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Table 3 Proteins involved in the proposed network as revealed by Ingenuity Pathway Analysis

From: Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species

No.

Uniprot ID

Name

Primary gene name

Function/catalytic activity

NSAF ratio

Low ROS

Medium ROS

High ROS

1

P60709

Actin,

ACTB

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells

1.48

1

2.34

cytoplasmic 1

2

P61163

Alpha-centractin

ACTR1A

Component of a multi-subunit complex involved in microtubule based vesicle motility. It is associated with the centrosome

1.82

1

33.08

3

Q9UHI8

A disintegrin and metalloproteinase with thrombospondin motifs 1

ADAMTS1

Cleaves aggrecan, a proteoglycan, and may be involved in its turnover. Has angiogenic inhibitor activity. Active metalloprotease, which may be associated with various inflammatory processes as well as development of cancer

2.28

1.73

2.46

4

P49189

4-trimethylaminobutyraldehyde dehydrogenase

ALDH9A1

Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine. Catalyzes the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction. Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1′

1

1

11.76

5

P25705

ATP synthase subunit alpha, mitochondrial

ATP5A1

Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain

2

3.53

9.55

6

P06576

ATP synthase subunit beta, mitochondrial

ATP5B

Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain

2.79

2.59

9.59

7

P36542

ATP synthase subunit gamma, mitochondrial

ATP5C1

Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain

1

2.12

4.83

8

P27797

Calreticulin

CALR

Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins and cleaves aggrecan at the 1938-Glu-|-Leu-1939 site, within the chondroitin sulfate attachment domain

0.94

0.94

3

9

P27824

Calnexin

CANX

Calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the ATP + H(2)O = ADP + phosphate

1

1

53.77

10

P78371

T-complex protein 1 subunit beta

CCT2

Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. As part of the BBS/CCT complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Known to play a role in vitro

1.41

1.58

11.35

11

P50991

T-complex protein 1 subunit delta

CCT4

Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. As part of the BBS/CCT complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia

0.37

1.43

3.39

12

P48643

T-complex protein 1 subunit epsilon

CCT5

Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. As part of the BBS/CCT complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Release of an N-terminal amino acid, preferentially alanine, from a wide range of peptides, amides and arylamides

0.57

1.39

10.45

13

P40227

T-complex protein 1 subunit zeta

CCT6A

Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. Known to play a role, in vitro in the folding of actin and tubulin

1

1

46.53

14

Q99832

T-complex protein 1 subunit eta

CCT7

Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. Known to play a role in vitro in the folding of actin and tubulin

2.26

2.48

8.1

15

Q13618

Cullin-3

CUL3

Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme, involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division

1

11.18

77.7

16

P07954

Fumaratehydratase, mitochondrial

FH

Also acts as a tumor suppressor

21.75

29.87

153.16

NADH + acceptor = NAD(+) + reduced acceptor

17

O14556

Glyceraldehyde-3-phosphate dehydrogenase, testis-specific

GAPDHS

May play an important role in regulating the switch between different pathways for energy production during spermiogenesis and in the spermatozoon. Required for sperm motility and male fertility

1

1.44

10.4

ATP + H(2)O = ADP + phosphate

18

P07900

Heat shock protein HSP 90-alpha

HSP90AA1

Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity

1.58

1

2.24

19

P14625

Endoplasmin

HSP90B1

Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors. Functions in endoplasmic reticulum associated degradation (ERAD)

1

1.54

3.02

20

P54652

Heat shock-related 70 kDa protein 2

HSPA2

In co-operation with other chaperones, Hsp70 stabilize pre-existent proteins against aggregation and mediate the folding of newly translated polypeptides in the cytosol as well as within organelles

1.43

1

1.93

21

P11021

78 kDa glucose-regulated protein

HSPA5

Probably plays a role in facilitating the assembly of multimeric protein complexes inside the endoplasmic reticulum. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10, probably to facilitate the release of DNAJC10 from its substrate

0.94

1

3.3

22

P10809

60 kDa heat shock protein, mitochondrial

HSPD1

Implicated in mitochondrial protein import and macromolecular assembly. May facilitate the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress condition

1.81

1

7.75

23

P52292

Importin subunit alpha-1

KPNA2

Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite nuclear localization signal motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus

1

1

12.34

24

P00338

L-lactate dehydrogenase A chain

LDHA

(S)-lactate + NAD(+) = pyruvate + NADH

2.02

2.16

2.28

25

P40926

Malate dehydrogenase, mitochondrial

MDH2

(S)-malate + NAD+ = oxaloacetate + NAD

1.09

7.08

8.62

26

P08473

Neprilysin

MME

Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development. Degrades a broad variety of small peptides with a preference for peptides shorter than 3 kDa containing neutral bulky aliphatic or aromatic amino acid residues

2.61

2.8

2.24

27

P28331

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial

NDUFS1

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain

2.44

1

4.11

28

P55786

Puromycin-sensitive aminopeptidase

NPEPPS

Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecule 4-aminobutanal + NAD+ + H2O = 4-aminobutanoate + NADH

1.53

0.67

3.19

29

Q9Y265

RuvB-like 1

RUVBL1

Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5′ to 3′) activity. Component of a SWR1-like complex that specifically mediates the removal of histone H2AZ/H2AFZ from the nucleosome

0.3

0.67

2.98

30

Q9Y230

RuvB-like 2

RUVBL2

Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5′ to 3′) activity. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AFZ from the nucleosome

1

0.75

13.69

31

P17987

T-complex protein 1 subunit alpha

TCP1

Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. As part of the BBS/CCT complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Known to play a role in folding of actin and tubulin

1.65

1.6

3.96

32

P68371

Tubulin beta-4B chain

TUBB4B

Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain

1.02

1.85

6.12

33

P31930

Cytochrome b-c1 complex subunit 1, mitochondrial

UQCRC1

This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This protein may mediate formation of the complex between cytochromes c and c1

1

1

21.68

34

P55072

Transitional endoplasmic reticulum ATPase

VCP

Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus

1.06

1.65

4.15

35

P63104

14-3-3 protein zeta/delta

YWHAZ

Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the(S)-malate = fumarate + H2O

1.22

0.99

2.12