Compilation of known and hypothetical prenylated CaaX proteins in the human genome.

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We generated n list of known and hypothetical prenylated proteins in the human genome based on the rules for CaaX substrate described in Reid, Terry, Casey and Beese (2004) "Crystallographic Analysis of CaaX Prenyltransferases Complexed with Substrates Defines Rules of Protein Substrate Selectivity" J. Mol Biol 343: 417-433.

In addition to highlighting the functional diversity of CaaX prenyltransferase substrates, this list may be useful for identifying novel prenylated proteins involved in oncogenesis and in understanding the biological effects of CaaX prenyltransferase inhibitors.

Columns 1, 2, 3, 4 and 5 show the protein name, associated genInfo identifier (GI) number, functional classification, cellular localization, and biological relevance, respectively. Column 6 shows the associated C-terminal Ca1a2X motif. Columns 7 and 8 mark the proposed modifying enzyme, FTase or GGTase-I, respectively. Substrates with published evidence of modification by that enzyme are marked with a Y, those hypothesized to be substrates are marked with an H; a * indicates prenylation by GGTase-I when FTase activity is compromised. Publication references for evidence of modification are shown in column 9 in the form of PubMed ID numbers (PMID).

Supplementary Table. Human CaaX prenyltransferase substrates

Name

GI

classification

cellular locallization

biological relevance

C

a1

a2

X

substrate for

PMID

FT

GGT-I

Apolipoprotein L3 (Apolipoprotein L-III)

17433280

apolipoprotein L family

cytoplasmic (probable)

may affect the movement of lipids in the cytoplasm or allow the binding of lipids to organelles defects result in juvenile-onset ceroid

C

H

T

H

H

CNL3 (Batten disease protein)

2498243

battenin family

liposomal membrane-associated

lipofuscinosis neuronal type 3 (CLN3), also known as Batten disease

C

Q

L

Q

Y

9151320

Rod cGMP-specific 3',5'-cyclic phosphodiesterase -subunit

2851392

cyclic nucelotide phosphodiesterase family

membrane-associated

visual signal transduction; defects result in autosomal recessive retinitis pigmentosa (ARRP)

C

C

I

Q

Y

1309771

Cyclin G2

9087132

cyclin family

cytoplasmic (by similarity)

may play a role in growth regulation and in negative regulation of cell cycle progesssion catalyzes the deacetylation of N-acetylaspartic

C

F

P

S

H

Aspartoacylase (Aminoacylase-2)

1168340

deacylase

high concentration in brain

acid (NAA) to produce acetate and L aspartate; defects cause Canavan disease

C

C

L

H

H

Prostacyclin receptor (Prostanoid IP receptor) (PGI receptor)

1172500

family 1 of G-protein coupled receptors

membrane-associated

signal transduction; receptor for prostacyclin

C

S

L

C

Y

10446129

Heterotrimeric G-protein -11 subunit

1730223

G protein family

membrane-associated (by similarity); high levels in all tissues tested except brain

signal transduction

C

V

I

S

Y

7665596

Heterotrimeric G-protein -T2 subunit

3023844

G protein family

membrane-associated (by similarity); retinal cones

signal transduction

C

L

I

S

H

Transducin chain (Guanine nucleotide-binding protein G(T) gamma-T1 subunit)

585181

G protein family

membrane-associated; retinal rod outer segment

signal transduction

C

V

I

S

Y

2217200

Interferon-induced guanylate-binding protein 1

417031

GBP family

primarily cytosolic (85%)

unknown

C

T

I

S

Y

8830800

-1,4-galactosyltransferase 7

13123990

glycosyltransferase family 7

membrane-associated (cis cisternae of Golgi stack); high levels in heart, pancreas and liver, medium in placenta and kidney, low in brain, skeletal muscle and lung

role in glycosylation pathway; defects result in progeroid Ehlers-Danlos syndrome (EDS)

C

T

F

S

H

DnaJ homolog subfamily A member 1 (HDJ-2)

1706474

heat shock protein

membrane-associated

may have role in protein import into mitochondria; co-chaperone of Hsc70

C

Q

T

S

Y

10873082

DnaJ homolog subfamily A member 4

27805462

heat shock protein

membrane-associated

unknown

C

Q

T

A

H

Type 5 inositol-1,4,5-triphosphate 5-phosphatase

8925284

inositol-1,4,5-trisphosphate 5phosphatase family

unknown

unknown

C

S

V

S

H

Type I inositol-1,4,5-trisphosphate 5-phosphatase

3122245

inositol-1,4,5-trisphosphate 5phosphatase family

membrane-associated; expressed in brain, with high levels in Purkinje cells

signal termination through hydrolysis of calcium-mobilizing second messenger Ins(1,4,5)P3

C

V

V

Q

Y

8626616

Name

GI

classification

cellular locallization

biological relevance

C

a1

a2

X

substrate for

PMID

FT

GGT-I

Lamin A/C (70 kDa lamin) (prelamin A)

125962

intermediate filament family

nuclear membrane

component of nuclear lamina, may provide framework for the nuclear envelope and may interact with chromatin; defects cause a variety of diseases including Emery-Dreifuss muscular dystrophy type 2 (EDMD2), dilated cardiomyopathy 1A (CMD1A), Hutchinson-Gilford progeria syndrome (HGPS), and Werner syndrome

C

S

I

M

Y

1557405

Lamin B1

125953

intermediate filament family

nucleoplasmic side of the inner nuclear membrane

component of nuclear lamina, may provide framework for the nuclear envelope and may interact with chromatin

C

A

I

M

Y

2684976

Lamin B2

23503078

intermediate filament family

nucleoplasmic side of the inner nuclear membrane

component of nuclear lamina, may provide framework for the nuclear envelope and may interact with chromatin

C

Y

V

M

H

CENP-E (Centromeric protein E)

399227

kinesin-like protein family

associated with kinteochores during congression, moves to spindle midzone at anaphase

microtubule motor; probably kinetochore motor

C

K

T

Q

Y

10852915

CENP-F (mitosin)

1345731

nuclear matrix; kinetochore/centromere and spindle during mitosis

involved in chromosome segregation during mitosis; interacts with retinoblastoma protein (RB), CENP-E and BUBR1

C

K

V

Q

Y

10852915

Paralemmin

22653899

paralemmin family

membrane-associated; widely expressed, with highest levels in brain and testis, intermediate levels in heart and adrenal gland

may help control cell shape

C

S

I

M

Y

9813098

Protein phosphatase 1 regulatory inhibitor subunit 16A

22256976

phosphatase inhibitor

plasma membrane

inhibits protein phosphatase 1 activity on phosphorylase, myosin light chain and myosin substrates

C

L

L

M

H

Protein phosphatase 1 regulatory inhibitor subunit 16B

22256977

phosphatase inhibitor

plasma membrane; high levels in vascular endothelium, CNS, lung, spleen, kidney, and testis

possible downstream target of TGF-beta1 signaling cascade in endothelial cells

C

R

I

S

H

Phosphorylase B kinase regulatory chain, liver isoform

1170685

phosphorylase b kinase regulatory chain family

primarily expressed in liver and other non-muscle tissue

involved in glycogen metabolism; defects associated with X-linked muscle glycogenosis

C

Q

M

Q

H

Phosphorylase B kinase regulatory chain, skeletal muscle isoform

1170683

phosphorylase b kinase regulatory chain family

primarily cytoplasmic, with small pool membrane-associated; expressed in muscle tissue

involved in glycogen metabolism; defects associated with X-linked muscle glycogenosis

C

A

M

Q

Y

1409665

Phosphorylase B kinase regulatory chain

2499582

phosphorylase b kinase regulatory chain family

primarily cytoplasmic, with small pool membrane-associated; expressed in muscle tissue

serine phosphorylation; glycogen metabolism

C

L

I

S

Y

1409665

Ubiquitin specific protease 32

22550104

protease

unknown

unknown

C

V

I

Q

Y

8617711

Peroxisomal farnesylated protein

729723

PXF/PEX19 family

outer surface of the peroxisome membrane

may be involved in peroxisomal biogenesis or assembly

C

L

I

M

Y

8188701

phosphorylation of rhodopsin; defects result in

Rhodopsin kinase

2833269

Ser/Thr protein kinase family, GPRK subfamily

membrane-associated; expressed in retina and pineal gland

Oguchi disease 2, autosomal recessive retinitis pigmentosa (ARRP), and autosomal

C

L

V

S

Y

1522899

dominant retinitis pigmentosa (ADRP)

RRP22 (Ras-related protein on chromosome 22)

3024572

small GTPase superfamily

membrane-associated

signal transduction

C

S

L

M

H

Name

GI

classification

cellular locallization

biological relevance

C

a1

a2

X

substrate for

PMID

FT

GGT-I

H-Ras

131869

small GTPase superfamily, Ras family

membrane-associated

signal transduction; mutations associated with a variety of human tumor types including bladder cancers and oral squamous cell carcinomas

C

V

L

S

Y

1751286

K-Ras 2A (Ki-Ras)

131875

small GTPase superfamily, Ras family

membrane-associated

signal transduction; mutations associated with a variety of human tumor types

C

I

I

M

Y

1751286

K-Ras 2B (Ki-Ras)

131879

small GTPase superfamily, Ras family

membrane-associated

signal transduction; mutations associated with a variety of human tumor types

C

V

I

M

Y

Y*

1751286

N-Ras

131883

small GTPase superfamily, Ras family

membrane-associated

signal transduction; mutations associated with a variety of human tumor types

C

V

V

M

Y

Y*

1751286

Rap-2a

131852

small GTPase superfamily, Ras family

membrane-associated

signal transduction

C

N

I

Q

Y

8424780

Di-Ras1 (small GTP-binding tumor suppressor 1)

21553323

small GTPase superfamily, Ras family, Di-Ras subfamily

membrane-associated; expressed in brain and heart

signal transduction; may have role in regulation of membrane transport

C

T

L

M

Y

Y*

12107278

Di-Ras2

21703367

small GTPase superfamily, Ras family, Di-Ras subfamily

membrane-associated; expressed in brain

signal transduction; may have role in regulation of membrane transport

C

V

I

M

H

12194967

Dexamethasone-induced Ras-related protein 1

38258272

small GTPase superfamily, RasD family

expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas; highest levels in heart

may have role in dexamethasone-induced alterations in cell morphology, growth and cell-extracellular matrix interactions

C

V

I

S

H

Rhes (Ras homolog enriched in striatum)

21362868

small GTPase superfamily, RasD family

membrane-associated; expressed in pancreatic endocrine cells (islets of Langerhans)

signal transduction; may be involved in mediating insulin secretory response to efaroxan

C

T

I

Q

Y

14724584

Rheb (Ras homolog enriched in brain 2)

6919957

small GTPase superfamily, Rheb family

membrane-associated; highest levels in skeletal and cardiac muscle

signal transduction

C

S

V

M

Y

9099708

Rho6 (Rnd1)

2500182

small GTPase superfamily, Rho family

membrane-associated; expressed in brain and liver

role in rearrangement of the actin cytoskeleton and formation of some neuritic processes

C

S

I

M

Y

9531558

RhoD

3024539

small GTPase superfamily, Rho family

membrane-associated; highest levels in heart, placenta, liver, skeletal muscle, and pancreas

may be involved in endosome dynamics; may coordinate membrane transport with function of cytoskeleton and aid in reorganization of actin cytoskeleton

C

V

V

T

H

RhoE (Rho8) (Rnd3)

1710230

small GTPase superfamily, Rho family

membrane-associated; ubiquitous

may have role in actin cytoskeleton organization and biogenesis, and cell adhesion

C

T

V

M

H

RhoI

13633743

small GTPase superfamily, Rho family

membrane-associated (by similarity); expressed in normal breast and ovarian epithelial cells, but not in breast and ovarian cancers

signal transduction

C

I

I

M

H

RhoN (Rho7) (Rnd2)

2507301

small GTPase superfamily, Rho family

membrane-associated (by similarity); high levels in testis

may have role in neuronal and hepatic functions

C

N

L

M

H

RhoQ (TC10)

134080

small GTPase superfamily, Rho family

membrane-associated

signal transduction

C

L

I

T

H

Rho-related BTB domain-containing protein 3

26006843

small GTPase superfamily, Rho family

membrane-associated (by similarity); high levels in neural and cardiac tissues, pancreas, placenta and testis

signal transduction

C

L

V

M

H

Stonin 1 (Stoned B-like factor)

33860221

Stoned B family

cytoplasmic, some fraction is membrane-associated

may be involved in endocytic machinery

C

I

T

Q

H

Name

GI

classification

cellular locallization

biological relevance

C

a1

a2

X

substrate for

PMID

FT

GGT-I

Tetraspan NET-7

11135165

tetraspanin (TM4SF) family

integral membrane protein (probable)

unknown

C

Y

P

N

H

Tetraspanin 1

12643622

tetraspanin (TM4SF) family

membrane-associated

unknown

C

N

L

Q

H

Protein tyrosine phosphatase PTPCAAX1

1777755

tyrosine phosphatase

membrane-associated

unknown

C

C

I

Q

Y

9018080

Protein tyrosine phosphatase PTPCAAX2

1777757

tyrosine phosphatase

membrane-associated

unknown

C

C

V

Q

Y

9018080

Protein tyrosine phosphatase type IVA, member 3 isoform 1

14589856

tyrosine phosphatase

membrane-associated

overexpression inhibits angiotensin-II-induced calcium mobilization and promotes cell growth

C

C

V

M

H

CAAX box protein 1 (Cerebral protein-5)

9087144

unknown

plasma membrane

unknown

C

V

L

A

H

LIM-only protein 6 (triple LIM domain protein 6)

22096354

unknown

widely expressed

unknown

C

I

V

A

H

Parkin coregulated gene protein (PARK2 coregulated)

46396493

unknown

cytoplasmic (probable)

susceptibility to leprosy is associated with PARK2

C

L

L

N

H

WD and tetratricopeptide repeats protein 1

41018470

unknown

unknown

unknown

C

R

P

S

H

Zinc finger DHHC domain containing protein 19

37999851

unknown

integral membrane protein (potential)

unknown

C

F

P

S

H

Hepatitis delta virus large antigen

46200326

viral protein

nuclear membrane

facilitates viral assembly and release

C

R

P

Q

Y

not expressed in normal tissues, except in testis;

B melanoma antigen 1 precursor

5915765

BAGE family

high levels in melanomas and other tumors (bladder, head and neck squamous cell, lung, and

unknown

C

F

I

F

H

H

breast carcinomas)

not expressed in normal tissues, except in testis;

B melanoma antigen 5 precursor

37537778

BAGE family

expressed in melanomas and bladder and lung

unknown

C

F

I

F

H

H

carcinomas

NADH-cytochrome b5 reductase

127846

reductase

membrane-bound on cytoplasmic side of the ER, soluble in erythrocytes

involved in microsomal electron transport system; desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and methemoglobin reduction (in erethrocytes); defects cause hereditary methemoglobinemia (HM)

C

F

V

F

H

H

inner surface of plasma membrane; high levels in

TC21 (R-Ras2)

2507282

small GTPase superfamily, Ras family

heart, placenta, and skeletal muscle; moderate levels in lung and liver; low levels in brain,

may transduce growth inhibitory signals across the cell membrane; antagonist of Ras proteins

C

V

I

F

Y

Y

7761092

kidney, and pancreas

Cdc42 homolog (G25K GTP-binding protein)

46397381

small GTPase superfamily, Rho family

membrane-associated

involved in epithelial cell polarization processes; induces formation of filopodia.

C

C

I

F

H

Y

1898776

Rac3 (Ras-related C3 botulinum toxin substrate 3)

46397673

small GTPase superfamily, Rho family

cytoplasmic, membrane-associated when activated; high levels in brain, heart, placenta, and pancreas

signal transduction

C

T

V

F

H

H

RhoB

132542

small GTPase superfamily, Rho family

membrane-associated

regulates signal transduction pathway affecting the assembly of focal adhesions and actin stress fibers

C

K

V

L

Y

Y

1400319

RhoH (GTP-binding protein TTF)

2500200

small GTPase superfamily, Rho family

membrane-associated (by similarity); expressed only in hemopoietic cells

involved in chromosomal translocation with BCL6

C

K

I

F

H

H

2',3'-cyclic nucleotide 3'-phosphodiesterase

1705945

2',3'-cyclic nucleotide 3'-phosphodiesterase

membrane-associated in brain white matter

phosphodiesterase

C

T

I

I

Y

7884818

Aldehyde dehydrogenase 7

1169285

aldehyde dehydrogenase family

high levels in kidney and lung

ethanol metabolism

C

T

L

L

H

Name

GI

classification

cellular locallization

biological relevance

C

a1

a2

X

substrate for

PMID

FT

GGT-I

Aldehyde dehydrogenase 8

1352247

aldehyde dehydrogenase family

high levels in salivary gland

ethanol metabolism

C

T

L

L

H

Cone cGMP-specific 3',5'-cyclic phosphodiesterase -subunit

1705960

cyclic nucleotide phosphodiesterase family

membrane-associated

visual signal transduction; cGMP-specific phosphodiesterase activity

C

L

M

L

H

Rod cGMP-specific 3',5'-cyclic phosphodiesterase -subunit

544052

cyclic nucleotide phosphodiesterase family

membrane-associated

visual signal transduction; necessary for the formation of a functional phosphodiesterase holoenzyme; defects result in autosomal recessive/dominant retinitis pigmentosa (ARRP/ADRP)

C

C

I

L

Y

1309771

Heterotrimeric G-protein -10 subunit

1730222

G protein family

membrane-associated (by similarity)

signal transduction

C

A

L

L

Y

7665596

Heterotrimeric G-protein -12 subunit

12229817

G protein family

membrane-associated (by similarity)

signal transduction

C

I

I

L

H

Heterotrimeric G-protein -13 subunit

20138402

G protein family

membrane-associated (by similarity)

signal transduction

C

T

I

L

H

membrane-associated (by similarity); expressed

Heterotrimeric G-protein -2 subunit

32699499

G protein family

in fetal tissues, including testis, adrenal gland,

signal transduction

C

A

I

L

Y

7782351

brain, white blood cells and brain

Heterotrimeric G-protein -3 subunit

232146

G protein family

membrane-associated (by similarity); high levels in brain; low levels in testis

signal transduction; activation of MAPK

C

A

L

L

Y

7665596

membrane-associated (by similarity); expressed

Heterotrimeric G-protein -4 subunit

1730219

G protein family

in brain, kidney, pancreas, skeletal muscle and

signal transduction

C

T

I

L

Y

7665596

faintly in cardiac muscle

Heterotrimeric G-protein -5 like subunit

12229849

G protein family

membrane-associated (by similarity)

signal transduction

C

S

F

L

H

Heterotrimeric G-protein -5 subunit

232147

G protein family

membrane-associated (by similarity); expressed in a variety of tissues

signal transduction

C

S

F

L

Y

7665596

membrane-associated (by similarity); expressed

Heterotrimeric G-protein -7 subunit

6016106

G protein family

in a variety of tissues; down-regulated in

signal transduction

C

I

I

L

Y

7665596

pancreatic cancer

Heterotrimeric G-protein -8 subunit

12232629

G protein family

membrane-associated (by similarity)

signal transduction

C

V

L

L

H

binds GTP, GDP, and GMP; induced by

Interferon-induced guanylate-binding protein 2

1169868

GBP family

membrane-associated

interferon gamma during macrophage

C

N

I

L

Y

8702422

activation