Gene symbol | Alias/Protein | Role in TMM | Reference(s) | Pathway | Status |
---|---|---|---|---|---|
MTR4 | MTREX | part of NEXT complex, which binds to hTRs cotranscriptionally to add oligo-A tails; forms the CBCN complex with CBCA to recruit exosomes; Also component of TRAMP complex that marks immature hTRs for degradation; | (Chi-Kang et al., 2015), (Tseng et al., 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
TENT4B | PAPD5 | Catalytic subunit of the TRAMP complex. | (Tseng et al., 2015), (Moon et al., 2015) | Telomerase | Version 2.0 |
PARN | Removes oligo-A tails from hTRs, leading to their maturation | (Tseng et al., 2015), (Moon et al., 2015), (Boyraz et al., 2016)) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
|
PABN1 | Promotes PARN-directed hTR maturation | (Tseng et al., 2015) | Telomerase | Version 0.0 Version 1.0 |
|
ZCCHC7 | AIR2 | Component of TRAMP complex that marks immature hTRs for degradation; | (Tseng et al., 2015) | Telomerase | Version 0.0 Version 2.0 |
PAPD5 | Component of TRAMP complex that marks immature hTRs for degradation; | (Tseng et al., 2015) | Telomerase | Version 0.0 Version 1.0 |
|
EXOSC10 | The major component of nuclear exosomes degrading immature hTRs. | (Tseng et al., 2015) | Telomerase | Version 0.0 Version 1.0 |
|
XRN1 | A component of cytoplasmic exosomes that may also degrade hTRs, after its export. | (Shukla et al., 2016) | Telomerase | Version 0.0 | |
DCP2 | A component of cytoplasmic exosomes that may also degrade hTRs, after its export. | (Shukla et al., 2016) | Telomerase | Version 0.0 | |
EXOSC3 | A component of nuclear exosomes that may also participate in degradation of immature hTRs. | (Tseng et al., 2015) | Telomerase | Version 0.0 | |
DIS3 | A component of nuclear exosomes that may also participate in degradation of immature hTRs. | (Tseng et al., 2015) | Telomerase | Version 0.0 | |
DKC1 | Dyskerin Pseudouridine Synthase 1 | Telomerase subunit; Part of dyskerin-NOP10-NHP2 complex, which protects hTR from degradation; | (Cohen et al., 2007), (Penzo et al., 2015), (Shukla et al., 2016) | Telomerase | Version 0.0 Version 1.0 |
STUB1 | CHIP ubiquitin ligase | cytoplasmic accumulation and degradation of hTERT | (Jeong et al., 2015), (Lee et al., 2010) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
NOP10 | Part of dyskerin-NOP10-NHP2 complex, which protects hTR from degradation | (Schmidt and Cech, 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
|
NHP2 | Part of dyskerin-NOP10-NHP2 complex, which protects hTR from degradation | (Schmidt and Cech, 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
|
NAF1 | Protects hTR-Dyskerin-NOP10-NHP2 complex against degradation | (Schmidt and Cech, 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
|
IPO7 | Importin 7 | Alternative nuclear import of hTERT | (Frohnert et al., 2014) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
RANBP2 | Nup358 | Alternative nuclear import of hTERT | (Frohnert et al., 2014) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
HSPA1A | HSP70 | cytoplasmic accumulation and degradation of hTERT | (Jeong et al., 2015) | Telomerase | Version 1.0 |
GAR1 | Replaces NAF1 in Cajal bodies | (Schmidt and Cech, 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
|
TERC | hTR | RNA component of telomerase | (Cohen et al., 2007), (Penzo et al., 2015), (Cayuela et al., 2005) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
TERT | hTERT | Catalytic subunit of telomerase | (Cohen et al., 2007) | Telomerase, ALT | Version 0.0 Version 1.0 Version 2.0 |
ABL1 | c-Abl | inhibits telomerase activity hTERT phosphorylation | (Kharbanda et al., 2000) | Telomerase | Version 0.0 |
KPNA1 | Importin alpha 5 | participates in nuclear import of hTERT | (Jeong et al., 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
RAN | GTPase that affects disassembly of importin-cargo complexes and is important for importin alpha 5 mediated nuclear import of hTERT. | (Jeong et al., 2015) | Telomerase | Version 2.0 | |
KPNB1 | Importin beta 1 | participates in nuclear import of hTERT | (Jeong et al., 2015) | Telomerase | To be tested |
PKC | All subunits included | PKC-mediated phosphorylation of hTERT promotes its binding to Hsp90 | (Chang et al., 2006) | Telomerase | Version 0.0 |
NCBP1 | part of CBCA complex, which binds to hTRs cotranscriptionally to add 5' caps; forms the CBCN complex with NEXT to recruit exosomes; | (Tseng et al., 2015) | Telomerase | Version 0.0 Version 1.0 |
|
SRRT | part of CBCA complex, which binds to hTRs cotranscriptionally to add 5' caps; forms the CBCN complex with NEXT to recruit exosomes; | (Tseng et al., 2015) | Telomerase | Version 0.0 Version 1.0 |
|
NCBP2 | part of CBCA complex, which binds to hTRs cotranscriptionally to add 5' caps; forms the CBCN complex with NEXT to recruit exosomes; | (Tseng et al., 2015) | Telomerase | Version 0.0 Version 1.0 |
|
RBM7 | part of NEXT complex, which binds to hTRs cotranscriptionally to add oligo-A tails; forms the CBCN complex with CBCA to recruit exosomes; | (Tseng et al., 2015) | Telomerase | Version 0.0 Version 1.0 |
|
ZCCHC8 | part of NEXT complex, which binds to hTRs cotranscriptionally to add oligo-A tails; forms the CBCN complex with CBCA to recruit exosomes; | (Tseng et al., 2015) | Telomerase | Version 0.0 | |
WRN | RecQ Helicase | found at APBs, however, its role in ALT is not established, since itâs shown to be required in some, but not all of the ALT cells | (Gocha et al., 2014) | ALT | Not included |
SUV39H1 | catalyses H3K9me3 heterochromatin assembly; deletion leads to ALT | (Blasco, 2007) | ALT | Version 0.0 Version 1.0 |
|
AKTIP | binds to the replication machinery component PCNA and is important for its association to replicative chromatin | (Burla et al., 2016) | ALT | To be tested | |
MND1 | Hop2-Mnd1 interaction with RAD51 | (Cho et al., 2014) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
KMT5C | SUV420H2 | catalyses H4K20me3 heterochromatin assembly; deletion leads to ALT | (Blasco, 2007) | ALT | Version 0.0 |
KMT5B | SUV420H1 | catalyses H4K20me3 heterochromatin assembly; deletion leads to ALT | (Blasco, 2007) | ALT | Version 0.0 |
SP100 | inhibits NBS1 localization in APBs. This and underexpression of MRN proteins leads to less t-circles. | (Jiang et al., 2005) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
NBN | Component of MRN complex, that colocalized to HR proteins in APB bodies; depletion of MRN leads to reduced telomere length | (Jiang et al., 2005), (Zhong et al., 2007), (Lafrance-Vanasse et al., 2015) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
MRE11A | Component of MRN complex, that colocalized to HR proteins in APB bodies; depletion of MRN leads to reduced telomere length | (Jiang et al., 2005), (Zhong et al., 2007), (Lafrance-Vanasse et al., 2015) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
RAD50 | Component of MRN complex, that colocalized to HR proteins in APB bodies; depletion of MRN leads to reduced telomere length | (Jiang et al., 2005), (Zhong et al., 2007), (Lafrance-Vanasse et al., 2015) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
SMC5 | Component of SMC5/6 complex, that sumoylates telomere binding proteins such as TRF1 and TRF2, leading to increased APB formation at telomeres | (Jiang et al., 2005), (Reddel et al., 2012), (Aragón, 2018 ), (Potts and Yu, 2007) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
SMC6 | Component of SMC5/6 complex, that sumoylates telomere binding proteins such as TRF1 and TRF2, leading to increased APB formation at telomeres | (Jiang et al., 2005), (Reddel et al., 2012), (Aragón, 2018 ), (Potts and Yu, 2007) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
NSMCE2 | Component of SMC5/6 complex, that sumoylates telomere binding proteins such as TRF1 and TRF2, leading to increased APB formation at telomeres | (Jiang et al., 2005), (Reddel et al., 2012), (Aragón, 2018 ), (Potts and Yu, 2007) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
RPA4 | RPA subunit; RPA promotes POT1 replacement with RAD51 | (Pickett et al., 2015) | ALT | Version 0.0 Version 1.0 |
|
RPA3 | RPA subunit; RPA promotes POT1 replacement with RAD51 | (Pickett et al., 2015), (Flynn et al., 2012) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
HNRNPA1 | inhibits replacement of POT1 with RPA | (Pickett et al., 2015), (Flynn et al., 2012) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
RPA2 | RPA subunit; RPA promotes POT1 replacement with RAD51 | (Pickett et al., 2015), (Flynn et al., 2012) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
FEN1 | cleaves the RNA(TERRA):DNA hybrids; limits telomere fragility | (Teasley et al., 2015) | ALT | Version 0.0 Version 1.0 |
|
RPA1 | RPA subunit; RPA promotes POT1 replacement with RAD51 | (Pickett et al., 2015), (Flynn et al., 2012) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
DAXX | (Lovejoy et al., 2012), (Dyer et al., 2017) | ALT | Version 0.0 Version 1.0 Version 2.0 |
||
RFC1 | sensing telomere damage; recruitment of polymerase delta | (Dilley et al., 2016) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
BRCA2 | " RAD51 mediator function in humans is carried out by another protein, BRCA2", "controls the assembly of human RAD51 into nucleoprotein filaments as demonstrated both in vivo and in vitro" | (Krejci et al., 2012) | ALT | Expression data not available for testing | |
H3F3A | H3.3 histone variant. Suppresses formation of G4 structures at telomeres, which are replication fork barriers at telomeres, trigger fork stalling and restart by homology directed repair, and are HR substrates. The purpose of H3.3 deposition at telomeres remains unclear. | (Dyer et al., 2017), (Clynes et al., 2015) | ALT | Version 2.0 | |
ATRX | (Lovejoy et al., 2012), (Dyer et al., 2017), (Clynes et al., 2015) | ALT | Version 0.0 Version 1.0 Version 2.0 |
||
ATR | Recruitment of Hop2-Mnd1 to telomeres | https://www.ncbi.nlm.nih.gov/pubmed/27760120, (Flynn et al., 2012), (Flynn et al., 2015) , (Deeg et al., 2016), (Dilley et al., 2016), | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
RAD52 | positive regulator of RAD51 loading | (Pickett et al., 2015), (Min et al., 2019), (Jia-Min Zhang et al., 2019) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
GEN1 | involved in HJ resolution in the absence of telomere synthesis | (Pickett et al., 2015) | ALT | Version 0.0 |
|
MUS81 | part of MUS81-EME1 complex, involved in HJ resolution in the absence of telomere synthesis | (Pickett et al., 2015) | ALT | Version 0.0 Version 1.0 |
|
EME1 | part of MUS81-EME1 complex, involved in HJ resolution in the absence of telomere synthesis | (Pickett et al., 2015) | ALT | Version 0.0 Version 1.0 |
|
SLX1A | part of SLX1-SLX4 complex, involved in HJ resolution in the absence of telomere synthesis | (Pickett et al., 2015), (Sobinoff et al., 2017) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
SLX1B | part of SLX1-SLX4 complex, involved in HJ resolution in the absence of telomere synthesis | (Pickett et al., 2015), (Sobinoff et al., 2017) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
SLX4 | part of SLX1-SLX4 complex, involved in HJ resolution in the absence of telomere synthesis | (Pickett et al., 2015), (Sobinoff et al., 2017) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
BLM | part of BTR complex, involved in HJ dissolution | (Pickett et al., 2015), (Sobinoff et al., 2017) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
RMI1 | part of BTR complex, involved in HJ dissolution | (Pickett et al., 2015), (Sobinoff et al., 2017) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
RMI2 | part of BTR complex, involved in HJ dissolution | (Pickett et al., 2015), (Sobinoff et al., 2017) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
TOP3A | part of BTR complex, involved in HJ dissolution | (Pickett et al., 2015), (Sobinoff et al., 2017) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
ZNF827 | recruits the NuRD complex to telomeres | (Conomos et al., 2014) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
NR2C2 | TR4 | promotes ZNF827 directed recruitment of NuRD complex to telomeres | (Conomos et al., 2014) | ALT | Version 0.0 Version 2.0 |
NR2F2 | COUP-TR2 | promotes ZNF827 directed recruitment of NuRD complex to telomeres | (Conomos et al., 2014) | ALT | Version 0.0 Version 1.0 Version 2.0 |
HDAC9 | egulates the formation of APBs | (Jamiruddin et al., 2016) | ALT | Version 0.0 | |
PML | constituent of ALT associated PML bodies (APB) | (Grobelny et al., 2000), (Chung et al., 2012) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
BRCA1 | constituent of ALT associated PML bodies (APB) | (Wu et al., 2003) | ALT | Version 1.0 | |
CBX5 | HP1 | constituent of ALT associated PML bodies (APB) | (Jiang et al., 2011) | ALT | Version 1.0 |
HIRA | required for ALT associated PML bodies (APB) formation | (Jiang et al., 2011) | ALT | Version 1.0 | |
FANCD2 | colocalizes to APB bodies; shown to be required for ALT; | (Fan et al., 2009) | ALT | Not included | |
TIMELESS | the TIMELESS/TIPIN complex suppresses telomeric mitotic DNA synthesis | (Min et al., 2017) | ALT | Not included | |
TIPIN | the TIMELESS/TIPIN complex suppresses telomeric mitotic DNA synthesis | (Min et al., 2017) | ALT | Not included | |
RAD51 | promoter of DNA invasion in HR | (Pickett et al., 2015), (Cho et al., 2014), (Jia-Min Zhang et al., 2019) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
PSMC3IP | HOP2 | Hop2-Mnd1 interaction with RAD51 | (Cho et al., 2014) | ALT | Version 0.0 Version 1.0 Version 2.0 |
POT1 | Binds to ssDNA and protects from strand invasions | (Winkel et al., 1989), (Flynn et al., 2012) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
POLD4 | accessory subunit of polymerase delta, which is required for for break induced telomere synthesis. But unlike POLD3, its depletion does not affect ALT. But it | (Dilley et al., 2016) | ALT | Not included | |
POLD3 | critical for break induced telomere synthesis | (Dilley et al., 2016) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
POLD1 | catalytic subunit of polymerase delta, which is required for for break induced telomere synthesis. | (Dilley et al., 2016) | ALT | Not included | |
PCNA | sensing telomere damage; recruitment of polymerase delta | (Dilley et al., 2016) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
SUV39H2 | catalyses H3K9me3 heterochromatin assembly; deletion leads to ALT | (Blasco, 2007) | ALT | Version 0.0 Version 1.0 |
|
CHEK1 | Recruitment of Hop2-Mnd1 to telomeres | (Dilley et al., 2016) | ALT | Version 0.0 Version 1.0 Version 2.0 |
|
ERCC1 | Forms a heterodimer with ERCC4 and supresses recombination with interstitial telomeric sequences. | (Zhu et al., 2003) | ALT | Version 2.0 | |
ERCC4 | Forms a heterodimer with ERCC1 and supresses recombination with interstitial telomeric sequences. | (Zhu et al., 2003) | ALT | Version 2.0 | |
WRAP53 | TCAB1 | Binds to hTRs in Cajal bodies; the role in complex assemby is not clear. | (Zhu et al., 2004), (Chen et al., 2018) | Telomerase | Version 0.0 Version 2.0 |
FXR1 | Binds and stabilizes hTR | (Majumder et al., 2016) | Telomerase | Version 0.0 Version 1.0 |
|
PTGES3 | p23 | Assures proper hTERT conformation for nuclear import to take place | (Forsythe et al., 2001), (Jeong et al., 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
HSP90AA1 | Isoform of HSP90, which assures proper hTERT conformation for nuclear import to take place | (Forsythe et al., 2001), (Jeong et al., 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
|
HSP90AA2 | Isoform of HSP90, which assures proper hTERT conformation for nuclear import to take place | (Forsythe et al., 2001), (Jeong et al., 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
|
HSP90AB1 | Isoform of HSP90, which assures proper hTERT conformation for nuclear import to take place | (Forsythe et al., 2001), (Jeong et al., 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
|
CST | Has dual role in the pathway. Recruits telomerase to telomeres, but limits its presence to one extension cycle only, competing with POT1-TPP1 for telomere binding. Recruits polymerase alpha to complete telomere synthesis. | (Chen et al., 2012) | Telomerase | Version 2.0 | |
CTC1 | Member of CST complex. | (Chen et al., 2012) | Telomerase | Version 2.0 | |
STN1 | Member of CST complex. Stimulates the activity of DNA polymerase alpha. | (Chen et al., 2012) | Telomerase | Version 2.0 | |
TEN1 | Member of CST complex. | (Chen et al., 2012) | Telomerase | Version 2.0 | |
DKC1 | Core component of telomerase: stabilizes the complex by binding to hTR. | (Schmidt and Cech, 2015) | Telomerase | Version 2.0 | |
RUVBL1 | Pontin | Participates in telomerase assembly, by affecting hTR levels through its interaction with dyskerin | (Cohen et al., 2007), (Penzo et al., 2015); (Schmidt and Cech, 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
RUVBL2 | Reptin | Participates in telomerase assembly, by affecting hTR levels through its interaction with dyskerin | (Cohen et al., 2007), (Penzo et al., 2015); (Schmidt and Cech, 2015) | Telomerase | Version 0.0 Version 1.0 Version 2.0 |
RNASEH1 | Regulates the amount of RNA-DNA hybrids in ALT cells | (Cohen et al., 2007) (Penzo et al., 2015); (Arora et al., 2014) | ALT | To be tested | |
HDAC1 | Part of NuRD complex, may open up the chromatin for HR | (Conomos et al., 2014) | ALT | Not included - to be tested again | |
HDAC2 | Part of NuRD complex, may open up the chromatin for HR | (Conomos et al., 2014) | ALT | Not included - to be tested again | |
SMARCAL1 | HARP | Stabilizes DNA by promotes branch migration and fork regression at stalled replication forks. Is enriched at ALT telomeres. | (Btous et a;. 2012), (Cox et al., 2016) | ALT | To be tested |