Reviewed, UniProtKB/Swiss-Prot P30429 (CED4_CAEEL)

Names and origin

Protein names

Recommended name:
    Cell death protein 4

Gene names

Name:	ced-4
ORF Names:	C35D10.9

Organism

Caenorhabditis elegans [Complete proteome]

Taxonomic identifier

6239 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Nematoda › Chromadorea › Rhabditida › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis

Protein attributes

Sequence length	571 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Isoform a plays a major role in programmed cell death (PCD, apoptosis). Egl-1 binds to and directly inhibits the activity of ced-9, releasing the cell death activator ced-4 from a ced-9/ced-4 containing protein complex and allowing ced-4 to activate the cell-killing caspase ced-3. Isoform b prevents PCD. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6
Subunit structure	Interacts with ced-9. Ref.4 Ref.6
Subcellular location	Mitochondrion. Note: In non cell death induced cells. Ced-9 is required for mitochondrial localization. Perinuclear in cell death induced cells. Ref.4 Ref.5
Developmental stage	Most abundant during embryogenesis and is also detected at later stages during periods of extensive programmed cell death. Ref.1
Disruption phenotype	Mutants exhibit a block in almost all programmed cell deaths that normally occur during development. Ref.1
Sequence similarities	Contains 1 CARD domain. Contains 1 NB-ARC domain.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Ref.1 Inferred from mutant phenotype. Source: UniProtKB regulation of apoptosis Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Ref.4 Inferred from direct assay. Source: UniProtKB mitochondrion Ref.5 Inferred from direct assay. Source: UniProtKB nucleus Ref.5 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.4 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2L1	Q07817	2	EBI-494118,EBI-78035	From a different organism.
CASP8	Q14790	1	EBI-494118,EBI-78060	From a different organism.
ced-3	P42573	3	EBI-536271,EBI-494247
ced-3	P42573	3	EBI-494118,EBI-494247
ced-9	P41958	7	EBI-494118,EBI-494110

Alternative products

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

Isoform b (identifier: P30429-1)

Also known as: Long;

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.

Note: Minor transcript.

Isoform a (identifier: P30429-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     212-234: ARVVSDTDDSHSITDFINRVLSR → K

Note: Major transcript.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 571

571

Cell death protein 4

PRO_0000089470

Regions

Domain

1 – 91

91

CARD

Domain

116 – 440

325

NB-ARC

Nucleotide binding

159 – 166

8

ATP Potential

Natural variations

Alternative sequence

212 – 234

23

ARVVS…RVLSR → K in isoform a.

VSP_013199

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

571

Helix Strand Turn

Details...

Helix

4 – 20

17

Helix

23 – 26

4

Helix

27 – 32

6

Helix

38 – 45

8

Beta strand

47 – 49

3

Helix

50 – 64

15

Beta strand

66 – 68

3

Helix

69 – 77

9

Helix

81 – 96

16

Helix

101 – 104

4

Turn

105 – 108

4

Helix

112 – 121

10

Helix

134 – 147

14

Beta strand

150 – 158

9

Helix

165 – 175

11

Turn

181 – 183

3

Beta strand

184 – 191

8

Helix

199 – 211

13

Turn

234 – 236

3

Helix

250 – 261

12

Beta strand

267 – 274

8

Helix

277 – 285

9

Beta strand

289 – 296

8

Helix

297 – 302

6

Beta strand

307 – 311

5

Helix

317 – 326

10

Helix

336 – 348

13

Helix

352 – 359

8

Beta strand

364 – 366

3

Helix

367 – 380

14

Beta strand

389 – 395

7

Helix

396 – 405

10

Helix

409 – 414

6

Helix

417 – 419

3

Helix

429 – 435

7

Helix

450 – 458

9

Turn

459 – 461

3

Beta strand

462 – 464

3

Beta strand

466 – 469

4

Beta strand

471 – 473

3

Beta strand

475 – 477

3

Helix

480 – 487

8

Helix

493 – 499

7

Turn

503 – 505

3

Helix

559 – 562

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform b (Long) [UniParc]. Last modified March 29, 2005. Version 2. Checksum: 6BE9893946B79E6C	FASTA	571	65,336
	10 20 30 40 50 60 MLCEIECRAL STAHTRLIHD FEPRDALTYL EGKNIFTEDH SELISKMSTR LERIANFLRI 70 80 90 100 110 120 YRRQASELGP LIDFFNYNNQ SHLADFLEDY IDFAINEPDL LRPVVIAPQF SRQMLDRKLL 130 140 150 160 170 180 LGNVPKQMTC YIREYHVDRV IKKLDEMCDL DSFFLFLHGR AGSGKSVIAS QALSKSDQLI 190 200 210 220 230 240 GINYDSIVWL KDSGTAPKST FDLFTDILLM LARVVSDTDD SHSITDFINR VLSRSEDDLL 250 260 270 280 290 300 NFPSVEHVTS VVLKRMICNA LIDRPNTLFV FDDVVQEETI RWAQELRLRC LVTTRDVEIS 310 320 330 340 350 360 NAASQTCEFI EVTSLEIDEC YDFLEAYGMP MPVGEKEEDV LNKTIELSSG NPATLMMFFK 370 380 390 400 410 420 SCEPKTFEKM AQLNNKLESR GLVGVECITP YSYKSLAMAL QRCVEVLSDE DRSALAFAVV 430 440 450 460 470 480 MPPGVDIPVK LWSCVIPVDI CSNEEEQLDD EVADRLKRLS KRGALLSGKR MPVLTFKIDH 490 500 510 520 530 540 IIHMFLKHVV DAQTIANGIS ILEQRLLEIG NNNVSVPERH IPSHFQKFRR SSASEMYPKT 550 560 570 TEETVIRPED FPKFMQLHQK FYDSLKNFAC C
	Isoform a (Short). Checksum: DB2A7969BDA50AF8	FASTA	549	62,878
	10 20 30 40 50 60 MLCEIECRAL STAHTRLIHD FEPRDALTYL EGKNIFTEDH SELISKMSTR LERIANFLRI 70 80 90 100 110 120 YRRQASELGP LIDFFNYNNQ SHLADFLEDY IDFAINEPDL LRPVVIAPQF SRQMLDRKLL 130 140 150 160 170 180 LGNVPKQMTC YIREYHVDRV IKKLDEMCDL DSFFLFLHGR AGSGKSVIAS QALSKSDQLI 190 200 210 220 230 240 GINYDSIVWL KDSGTAPKST FDLFTDILLM LKSEDDLLNF PSVEHVTSVV LKRMICNALI 250 260 270 280 290 300 DRPNTLFVFD DVVQEETIRW AQELRLRCLV TTRDVEISNA ASQTCEFIEV TSLEIDECYD 310 320 330 340 350 360 FLEAYGMPMP VGEKEEDVLN KTIELSSGNP ATLMMFFKSC EPKTFEKMAQ LNNKLESRGL 370 380 390 400 410 420 VGVECITPYS YKSLAMALQR CVEVLSDEDR SALAFAVVMP PGVDIPVKLW SCVIPVDICS 430 440 450 460 470 480 NEEEQLDDEV ADRLKRLSKR GALLSGKRMP VLTFKIDHII HMFLKHVVDA QTIANGISIL 490 500 510 520 530 540 EQRLLEIGNN NVSVPERHIP SHFQKFRRSS ASEMYPKTTE ETVIRPEDFP KFMQLHQKFY DSLKNFACC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death." Yuan J., Horvitz H.R. Development 116:309-320(1992) [PubMed: 1286611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A), FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
[2]	"Genome sequence of the nematode C. elegans: a platform for investigating biology." The C. elegans sequencing consortium Science 282:2012-2018(1998) [PubMed: 9851916] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Bristol N2.
[3]	"An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor." Shaham S., Horvitz H.R. Cell 86:201-208(1996) [PubMed: 8706125] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING.
[4]	"Interaction and regulation of subcellular localization of CED-4 by CED-9." Wu D., Wallen H.D., Nunez G. Science 275:1126-1129(1997) [PubMed: 9027313] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CED-9.
[5]	"Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death." Chen F., Hersh B.M., Conradt B., Zhou Z., Riemer D., Gruenbaum Y., Horvitz H.R. Science 287:1485-1489(2000) [PubMed: 10688797] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4." Yan N., Gu L., Kokel D., Chai J., Li W., Han A., Chen L., Xue D., Shi Y. Mol. Cell 15:999-1006(2004) [PubMed: 15383288] [Abstract] Cited for: FUNCTION, INTERACTION WITH CED-9.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X69016 Genomic DNA. Translation: CAA48781.1.
U21324 Genomic DNA. Translation: AAA62564.1.
U21324 Genomic DNA. Translation: AAX22294.1.

PIR

S72566.

RefSeq

NP_001021203.1.

UniGene

Cel.10679

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2A5Y	X-ray	2.60	B/C	1-571	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:1016N.

IntAct

P30429. 6 interactions.

Genome annotation databases

Ensembl

C35D10.9. Caenorhabditis elegans. [Contig view]

GeneID

175643.

Organism-specific databases

WormBase

WBGene00000418. ced-4.

WormPep

C35D10.9a. CE01203. [WorfDB]
C35D10.9b. CE38154. [WorfDB]

Phylogenomic databases

OMA

P30429. TRDVEIS.

Gene expression databases

ArrayExpress

P30429.

Family and domain databases

InterPro

IPR016854. Apop_reg_Ced-4.
IPR001315. CARD.
IPR002182. NB-ARC.
[Graphical view]

Pfam

PF00619. CARD. 1 hit.
PF00931. NB-ARC. 1 hit.
[Graphical view]

PIRSF

PIRSF027202. Apop_reg_Ced-4. 1 hit.

SMART

SM00114. CARD. 1 hit.
[Graphical view]

PROSITE

PS50209. CARD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

889028.

Entry information

Entry name

CED4_CAEEL

Accession

Primary (citable) accession number: P30429
Secondary accession number(s): Q5BHI5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	March 29, 2005
Last modified:	June 16, 2009
This is version 74 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Caenorhabditis annotation project