Additional file 2: Table S2: CBA-dependent alterations in mRNA expression at endstage SIV infection
Downregulated genes
Fold Change
Enzymes/Enzymatic Activity
Amino acid synthesis/degradation:
AASS
Promotes lysine degradation
AMT
Catalyzes the degradation of glycine
APIP
Functions in the methionine salvage pathway
GLS
Involved in the catabolism of glutamine
GNMT
Methylates glycine during the metabolism of Methionine
GPT2
Transamination to provide pyruvate and glutamate
ILVBL
First step in branched chain amino acid synthesis
Small molecule modifiers:
CA2
Carbonic anhydrase - hydrates CO2
PDE4A
Cyclic nucleotide phosphodiesterase - hydrolyzes cAMP
PLCD4
Phospholipase - hydrolyzes PIP2 to DAG and IP3
PTGIS
Catalyzes the isomerization of prostaglandin
SULT1A2
Sulfate conjugation of hormones, neurotransmitters, and drugs
TPMT
S-methylation of thiopurine drugs
Lipid enzymology:
AGPAT5
Involved in de novo phospholipid synthesis
ST8SIA5
Golgi protein - synthesis of gangliosides
CHPT1
Catalyzes phosphatidyl choline biosynthesis
PIGZ
Mannosyltransferase – glycosylphosphatidylinositol-anchor
biosynthesis
THRSP
Regulates
lipogenesis
Protein modifications/proteases:
ADAMTS8
A disintigrin and metalloproteinase
B3GALTL
Glucosyltransferase enzyme
ECE1
Processing of endothelin precursors
FICD
Adenylyltransferase - regulates proteins by transferring AMP
PSMD10
Chaperone for the assembly of the 26S proteasome
SCPEP1
Serine carboxypeptidase
Ligand biosynthesis:
ALDH1A2
Aldehyde dehydrogenase - synthesis of retinoic acid
CYP26B1
Cytochrome P450 family member - metabolism of retinoic acid
HSD3B7
Biosynthesis of hormonal steroids
Miscellaneous:
ALAS2
Mitochondrial - catalyzes first step in heme biosynthesis
MSRB3
Reduces methionine sulfoxide to methionine
UROS
Porphyryn and heme biosynthesis
Saccharide/sugar enzymology:
EXTL2
Glycosyltransferase - biosynthesis of heparin sulfate
HS6ST1
Heparin sulfate biosynthetic enzyme - neuronal development
XYLT2
xylosyltransferase - first step in biosynthesis of glycosaminoglycans
Fatty acid enzymology:
ACOT11
Acyl-CoA thioesterase - converts fatty acids to non-fatty acid CoA
form
General Cellular Functioning
-1.80
-2.09
-1.81
-1.67
-1.66
-1.63
-1.62
-1.67
-2.59
-2.43
-2.14
-1.67
-3.39
-1.55
-1.73
-1.63
-1.60
-2.01
-2.38
-2.06
-1.54
-1.59
1.57
1.59
-1.71
-1.58
-1.57
-2.26
-2.00
-1.62
-2.06
-1.57
-1.58
-1.53
Nucleotide biogenesis/regulation-related enzymes:
AARS2
Alanyl-tRNA synthetase
ADSSL1
Regulates nucleotide levels (converts IMP to AMP)
ALKBH8
tRNA modification of Wobble position of anticodon loop
APOBEC2
C to U editing enzyme
ENDOD1
Possible DNase or RNase
KRR1
40S ribosome biogenesis
POLQ
Nicked double strand DNA polymerase - DNA repair
Cellular organelles/cellular trafficking:
BICD1
Involved in transport from Golgi to ER
PLCL2
May regulate Ins(1,4,5)P3 around endoplasmic reticulum
REEP1
ER network formation and remodeling
SYPL2
Communication between sarcoplasmic reticulum membranes
TRAK1
Involved in endosome to lysosome trafficking
TTC8
Coat complex to sort proteins to primary cilia
Transcription/RNA splicing/translation:
CPEB3
Poly-adenylation RNA binding protein
EEF2K
Translational elongation factor
SAMD4A
Acts as a translational repressor
SETBP1
Binds SET, which is involved in DNA replication
SF3A1
mRNA splicing factor
YBX2
Involved in regulating stability and translocation of mRNA
Histone/histone function:
H2AFY2
Histone H2A
HIST1H4C
Histone cluster 1 H4c
MLL5
Histone methyltransferase - transcriptional activation
SETD8
Monomethylates histones and non-histone proteins
Chromosome stability/function:
KLHDC3
May be involved with meiotic recombination
PTTG1
Regulatory protein in chromosome stability
Vesicle transport:
NAPA
Critical in docking and fusion or vesicles to target membranes
Kinases and Phosphatases
General kinases:
CSNK1G2
Casein kinase 1
DCK
Phosphorylates deoxyribonucleic acids
MAPK4
Atypical MAP kinase - phosphorylates microtubule associate proteins
MAST3
Microtubule associated kinase
PIK3C2B
Phosphoinositide 3-kinase family member
PIK3CB
Catalytic subunit of PI3 kinase
RPS6KB2
Phosphorylates ribosomal protein S6
STK11
Kinase involved in cell polarity
WNK2
Kinase involved with electrolyte homeostasis
Kinases in signaling cascades:
LATS1
Kinase in Hippo pathway - regulates proliferation, death and migration
MAP3K10
MAP Kinase kinase kinase - activate JNK pathway
MAP3K12
MAP kinase kinase kinase - JNK pathway
Kinase - essential activator of Wnt pathway
TNIK
Kinase/phosphatase
regulators:
-1.91
-1.51
-1.52
-1.66
-1.58
-1.55
-1.57
-1.64
-1.60
-1.77
-1.91
-1.61
-1.71
-1.50
-1.84
-1.50
-1.98
-1.89
-1.70
-1.86
-1.61
-1.56
-1.50
-1.51
-1.53
-1.64
-1.88
-1.51
-1.53
-1.51
-2.48
-1.79
-1.51
-1.56
-1.63
-1.51
-1.90
-1.83
-1.78
AKAP6
DUSP7
PAQR3
PHLDA3
Phosphatases:
DUPD1
PPP1R16A
PPP2R3A
PTPN3
Anchors PKA to endoplasmic reticulum membrane
Phosphatase - regulates MAP kinase
Regulates Raf1 kinase - sequesters it to Golgi
Repressor of Akt function
-1.55
-1.84
-1.55
-1.63
Phosphatase and pro-isomerase
Protein phosphatase 1 - regulatory subunit
Protein phosphatase 2 - regulatory subunit
Protein tyrosine phosphatase
-1.98
-1.95
-2.02
-1.56
Ion Channels
Potassium (K+) channels:
ABCC9
Subunit of ATP-sensitive K+ channel
IRX5
Negatively regulates K+ channel gene expression
KCNA5
K+ channel - may regulate the secretion of insulin
KCNB1
Voltage dependent K+ ion permeability of excited membranes
KCNC4
Voltage dependent K+ ion permeability of excited membranes
KCNJ12
Inwardly rectifying K+ channel - controls resting membrane potential
KCNJ2
Inward rectifying potassium channel
KCNT1
Na+ activated K+ channel
LGI1
Regulates voltage-gated potassium channels
Sodium (Na+)/Chloride (Cl-) channels:
CLCNKA
Voltage gated chloride channel
CLIC5
Intracellular chloride channel
SCN4B
Modulates sodium gating kinetics
SLC12A2
Na+ and Cl- transport and readsorption
SLC6A16
Na+/Cl- neurotransmitter transporter
SLC26A10
Chloride/bicarbonate exchanger
SLC38A8
Potential Na+ amino acid antiporter
Miscellaneous channels/transporters:
CNGB1
Cyclic nucleotide gated channel - nonselective cation channel
PDZD2
Bind cytoplasmic side of ion channels
SLC36A2
Proton-coupled amino acid transporter
XK
Possible Na+-dependent transport of neutral amino acids
Receptors
Signal transduction receptors:
ESR1
Estrogen receptor - nuclear hormone receptor
FZD4
Frizzled - receptor for Wnt signaling pathway
GPR125
G-protein coupled receptor
LPHN2
G-protein coupled receptor - cell adhesion
RARB
Retinoic acid receptor - cell growth and differentiation
Lipid receptors:
LRP12
May be part of LDL receptor - internalization of lipophilic molecules
OSBPL1A
Intracellular lipid receptor
OSBPL6
Oxysterol binding protein - intracellular lipid receptor
Receptors for physiologic responses:
NPR3
Natriuretic peptide receptor - regulate blood volume and pressure
TMEM158
Similar to receptor involved in neural survivals
UNC5A
Receptor required for axon guidance
-1.91
-1.99
-2.11
-1.66
-1.65
-1.77
-1.52
-1.57
-3.78
-1.52
-1.57
-3.16
-2.04
-1.81
-1.51
-2.06
-1.66
-1.77
-1.81
-2.16
-3.06
-1.65
-1.65
-1.73
-2.27
-1.58
-1.52
-2.21
-3.42
-1.73
-1.59
Neuronal receptors:
DLG2
Required for perception of chronic pain - interacts with NMDA receptor
RIC3
Promotes the expression of acetylcholine receptors
Regulators of uptake/transport:
SHBG
Androgen transport protein - receptor mediated processes
TFRC
Transferrin receptor - regulate uptake of iron
Transcriptional regulation
Transcription factors/activators:
ATP1B4
Transcriptional regulator in muscle development - TGFbeta signaling
CAMTA1
Transcriptional activator - tumor suppressor
IRX3
Transcription factor - SHH-dependent neural patterning
NFYB
Transcriptional activator of collagen and beta-actin (among others)
PITX1
Transcriptional regulator - hormone regulated activity of prolactin
SOX18
Transcription factor with unknown targets
VGLL2
May activate gene expression during muscle development
ZNF3
Zinc finger - involved in cell differentiation and/or cell proliferation
ZNF165
Possible transcriptional regulator
ZNF784
Zinc finger protein - possible transcriptional regulator
Modified histones:
MTF2
Binds trimethylated histone H3 - transcriptional regulator
SMYD1
Methylates histone H3 - transcriptional repressor
Transcriptional cofactors/regulators:
LMCD1
Transcriptional cofactor involved in cardiac hypertrophy
MKL1
Transcriptional coactivator - inhibits TNF induced cell death
Transcriptional repressors:
HES5
Transcriptional repressor involved in cell differentiation
Ca+2-dependent functions
Ca+2 channel/Ca+2 dependent channel:
ADRB2
Beta adrenergic receptor - effector for Ca+2 channels
ATP2B2
Ca+2 export-dependent ATP hydrolase
CACNG6
Voltage dependent Ca+2 channel subunit
KCNN3
Intracellular Ca+2 activated potassium channel
KCNIP3
Ca+2-dependent regulator of K+ channels
Ca+2 regulated enzymes/activities:
ADCY1
Adenylate cyclase regulated by Ca+2
CADM1
Ca+2-dependent cell adhesion molecule
+2
CALM2
Ca -dependent regulator of kinases and phosphatases
CIB2
Calcium and integrin binding protein - Ca+2 binding regulatory protein
TNNI1
Confers Ca+2 sensitivity to muscle actomyosin
+2
Ca mobilization:
CASQ1
Muscle specific sarcoplasmic reticulum Ca+2 sensor
JPH2
Crosstalk between ECM and intracellular Ca+2 release
Neuronal Ca+2 activities:
CAMK2A
Ca+2/Calmodulin dependent kinase - prominent in CNS
KCNN2
K+ channel activated by intracellular Ca+2 - regulates neuronal excitability
Glycolysis/Energy metabolism
Glycolysis/TCA cycle:
-1.83
-1.80
-2.36
-2.28
-2.52
-1.95
-2.29
-1.52
-1.59
-1.56
-1.51
-1.58
-1.69
-1.54
-1.58
-1.93
-1.85
-1.58
-1.86
-1.65
-5.10
-1.77
-1.68
-1.50
-1.54
-2.17
-1.57
-1.72
-1.67
-1.57
-1.73
-1.71
-3.96
AACS
Acetoacetyl CoA synthetase - synthesizes Acetyl CoA
PFKFB4
Phosphofructo kinase – involved in glycolysis
PGAM2
Phosphoglycerate mutase – involved in the glycolytic pathway
PPP1R3C
Regulatory subunit of phosphatase - limits glycogen breakdown
PYGB
Mediates rate determining step in glycogen degradation
SLC37A4
Transports G-6-P from cytoplasm to lumen of the ER
TPI1
Triosephosphate isomerase – involved in glycolysis and gluconeogenesis
Lipid/glycerol metabolism:
CROT
Fatty acid beta oxidation and lipid metabolism
GK
Glycerol kinase - regulates glycerol uptake and metabolism
GPD1
Glycerol-3-phosphate dehydrogenase – carbohydrate/lipid metabolism
Energy molecule biosynthesis:
COQ3
Methylates coenzyme Q - CoQ biosynthesis
GATM
Biosynthesis of guanidinoacetate – immediate precursor of creatine
Insulin-related:
MAFB
Activates insulin and glucagon promoters
SLC2A4
Insulin regulated glucose transporter
Miscellaneous:
COQ10A
Required for function of Coenzyme Q in respiratory pathway
Ubiquitination/SUMOylation
ASB10
Substrate recognition for ECS E3 ubiquitin ligase
ASB12
Possible substrate recognition component of E3 ubiquitin ligase
ASB15
Possible substrate recognition component of E3 ubiquitin ligase
CUL3
Cullin - polyubiquitination and protein degradation
FBXO3
Substrate recognition for E3 ubiquitin ligase complex
MAGEE1
Enhance ubiquitin ligase activity
MAGEF1
May enhance ubiquitin ligase activity
ZYG11B
Possible target recruitment of E3 ubiquitin ligase
Ubiquitin enzymes:
HERC5
Interferon-induced E3 ubiquitin ligase
MARCH6
E3 ubiquitin protein ligase
RNF144B
E3 ubiquitin protein ligase
USP15
De-ubiquitinating enzyme
Myogenic functions
Muscle cell function:
ALKBH4
Demethylates actin - regulates actin-myosin processes
MYLK2
Myosin light chain kinase - muscle contraction
MYOZ3
Helps tether calcineurin to sarcomeres in skeletal muscle
PVALB
Parvalbumin - involved in relaxation after contraction
TTN
Component in muscle assembly - balances forces between sarcomeres
Muscle cell structure/integrity
CAV3
Caveolin - involved in muscle membrane repair after mechanical stress
CTF1
Secreted cytokine that induces myocyte hypertrophy
CTNNA3
Involved in cell-cell adhesion in muscle cells
SSPN
DGC network - link between cytoskeleton and ECM in muscle cells
SYNC1
Muscle intermediate filament protein - structural role in striated muscle
Muscle cell biology:
MEF2C
Myogenic factor
-1.57
-1.72
-1.85
-3.98
-1.92
-2.17
-1.84
-2.06
-1.56
-1.53
-1.73
-5.06
-1.84
-1.90
-1.81
-1.71
-1.58
-2.16
-1.60
-1.74
-1.90
-2.00
-2.37
1.53
-1.90
-1.78
-1.53
-1.51
-2.09
-2.50
-3.86
-1.51
-1.97
-1.53
-1.76
-1.77
-1.72
-1.59
PITX2
PTPLA
Controls cell proliferation and muscle expansion
Muscle specific very long chain fatty acid synthesis
Signaling Pathways
Miscellaneous signaling:
IRS1
Involved in insulin signaling
PDE1A
Signal transduction - cyclic nucleotide phosphodiesterase
Wnt signaling:
RSPO3
Activator of canonical Wnt signaling
WISP2
Wnt signaling pathway - relevant for malignant transformation
WNT4
Ligand in the Wnt signaling pathway
TGFbeta signaling:
SMAD6
Negatively regulates TGF beta signaling
TGFB2
TGF beta - multiple effects
TNF signaling:
IER3
Protects cells from Fas or TNF induced apoptosis
PEBP4
Promotes cellular resistance to TNF-apoptosis
Neuronal Function
Neuronal survival/plasticity/regeneration:
ARMETL1
Trophic factor for dopamine neurons
MPDZ
Synaptic plasticity in excitatory synapses
SEMA6C
Semaphorin possibly important for neural regeneration
WDR62
Neuronal proliferation and migration
CNS development:
ARX
Transcription factor involved in CNS development
CRIM1
Interacts with growth factors during CNS development
GPC4
Cell surface heparin sulfate proteoglycan
PHYHIPL
Possible role in development of CNS
Neuronal orientation/polarization:
BTBD3
Regulates dendritic field orientation
EGFLAM
Necessary for proper bipolar dendritic tip apposition
RILPL2
Involved in cell shape and neuronal morphogenesis
Neurotransmitters:
GLRB
Glycine receptor - neurotransmitter-gated ion channel
Cell Growth/Cell Cycle Regulation
Cell cycle regulators:
ARID4A
Binds to pRb to regulate cellular proliferation
CABLES1
Cell cycle dependent kinase binding protein
CDKN3
Cell cycle regulator - interacts with and dephosphorylates CDK2
NEDD1
Required for mitosis progression
SPIN2B
Regulates cell cycle progression
Signal transduction cell growth regulation:
TOB1
Anti-proliferative protein through ERBB signaling
TRAF3IP3
Mediates cell growth by modifying JNK pathway
Transporters
Cellular transporters:
NIPSNAP3B
Possible role in vesicular transport
-1.61
-1.66
-1.75
-1.83
-2.28
-1.58
-1.58
-1.55
-1.98
-1.72
-1.89
-1.54
-1.86
-1.67
-1.81
-2.99
-1.74
-2.05
-2.36
-2.08
-1.69
-1.52
-2.05
-2.00
-1.56
-1.59
-1.74
-1.98
-2.31
-1.66
-3.06
SLC29A1
Mediates influx and efflux of nucleosides across membrane
SLC35E4
Putative transporter
XPO4
Regulates transport of proteins between cytoplasm and nucleus
Small molecule/metal transport:
CNNM4
Cycling M4 - possible metal transport
HBA2
Hemoglobin alpha - oxygen transport
HBB
Hemoglobin beta chain
Mitochondrial Function
Mitochondrial maintenance:
KIF1B
Kinesin - anterograde transport of mitochondria
OSGEPL1
Involved in mitochondrial genome maintenance
PINK1
Mitochondrial kinase - protects against mitochondrial dysfunction
Mitochondrial uptake/transport:
MRS2
May mediate influx of Mg+2 into mitochondria
SLC25A12
Exchanges aspartate for glutamate across mitochondrial membrane
SLC25A21
Mitochondrial transporter of 2-oxoadipate - precursor of Acetyl CoA
Miscellaneous
CCDC28B
FILIP1L
HIGD1B
PER3
TMEM79
Modulates mTORC2 assembly and function
Regulator of antiangiogenic activity
Membrane associated - hypoxia inducible gene
Component of the circadian clock mechanism
Contributes to epidermal integrity
-1.69
-2.41
-1.60
-2.16
-2.21
-1.72
-1.66
-1.98
-1.79
-1.70
-1.77
-1.66
-1.80
-2.19
-1.76
-1.60
-1.63
Actin/Microtubule Proteins
FSCN1
Organizes actin filaments - migration and motility
MAP7
Microtubule associated protein - reorganization and polarization
SGCB
Sarcoglycan - connects F-actin to ECM
TMOD4
Blocks elongation and depolymerization of actin ends
XIRP2
Protects actin filaments from depolymerization
-1.72
-3.00
-2.35
-1.53
-1.61
G-protein Coupled Activities
ARHGAP18
Rho GTPase activation protein
ARHGEF10L
Guanine nucleotide exchange factor for Rho
ARHGEF17
Rho guanine nucleotide exchange factor
RASGRP3
Guanine nucleotide exchange factor for Ras and Raf
-1.76
-1.51
-1.73
-1.74
Cellular Adhesion
FRAS1
ITGA10
LPP
-1.72
-1.56
-1.52
ECM protein - involved in adhesion and organogenesis
Integrin alpha - receptor for collagen and important for adhesion
Structural role at sites of adhesion, cell shape and motility
Differentiation and Development
SLFN5
May be involved in hematopoietic cell differentiation
TSPAN33
Involved with erythropoiesis
ZFPM2
Involved in heart morphogenesis and coronary vessel development
-1.81
-1.83
-2.01
Extracellular Matrix
ADAMTSL2
-1.61
Secreted glycoprotein - binds the cell surface and ECM
CCDC88A
IMPG2
Enhances Akt signaling - cytoskeletal remodeling and cell migration
Proteoglycan - binds chondroitin sulfate and hyaluranon
-1.57
-1.72
Cytoskeleton:
PAK1
Cell motility - link Rho GTPases to cytoskeletal reorganization
-1.74
Upregulated genes
Enzymes/Enzymatic Activity
Lipid enzymology:
DDHD1
Phospholipase - hydrolyzes phosphatidic acid
LIPG
Lipase - hydrolyzes HDL
PLA1A
Hydrolysis of glycerophospholipids
PLA2G2A
Regulates phospholipid metabolism
PLCD3
Phospholipase C - hydrolyzes PIP to diacylglycerol and inositol
PON3
Hydrolyzes lactones and inhibit oxidation of LDL
Miscellaneous:
AKR1B10
Aldo/keto reductase - reduce aliphatic and aromatic aldehydes
LIPA
Lysosomal protein - catalyze hydrolysis of cholesterol and triglycerides
METTL3
Adenosine-methyltransferase - methylates internal A's on mRNA
METTL6
Probable methyltransferase
SALL3
Decreases DNMT-3 CpG methylation
SARS
Serine tRNA aminoacyl transferase
Saccharide/sugar enzymology:
B4GALT5
Synthesis of complex n-linked oligosaccharides
CHSY3
Glycosyltransferase
IDUA
Iduronidase alpha - hydrolyzes terminal alpha iduronic acid
MAN1A2
Mannosidase - maturation of Asn-linked oligosacharrides
MPI
Enzyme involved in the synthesis of GDP-Mannose
Acetyltranferases/deacetylaces:
CHD1
Chromatin remodeler - member of histone acetyltransferase complex
HDAC4
Histone deacetylase 4
SIRT1
Protein deacetylase - multiple functions
YEATS4
Member of histone acetyltransferase complex
Fatty acid enzymology:
CPT1B
Long chain beta oxidation fatty acid pathway
ELOVL5
Synthesis of long chain fatty acids
FADS1
Promotes the desaturation of fatty acids
ZDHHC7
Broad specificity palmitoyltransferase
Protein modification/proteases:
AEBP1
Carboxypeptidase A family - reduce adipocyte differentiation
CPA4
Carboxypeptidase
PAPPA
Metalloproteinase that cleave IGFBP 4 and 5 (increases free IGF)
Amino acid synthesis/degradation:
BCAT1
Catabolism of leucine, isoleucine, and valine
PHGDH
Involved with L-serine synthesis
PRPS2
Involved with nucleotide synthesis
Cell membrane protein anchoring:
HHATL
Negatively regulates palmitoylation of SHH
PIGU
Part of GPI transamidase - attaches GP-anchors to proteins
+2.21
+2.71
+1.53
+1.52
+1.86
+1.66
+2.62
+1.60
+1.73
+1.58
+2.05
+1.58
+2.23
+1.58
+2.06
+1.64
+1.84
+1.66
+2.36
+1.67
+1.67
+1.66
+2.11
+1.65
+1.57
+1.62
+3.13
+3.13
+1.87
+1.52
+1.53
+1.61
+2.08
PIGW
Involved with the biosynthesis of the GPI anchor
Protein folding/structure:
PPIL2
Peptidylprolyl isomerase - facilitates folding of proteins
SELM
Thiol-disulfide oxidoreductase - disulfide bond formation
General Cellular Functioning
Vesicle/organelle transport:
DYNC1I1
Cytoplasmic dynein – motility of cytoplasmic vesicles and organelles
EXOC5
Assists docking of exocytic vesicles on plasma membrane
EXPH5
Possible involvement in vesicle transport
GOLSYN
Part of kinesin motor adaptor complex - axonal transport
GOPC
Intracellular protein trafficking and degradation
SEC24D
Coat of ER-derived vesicles - transport from ER to Golgi
VPS37B
Regulates vesicular trafficking
Transcription/RNA splicing/translation:
CRKRS
CDK12 - regulates transcription elongation and mRNA splicing
EAF1
ELL transactivating factor - promote RNA Pol II transcription
PRPF8
Assists in the assembly of the snRNP complex
RBM35B
Regulates mRNA splicing
RPL29
Ribosomal protein
RPS21
Ribosomal protein
RNA processing:
EIF2C4
Member of the RISC complex
NOL11
Nucleolar protein - rRNA processing
RBM7
Possible involvement in RNA processing
TSEN2
Involved in maturation of tRNA
DNA repair:
MLH3
DNA mismatch repair protein
PMS1
DNA mismatch repair protein
REV3L
Involved in translesion DNA synthesis
Histone/histone function:
BAZ1A
Part of a chromatin remodeling complex
HIST1H1D
Histone H1
HIST1H2AC
Histone H1
Chromosome stability/function:
ESPL1
Caspase-like protease - cleaves cohesin – chromosome segregation
RCC2
Regulator of chromosome condensation
Nuclear pore/nuclear membrane integrity:
NUP188
Nucleoporin - present in nuclear pore complex
TMEM43
Maintaining nuclear membrane structure
Miscellaneous:
OFD1
Centriole protein - involved in biogenesis of cilium
Transcriptional Regulation
Transcription factors – activators:
ARNTL
Transcriptional activator - circadian clock
CCDC59
Transcriptional activator
ETS2
Transcription factor - development/apoptosis - regulates telomeres
FOS
Part of the FOS/Jun complex - transcriptional regulation
JUNB
Part of the FOS/Jun complex - transcriptional regulation
+2.00
+1.62
+1.56
+1.75
+1.50
+2.04
+1.67
+1.60
+1.79
+1.85
+1.53
+2.09
+1.61
+1.51
+1.53
+1.78
+2.01
+1.90
+1.76
+1.52
+1.53
+1.64
+1.58
+1.52
+1.52
+1.52
+1.72
+1.51
+1.82
+1.59
+1.57
+1.62
+1.56
+2.27
+2.90
+2.61
LITAF
LPS-induced - mediates TNF alpha expression
PRRX2
Role in fetal skin development
Transcription co-factors/regulators:
ARID5B
Transcriptional coactivator involved in adipogenesis
DDX21
Helicase in Jun-activated transcription
EGR1
Transcriptional regulator of differentiation and mitogenesis
NCOA7
Enhances nuclear receptor transcriptional activity
NFIL3
Transcriptional regulator that binds to ATF sites
Transcription inhibitors:
PHC1
Polycomb group - maintain transcriptionally repressive state
PTGES3
Molecular chaperone - disrupts transcriptional activation complexes
Cellular Adhesion
Promotes cellular adhesion/cell-cell interactions:
CYR61
Angiogenic inducer - promotes adhesion of endothelial cells
EFNA1
Ephrin ligand - promotes migration, repulsion and adhesion
THBS1
Mediates cell-cell and cell-matrix interactions
THBS2
Mediates cell-cell and cell-matrix interactions
Ca+2-dependent adhesion molecules
CDH11
Cadherin - Ca+2-dependent adhesion molecule
CDH26
Cadherin - Ca+2-dependent cell adhesion molecule
PCDHA5
Neuronal Ca+2-dependent cell adhesion protein
Promotes loss of adhesion:
PNN
Reverses expression of E-cadherin expression
PPFIA4
Regulates the disassembly of focal adhesions
RND3
GTPase superfamily with no GTPase activity - promotes loss of adhesion
Neuronal adhesion molecules:
NCAM1
Neural cell adhesion molecule - cell-cell adhesion
NINJ1
Cell adhesion molecule that promotes axonal nerve growth
Miscellaneous:
RHOB
Ras homolog - affects cell adhesion and growth factor signaling
SEMA3F
Semaphorin - cell motility and adhesion
Proteases/peptidases:
ADAM33
Metallopeptidase involved in mediating cell-cell interactions
RELN
ECM serine protease important for cell adhesion
Extracellular Matrix
Collagen and collagen deposition:
COL1A1
Collagen type 1A
COL1A2
Collagen Type 1
CTHRC1
Negative regulator of collagen matrix deposition
LOX
Extracellular copper enzyme that initiates the crosslinking of collagens
Proteases/peptidases:
HTRA3
Serine protease - cleave ECM proteoglycans
MMP11
Matrixmetallopeptidase - ECM degradation
PLAU
Serine protease involved in degradation of extracellular matrix
Protease/peptidase inhibitors:
SERPINE1
Ser proteinase inhibitor - inhibitor of fibrinolysis
SERPINA1
Inhibitor of serine proteases - elastin is primary target
Cell surface proteoglycans:
+2.24
+1.75
+1.83
+1.60
+1.76
+1.99
+2.30
+1.91
+1.57
+2.62
+1.60
+1.79
+1.87
+1.55
+1.67
+1.59
+2.07
+1.76
+2.38
+1.66
+1.50
+2.38
+1.58
+1.52
+1.78
+1.51
+1.55
+2.44
+2.37
+2.17
+5.29
+1.51
+2.48
+1.52
SDC4
Cell surface proteoglycan - binds heparin sulfate
UGDH
Biosynthesis of glycosaminoglycans like chondroitin and heparin sulfate
General ECM proteins
FREM2
ECM protein - required for integrin of skin epithelium
VCAN
Versican - member of the extracellular matrix
Actin/Microtubule Proteins
Actin polymerization/accumulation/reorganization:
ACTR3
Regulator of actin polymerization
SHRM
Controls cell shape through the accumulation of F-actin
SPIRE1
Actin nucleation factor - vesicular transport
XIRP1
Protect actin filaments from depolymerization
Actin depolymerization/turnover:
MICAL1
Promotes depolymerization of F-actin
MICAL2
Monooxygenase - depolymerization of F-actin
RHPN2
Binds GTP-Rho - increase turnover of F-actin structures
Miscellaneous:
TUBA1B
Tubulin - major component of microtubules
Structural:
NES
Member of the intermediate filament protein family
Transporters
Small molecule/metal transport:
SCARA5
Mediates ferritin bound uptake of iron
SLC2A3
Glucose transporter
SLC7A5
Involved in cellular amino acid transport
SLC16A6
Solute carrier - rapid transport of monocarboxylates
SLC16A10
Mediates uptake of aromatic amino acids
SLC39A6
Zinc-influx transporter
SLC39A14
Zinc transporter
SLC43A2
Na+, Cl-, and pH-dependent transporter of large amino acids
Molecular release:
GNRH1
Stimulates release of gonadotropins
SLCO2A1
Mediate release of prostaglandin from cells
Phagocytosis/endocytosis:
AAK1
Regulates clathirin-mediated endocytosis
SRPX
May be involved in phagocytosis
Miscellaneous:
PLVAP
May function in microvascular permeability
Cell Growth/Cell Cycle Regulation
Growth inhibitory factors:
BTG1
Anti-proliferative protein - high in G0 phase
DDIT4L
Inhibits cell growth by regulating TOR signaling
FBXO31
Involved with G1 arrest following DNA damage
LATS2
Negative regulator - inhibits proliferation/promotes apoptosis
Cell cycle regulators:
CCND2
Cyclin D2 - G1 progression
CDKN1B
Cell cycle regulator involved in G1 arrest
CKS2
Promotes catalytic activity of cyclin dependent kinases
+1.54
+2.04
+1.65
+1.67
+1.51
+1.50
+1.64
+1.75
+2.47
+2.04
+1.52
+1.53
+1.66
+1.73
+1.98
+1.77
+4.06
+1.72
+1.73
+2.12
+1.58
+1.69
+1.72
+1.67
+1.53
+2.55
+1.63
+1.73
+1.63
+2.44
+1.60
+1.53
+2.17
Growth promoting factors:
MYC
Multifunctional transcription factor - cell growth
NEK6
Kinase required for metaphase progression
WDR82
Chromatin modification - regulates transition from mitosis to interphase
Miscellaneous:
ZFP36L1
Probably transcription factor - response to growth factors
Receptors
Miscellaneous:
GPR179
Orphan receptor involved in vision
LTBR
TNF receptor super family member - promotes apoptosis
NR2F2
RAR activated nuclear receptor
PROCR
Receptor for activated protein C - blood coagulation
TNFRSF6B
Decoy receptor that protects against apoptosis
Acetylcholine receptor – neurotransmitter:
CHRNA1
Acetylcholine receptor - ion conduction
CHRNB1
Acetylcholine receptor - ion conduction
CHRND
Acetylcholine receptor - ion conduction
G-protein coupled receptors:
GDI2
GDP dissociation factor - release of GDP from G binding proteins
GPR64
G-protein coupled receptor - possibly involvement in epididymal function
OR4B1
G-protein coupled receptor - olfactory receptor
Ubiquitination/SUMOylation
Ubiquitin enzymes:
FBXO10
Member of SCF E3 ubiquitin ligase complex
FBXO30
Member of E3 ubiquitin ligase complex
RNF167
E3 ubiquitin protein ligase (ring finger protein)
TRIM9
Ubiquitin ligase - proteasomal degradation
SUMOylation:
RANBP2
Enhances SUMOylation
SAE1
E1 ligase for SUMO and SUMOylation
Ubiquitin-dependent degradation:
SPSB1
Mediator of ubiquitin-dependent degradation
USP8
Ubiquitin-specific peptidase
Deubiquitinating:
VCPIP1
Deubiquitinating enzyme post mitosis
Myogenic Functions:
Positive regulators:
CSRP3
Positive regulator of myogenesis
HES6
Suppressor of HES1 (HES1 is a negative regulator of myogenesis)
MYH3
Myosin heavy chain 3 - muscle contraction
MYH8
Myosin heavy chain 8 - muscle contraction
Muscle cell functions:
ABHD2
Possible smooth muscle migration
ANKRD1
Transcription factor – myofibrillar stretch sensory
GJA1
Heart gap junction gene - important for synchronized contraction
Negative regulator:
TMEM119
May promote differentiation of myoblasts into osteoblasts
+2.02
+1.53
+1.53
+1.58
+1.49
+2.66
+1.60
+2.15
+1.84
+2.95
+1.95
+8.02
+1.62
+1.64
+1.64
+1.62
+1.61
+1.49
+1.75
+1.97
+1.61
+2.23
+1.67
+1.62
+2.68
+1.90
+2.10
+3.27
+1.68
+2.02
+3.44
+1.85
Signaling Pathways
Wnt/FGF signaling:
SFRP1
SHISA2
TLE3
Miscellaneous:
ABHD6
HEY2
Soluble frizzled like protein - modulates Wnt signaling
Attenuates FGF and Wnt signaling
Transcriptional co-repressor in Wnt signaling
+1.65
+2.42
+1.55
May be a regulator of endocannabinoid signaling pathways
Downstream Notch effector - cardiovascular development
+1.72
+1.53
Kinases/Phosphatases
General kinases:
PIM1
Ser/Thr kinase - prevent apoptosis and promote survival
PIM2
Ser/Thr kinase - prevent apoptosis and promote survival
PRKCI
Protein kinase C iota
SNF1LK
Na+-inducible Ser/Thr kinase - multifunctional
Miscellaneous:
CLP1
Polynucleotide kinase - phosphorylate dsRNA
Mitochondrial Function
Miscellaneous:
MRPL38
Mitochondrial ribosomal protein
SOD2
Mitochondrial superoxide dismutase
Mitochondrial energy production:
CYP1B1
Cytochrome P450 subunit B1
MTHFD1L
Tetrahydrofolate synthesis in the mitochondria
Mitochondrial uptake/transport:
CCDC109B
Negatively modulates Ca+2 uptake into mitochondria
DNAJA1
Chaperon - transport of proteins into mitochondria
Protein Folding/Turnover/Degradation
Miscellaneous:
CTSL1
Lysosomal cysteine proteinase - involved in protein turnover
FKBP11
Accelerate protein folding during protein synthesis
PSMG3
Chaperone promotes assembly of 20S proteasome
UBLCP1
Decreases proteolytic activity of 26S proteasome
Receptor turnover/degradation:
CHMP1B
Involved in degradation of surface receptor proteins
CHMP2B
Involved with the recycling or degradation of cell surface receptors
Glycolysis/Energy Metabolism
ADH1A
Alcohol dehydrogenase
ADH1C
Alcohol dehydrogenase
ENO1
Enolase - glycolytic enzyme
PDK4
Ser/Thr kinase - glucose and fatty acid metabolism
PFKFB3
6-phosphofructokinase – involved in glycolysis
PFKP
Phosphofructokinase – involved in glycolysis
Ca+2-Dependent Functions
Ca+2 channel/Ca+2-dependent channel
+2.24
+2.30
+1.56
+1.71
+1.64
+1.76
+1.97
+2.09
+1.87
+1.56
+1.58
+1.51
+1.55
+1.50
+1.97
+1.52
+1.79
+1.51
+1.52
+1.89
+2.26
+1.60
+1.64
BEST3
SRI
STC1
Miscellaneous:
NCALD
NUCB2
Calcium sensitive chloride channels
Ca+2 binding protein - modulates calcium channels
Stimulates phosphate and calcium reuptake
+1.78
+1.60
+1.75
Ca+2-dependent regulator of G-proteins (membrane associated)
Ca+2 binding - release of TNF from vascular endothelial cells
+1.67
+1.70
Cytoskeleton
LAMB1
MARCKSL1
SEMA4D
TCHH
VIL2
Laminin b - part of the basement membrane
Controls cell movement by regulating the actin cytoskeleton
Receptor for plexin - reorganization of actin cytoskeleton
Serves as scaffold protein to organize cell envelope
Intermediate between plasma membrane and actin cytoskeleton
+1.86
+1.80
+2.01
+1.51
+1.58
Apoptotic
ADAMTSL4
GRAMD4
MEGF10
TNFRSF10A
Metalloproteinase - positive regulator of apoptosis
Mediator of E2F1A apoptosis
Mediator of apoptotic cell phagocytosis
TNF family member - pro-apoptotic
+1.54
+1.51
+1.58
+1.71
Neuronal Function
CRYBB2
Crystallin – possible neurite promoting factor
DCLK1
Involved with Ca+2 signaling - involved in neuronal migration
FGF9
Produced by neurons - growth stimulating effect on glial cells
KIF5A
Kinesin protein - slow axonal transport of neurofilament proteins
+1.55
+2.47
+1.91
+1.54
Differentiation and Development
GDF15
Bone morphogenic protein - member of TGFbeta family
MGP
Associates with bone matrix - inhibits bone formation
VEGFC
Promotes angiogenesis
+1.52
+1.80
+1.54
Metallothionein (Metal Binding/Anti-Oxidant)
MT1A
Metallothionein protein
MT1E
Metallothionein 1E - metal binding
MT2A
Metallothionein protein
+1.52
+1.91
+1.52
Ion Transport
ATP1A1
ATP-dependent Na and K transport
+1.73
Gene name, function and fold-change vs. SUC/SIV macaques are shown for each category
and sub-category according to their biological function.