Q92843 (B2CL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bcl-2-like protein 2
Short name=Bcl2-L-2

Alternative name(s):
Apoptosis regulator Bcl-W

Gene names

Name:	BCL2L2
Synonyms:	BCLW, KIAA0271

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

General annotation (Comments)

Function	Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX. Ref.1
Subunit structure	Interacts with BOP By similarity.
Subcellular location	Mitochondrion membrane; Peripheral membrane protein. Note: Loosely associated with the mitochondrial membrane in healthy cells. During apoptosis, tightly bound to the membrane. Ref.8 Ref.9
Tissue specificity	Expressed (at protein level) in a wide range of tissues with highest levels in brain, spinal cord, testis, pancreas, heart, spleen and mammary glands. Moderate levels found in thymus, ovary and small intestine. Not detected in salivary gland, muscle or liver. Also expressed in cell lines of myeloid, fibroblast and epithelial origin. Not detected in most lymphoid cell lines. Ref.8
Domain	The BH4 motif seems to be involved in the anti-apoptotic function. The BH1 and BH2 motifs form a hydrophobic groove which acts as a docking site for the BH3 domain of some pro-apoptotic proteins. The C-terminal residues of BCL2L2 fold into the BH3-binding cleft and modulate pro-survival activity by regulating ligand access. When BH3 domain-containing proteins bind, they displace the C-terminus, allowing its insertion into the membrane and neutralizing the pro-survival activity of BCL2L2.
Sequence similarities	Belongs to the Bcl-2 family.
Sequence caution	The sequence BAA19666.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Sertoli cell proliferation Inferred from electronic annotation. Source: Compara apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptotic process Inferred from mutant phenotype PubMed 17289999. Source: UniProtKB spermatogenesis Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BAX	Q07812	3	EBI-707714,EBI-516580
BBC3	Q9BXH1	2	EBI-707714,EBI-519884
BCL2L11	O43521	4	EBI-707714,EBI-526406
BID	P55957	5	EBI-707714,EBI-519672
BIK	Q13323	2	EBI-707714,EBI-700794
Bmf	Q91ZE9	2	EBI-707714,EBI-708032	From a different organism.

Alternative products

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

Isoform 1 (identifier: Q92843-1)

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 3 (identifier: Q92843-2)

Also known as: BCL2L2-PABPN1;

The sequence of this isoform differs from the canonical sequence as follows:
     145-193: AEFTALYGDG...VTVGAFFASK → ELEAIKARVR...ARATSWYSPY

Note: Based on a readthrough transcript which may produce a BCL2L2-PABPN1 fusion protein. No experimental confirmation available. Contains a phosphoserine at position 177.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 193

193

Bcl-2-like protein 2

PRO_0000143066

Regions

Motif

9 – 29

21

BH4

Motif

85 – 104

20

BH1

Motif

136 – 151

16

BH2

Natural variations

Alternative sequence

145 – 193

49

AEFTA…FFASK → ELEAIKARVREMEEEAEKLK ELQNEVEKQMNMSPPPGNAG PVIMSIEEKMEADARSIYVG NVDYGATAEELEAHFHGCGS VNRVTILCDKFSGHPKGFAY IEFSDKESVRTSLALDESLF RGRQIKVIPKRTNRPGISTT DRGFPRARYRARTTNYNSSR SRFYSGFNSRPRGRVYRGRA RATSWYSPY in isoform 3.

VSP_042064

Natural variant

133

1

Q → R. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7
Corresponds to variant rs910332 [ dbSNP | Ensembl ].

VAR_048418

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

193

Helix Strand Turn

Details...

Helix

10 – 24

15

Beta strand

30 – 32

3

Helix

33 – 35

3

Helix

41 – 70

30

Helix

72 – 74

3

Helix

75 – 88

14

Helix

92 – 112

21

Helix

117 – 131

15

Turn

132 – 134

3

Helix

135 – 140

6

Helix

143 – 151

9

Helix

156 – 168

13

Turn

171 – 176

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 3542243A532B1762	FASTA	193	20,746
	10 20 30 40 50 60 MATPASAPDT RALVADFVGY KLRQKGYVCG AGPGEGPAAD PLHQAMRAAG DEFETRFRRT 70 80 90 100 110 120 FSDLAAQLHV TPGSAQQRFT QVSDELFQGG PNWGRLVAFF VFGAALCAES VNKEMEPLVG 130 140 150 160 170 180 QVQEWMVAYL ETQLADWIHS SGGWAEFTAL YGDGALEEAR RLREGNWASV RTVLTGAVAL 190 GALVTVGAFF ASK
	Isoform 3 (BCL2L2-PABPN1) [UniParc]. Checksum: F2C9A67BF3D38122	FASTA	333	37,171
	10 20 30 40 50 60 MATPASAPDT RALVADFVGY KLRQKGYVCG AGPGEGPAAD PLHQAMRAAG DEFETRFRRT 70 80 90 100 110 120 FSDLAAQLHV TPGSAQQRFT QVSDELFQGG PNWGRLVAFF VFGAALCAES VNKEMEPLVG 130 140 150 160 170 180 QVQEWMVAYL ETQLADWIHS SGGWELEAIK ARVREMEEEA EKLKELQNEV EKQMNMSPPP 190 200 210 220 230 240 GNAGPVIMSI EEKMEADARS IYVGNVDYGA TAEELEAHFH GCGSVNRVTI LCDKFSGHPK 250 260 270 280 290 300 GFAYIEFSDK ESVRTSLALD ESLFRGRQIK VIPKRTNRPG ISTTDRGFPR ARYRARTTNY 310 320 330 NSSRSRFYSG FNSRPRGRVY RGRARATSWY SPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Bcl-w, a novel member of the Bcl-2 family, promotes cell survival." Gibson L., Holmgreen S.P., Huang D.C., Bernard O., Copeland N.G., Jenkins N.A., Sutherland G.R., Baker E., Adams J.M., Cory S. Oncogene 13:665-675(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANT ARG-133.
[2]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-133. Tissue: Brain.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-133.
[4]	"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 1), VARIANT ARG-133. Tissue: Cerebellum.
[5]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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], VARIANT ARG-133.
[7]	"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] (ISOFORMS 1 AND 3), VARIANT ARG-133. Tissue: Brain, Lung and Rhabdomyosarcoma.
[8]	"Tissue expression and subcellular localization of the pro-survival molecule Bcl-w." O'Reilly L.A., Print C., Hausmann G., Moriishi K., Cory S., Huang D.C.S., Strasser A. Cell Death Differ. 8:486-494(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity." Wilson-Annan J., O'Reilly L.A., Crawford S.A., Hausmann G., Beaumont J.G., Parma L.P., Chen L., Lackmann M., Lithgow T., Hinds M.G., Day C.L., Adams J.M., Huang D.C.S. J. Cell Biol. 162:877-887(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 (ISOFORM 3), MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 (ISOFORM 3), MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 (ISOFORM 3), MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 (ISOFORM 3), MASS SPECTROMETRY.
[15]	"The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity." Hinds M.G., Lackmann M., Skea G.L., Harrison P.J., Huang D.C.S., Day C.L. EMBO J. 22:1497-1507(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-183.
[16]	"Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix." Denisov A.Y., Madiraju M.S.R., Chen G., Khadir A., Beauparlant P., Attardo G., Shore G.C., Gehring K. J. Biol. Chem. 278:21124-21128(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 2-171.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U59747 mRNA. Translation: AAB09055.1.
D87461 mRNA. Translation: BAA19666.2. Different initiation.
BT019549 mRNA. Translation: AAV38356.1.
AK289519 mRNA. Translation: BAF82208.1.
AL049829 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW66169.1.
BC011637 mRNA. No translation available.
BC021198 mRNA. Translation: AAH21198.1.
BC104789 mRNA. Translation: AAI04790.1.
BC113522 mRNA. Translation: AAI13523.1.

IPI

IPI00023787.

RefSeq

NP_001186768.1. NM_001199839.1.
NP_004041.1. NM_004050.4.

UniGene

Hs.410026.
Hs.735863.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MK3	NMR	-	A	2-171	[»]
1O0L	NMR	-	A	1-183	[»]
1ZY3	NMR	-	A	2-171	[»]
2Y6W	X-ray	2.00	A/B	1-164	[»]

ProteinModelPortal

Q92843.

SMR

Q92843. Positions 1-183.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33700N.

IntAct

Q92843. 12 interactions.

STRING

9606.ENSP00000250405.

PTM databases

PhosphoSite

Q92843.

Polymorphism databases

DMDM

296434404.

Proteomic databases

PaxDb

Q92843.

PRIDE

Q92843.

Protocols and materials databases

DNASU

599.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000250405; ENSP00000250405; ENSG00000129473.
ENST00000553781; ENSP00000451320; ENSG00000258643.
ENST00000557008; ENSP00000452479; ENSG00000258643.

GeneID

599.

KEGG

hsa:599.

UCSC

uc001wjg.4. human.

Organism-specific databases

CTD

599.

GeneCards

GC14P023776.
GC14P023777.

HGNC

HGNC:995. BCL2L2.
HGNC:42959. BCL2L2-PABPN1.

HPA

CAB040539.
HPA000637.

MIM

601931. gene.

neXtProt

NX_Q92843.

PharmGKB

PA25307.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG300479.

HOGENOM

HOG000056452.

InParanoid

Q92843.

KO

K02163.

OMA

WEEQHAT.

OrthoDB

EOG4RBQKR.

PhylomeDB

Q92843.

Gene expression databases

ArrayExpress

Q92843.

Bgee

Q92843.

CleanEx

HS_BCL2L2.

Genevestigator

Q92843.

GermOnline

ENSG00000129473. Homo sapiens.

Family and domain databases

InterPro

IPR013280. Apop_reg_BclW.
IPR002475. Bcl2-like.
IPR020717. Bcl2_BH1_motif_CS.
IPR020726. Bcl2_BH2_motif_CS.
IPR003093. Bcl2_BH4.
IPR020731. Bcl2_BH4_motif_CS.
IPR026298. Blc2_fam.
[Graphical view]

PANTHER

PTHR11256. PTHR11256. 1 hit.
PTHR11256:SF13. PTHR11256:SF13. 1 hit.

Pfam

PF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]

PRINTS

PR01865. APOPREGBCLW.
PR01862. BCL2FAMILY.

SMART

SM00265. BH4. 1 hit.
[Graphical view]

PROSITE

PS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01260. BH4_1. 1 hit.
PS50063. BH4_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL4677.

ChiTaRS

BCL2L2. human.

EvolutionaryTrace

Q92843.

GenomeRNAi

599.

NextBio

2439.

SOURCE

Search...

Entry information

Entry name

B2CL2_HUMAN

Accession

Primary (citable) accession number: Q92843
Secondary accession number(s): A8K0F4, Q2M3U0, Q5U0H4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 129 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.