STRINGSTRING
ANKZF1 ANKZF1 YME1L1 YME1L1 CALML3 CALML3 METAP1D METAP1D EIF2AK3 EIF2AK3 CEBPB CEBPB HSPA4 HSPA4 ATP23 ATP23 NEMF NEMF HSPA9 HSPA9 CHCHD4 CHCHD4 SKP1 SKP1 HSPE1 HSPE1 CLPP CLPP TRAP1 TRAP1 GFER GFER PMPCB PMPCB DNAJB1 DNAJB1 EIF2S1 EIF2S1 TIMM10 TIMM10 USP30 USP30 HTRA2 HTRA2 CLPB CLPB DNAJA3 DNAJA3 EIF2AK4 EIF2AK4 GRPEL1 GRPEL1 AFG3L2 AFG3L2 IMMP1L IMMP1L TOMM70 TOMM70 GABARAPL2 GABARAPL2 EIF2AK1 EIF2AK1 HSCB HSCB TOMM22 TOMM22 TXN2 TXN2 DARS2 DARS2 SOCS1 SOCS1 SPG7 SPG7 PARL-2 PARL-2 BCL2L13 BCL2L13 LTN1 LTN1 DDIT3 DDIT3 TIMM50 TIMM50 SP6 SP6 TOMM5 TOMM5 CD200 CD200 NDUFB2 NDUFB2 GABARAPL1 GABARAPL1 TOMM40 TOMM40 CISH CISH CALCOCO2 CALCOCO2 DELE1 DELE1 ATF5 ATF5 MAPK9 MAPK9 IMMP2L IMMP2L TOMM6 TOMM6 TAX1BP1 TAX1BP1 TIMM9 TIMM9 VDAC1 VDAC1 DNAJC19 DNAJC19 PITRM1 PITRM1 OPTN OPTN FUNDC1 FUNDC1 PINK1 PINK1 ROMO1 ROMO1 RNF8 RNF8 MCU MCU ENDOG ENDOG PTEN PTEN PMPCA PMPCA HSP90AB1 HSP90AB1 OMA1 OMA1 JUN JUN BNIP3 BNIP3 SDHC SDHC TIMM17A TIMM17A PRKN PRKN TOMM20 TOMM20 LONP1 LONP1 VCP VCP TOMM7 TOMM7 XPNPEP3 XPNPEP3 UBE2I UBE2I SAMM50 SAMM50 NBR1 NBR1 SP100 SP100 ATAD1 ATAD1 UBA1 UBA1 HSP90AA1 HSP90AA1 GRPEL2 GRPEL2 CD300C CD300C EFNA5 EFNA5 PARL PARL
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
Node Color
colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
Edges:
Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding to each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
Your Input:
ANKZF1Ankyrin repeat and zinc finger domain-containing protein 1; Plays a role in the cellular response to hydrogen peroxide and in the maintenance of mitochondrial integrity under conditions of cellular stress. Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway (By similarity). Belongs to the ANKZF1/VMS1 family. (726 aa)
YME1L1ATP-dependent zinc metalloprotease YME1L1; ATP-dependent metalloprotease that catalyzes the degradation of folded and unfolded proteins with a suitable degron sequence in the mitochondrial intermembrane region. Plays an important role in regulating mitochondrial morphology and function by cleaving OPA1 at position S2, giving rise to a form of OPA1 that promotes maintenance of normal mitochondrial structure and mitochondrial protein metabolism. Ensures cell proliferation, maintains normal cristae morphology and complex I respiration activity, promotes antiapoptotic activity and protects [...] (773 aa)
CALML3Calmodulin-like protein 3; May function as a specific light chain of unconventional myosin-10 (MYO10), also enhances MYO10 translation, possibly by acting as a chaperone for the emerging MYO10 heavy chain protein. May compete with calmodulin by binding, with different affinities, to cellular substrates. (149 aa)
METAP1DMethionine aminopeptidase 1D, mitochondrial; Removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed (By similarity). May play a role in colon tumorigenesis; Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily. (335 aa)
EIF2AK3Eukaryotic translation initiation factor 2-alpha kinase 3; Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2- alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated [...] (1116 aa)
CEBPBCCAAT/enhancer-binding protein beta; Important transcription factor regulating the expression of genes involved in immune and inflammatory responses. Plays also a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant functions with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipo [...] (345 aa)
HSPA4Heat shock protein family A member 4; Belongs to the heat shock protein 70 family. (840 aa)
ATP23Mitochondrial inner membrane protease ATP23 homolog; ATP23 metallopeptidase and ATP synthase assembly factor homolog. (246 aa)
NEMFNuclear export mediator factor NEMF; Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation. NEMF is responsible for selective recognition of stalled 60S subunits by recognizing an exposed, nascent chain-conjugated tRNA moiety. NEMF is important for the stable association of LTN1 to the complex. May indirectly play a role in nuclear export. (1076 aa)
HSPA9Stress-70 protein, mitochondrial; Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU. Regulates erythropoiesis via stabilization of ISC assembly. May play a role in the control of cell proliferation and cellular aging (By similarity). Belongs to the heat shock protein 70 family. (679 aa)
CHCHD4Mitochondrial intermembrane space import and assembly protein 40; Central component of a redox-sensitive mitochondrial intermembrane space import machinery which is required for the biogenesis of respiratory chain complexes. Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17, COX19, MICU1 and COA7. Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Required for the import of COA7 in the IMS. Precursor proteins to be imported into the IMS are translo [...] (155 aa)
SKP1S-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. SCF(BTRC [...] (163 aa)
HSPE110 kDa heat shock protein, mitochondrial; Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per [...] (102 aa)
CLPPATP-dependent Clp protease proteolytic subunit, mitochondrial; Protease component of the Clp complex that cleaves peptides and various proteins in an ATP-dependent process. Has low peptidase activity in the absence of CLPX. The Clp complex can degrade CSN1S1, CSN2 and CSN3, as well as synthetic peptides (in vitro) and may be responsible for a fairly general and central housekeeping function rather than for the degradation of specific substrates. Cleaves PINK1 in the mitochondrion. (277 aa)
TRAP1Heat shock protein 75 kDa, mitochondrial; Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA; Belongs to the heat shock protein 90 family. (704 aa)
GFERFAD-linked sulfhydryl oxidase ALR; [Isoform 1]: FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen. (205 aa)
PMPCBMitochondrial-processing peptidase subunit beta; Catalytic subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins (Probable). Preferentially, cleaves after an arginine at position P2 (By similarity). Required for PINK1 turnover by coupling PINK1 mitochondrial import and cleavage, which results in subsequent PINK1 proteolysis. (489 aa)
DNAJB1DnaJ homolog subfamily B member 1; Interacts with HSP70 and can stimulate its ATPase activity. Stimulates the association between HSC70 and HIP. Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro). (340 aa)
EIF2S1Eukaryotic translation initiation factor 2 subunit 1; Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre- initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF- 2 must exchange with GTP by way of a reaction catalyzed [...] (315 aa)
TIMM10Mitochondrial import inner membrane translocase subunit Tim10; Mitochondrial intermembrane chaperone that participates in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. May also be required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. Belongs to the small Tim family. (90 aa)
USP30Ubiquitin carboxyl-terminal hydrolase 30; Deubiquitinating enzyme tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin's ability to drive mitophagy. Preferentially cleaves 'Lys-6'- and 'Lys-11'-linked polyubiquitin chains, 2 types of linkage that participate to mitophagic signaling. Does not cleave efficiently polyubiquitin phosphorylated at 'Ser-65'. Acts as negative regulator of mitochondria [...] (517 aa)
HTRA2Serine protease HTRA2, mitochondrial; Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase- independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive; Belongs to the peptidase S1C family. (458 aa)
CLPBCaseinolytic peptidase B protein homolog; May function as a regulatory ATPase and be related to secretion/protein trafficking process. (707 aa)
DNAJA3DnaJ homolog subfamily A member 3, mitochondrial; Modulates apoptotic signal transduction or effector structures within the mitochondrial matrix. Affect cytochrome C release from the mitochondria and caspase 3 activation, but not caspase 8 activation. Isoform 1 increases apoptosis triggered by both TNF and the DNA-damaging agent mytomycin C; in sharp contrast, isoform 2 suppresses apoptosis. Can modulate IFN-gamma-mediated transcriptional activity. Isoform 2 may play a role in neuromuscular junction development as an effector of the MUSK signaling pathway. (480 aa)
EIF2AK4eIF-2-alpha kinase GCN2; Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2- alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability. Plays a role as an activator of the integrated stress response (ISR) required for adapatation to amino acid starvation. Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a transla [...] (1649 aa)
GRPEL1GrpE protein homolog 1, mitochondrial; Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner (By similarity). Seems to control the nucleotide-dependent binding of mitochondrial HSP70 to substrate proteins. Belongs to the GrpE family. (217 aa)
AFG3L2AFG3-like protein 2; ATP-dependent protease which is essential for axonal and neuron development. In neurons, mediates degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU. Required for the maturation of paraplegin (SPG7) after its cleavage by mitochondrial-processing peptidase (MPP), converting it into a proteolytically active mature form (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mito [...] (797 aa)
IMMP1LMitochondrial inner membrane protease subunit 1; Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space. Known to process the nuclear encoded protein DIABLO. (166 aa)
TOMM70Mitochondrial import receptor subunit TOM70; Receptor that accelerates the import of all mitochondrial precursor proteins. (608 aa)
GABARAPL2Gamma-aminobutyric acid receptor-associated protein-like 2; Ubiquitin-like modifier involved in intra-Golgi traffic. Modulates intra-Golgi transport through coupling between NSF activity and SNAREs activation. It first stimulates the ATPase activity of NSF which in turn stimulates the association with GOSR1 (By similarity). Involved in autophagy. Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Whereas LC3s are involved [...] (117 aa)
EIF2AK1Eukaryotic translation initiation factor 2-alpha kinase 1; Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser- 51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-se [...] (630 aa)
HSCBIron-sulfur cluster co-chaperone protein HscB, mitochondrial; Acts as a co-chaperone in iron-sulfur cluster assembly in both mitochondria and the cytoplasm. Required for incorporation of iron-sulfur clusters into SDHB, the iron- sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain. Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20. Also mediates complex formation between components [...] (235 aa)
TOMM22Mitochondrial import receptor subunit TOM22 homolog; Central receptor component of the translocase of the outer membrane of mitochondria (TOM complex) responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with the peripheral receptor TOM20 functions as the transit peptide receptor and facilitates the movement of preproteins into the translocation pore. Required for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases (By similarity); Belongs to the Tom22 family. (142 aa)
TXN2Thioredoxin, mitochondrial; Important for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Possesses a dithiol-reducing activity; Belongs to the thioredoxin family. (166 aa)
DARS2Aspartate--tRNA ligase, mitochondrial; aspartyl-tRNA synthetase 2, mitochondrial. (645 aa)
SOCS1Suppressor of cytokine signaling 1; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase activity. In vitro, also suppresses Tec protein-tyrosine activity. Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival (By similarity). Probable substrate recognition component of an [...] (211 aa)
SPG7Paraplegin; ATP-dependent zinc metalloprotease. Plays a role in the formation and regulation of the mitochondrial permeability transition pore (mPTP) and its proteolytic activity is dispensable for this function ; In the N-terminal section; belongs to the AAA ATPase family. (795 aa)
PARL-2Presenilins-associated rhomboid-like protein, mitochondrial. (408 aa)
BCL2L13Bcl-2-like protein 13; May promote the activation of caspase-3 and apoptosis. (509 aa)
LTN1E3 ubiquitin-protein ligase listerin; E3 ubiquitin-protein ligase component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation. Ubiquitination leads to VCP/p97 recruitment for extraction and degradation of the incomplete translation product (By similarity). (1812 aa)
DDIT3DNA damage-inducible transcript 3 protein; Multifunctional transcription factor in ER stress response. Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress. Plays a dual role both as an inhibitor of CCAAT/enhancer- binding protein (C/EBP) function and as an activator of other genes. Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression [...] (192 aa)
TIMM50Mitochondrial import inner membrane translocase subunit TIM50; Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Has some phosphatase activity in vitro; however such activity may not be relevant in vivo. (456 aa)
SP6Transcription factor Sp6; Promotes cell proliferation; Belongs to the Sp1 C2H2-type zinc-finger protein family. (376 aa)
TOMM5Mitochondrial import receptor subunit TOM5 homolog; Translocase of outer mitochondrial membrane 5. (92 aa)
CD200OX-2 membrane glycoprotein; Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues. (294 aa)
NDUFB2NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial; Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. (105 aa)
GABARAPL1Gamma-aminobutyric acid receptor-associated protein-like 1; GABA type A receptor associated protein like 1. (146 aa)
TOMM40Mitochondrial import receptor subunit TOM40 homolog; Channel-forming protein essential for import of protein precursors into mitochondria; Belongs to the Tom40 family. (361 aa)
CISHCytokine-inducible SH2-containing protein; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasom [...] (275 aa)
CALCOCO2Calcium-binding and coiled-coil domain-containing protein 2; Xenophagy-specific receptor required for autophagy-mediated intracellular bacteria degradation. Acts as an effector protein of galectin-sensed membrane damage that restricts the proliferation of infecting pathogens such as Salmonella typhimurium upon entry into the cytosol by targeting LGALS8-associated bacteria for autophagy. Initially orchestrates bacteria targeting to autophagosomes and subsequently ensures pathogen degradation by regulating pathogen-containing autophagosome maturation. Bacteria targeting to autophagosomes [...] (470 aa)
DELE1DAP3-binding cell death enhancer 1; Essential for the induction of death receptor-mediated apoptosis through the regulation of caspase activation. (515 aa)
ATF5Cyclic AMP-dependent transcription factor ATF-5; Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), ATF5-specific response element (ARE) (consensus: 5'- C[CT]TCT[CT]CCTT[AT]-3') but also the amino acid response element (AARE), present in many viral and cellular promoters. Critically involved, often in a cell type-dependent manner, in cell survival, proliferation, and differentiation. Its transcriptional activity is enhanced by CCND3 and s [...] (282 aa)
MAPK9Mitogen-activated protein kinase 9; 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 MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as J [...] (424 aa)
IMMP2LMitochondrial inner membrane protease subunit 2; Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space. Known to process the nuclear encoded protein DIABLO; Belongs to the peptidase S26 family. IMP2 subfamily. (175 aa)
TOMM6Mitochondrial import receptor subunit TOM6 homolog; Translocase of outer mitochondrial membrane 6. (74 aa)
TAX1BP1Tax1-binding protein 1; Inhibits TNF-induced apoptosis by mediating the TNFAIP3 anti- apoptotic activity. Degraded by caspase-3-like family proteins upon TNF-induced apoptosis. May also play a role in the pro-inflammatory cytokine IL-1 signaling cascade. (789 aa)
TIMM9Mitochondrial import inner membrane translocase subunit Tim9; Mitochondrial intermembrane chaperone that participates in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. May also be required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. Belongs to the small Tim family. (89 aa)
VDAC1Voltage-dependent anion-selective channel protein 1; Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. May participate in the formation of the permeability transition p [...] (283 aa)
DNAJC19Mitochondrial import inner membrane translocase subunit TIM14; Probable component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. May act as a co-chaperone that stimulate the ATP-dependent activity (By similarity); Belongs to the TIM14 family. (116 aa)
PITRM1Presequence protease, mitochondrial; Metalloendopeptidase of the mitochondrial matrix that functions in peptide cleavage and degradation rather than in protein processing. Has an ATP-independent activity. Specifically cleaves peptides in the range of 5 to 65 residues. Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference. Degrades the transit peptides of mitochondrial proteins after their cleavage. Also degrades other unstructured peptides. It is also able to degrade amyloid-beta protein 40, one of the peptides produ [...] (1038 aa)
OPTNOptineurin; Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation. In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta. Plays a neuroprotective role in the eye and [...] (577 aa)
FUNDC1FUN14 domain-containing protein 1; Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control. (155 aa)
PINK1Serine/threonine-protein kinase PINK1, mitochondrial; Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) by mediating activation and translocation of PRKN. Targets PRKN to dysfunctional depolarized mitochondria through the phosphorylation of MFN2. Activates PRKN in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PRKN and (2) mediating phosphorylation of ubiquitin, converting PRKN to its fully-active form. Required for ubiquinone reduct [...] (581 aa)
ROMO1Reactive oxygen species modulator 1; Induces production of reactive oxygen species (ROS) which are necessary for cell proliferation. May play a role in inducing oxidative DNA damage and replicative senescence. May play a role in the coordination of mitochondrial morphology and cell proliferation; Belongs to the MGR2 family. (79 aa)
RNF8E3 ubiquitin-protein ligase RNF8; E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53 [...] (485 aa)
MCUCalcium uniporter protein, mitochondrial; Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria. Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex). Activity is regulated by MICU1 and MICU2. At low Ca(2+) levels MCU activity is down-regulated by MICU1 and MICU2; at higher Ca(2+) levels MICU1 increases MCU activity. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Involved in buffe [...] (351 aa)
ENDOGEndonuclease G, mitochondrial; Cleaves DNA at double-stranded (DG)n.(DC)n and at single- stranded (DC)n tracts. In addition to deoxyribonuclease activities, also has ribonuclease (RNase) and RNase H activities. Capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA (By similarity); Belongs to the DNA/RNA non-specific endonuclease family. (297 aa)
PTENPhosphatase and tensin homolog; Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine- phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4- diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5- tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor [...] (403 aa)
PMPCAMitochondrial-processing peptidase subunit alpha; Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins. (525 aa)
HSP90AB1Heat shock protein HSP 90-beta; 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. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co- chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interact [...] (724 aa)
OMA1Metalloendopeptidase OMA1, mitochondrial; Metalloprotease that is part of the quality control system in the inner membrane of mitochondria. Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation and negative regulation of mitochondrial fusion. May also cleave UQCC3 under these conditions. Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions. Belongs to the peptidase [...] (524 aa)
JUNTranscription factor AP-1; Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells. Binds to the USP28 promoter in colorectal cancer (CRC) cells. Belongs to the bZIP family. Jun subfamily. (331 aa)
BNIP3BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer [...] (259 aa)
SDHCSuccinate dehydrogenase cytochrome b560 subunit, mitochondrial; Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q); Belongs to the cytochrome b560 family. (169 aa)
TIMM17AMitochondrial import inner membrane translocase subunit Tim17-A; Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. (171 aa)
PRKNE3 ubiquitin-protein ligase parkin; Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'- linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of m [...] (465 aa)
TOMM20Mitochondrial import receptor subunit TOM20 homolog; Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with TOM22 functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the TOM40 translocation pore (By similarity). Required for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases. Belongs to the Tom20 family. (145 aa)
LONP1Lon protease homolog, mitochondrial; ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand- specific manner. May regulate mi [...] (959 aa)
VCPTransitional endoplasmic reticulum ATPase; 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 occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is neces [...] (806 aa)
TOMM7Mitochondrial import receptor subunit TOM7 homolog; Required for assembly and stability of the TOM complex. Positive regulator of PRKN translocation to damaged mitochondria. Acts probably by stabilizing PINK1 on the outer membrane of depolarized mitochondria; Belongs to the Tom7 family. (55 aa)
XPNPEP3Xaa-Pro aminopeptidase 3; Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala. Also shows low activity towards peptides with Ala or Ser at the P1 position. (507 aa)
UBE2ISUMO-conjugating enzyme UBC9; Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3, SUMO4 and SUMO1P1/SUMO5 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation. Sumoylates p53/TP53 at 'Lys-386'. Mediates sumoylation of ERCC6 which is essential for its transcription-coupled nucleotide excision repair activity. Belongs to the ubiqu [...] (158 aa)
SAMM50Sorting and assembly machinery component 50 homolog; Plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes. Required for the assembly of TOMM40 into the TOM complex. (469 aa)
NBR1Next to BRCA1 gene 1 protein; Acts probably as a receptor for selective autophagosomal degradation of ubiquitinated targets. (966 aa)
SP100Nuclear autoantigen Sp-100; Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it ma [...] (885 aa)
ATAD1ATPase family AAA domain-containing protein 1; ATPase that plays a critical role in regulating the surface expression of AMPA receptors (AMPAR), thereby regulating synaptic plasticity and learning and memory. Required for NMDA-stimulated AMPAR internalization and inhibition of GRIA1 and GRIA2 recycling back to the plasma membrane; these activities are ATPase-dependent (By similarity). (361 aa)
UBA1Ubiquitin-like modifier-activating enzyme 1; Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites. (1058 aa)
HSP90AA1Heat shock protein HSP 90-alpha; 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 which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a ra [...] (854 aa)
GRPEL2GrpE protein homolog 2, mitochondrial; Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. Seems to control the nucleotide-dependent binding of mitochondrial HSP70 to substrate proteins. Stimulates ATPase activity of mt-HSP70. May also serve to modulate the interconversion of oligomeric (inactive) and monomeric (active) forms of mt-HSP70 (By similarity); Belongs to the GrpE family. (225 aa)
CD300CCMRF35-like molecule 6; CD300c molecule; Belongs to the CD300 family. (224 aa)
EFNA5Ephrin-A5; Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Induces compartmentalized signaling within a caveolae-like memb [...] (228 aa)
PARLPresenilins-associated rhomboid-like protein, mitochondrial; Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP). Promotes changes in mitochondria morphology regulated by phosphorylation of P- beta domain. (379 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (18%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.