00000035383; ENSG00000033122.
GeneID	57554.
KEGG	hsa:57554.
UCSC	uc001deo.1. human. uc001dep.1. human.
Organism-specific databases
CTD	57554.
GeneCards	GC01P069998.
H-InvDB	HIX0000691.
HGNC	HGNC:18531. LRRC7.
HPA	HPA002314. HPA005625.
neXtProt	NX_Q96NW7.
PharmGKB	PA134879588.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00600000084222.
HOVERGEN	HBG052305.
InParanoid	Q96NW7.
PhylomeDB	Q96NW7.
Gene expression databases
ArrayExpress	Q96NW7.
Bgee	Q96NW7.
CleanEx	HS_LRRC7.
Genevestigator	Q96NW7.
Family and domain databases
InterPro	IPR001611. Leu-rich_rpt. IPR001478. PDZ/DHR/GLGF. [Graphical view]
Pfam	PF00560. LRR_1. 1 hit. PF00595. PDZ. 1 hit. [Graphical view]
SMART	SM00228. PDZ. 1 hit. [Graphical view]
SUPFAM	SSF50156. PDZ. 1 hit.
PROSITE	PS51450. LRR. 15 hits. PS50106. PDZ. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	64030.

Entry information

Entry name

LRRC7_HUMAN

Accession

Primary (citable) accession number: Q96NW7
Secondary accession number(s): Q5VXC2 , Q5VXC3, Q68D07, Q86VE8, Q8WX20, Q9P2I2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 91 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.