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VCL VCL SPN SPN ITGAM ITGAM ACTB ACTB RAD51 RAD51 PBK PBK RAD17 RAD17 PTPRC PTPRC CHEK1 CHEK1 CD8A CD8A BCL2 BCL2 XRCC5 XRCC5 RPA2 RPA2 CD40 CD40 CD3E CD3E MTOR MTOR XRCC6 XRCC6 RAD52 RAD52 SMARCAL1 SMARCAL1 ATR ATR ATRIP ATRIP SWAP70 SWAP70 PRKDC PRKDC CFLAR CFLAR AOC3 AOC3 RAD9A RAD9A ATM ATM ETAA1 ETAA1 TP53 TP53 TOPBP1 TOPBP1 HUS1 HUS1 BACH2 BACH2 TRIM28 TRIM28 MLH1 MLH1 IL4 IL4 STN1 STN1 CD4 CD4
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splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
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query proteins and first shell of interactors
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second shell of interactors
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proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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experimentally determined
Predicted Interactions
gene neighborhood
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gene co-occurrence
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co-expression
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VCLVinculin; Actin filament (F-actin)-binding protein involved in cell- matrix adhesion and cell-cell adhesion. Regulates cell-surface E- cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion; Belongs to the vinculin/alpha-catenin family. (1134 aa)
SPNCD43 cytoplasmic tail; Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN) (By similarity). Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression [...] (400 aa)
ITGAMIntegrin alpha-M; Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin ITGAM/ITGB2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. Regulates neutrophil migration. In association with beta subunit ITGB2/CD18, required for CD177-PRTN [...] (1153 aa)
ACTBActin, cytoplasmic 1, N-terminally processed; Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells. Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction. In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA. (375 aa)
RAD51DNA repair protein RAD51 homolog 1; Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR). Binds to single and double-stranded DNA and exhibits DNA-dependent ATPase activity. Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template. Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange. Part of a PALB2-scaffolded HR [...] (340 aa)
PBKLymphokine-activated killer T-cell-originated protein kinase; Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin- induced DNA damage; Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. (333 aa)
RAD17Cell cycle checkpoint protein RAD17; Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. Has a weak ATPase activity required for binding to chromatin. Participates in the recruitment of the RAD1-RAD9-HUS1 complex and RHNO1 onto chromatin, and in CHEK1 activation. May also serve as a sensor of DNA replication progression, and may be involved in homologous recombination. Belongs to the rad17/RAD24 family. (681 aa)
PTPRCReceptor-type tyrosine-protein phosphatase C; Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity); Belongs to the protein-tyrosine phosphatase family. Receptor class 1/6 subfamily. (1306 aa)
CHEK1Serine/threonine-protein kinase Chk1; Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and pho [...] (492 aa)
CD8AT-cell surface glycoprotein CD8 alpha chain; Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Sr [...] (235 aa)
BCL2Apoptosis regulator Bcl-2; Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release. (239 aa)
XRCC5X-ray repair cross-complementing protein 5; Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic s [...] (732 aa)
RPA2Replication protein A 32 kDa subunit; As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRI [...] (278 aa)
CD40Tumor necrosis factor receptor superfamily member 5; Receptor for TNFSF5/CD40LG. Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarity). (277 aa)
CD3ET-cell surface glycoprotein CD3 epsilon chain; Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR- mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation o [...] (207 aa)
MTORSerine/threonine-protein kinase mTOR; Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF [...] (2549 aa)
XRCC6X-ray repair cross-complementing protein 6; Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic s [...] (609 aa)
RAD52DNA repair protein RAD52 homolog; Involved in double-stranded break repair. Plays a central role in genetic recombination and DNA repair by promoting the annealing of complementary single-stranded DNA and by stimulation of the RAD51 recombinase. (418 aa)
SMARCAL1SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1; ATP-dependent annealing helicase that binds selectively to fork DNA relative to ssDNA or dsDNA and catalyzes the rewinding of the stably unwound DNA. Rewinds single-stranded DNA bubbles that are stably bound by replication protein A (RPA). Acts throughout the genome to reanneal stably unwound DNA, performing the opposite reaction of many enzymes, such as helicases and polymerases, that unwind DNA. May play an important role in DNA damage response by acting at stalled replication forks. (954 aa)
ATRSerine/threonine-protein kinase ATR; Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]- Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage respon [...] (2644 aa)
ATRIPATR-interacting protein; Required for checkpoint signaling after DNA damage. Required for ATR expression, possibly by stabilizing the protein. Belongs to the ATRIP family. (791 aa)
SWAP70Switch-associated protein 70; Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which, independently of RAS, transduces signals from tyrosine kinase receptors to RAC. It also mediates signaling of membrane ruffling. Regulates the actin cytoskeleton as an effector or adapter protein in response to agonist stimulated phosphatidylinositol (3,4)-bisphosphate production and cell protrusion (By similarity). (585 aa)
PRKDCDNA-dependent protein kinase catalytic subunit; Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act [...] (4128 aa)
CFLARCASP8 and FADD-like apoptosis regulator subunit p12; Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity. Belongs to the peptidase C1 [...] (480 aa)
AOC3Membrane primary amine oxidase; Cell adhesion protein that participates in lymphocyte extravasation and recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin- independent fashion. Has semicarbazide-sensitive (SSAO) monoamine oxidase activity. May play a role in adipogenesis. (763 aa)
RAD9ACell cycle checkpoint control protein RAD9A; Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN [...] (391 aa)
ATMSerine-protein kinase ATM; Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]- Q. Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospec [...] (3056 aa)
ETAA1Ewing's tumor-associated antigen 1; Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity. Recruited to stalled replication forks via interaction with the RPA complex and directly stimulates ATR kinase activity independently of TOPBP1. Probably only regulates a subset of ATR targets. (926 aa)
TP53Cellular 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. Its pro-apoptotic activity is activated via its intera [...] (393 aa)
TOPBP1DNA topoisomerase 2-binding protein 1; Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR. (1522 aa)
HUS1Checkpoint protein HUS1; Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity [...] (280 aa)
BACH2Transcription regulator protein BACH2; Transcriptional regulator that acts as repressor or activator (By similarity). Binds to Maf recognition elements (MARE) (By similarity). Plays an important role in coordinating transcription activation and repression by MAFK (By similarity). Induces apoptosis in response to oxidative stress through repression of the antiapoptotic factor HMOX1. Positively regulates the nuclear import of actin (By similarity). Is a key regulator of adaptive immunity, crucial for the maintenance of regulatory T-cell function and B-cell maturation ; Belongs to the bZI [...] (841 aa)
TRIM28Transcription intermediary factor 1-beta; Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression [...] (835 aa)
MLH1DNA mismatch repair protein Mlh1; Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing t [...] (756 aa)
IL4Interleukin-4; Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages (By similarity). Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4 (By [...] (153 aa)
STN1CST complex subunit STN1; Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation. However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST comp [...] (368 aa)
CD4T-cell surface glycoprotein CD4; Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kina [...] (458 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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