Table 2.
Statistically different phosphopeptides between CN‐105 and vehicle in ischemic stroke
| Protein Name | Gene symbol and UniProtKB number | Modified peptide sequencea (phosphotyrosine position) | CN‐105 v vehicle fold change | P ‐value (two‐tailed t‐test) | Biological process of protein | Function of specific phosphorylation site |
|---|---|---|---|---|---|---|
| Upregulated Phosphopeptides | ||||||
| Disks large‐associated protein 2 | Dlgap2, Q8BJ42 | MHYSSHYDTR (169) | 2.416 | 0.040 | May play a role in the molecular organization of synapses and neuronal cell signaling. | Unknown |
| Golgi integral membrane protein 4 | Golim4, Q8BXA1 | GRQEHYEEEEDEEDGAAVAEK (633) | 2.039 | 0.037 | Plays a role in endosome to Golgi protein trafficking | Controlled by leptin in mouse liver. |
| Histone H4 | Hist1h4a, P62806 | KTVTAMDVVYALK (88) | 2.473 | 0.036 | Chromatin organization | Unknown |
| TVTAMDVVYALK (88) | 2.057 | 0.026 | ||||
| Insulin receptor substrate 2 | Irs2, P81122 | SDDYMPMSPTSVSAPK (671) | 13.414 | 0.048 | Transmembrane receptor protein tyrosine kinase signaling | Insulin induce phosphorylation at Y671, which in turn activate PI3K/Akt/eNOS pathway in endothelial cells. |
| Probable phospholipid‐transporting ATPase IA | Atp8a1, P70704 | NTQWVHGIVVYTGHDTK (269) | 9.686 | 0.020 | Anion transport, Catabolic process | Unknown |
| Sodium/potassium‐transporting ATPase subunit alpha‐1 | Atp1a1, Q8VDN2 | KYGTDLSR (55) | 2.259 | 0.036 | Homeostatic process, Catabolic process | Unknown |
| Downregulated Phosphopeptides | ||||||
| 1‐phosphatidylinositol‐4,5‐bisphosphate phosphodiesterase gamma‐1 | Plcg1, Q62077 | KLAEGSAYEEVPTSVMYSENDISNSIK (472) | −3.211 | 0.043 | Intracellular signal transduction via G‐protein‐coupled receptor signaling and Phospholipid metabolic process | Human analog controlled by ephrin_B1 |
| 14‐3‐3 protein beta/alpha | Ywhab, Q9CQV8 | QTTVSNSQQAYQEAFEISKK (151) | −2.391 | 0.037 | Cell cycle | Unknown |
| QTTVSNSQQAYQEAFEISK (151) | −2.434 | 0.028 | ||||
| Alpha‐enolase | Eno1, P17182 | SGKYDLDFK (257) | −2.078 | 0.035 | Glycolysis | Unknown |
| Ankyrin‐2 | Ank2, Q8C8R3 | NGYTPLHIAAK (630) | −2.338 | 0.010 | Protein localization and Intracellular protein transport | Unknown |
| QELEDNDKYQQFR (2113) | −6.332 | 0.014 | Novel phosphorylation site | |||
| Band 4.1‐like protein 1 | Epb41l1, Q9Z2H5 | HLTQQDTRPAEQSLDMDDKDYSEADGLSER (68) | −3.678 | 0.021 | May confer stability and plasticity to neuronal membrane | Unknown |
| Band 4.1‐like protein 3 | Epb41l3, Q9WV92 | DSVSAAEVGTGQYATTK (479) | −2.577 | 0.024 | Inhibits cell proliferation and promotes apoptosis. | Human isoform 2 (Y471) controlled by ephrin_B1. |
| Calcium‐dependent secretion activator 2 | Cadps2, Q8BYR5 | TYDTLHR (1273) | −3.236 | 0.012 | Exocytosis | Novel phosphorylation site |
| Calmodulin‐regulated spectrin‐associated protein 2 | Camsap1 l1, Q8C1B1 | EEAAGAEDEKVYTDR (799) | −2.566 | 0.032 | Regulator of noncentrosomal microtubule dynamics and organization. | Novel phosphorylation site |
| Calmodulin‐regulated spectrin‐associated protein 3 | Kiaa1543, Q80VC9 | APIYISHPENPSK (520) | −2.143 | 0.033 | Regulator of noncentrosomal microtubule dynamics and organization. | Unknown |
| Casein kinase I isoform delta | Csnk1d, Q9DC28 | YASINTHLGIEQSR (179) | −2.342 | 0.012 | Cellular component morphogenesis and endocytosis | Novel phosphorylation site |
| CLIP‐associating protein 2 | Clasp2, Q8BRT1 | DYNPYNYSDSISPFNK (1014) | −2.972 | 0.044 | Cell cycle. | Unknown |
| CMRF35‐like molecule 8 | Cd300a, Q6SJQ0 | AEYSEIQKPR (303) | −4.043 | 0.048 | Intracellular protein transport and receptor‐mediated endocytosis | Unknown |
| Coronin‐1A | Coro1a, O89053 | ADQCYEDVR (25) | −3.084 | 0.038 | Cytoskeleton organization | Unknown |
| HVFGQPAKADQCYEDVR (25) | −5.976 | 0.042 | ||||
| Coronin‐2A | Coro2a, Q8C0P5 | ENCYDSVPITR (26) | −2.633 | 0.040 | Cytoskeleton organization | Unknown |
| Cytochrome c‐type heme lyase | Hccs, P53702 | AYDYVECPVTGAR (67) | −5.111 | 0.006 | Cell cycle and coenzyme metabolic process | Unknown |
| Cytoplasmic dynein 1 heavy chain 1 | Dync1h1, Q9JHU4 | AISKDHLYGTLDPNTR (2263) | −4.501 | 0.031 | Cellular component morphogenesis, Cell cycle, Cellular component movement, Intracellular protein transport | Unknown |
| Dynamin‐1 | Dnm1, P39053 | RIEGSGDQIDTYELSGGAR (354) | −2.404 | 0.044 | Cellular component morphogenesis, Intracellular protein transport, Endocytosis | Unknown |
| IEGSGDQIDTYELSGGAR (354) | −2.893 | 0.045 | ||||
| EVDEYKNFRPDDPAR (314) | −3.247 | 0.018 | Novel phosphorylation site | |||
| LQSQLLSIEKEVDEYK (314) | −4.276 | 0.038 | ||||
| Dynamin‐1‐like protein | Dnm1l, Q8K1M6 | NKLYTDFDEIR (107) | −2.832 | 0.047 | Cellular component morphogenesis, Intracellular protein transport, Endocytosis | Novel phosphorylation site |
| EH domain‐containing protein 3 | Ehd3, Q9QXY6 | ELVNNLAEIYGR (339) | −3.179 | 0.043 | Synaptic transmission, Intracellular protein transport, Endocytosis, Neurotransmitter secretion | Unknown |
| Eukaryotic translation initiation factor 4 gamma 1 | Eif4g1, Q6NZJ6 | KVEYTLGEESEAPGQR (1424) | −2.610 | 0.029 | Apoptosis | Unknown |
| Glutaminase kidney isoform | Gls, D3Z7P3 | YAIAVNDLGTEYVHR (309) | −5.463 | <0.001 | Cellular amino acid biosynthetic catabolic process | Unknown |
| Glutathione S‐transferase P 1 | Gstp1, P19157 | YVTLIYTNYENGKNDYVK (119) | −2.652 | 0.029 | Conjugation of reduced glutathione | Novel phosphorylation site |
| Heat shock protein 105 | Hsph1, Q61699 | NAVEECVYEFRDK (644) | −2.354 | 0.043 | Protein complex assembly | Unknown |
| LysM and putative peptidoglycan‐binding domain‐containing protein 2 | Lysmd2, Q9D7V2 | DEESPYAASLYHS (208) | −3.571 | 0.030 | Unknown | Unknown |
| Microtubule‐associated protein 6 | Map6, Q7TSJ2 | SLYSEPFKECPK (493) | −3.469 | 0.020 | Microtubule stabilization | Unknown |
| Myosin‐Va | Myo5a, Q99104 | RTDSTHSSNESEYTFSSEFAETEDIAPR (1124) | −6.827 | 0.041 | Cellular component morphogenesis, Intracellular signal transduction, Cell cycle, Cytokinesis, Muscle development, Intracellular protein transport, Muscle contraction, Sensory perception | Unknown |
| Myotrophin | Mtpn, P62774 | DYVAKGEDVNR (21) | −3.285 | 0.005 | Promotes dimerization of NF‐kappa‐B subunits and regulates NF‐kappa‐B transcription factor activity | Unknown |
| Myotubularin‐related protein 5 | Sbf1, Q6ZPE2 | RSTSTLYSQFQTAESENR (1751) | −4.030 | 0.005 | Intracellular protein transport, Phospholipid metabolic process | Human analog controlled by Ephrin B1 |
| Neurochondrin | Ncdn, Q9Z0E0 | SMIDDTYQCLTAVAGTPR (156) | −3.042 | 0.044 | Signal transduction | Novel phosphorylation site |
| Peptidyl‐prolyl cis‐trans isomerase A | Ppia, P17742 | SIYGEKFEDENFILK (79) | −2.432 | 0.049 | Accelerate the folding of proteins | Unknown |
| Phosphatidylethanolamine‐binding protein 1 | Pebp1, P70296 | LYEQLSGK (181) | −2.263 | 0.040 | Binds ATP, opioids and phosphatidylethanolamine | Regulated by Catsper1 in murine sperm |
| Phosphoglycerate kinase 1 | Pgk1, P09411 | LGDVYVNDAFGTAHR (161) | −3.703 | 0.011 | Glycolysis | Unknown |
| Probable cationic amino acid transporter | Slc7a14, Q8BXR1 | EQALHQSTYQR (693) | −2.369 | 0.040 | Amino acid transporter, Anion transport | Unknown |
| Probable G‐protein‐coupled receptor 158 | Gpr158, Q8C419 | KLYAQLEIYKR (722) | −2.507 | 0.003 | G‐protein‐coupled receptor signaling | Novel phosphorylation site |
| Programmed cell death 6‐interacting protein | Pdcd6ip, Q9WU78 | IYGGLTSK (608) | −4.124 | 0.002 | Unknown orphan receptor. | Novel phosphorylation site |
| Protein arginine N‐methyltransferase 8 | Prmt8, Q6PAK3 | RGEEIYGTISMKPNAK (355) | −2.181 | 0.039 | Chromatin organization, Regulation of nucleobase‐containing compound metabolic process, Biosynthetic process, Transcription | Unknown |
| Protein EFR3 homolog B | Efr3b, Q6ZQ18 | KKEAPYMLPEDVFVEKPR (629) | −2.364 | 0.006 | Component of a complex required to localize phosphatidylinositol 4‐kinase (PI4K) to the plasma membrane | Novel phosphorylation site |
| Protein FAM126B | Fam126b, Q8C729 | YSTISLQEDR (487) | −2.301 | 0.026 | Mediates cellular transport and reorganization of the microtubule cytoskeleton | Unknown |
| Protein kinase C and casein kinase substrate in neurons protein 1 | Pacsin1, Q61644 | GPQYGSLER (74) | −3.649 | 0.012 | Cellular component morphogenesis, Cell differentiation, Nervous system development, Endocytosis | Novel phosphorylation site |
| Protein XRP2 | Rp2, Q9EPK2 | DYMFSGLKDETVGRLPGK (37) | −3.700 | 0.025 | Purine nucleobase metabolic process | Unknown |
| Putative tyrosine‐protein phosphatase auxilin | Dnajc6, Q80TZ3 | HLDHYTVYNLSPK (134) | −2.616 | 0.034 | Intracellular protein transport, Endocytosis | Novel phosphorylation site |
| Receptor‐type tyrosine‐protein phosphatase‐like N | Ptprn, Q60673 | LAALGPEGAHGDTTFEYQDLCR (628) | −2.592 | 0.031 | Plays a role in vesicle‐mediated secretory processes | Unknown |
| Regulator of G‐protein signaling 6 | Rgs6, Q9Z2H2 | SVYGVTDETQSQSPVHIPSQPIRK (234) | −3.918 | 0.042 | Regulation of nucleobase‐containing compound metabolic process, Regulation of phosphate metabolic process, Catabolic process | Novel phosphorylation site |
| Rho GTPase‐activating protein 1 | Arhgap1, Q5FWK3 | HQIVEVAGDDKYGR (81) | −2.031 | 0.043 | Regulation of nucleobase‐containing compound metabolic process, Regulation of phosphate metabolic process, Regulation of catalytic activity, Catabolic process. | Unknown |
| Rho GTPase‐activating protein 35 | Arhgap35, Q91YM2 | KMQASPEYQDYVYLEGTQK (308) | −3.163 | 0.035 | Regulation of nucleobase‐containing compound metabolic process, Regulation of phosphate metabolic process, Regulation of catalytic activity, Catabolic process | Growth factors induce phosphorylation of thyrosine at position 308, which disrupts its ability to bind with General Transcription Factor II‐I. |
| SH3 and cysteine‐rich domain‐containing protein 2 | Stac2, Q8R1B0 | ESPPTGTSGKVDPVYETLR (205) | −2.054 | 0.044 | Unknown | Unknown |
| SH3 and PX domain‐containing protein 2B | Sh3pxd2b, A2AAY5 | TEPAQSEDHVDIYNLR (661) | −3.128 | 0.040 | Intracellular signal transduction | Unknown |
| SLIT‐ROBO Rho GTPase‐activating protein 3 | Srgap3, Q812A2 | NDLQSPTEHISDYGFGGVMGR (845) | −2.312 | 0.024 | Regulation of nucleobase‐containing compound metabolic process, Regulation of phosphate metabolic process, Cellular component movement, Locomotion, Catabolic process | Unknown |
| Src substrate cortactin | Cttn, Q60598 | NASTFEEVVQVPSAYQK (334) | −3.605 | 0.030 | Cellular component morphogenesis | Phosphorylation is by proto‐oncogene tyrosine‐protein kinase Src and dephosphorylation is by protein tyrosine phosphophatase 1B. |
| Synaptic vesicle glycoprotein 2B | Sv2b, Q8BG39 | YRDNYEGYAPSDGYYR (10) | −2.635 | 0.004 | Synaptic transmission, Neurotransmitter secretion | Unknown |
| DNYEGYAPSDGYYR (10) | −3.735 | 0.016 | ||||
| Synaptogyrin‐3 | Syngr3, Q8R191 | GYQVPAY (224) | −3.971 | 0.026 | Positive regulation of dopamine transporter activity | Novel phosphorylation site |
| Syntaxin‐binding protein 1 | Stxbp1, O08599 | ERISEQTYQLSR (473) | −2.563 | 0.035 | Lysosomal transport, Intracellular protein transport, Synaptic vesicle exocytosis, Neurotransmitter secretion | Unknown |
| ISEQTYQLSR (473) | −2.843 | 0.015 | ||||
| YSTHLHLAEDCMK (344) | −2.920 | 0.019 | Novel phosphorylation site | |||
| HYQGTVDKLCR (358) | −3.161 | 0.025 | Novel phosphorylation site | |||
| Thioredoxin reductase 1, cytoplasmic | Txnrd1, Q9JMH6 | VVYENAYGR (245) | −2.016 | 0.032 | Respiratory electron transport chain | Phosphorylation is by proto‐oncogene tyrosine‐protein kinase Src. Phosphorylation of human analog (tyrosine 281) reduced by ZAP70 and upregulated in neuroblastoma. |
| Triosephosphate isomerase | Tpi1, P17751 | IIYGGSVTGATCK (259) | −2.893 | 0.029 | Glycolysis and gluconeogensis | Unknown |
| Tubulin polymerization‐promoting protein | Tppp, Q7TQD2 | VDLVDESGYVPGYK (200) | −3.438 | 0.008 | Microtubule functions | Unknown |
| Type I inositol 3,4‐bisphosphate 4‐phosphatase | Inpp4a, Q9EPW0 | VQDDGGSDQNYDVVTIGAPAAHCQGFK (355) | −2.552 | 0.013 | Regulation of megakaryocyte and fibroblast proliferation | Unknown |
| HYRPPEGTYGKVET (934) | −3.111 | 0.031 | Unknown | |||
| Tyrosine‐protein kinase | Lyn, P25911 | VIEDNEYTAR (397) | −2.289 | 0.015 | Cell adhesion, Transmembrane receptor protein tyrosine kinase signaling, Cell proliferation, Cellular component movement, Cell differentiation, Apoptosis, Hemopoiesis, Nervous system development, Immune system response, Exocytosis, Locomotion, Coagulation, Stress response | Phosphorylation of tyrosine in at tyrosine 397, located within the activation loop, is required for its kinase activity. Lyn is activated by B‐cell receptor and inhibited by CD45. |
| UPF0554 protein C2orf43 homolog | Ldah, Q8BVA5 | IEDVYGLNGQIEHK (111) | −2.475 | 0.015 | Serine lipid hydrolase associated with lipid droplets | Novel phosphorylation site |
| Vesicular inhibitory amino acid transporter | Slc32a1, O35633 | SEGEPCGDEGAEAPVEGDIHYQR (Y85) | −2.321 | 0.020 | Amino acid transporter, Anion transport | Unknown |
| Wolframin | Wfs1, P56695 | NYIALDDFVELTKK (242) | −7.251 | 0.045 | Regulation of cellular Ca2 + homeostasis | Unknown |
a
Underlined amino acid represents phosphorylated tyrosine and numbers in brackets indicate the phosphotyrosine position.