SGD Worm-Yeast Protein Comparison: Comparing Protein Domains in Worm and Yeast

Domain

Brief description

Y^a

W^b

R^c

Comment

Domains found only in the worm

PTB

Phosphotyrosine binding domain

0

11

-

Orthologous proteins with this domain seen in vertebrates

Nuclear hormone receptors (NHR)

Transcription factors with ligand and DNA binding Zn-finger domains

0

270

-

Worm-specific clusters of these proteins indicate several gene duplication events specific to the nematodes

EGF

Calcium-binding cysteine-rich repeats seen in epidermal growth factor and numerous other extracellular proteins

0

135

-

Orthologs for some of these proteins detectable in vertebrates and Drosophila

Degenerins

Amiloride-sensitive Na⁺ channels

0

28

-

Orthologs in vertebrates

T-box

DNA-binding domain of transcription factors

0

21

-

Orthologs in vertebrates and Drosophila

FMRFamides

Neuropeptides

0

20

-

Orthologs in invertebrates; distant homologs in vertebrates

Cadherin

Calcium-dependent cell adhesion module

0

18

-

Orthologs in vertebrates

Paired box

DNA-binding domain with 2 helix-turn-helix (HTH) units

0

18

-

In some transcription regulators, combined with the homeodomain; orthologs of these forms seen in vertebrates

SMAD

Transcription factors

0

8

-

Orthologs in vertebrates and Drosophila

Insulin-like peptides

Peptide hormones

0

7

-

Orthologs in vertebrates

Laminin NT

N-terminal globular domain of the extracellular matrix protein laminin

0

5

-

Orthologs in vertebrates

Domains found only in yeast

APSES

A fungal-specific DNA-binding domain seen in Swi4

6

0

-

Regulators of filamentous growth and cell cycle progression. Orthologs in filamentous fungi

C6

A fungal-specific binuclear Zn- binding cluster

54

0

-

Orthologs of many of these proteins seen in S. pombe suggesting an early expansion in the fungi

Conserved domains

MATH

Globular domain shared by Meprin (metalloproteases) and the TRAFs (apoptosis effectors)

1

94

31.8

In C. elegans, found most frequently (>25) in combination with the POZ domain. Orthologous protein with this configuration seen in plants and vertebrates. Previously not detected in yeast.

Voltage gated Channels

Ion channels typified by K⁺ channel shaker

1

68

23.0

Over 20 worm proteins appear equivalent to the yeast protein in domains organization; several additional domain configuration in the worm, e.g. combinations with PAS and POZ domains

SH2 domain

Phosphotyrosine-binding domain (Src homology domain 2)

1

57

19.3

In C. elegans, mostly combined with the animal-specific tyrosine kinase domain (>10 members). The SPT6 configuration is highly conserved throughout eukaryotes.

POZ

Protein-protein interaction domain first identified in Zn finger transcription regulators (e.g. Tramtrack) and poxvirus proteins also containing the KELCH repeats

4

156

13.2

No clear equivalents of the configurations seen in yeast detected in animals. The combinations with the MATH domain and K channels are animal-specific. Previously not detected in yeast.

cNMP cyclase

Catalytic domain of cyclic nucleotide (cAMP and cGMP ) biosynthesis enzymes

1

36

12.2

The animal proteins are very different from the fungal ones and occur either as multi-pass membrane proteins or as a single-pass membrane protein with an inactive kinase domain (the most common configuration in C. elegans)

PDZ domain

Protein-protein interaction domain binding C-termini of membrane-associated polypeptides

2

66

11.2

The only orthologous configuration is the proteasomal protein, in which PDZ is the only recognizable domain

PTPase

Phosphotyrosine phosphatase

3

83

9.4

In C. elegans, combines with SH2 and is also found as intraprotein domain duplications (configurations absent in yeast)

FNIII

Fibronectin III domain, adhesion module in animal extracellular proteins

2

55

9.3

In yeast, found in intracellular proteins that have no orthologs in animals

LON protease

Serine protease domain frequently combined with a AAA ATPases

1

15

5.1

The only orthologous configuration is the combination with the AAA ATPase domain. Most of the worm proteins contain only the protease domain.

LIM domain

Cysteine-rich domain involved in protein-protein interactions and possibly DNA binding

3

38

4.3

C. elegans has the LIM-homeodomain combination that is highly conserved in animals but missing in yeast; the fungal LIM-rho GAP combination is not found in C. elegans. The relationships between multi-LIM proteins are uncertain.

Homeodomain

HTH-containing DNA-binding domain

8

93

3.9

The atypical yeast homeodomains, such as Cup9, may be orthologous to the equivalent proteins from C. elegans, but the rest appear to have no clear orthologs.

SCP domain

Cysteine-rich module seen in snake/ insect toxins and plant pathogenesis response protein

3

34

3.8

No clear orthologs in yeast and worm. Previously not detected in yeast.

HINT domain

Domain shared by hedgehog and inteins; involved in autoproteolysis and protein splicing

1

11

3.7

The yeast HINT is in an intein, while worm HINT modules are associated with several distinct conserved domains predcited to be extracellular.

vWA domain

Von Willebrand factor A domain; Mg²⁺-binding adhesion module

4

43

3.6

Intracellular forms involved in transcriptional regulation have orthologs in both taxa, whereas extracellular forms are seen only in C. elegans. Previously not detected in yeast.

LRR

Leucine-rich repeat involved in protein-protein interaction

8

85

3.6

Intracellular forms involved in transcriptional regulation have orthologs in both taxa while extracellular forms are seen only C. elegans.

ZZ

Cysteine-rich module seen in transcriptional adaptors like ADA2

1

10

3.4

The yeast protein, ADA2, has an ortholog in humans but not in the worm.

Calmodulin-like EF hands

Calcium-binding helical acidic domains

8

72

3.0

Stand-alone calmodulins are orthologous but the combinations with diacyl glycerol kinases and other domains are C. elegans specific.

cNMP-binding domain

Cyclic nucleotide-binding domain; the protein kinase A regulatory subunit

2

17

2.9

The yeast proteins seem to be represented by orthologs in the worm; several unique domain combinations in animals.

RGS domain

Activator of GTP hydrolysis for heterotrimeric G-proteins

2

16

2.7

Both yeast proteins are represented by orthologs in the worm but the combination with the protein kinase domain is unique to animals.

cNMP PDE

Metal dependent cyclic nucleotide phosphodiesterase

1

7

2.4

The yeast enzyme has a clear ortholog in the worm.

Chromodomain

Globular domain seen in chromatin proteins (e.g. Polycomb)

3

20

2.2

The CHD1 chromodomain-containing helicase is orthologous in yeast and animals. Several novel domain combinations in animals e. g. with SET.

Adenoviral proteases

Protease with an active histidine and cysteine typified by the adenoviral processing proteases

2

13

2.2

The yeast protein SMT4 has orthologs in the worm and other animals as well as in plants.

DAG kinase

Diacyl glycerol kinase catalytic domain

2

10

1.6

Both yeast proteins are represented by orthologs in the worm. Novel domain combinations in animals, e. g. with F-box.

Ankyrin

A helical repeat typified by ankyrin repetitive units

20

92

1.6

SET domain

Conserved globular domain seen in chromatin proteins

6

27

1.5

Several novel domain organization, the only 2partially conserved 2orthologs include a Trithorax like protein of yeast

KH domain

RNA-binding domain typified by hnRNP K

6

27

1.5

Orthologous relationships are seen amidst the components of the splicing machinery

SAM domain

Protein-protein interaction domain seen in Ste kinases and other signaling molecules.

5

21

1.4

Novel combination with other domains in animals

RING finger

Cysteine-rich, metal-binding protein-protein interaction domain

30

129

1.4

Few orthologous combinations are recognizable such as the combination of the RING domain with the SNF/SWI ATPases

MYND finger

A Zn-binding motif seen in chromosomal and some cytoplasmic proteins

2

8

1.3

Several novel domain combinations in animals. Orthologs for none of the yeast proteins so far in worm

Arrestin

Proteins first characterized as modulators of 7 transmembrane receptor signaling

8

30

1.3

Several arrestin like proteins are identified in yeast but they clearly form a yeast specific family. While many of the worm proteins form worm specific families.

C2H2 finger

Zn-chelating DNA binding domain (classic Zn finger)

40

157

1.3

Only the basal transcription factor TFIIIA show shared orthologs, most of the rest do not share orthologs

Protein kinase (STY)

Catalytic domain of protein kinases phosphorylating serine, threonine and tyrosine

118

435

1.2

Several orthologous families are recognizable but tyrosine kinases are specific to animals

Forkhead

Wing helix-containing DNA-binding domain

5

17

1.2

No clear shared orthologs

bHLH

Basic helix-loop-helix DNA-binding domain

10

34

1.2

No real orthologs between the taxa, animal specific combination with PAS seen in C. elegans

RHO GEF

GDP exchange factor for the RHO subfamily of GTPases

5

18

1.2

Some show orthologous relationships

C2 domain

Lipid-binding membrane association domain seen in several kinases and membrane associated proteins

12

40

1.1

Combination with kinase domains is conserved across taxa

UB

Ubiquitin domain

9

28

1.1

Shared orthologs include ribosomal and repair proteins, while the worm poly- ubiquitins have no orthologs in yeast

WW domain

A proline-rich tract interaction domain

5

16

1.1

BRCT domain

BRCA1 C- terminal domain; a common domain seen in numerous checkpoint control and repair proteins

11

30

1.0

Few shared orthologs are seen such as Rev1 and DNA ligase. Novel configurations in animals such as a combination with Ring fingers and Ankyrin domains

FYVE finger

Zn-chelating, phosphatidylinositol(3)-phosphate binding domain

5

15

1.0

Some orthologous combination like with the Ring finger and PI3K domains are seen

Papain-like proteases

Thiol proteases typified by papain

10

30

1.0

Calcineurin-like phosphatase

A metal-dependent hydrolase domain seen in protein phosphatases, nucleases and DNA polymerase subunits

23

66

0.9

Orthologous relationships amidst the protein phosphatases and Mre11 like nucleases and DNA polymerase subunits

PH domain

The plecstrin homology domain involved in lipid binding and protein-protein interactions

19

52

0.9

Shared ortholog include combination with GAP domains.

RHO GAP

GTPase activating domain of the Rho subfamily of small GTPases

8

19

0.9

DSP

Dual specificity phosphatases (e. g. CDC25 and MAP kinase phosphatase)

7

18

0.9

Clear orthologs are seen for yeast proteins involved in cell cycle regulation

SPRY

A domain conserved in ryanodine receptors and several chromatin proteins (e.g. ASH2)

4

11

0.9

PHD finger

A Zn-chelating, non-specific DNA- binding domain

16

40

0.8

Several novel domain configurations in animals, no clear orthologs except a few proteins sharing a SET domain in addition

Small GTPases

Small (< 30 kDa in stand-alone forms) GTP-hydrolysing signaling proteins

37

84

0.8

Several of these form subfamilies which are conserved between the 2 taxa

SH3 domain

Proline-rich tract binding domain

23

57

0.8

Few real orthologs such as the combination with the myosin ATPase are seen

TPR

a-helical tetratricopeptide repeat involved in protein-protein interactions

23

55

0.8

RRM

RNA recognition motif — the most common RNA-binding domain

41

88

0.7

Several shared orthologs in the pre mRNA processing machinery

PBD domain

A protein-protein interaction binding the small GTPase RHO

3

6

0.7

A combination with kinase domain has orthologsin both taxa

Bright

AT-rich DNA-binding domain seen in several chromatin proteins

2

4

0.7

Several unique combinations are seen in animals but orthologs are seen only for the combinations with the JOR domain

Kelch repeats

A b-propeller forming repeat typified by the actin binding protein kelch

8

17

0.7

GAF domain

A ligand-binding signaling domain

1

2

0.7

TBC domain

A common domain seen in spindle checkpoint assembly proteins and Rab GTPase interacting proteins.

10

20

0.7

Some orthologous proteins are seen.

HMG1 domain

AT tract and minor groove-interacting DNA-binding domain

8

15

0.6

Several novel multidomain configurations in animals

DNAJ

A helical domain which acts as a cofactor for the Hsp70 and Hsp90 chaperones

19

36

0.6

Several yeast proteins have orthologs in animals

Cyclophilin

Peptidyl-prolyl isomerase typified by the cyclophilin-binding protein

9

16

0.6

Some have ortholog relationships

bZIP

Basic leucine zipper DNA-binding domain

13

23

0.6

Only one discernable ortholog, the rest appear to have independently evolved

FKBP

Peptidyl-prolyl isomerase typified by the FK506 binding protein

4

8

0.6

Some have ortholog relationships

Cyclin box

a-helical domain seen in cyclins, TFIIB and retinoblastoma protein

15

26

0.6

Rb is unique to the animals

DHHC domain

A predicted metal-binding domain

9

17

0.6

UB hydrolase

Ubiquitin C-terminal hydrolase catalytic domain (deubiquitinating enzyme)

18

30

0.6

Most show orthologous relationships

UBC domain

The ubiquitin conjugating enzyme (E2) catalytic domain

15

25

0.6

Most show orthologous relationships; there are apparently inactivated forms in both yeast and the worm

PAS domain

A redox/light sensing domain

5

8

0.5

Only one combination with a protein kinase domain has shared orthologs

RAS GEF

GDP exchange factor for the RAS subfamily GTPases

5

8

0.5

Some have ortholog relationships

Bromodomain

A conserved domain found in several chromatin proteins

11

16

0.5

Few orthologs are seen like the combination with the SNF/SWI helicases and acetyltransferase

ARM repeats

Armadillo repeats- helical interaction motifs seen in nuclear transport proteins, signaling proteins and phosphatase regulators

21

28

0.5

The nuclear transport proteins and the APC proteins show orthologous relationspis

14-3-3

A protein-protein interaction domain with a broad specificity

2

3

0.5

HECT domain

Ubiquitin-conjugating enzyme catalytic domain (E6)

5

8

0.5

Most show orthologous relationships

Histone acetylase

Amino group acetyltransferase - commonly involved in chromatin organization by acting on histone tails

15

21

0.5

Several show orthologous relationships

PI3K

Phosphatidyl inositol 3 kinases

8

8

0.5

Many show ortholgous relationships including those with multidomain combination like PH and FYVE domains

Zn metalloproteases

Zn-dependent proteases typified by insulinase

8

10

0.4

Some show orthologous relationships

CBS

Cystathione beta-synthase domain; a widespread conserved domain with an known function

11

13

0.4

Orthologous relationships seen in metabolic enzymes and protein kinase regulatory subunits like SPT14

UBA

A conserved domain seen in several proteins of the ubiquitination pathway

6

7

0.4

Most show orthologous relationships

Histone deacetylase

The catalytic domain of aminoacetyl hydrolases

6

8

0.4

Most show orthologous relationships

AAA ATPases

A superfamily of ATPases including regulators of replication and ATP-dependent chaperones

47

53

0.4

Most show orthologous relationships

WD40 repeats

b-propeller-forming repeat motif with a typical WD signature

110

127

0.4

Some clearly discernable ortholog families like the G protein b subunits.

PP2C

Protein phosphatases typified by the animal protein phosphatase 2C

9

10

0.4

SWI/SNF helicase

Large ATPases (member of the helicase supefamily II) involved in chromatin dynamics and repair

17

21

0.4

Most show orthologous relationships

HSP70

ATP-dependent chaperones

14

13

0.3

S1 domain

RNA/DNA binding domain of the oligonucleotide-binding fold

3

3

0.3

Most show orthologous relationships

RAS GAP

GTPase-activating domain for the RAS family of small GTPases

5

4

0.3

Some show orthologous relationships

FHA domain

A phosphoserine-binding domain seen in checkpoint regulator proteins

15

12

0.3

Not many clearly definable orthologous relationships

Actin

Cytoskeletal filament ATPase and related proteins

12

10

0.3

Some yeast actin related proteins have clear orthologs in C elegans

GATA finger

Zn-chelating DNA-binding domain seen in transcriptional regulators

17

14

0.3

No real orthologous relationships

PX domain

A possible protein-protein interaction domain seen in Bem-1 and PI3 kinases

12

9

0.3

Some orthologous relationships like in PLD isoforms

RANBD

RAN GTPase binding domains

3

2

0.2

MADS domain

A DNA-binding domain seen in SRF and MCM1 proteins

4

2

0.2

HSF domain

Heat shock transcription factor-type Winged helix DNA-binding domain

5

1

0.1

The only worm protein has an ortholog in yeast