
## Interactions with experimental support

-   **CDK2** Cyclin-dependent kinase 2; Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. [PMID: 10022118, PMID: 10874474, PMID: 10878006, PMID: 10918595, PMID: 11132966, PMID: 11302688, PMID: 11463845, PMID: 11477082, PMID: 12361598, PMID: 12383116, PMID: 12417722, PMID: 12800980, PMID: 12839982, PMID: 12949733, PMID: 13678583, PMID: 15232106, PMID: 15557281, PMID: 15647383, PMID: 15890360, PMID: 16765349, PMID: 16962592, PMID: 17418410, PMID: 17698606, PMID: 18850315, PMID: 20102411, PMID: 20587660, PMID: 20839231, PMID: 23007395, PMID: 23443559, PMID: 23455922, PMID: 23602568, PMID: 24218572, PMID: 24358021, PMID: 24407240, PMID: 25241761, PMID: 25416956, PMID: 25483090, PMID: 26186194, PMID: 26496610, PMID: 27215384, PMID: 28514442, PMID: 29510343, PMID: 29666278, PMID: 30833792, PMID: 31112565, PMID: 8242751, PMID: 8622677, PMID: 8641969, PMID: 8756624, PMID: 9218599, PMID: 9284049, PMID: 9380407, PMID: 9464540, PMID: 9472014, PMID: 9546435, PMID: 9632134, PMID: 9658399, PMID: 9660939, PMID: 9736735, PMID: 9840943, PMID: 9858587]
-   **PCNA** Proliferating cell nuclear antigen; Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'- phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. [PMID: 10022118, PMID: 10873631, PMID: 11254741, PMID: 11302688, PMID: 11313979, PMID: 11350925, PMID: 11463845, PMID: 11559705, PMID: 12930846, PMID: 12964161, PMID: 15576034, PMID: 16082198, PMID: 16189514, PMID: 16474839, PMID: 16510448, PMID: 16616141, PMID: 17115032, PMID: 17588519, PMID: 18086887, PMID: 19704162, PMID: 19895794, PMID: 20605778, PMID: 20606006, PMID: 21415862, PMID: 21988832, PMID: 22383522, PMID: 23139781, PMID: 23223023, PMID: 23443559, PMID: 25411249, PMID: 25416956, PMID: 25502805, PMID: 26186194, PMID: 26272819, PMID: 26496610, PMID: 27107012, PMID: 28514442, PMID: 29510343, PMID: 30217970, PMID: 30301766, PMID: 30623174, PMID: 30833792, PMID: 31112565, PMID: 31515488, PMID: 32296183, PMID: 7780738, PMID: 7911228, PMID: 7915843, PMID: 8662825, PMID: 8861913, PMID: 8861969, PMID: 9465025, PMID: 9545252, PMID: 9546435]
-   **CCND1** G1/S-specific cyclin-D1; Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. [PMID: 12383116, PMID: 15232106, PMID: 15695403, PMID: 16082198, PMID: 17420273, PMID: 17556661, PMID: 21516116, PMID: 21654808, PMID: 21988832, PMID: 23007395, PMID: 23443559, PMID: 25416956, PMID: 26203195, PMID: 27107012, PMID: 28514442, PMID: 30833792, PMID: 31515488, PMID: 7478582, PMID: 8242751, PMID: 8657154, PMID: 8662825, PMID: 8756624, PMID: 9106657, PMID: 9823309, PMID: 9837900]
-   **CDK4** Cyclin-dependent kinase 4; Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. [PMID: 10022865, PMID: 11463845, PMID: 12383116, PMID: 15169570, PMID: 15232106, PMID: 15695403, PMID: 16962592, PMID: 17556661, PMID: 18850315, PMID: 20102411, PMID: 23007395, PMID: 23443559, PMID: 28514442, PMID: 30833792, PMID: 8242751, PMID: 8622677, PMID: 8756624, PMID: 9106657, PMID: 9464540, PMID: 9632134, PMID: 9658399]
-   **CCNE1** G1/S-specific cyclin-E1; Essential for the control of the cell cycle at the G1/S (start) transition. [PMID: 11477082, PMID: 12839982, PMID: 13678583, PMID: 16765349, PMID: 17293600, PMID: 21988832, PMID: 23443559, PMID: 24771265, PMID: 25241761, PMID: 30833792, PMID: 8242751, PMID: 8662825, PMID: 8756624, PMID: 8891332, PMID: 9218599, PMID: 9380407, PMID: 9472014, PMID: 9632134, PMID: 9660939, PMID: 9716181]
-   **TP53** Cellular tumor antigen p53; Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. [PMID: 11896572, PMID: 12897156, PMID: 16616141, PMID: 17371838, PMID: 17719542, PMID: 17906639, PMID: 18485870, PMID: 18614011, PMID: 19249676, PMID: 19410543, PMID: 20228809, PMID: 21317932, PMID: 21423215, PMID: 21900206, PMID: 23870121, PMID: 25241761, PMID: 27626385, PMID: 9121469]
-   **CCND3** G1/S-specific cyclin-D3; Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. [PMID: 15232106, PMID: 16189514, PMID: 21988832, PMID: 23443559, PMID: 23880157, PMID: 25241761, PMID: 25416956, PMID: 26186194, PMID: 26496610, PMID: 27107012, PMID: 28514442, PMID: 30217970, PMID: 30833792, PMID: 31515488, PMID: 32296183, PMID: 8756624, PMID: 9716181]
-   **CCND2** G1/S-specific cyclin-D2; Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. [PMID: 10022865, PMID: 11971966, PMID: 15169570, PMID: 16189514, PMID: 16765349, PMID: 23443559, PMID: 25241761, PMID: 25416956, PMID: 26186194, PMID: 27107012, PMID: 28514442, PMID: 30217970, PMID: 31515488, PMID: 32296183, PMID: 8756624, PMID: 9823309]
-   **CCNA2** Cyclin-A2; Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin- dependent protein kinases CDK1 or CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle. [PMID: 12947099, PMID: 15890360, PMID: 17679094, PMID: 21308745, PMID: 23443559, PMID: 26186194, PMID: 26496610, PMID: 28514442, PMID: 30833792, PMID: 8242751, PMID: 8662825, PMID: 8756624, PMID: 9380407, PMID: 9632134, PMID: 9660939]
-   **CCNA1** Cyclin-A1; May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions. May primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells. Belongs to the cyclin family. Cyclin AB subfamily. [PMID: 10022926, PMID: 12383116, PMID: 15232106, PMID: 16009130, PMID: 16982699, PMID: 25241761, PMID: 26264872, PMID: 29997244, PMID: 32814053, PMID: 7478582, PMID: 8756624]
-   **SKP2** S-phase kinase-associated protein 2; Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. [PMID: 13678583, PMID: 15980415, PMID: 16376880, PMID: 17477906, PMID: 17679094, PMID: 18794347, PMID: 19686743, PMID: 23261596, PMID: 25241761, PMID: 30833792, PMID: 32035614]
-   **CDK1** Cyclin-dependent kinase 1; Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. [PMID: 11559705, PMID: 17679094, PMID: 21308745, PMID: 23602568, PMID: 24218572, PMID: 26186194, PMID: 26496610, PMID: 28514442, PMID: 30833792, PMID: 9467962]
-   **CCNE2** G1/S-specific cyclin-E2; Essential for the control of the cell cycle at the late G1 and early S phase; Belongs to the cyclin family. Cyclin E subfamily. [PMID: 15232106, PMID: 23443559, PMID: 24358021, PMID: 26186194, PMID: 26496610, PMID: 28514442, PMID: 30833792, PMID: 9840927, PMID: 9840943]
-   **CCNB1** G2/mitotic-specific cyclin-B1; Essential for the control of the cell cycle at the G2/M (mitosis) transition; Belongs to the cyclin family. Cyclin AB subfamily. [PMID: 11559705, PMID: 15251430, PMID: 16082198, PMID: 17679094, PMID: 23443559, PMID: 25241761, PMID: 30833792, PMID: 8662825]
-   **CDK3** Cyclin-dependent kinase 3; Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. [PMID: 23443559, PMID: 23602568, PMID: 24218572, PMID: 26186194, PMID: 28514442, PMID: 32296183, PMID: 9811456]
-   **MDM2** E3 ubiquitin-protein ligase Mdm2; E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. [PMID: 14633995, PMID: 14761977, PMID: 17373842, PMID: 20086099, PMID: 20308078, PMID: 25241761]
-   **STAT3** Signal transducer and activator of transcription 3; Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. [PMID: 10764767, PMID: 15286705, PMID: 20686606, PMID: 21184768, PMID: 23750211, PMID: 25241761]
-   **DTL** Denticleless protein homolog; Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2. CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. [PMID: 18703516, PMID: 18794347, PMID: 20606006, PMID: 21628527, PMID: 23213251]
-   **CDK5** Cyclin-dependent-like kinase 5; Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. [PMID: 15890360, PMID: 23443559, PMID: 23455922, PMID: 23602568, PMID: 30833792]
-   **AKT1** RAC-alpha serine/threonine-protein kinase; AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. [PMID: 11463845, PMID: 11756412, PMID: 16982699, PMID: 25241761]
-   **CDK6** Cyclin-dependent kinase 6; Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e. g. erythroid and hematopoietic cells). [PMID: 10022865, PMID: 15232106, PMID: 20102411, PMID: 28514442]
-   **CDKN1A** Cyclin-dependent kinase inhibitor 1; May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin- dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D- CDK4 complex. [PMID: 15232106, PMID: 8861913, PMID: 15232106, PMID: 8861913]
-   **CASP3** Caspase-3 subunit p12; Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. [PMID: 10022118, PMID: 25241761, PMID: 9660939, PMID: 9799125]
-   **EP300** Histone acetyltransferase p300; Functions as histone acetyltransferase and regulates transcription via chromatin remodeling. Acetylates all four core histones in nucleosomes. Histone acetylation gives an epigenetic tag for transcriptional activation. Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. [PMID: 17906639, PMID: 18263614, PMID: 20228809, PMID: 27626385]
-   **GADD45A** Growth arrest and DNA damage-inducible protein GADD45 alpha; In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity (By similarity). Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase; Belongs to the GADD45 family. [PMID: 10912791, PMID: 10973963, PMID: 16772293, PMID: 7478594]
-   **CDK14** Cyclin-dependent kinase 14; Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by mediating the phosphorylation of LRP6 at 'Ser-1490', leading to the activation of the Wnt signaling pathway. Acts as a regulator of cell cycle progression and cell proliferation via its interaction with CCDN3. Phosphorylates RB1 in vitro, however the relevance of such result remains to be confirmed in vivo. [PMID: 17517622, PMID: 23602568, PMID: 26186194, PMID: 28514442]
-   **BCCIP** BRCA2 and CDKN1A-interacting protein; During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole. Isoform 2/alpha is particularly important for the regulation of microtubule anchoring, microtubule stability, spindle architecture and spindle orientation, compared to isoform 1/beta. May promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. [PMID: 10878006, PMID: 14726710, PMID: 19713748]
-   **ESR1** Estrogen receptor; Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE- independent signaling. [PMID: 12897156, PMID: 15743834, PMID: 17911387]
-   **CUL4A** Cullin-4A; Core component of multiple cullin-RING-based E3 ubiquitin- protein ligase complexes which mediate the ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. [PMID: 18794347, PMID: 26613412, PMID: 30945288]
-   **PARP1** Poly [ADP-ribose] polymerase 1; Poly-ADP-ribosyltransferase that mediates poly-ADP- ribosylation of proteins and plays a key role in DNA repair. Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D- ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. [PMID: 12930846, PMID: 20302655, PMID: 20303835]
-   **SKP1** S-phase kinase-associated protein 1; Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. [PMID: 16376880, PMID: 25241761, PMID: 27215384]
-   **PSMA3** Proteasome subunit alpha type-3; Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP- dependent degradation of ubiquitinated proteins. [PMID: 11350925, PMID: 20086099, PMID: 20308078]
-   **SET** Protein SET; Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. [PMID: 12407107, PMID: 16474839, PMID: 27626385]
-   **CKS1B** Cyclin-dependent kinases regulatory subunit 1; Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function. [PMID: 23443559, PMID: 28514442, PMID: 30833792]
-   **TEX11** Testis-expressed protein 11; Regulator of crossing-over during meiosis. Involved in initiation and/or maintenance of chromosome synapsis and formation of crossovers. [PMID: 16189514, PMID: 25416956, PMID: 30217970]
-   **DDB1** DNA damage-binding protein 1; Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. [PMID: 18703516, PMID: 18794347, PMID: 23443559]
-   **UBB** Polyubiquitin-B; [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). [PMID: 17662948, PMID: 19541625, PMID: 23443559]
-   **CREBBP** CREB-binding protein; Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non- histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers. [PMID: 15743834, PMID: 25241761, PMID: 27626385]
-   **HDAC1** Histone deacetylase 1; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. [PMID: 16082198, PMID: 20154723, PMID: 25241761]
-   **CDC20** Cell division cycle protein 20 homolog; Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. [PMID: 17679094, PMID: 23443559, PMID: 30833792]
-   **PSME3** Proteasome activator complex subunit 3; Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. [PMID: 17588519, PMID: 21445096, PMID: 27215384]
-   **NPM1** Nucleophosmin; Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. [PMID: 15964625, PMID: 19221506]
-   **USP11** Ubiquitin carboxyl-terminal hydrolase 11; Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains. Inhibits the degradation of target proteins by the proteasome. Cleaves preferentially 'Lys-6' and 'Lys-63'-linked ubiquitin chains. Has lower activity with 'Lys-11' and 'Lys-33'-linked ubiquitin chains, and extremely low activity with 'Lys-27', 'Lys-29' and 'Lys-48'-linked ubiquitin chains (in vitro). Plays a role in the regulation of pathways leading to NF-kappa-B activation. [PMID: 23443559, PMID: 29666278]
-   **BAG6** Large proline-rich protein BAG6; ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins. Functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client proteins in a soluble state and participates to their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. [PMID: 21900206, PMID: 21988832]
-   **RELA** Transcription factor p65; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain- containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. [PMID: 22348975, PMID: 25040843]
-   **MGMT** Methylated-DNA--protein-cysteine methyltransferase; Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated; Belongs to the MGMT family. [PMID: 16226712, PMID: 29510343]
-   **MDM4** Protein Mdm4; Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions; Belongs to the MDM2/MDM4 family. [PMID: 18086887, PMID: 21148311]
-   **UBC** Polyubiquitin-C; [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). [PMID: 19536131, PMID: 19541625]
-   **FLAD1** Molybdenum cofactor biosynthesis protein-like region; Catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme. In the C-terminal section; belongs to the PAPS reductase family. FAD1 subfamily. [PMID: 21900206, PMID: 21988832]
-   **CDC45** Cell division control protein 45 homolog; Required for initiation of chromosomal DNA replication; Belongs to the CDC45 family. [PMID: 15232106, PMID: 25241761]
-   **MAPK8** Mitogen-activated protein kinase 8; Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress- activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. [PMID: 12058028, PMID: 20102411]
-   **SMAD4** Mothers against decapentaplegic homolog 4; In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac- specific gene expression. [PMID: 15084259, PMID: 25241761]
-   **CDC6** Cell division control protein 6 homolog; Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated. [PMID: 15232106, PMID: 25241761]
-   **KRT31** Keratin, type I cuticular Ha1; Keratin 31. [PMID: 25416956, PMID: 32296183]
-   **DOCK7** Dedicator of cytokinesis protein 7; Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization. As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. Has a role in pigmentation (By similarity). [PMID: 21900206, PMID: 23443559]
-   **TRIM54** Tripartite motif-containing protein 54; May bind and stabilize microtubules during myotubes formation. [PMID: 25416956, PMID: 32296183]
-   **TUBA1A** Detyrosinated tubulin alpha-1A chain; 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. [PMID: 21900206, PMID: 23443559]
-   **SPRED1** Sprouty-related, EVH1 domain-containing protein 1; Tyrosine kinase substrate that inhibits growth-factor- mediated activation of MAP kinase. Negatively regulates hematopoiesis of bone marrow (By similarity). [PMID: 21900206, PMID: 32814053]
-   **POLR2A** DNA-directed RNA polymerase II subunit RPB1; DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. [PMID: 21088000, PMID: 23870121]
-   **HNRNPK** Heterogeneous nuclear ribonucleoprotein K; One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). [PMID: 19249676, PMID: 21988832]
-   **PSMD2** 26S proteasome non-ATPase regulatory subunit 2; Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair; Belongs to the proteasome subunit S2 family. [PMID: 18086887, PMID: 29777785]
-   **TSG101** Tumor susceptibility gene 101 protein; Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. [PMID: 11943869, PMID: 24244542]
-   **GADD45G** Growth arrest and DNA damage-inducible protein GADD45 gamma; Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK; Belongs to the GADD45 family. [PMID: 10455148, PMID: 11022036]

The interactions list has been truncated to include only interactions with the strongest support from the literature.
