| UniProt ID | DNA2_HUMAN | |
|---|---|---|
| UniProt AC | P51530 | |
| Protein Name | DNA replication ATP-dependent helicase/nuclease DNA2 | |
| Gene Name | DNA2 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 1060 | |
| Subcellular Localization | Nucleus. Mitochondrion. Was initially reported to be exclusively mitochondrial (PubMed:18995831). However, it was later shown to localize both in mitochondrion and nucleus (PubMed:19487465). | |
| Protein Description | Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double-strand break (DSB) repair: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. Also involved in DNA replication checkpoint independently of Okazaki fragments processing. Possesses different enzymatic activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5'-3' helicase and endonuclease activities. While the ATPase and endonuclease activities are well-defined and play a key role in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase activity is subject to debate. According to various reports, the helicase activity is weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function.. | |
| Protein Sequence | MEQLNELELLMEKSFWEEAELPAELFQKKVVASFPRTVLSTGMDNRYLVLAVNTVQNKEGNCEKRLVITASQSLENKELCILRNDWCSVPVEPGDIIHLEGDCTSDTWIIDKDFGYLILYPDMLISGTSIASSIRCMRRAVLSETFRSSDPATRQMLIGTVLHEVFQKAINNSFAPEKLQELAFQTIQEIRHLKEMYRLNLSQDEIKQEVEDYLPSFCKWAGDFMHKNTSTDFPQMQLSLPSDNSKDNSTCNIEVVKPMDIEESIWSPRFGLKGKIDVTVGVKIHRGYKTKYKIMPLELKTGKESNSIEHRSQVVLYTLLSQERRADPEAGLLLYLKTGQMYPVPANHLDKRELLKLRNQMAFSLFHRISKSATRQKTQLASLPQIIEEEKTCKYCSQIGNCALYSRAVEQQMDCSSVPIVMLPKIEEETQHLKQTHLEYFSLWCLMLTLESQSKDNKKNHQNIWLMPASEMEKSGSCIGNLIRMEHVKIVCDGQYLHNFQCKHGAIPVTNLMAGDRVIVSGEERSLFALSRGYVKEINMTTVTCLLDRNLSVLPESTLFRLDQEEKNCDIDTPLGNLSKLMENTFVSKKLRDLIIDFREPQFISYLSSVLPHDAKDTVACILKGLNKPQRQAMKKVLLSKDYTLIVGMPGTGKTTTICTLVRILYACGFSVLLTSYTHSAVDNILLKLAKFKIGFLRLGQIQKVHPAIQQFTEQEICRSKSIKSLALLEELYNSQLIVATTCMGINHPIFSRKIFDFCIVDEASQISQPICLGPLFFSRRFVLVGDHQQLPPLVLNREARALGMSESLFKRLEQNKSAVVQLTVQYRMNSKIMSLSNKLTYEGKLECGSDKVANAVINLRHFKDVKLELEFYADYSDNPWLMGVFEPNNPVCFLNTDKVPAPEQVEKGGVSNVTEAKLIVFLTSIFVKAGCSPSDIGIIAPYRQQLKIINDLLARSIGMVEVNTVDKYQGRDKSIVLVSFVRSNKDGTVGELLKDWRRLNVAITRAKHKLILLGCVPSLNCYPPLEKLLNHLNSEKLIIDLPSREHESLCHILGDFQRE | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 14 | Phosphorylation | LELLMEKSFWEEAEL HHHHHHHCHHHHCCC | 28348404 | ||
| 28 | Ubiquitination | LPAELFQKKVVASFP CCHHHHHHHHHHCCC | 21963094 | ||
| 28 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 28 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 29 | Ubiquitination | PAELFQKKVVASFPR CHHHHHHHHHHCCCC | 22817900 | ||
| 31 | Ubiquitination | ELFQKKVVASFPRTV HHHHHHHHHCCCCEE | 22817900 | ||
| 33 | Phosphorylation | FQKKVVASFPRTVLS HHHHHHHCCCCEEEC | - | ||
| 34 | Ubiquitination | QKKVVASFPRTVLST HHHHHHCCCCEEECC | 21963094 | ||
| 58 | Ubiquitination | AVNTVQNKEGNCEKR EEEEEECCCCCCEEE | 21963094 | ||
| 59 | Ubiquitination | VNTVQNKEGNCEKRL EEEEECCCCCCEEEE | 22817900 | ||
| 64 | Ubiquitination | NKEGNCEKRLVITAS CCCCCCEEEEEEEEE | - | ||
| 77 | Ubiquitination | ASQSLENKELCILRN EEHHCCCCCEEEEEC | - | ||
| 114 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 127 | Ubiquitination | YPDMLISGTSIASSI CCCEEECCCHHHHHH | 27667366 | ||
| 129 | Ubiquitination | DMLISGTSIASSIRC CEEECCCHHHHHHHH | 21963094 | ||
| 143 | Ubiquitination | CMRRAVLSETFRSSD HHHHHHHHHHHHCCC | 23503661 | ||
| 167 | Ubiquitination | TVLHEVFQKAINNSF HHHHHHHHHHHHCCC | 22817900 | ||
| 170 | Ubiquitination | HEVFQKAINNSFAPE HHHHHHHHHCCCCHH | 21963094 | ||
| 178 | Ubiquitination | NNSFAPEKLQELAFQ HCCCCHHHHHHHHHH | 23503661 | ||
| 178 (in isoform 2) | Ubiquitination | - | - | ||
| 194 | Ubiquitination | IQEIRHLKEMYRLNL HHHHHHHHHHHHCCC | 29967540 | ||
| 197 | Phosphorylation | IRHLKEMYRLNLSQD HHHHHHHHHCCCCHH | 22210691 | ||
| 202 | Phosphorylation | EMYRLNLSQDEIKQE HHHHCCCCHHHHHHH | 25159151 | ||
| 207 | Ubiquitination | NLSQDEIKQEVEDYL CCCHHHHHHHHHHHH | 29967540 | ||
| 208 | Ubiquitination | LSQDEIKQEVEDYLP CCHHHHHHHHHHHHH | 23503661 | ||
| 219 | Ubiquitination | DYLPSFCKWAGDFMH HHHHHHHHHHHHHCC | 29967540 | ||
| 227 | Ubiquitination | WAGDFMHKNTSTDFP HHHHHCCCCCCCCCC | 29967540 | ||
| 257 | Ubiquitination | TCNIEVVKPMDIEES CCEEEEECCCCHHHH | 29967540 | ||
| 264 | Phosphorylation | KPMDIEESIWSPRFG CCCCHHHHCCCCCCC | - | ||
| 264 | Ubiquitination | KPMDIEESIWSPRFG CCCCHHHHCCCCCCC | 21890473 | ||
| 265 | Ubiquitination | PMDIEESIWSPRFGL CCCHHHHCCCCCCCC | 21963094 | ||
| 267 | Phosphorylation | DIEESIWSPRFGLKG CHHHHCCCCCCCCCC | 24719451 | ||
| 275 | Ubiquitination | PRFGLKGKIDVTVGV CCCCCCCEEEEEEEE | - | ||
| 279 | Ubiquitination | LKGKIDVTVGVKIHR CCCEEEEEEEEEEEC | 23503661 | ||
| 292 | Phosphorylation | HRGYKTKYKIMPLEL ECCCCCEEEEEEEEE | - | ||
| 293 | Ubiquitination | RGYKTKYKIMPLELK CCCCCEEEEEEEEEC | 29967540 | ||
| 300 | Ubiquitination | KIMPLELKTGKESNS EEEEEEECCCCCCCC | 29967540 | ||
| 300 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 300 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 303 | Ubiquitination | PLELKTGKESNSIEH EEEECCCCCCCCCHH | - | ||
| 303 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 303 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 307 | Phosphorylation | KTGKESNSIEHRSQV CCCCCCCCCHHHHHH | 24719451 | ||
| 320 | Ubiquitination | QVVLYTLLSQERRAD HHHHHHHHCCHHCCC | 21890473 | ||
| 320 | Ubiquitination | QVVLYTLLSQERRAD HHHHHHHHCCHHCCC | 21890473 | ||
| 321 | Phosphorylation | VVLYTLLSQERRADP HHHHHHHCCHHCCCC | - | ||
| 351 | Ubiquitination | VPANHLDKRELLKLR CCHHHCCHHHHHHHH | 27667366 | ||
| 351 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 351 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 377 | Ubiquitination | SKSATRQKTQLASLP CHHHCHHHHHHHCHH | 29967540 | ||
| 377 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 377 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 381 | Ubiquitination | TRQKTQLASLPQIIE CHHHHHHHCHHHHHH | 27667366 | ||
| 386 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 389 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 391 | Ubiquitination | PQIIEEEKTCKYCSQ HHHHHHHHHHHHHHH | 22817900 | ||
| 394 | Ubiquitination | IEEEKTCKYCSQIGN HHHHHHHHHHHHHHH | 21963094 | ||
| 395 | Phosphorylation | EEEKTCKYCSQIGNC HHHHHHHHHHHHHHH | 29496907 | ||
| 400 | Ubiquitination | CKYCSQIGNCALYSR HHHHHHHHHHHHHHH | 21890473 | ||
| 405 | Phosphorylation | QIGNCALYSRAVEQQ HHHHHHHHHHHHHHC | 29496907 | ||
| 406 | Phosphorylation | IGNCALYSRAVEQQM HHHHHHHHHHHHHCC | 24719451 | ||
| 421 | Ubiquitination | DCSSVPIVMLPKIEE CCCCCCEEEECCHHH | 22817900 | ||
| 424 | Ubiquitination | SVPIVMLPKIEEETQ CCCEEEECCHHHHHH | 21963094 | ||
| 425 | Ubiquitination | VPIVMLPKIEEETQH CCEEEECCHHHHHHH | - | ||
| 437 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 459 | Ubiquitination | SQSKDNKKNHQNIWL HCCCCCCCCCCCEEE | 29967540 | ||
| 463 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 474 | Ubiquitination | MPASEMEKSGSCIGN EEHHHHHCCCCCHHH | 29967540 | ||
| 489 | Ubiquitination | LIRMEHVKIVCDGQY HHCEEEEEEEECCCE | 21963094 | ||
| 503 | Ubiquitination | YLHNFQCKHGAIPVT EEEEEECCCCCEECC | 23503661 | ||
| 503 (in isoform 2) | Ubiquitination | - | - | ||
| 519 | Ubiquitination | LMAGDRVIVSGEERS CCCCCEEEECCCCHH | 21963094 | ||
| 533 | Ubiquitination | SLFALSRGYVKEINM HHHHHHCCCEEEECC | 23503661 | ||
| 536 | Ubiquitination | ALSRGYVKEINMTTV HHHCCCEEEECCEEE | - | ||
| 567 | Acetylation | FRLDQEEKNCDIDTP EECCHHHHCCCCCCC | 25953088 | ||
| 567 | Ubiquitination | FRLDQEEKNCDIDTP EECCHHHHCCCCCCC | 29967540 | ||
| 580 | Ubiquitination | TPLGNLSKLMENTFV CCCCHHHHHHHCCHH | 29967540 | ||
| 589 | Ubiquitination | MENTFVSKKLRDLII HHCCHHCHHHHHHHH | 29967540 | ||
| 590 | Ubiquitination | ENTFVSKKLRDLIID HCCHHCHHHHHHHHH | - | ||
| 608 | Ubiquitination | PQFISYLSSVLPHDA HHHHHHHHHCCCCCC | 21890473 | ||
| 614 | Ubiquitination | LSSVLPHDAKDTVAC HHHCCCCCCHHHHHH | 23000965 | ||
| 618 | Phosphorylation | LPHDAKDTVACILKG CCCCCHHHHHHHHCC | - | ||
| 624 | Acetylation | DTVACILKGLNKPQR HHHHHHHCCCCHHHH | 25953088 | ||
| 624 | Ubiquitination | DTVACILKGLNKPQR HHHHHHHCCCCHHHH | 21890473 | ||
| 624 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 624 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 628 | Ubiquitination | CILKGLNKPQRQAMK HHHCCCCHHHHHHHH | 29967540 | ||
| 641 | Ubiquitination | MKKVLLSKDYTLIVG HHHHHHCCCEEEEEE | - | ||
| 652 | Phosphorylation | LIVGMPGTGKTTTIC EEEECCCCCHHHHHH | - | ||
| 654 | Ubiquitination | VGMPGTGKTTTICTL EECCCCCHHHHHHHH | 21890473 | ||
| 666 | Phosphorylation | CTLVRILYACGFSVL HHHHHHHHHCCCHHH | - | ||
| 671 | Phosphorylation | ILYACGFSVLLTSYT HHHHCCCHHHHHCCC | - | ||
| 671 (in isoform 2) | Phosphorylation | - | 25159151 | ||
| 672 (in isoform 2) | Phosphorylation | - | 25159151 | ||
| 693 | Ubiquitination | LLKLAKFKIGFLRLG HHHHHHHCCCEEHHH | - | ||
| 704 | Ubiquitination | LRLGQIQKVHPAIQQ EHHHCCCHHCHHHHH | - | ||
| 710 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 730 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 744 | Ubiquitination | LIVATTCMGINHPIF HHEHHHCCCCCCHHH | 21890473 | ||
| 750 | Ubiquitination | CMGINHPIFSRKIFD CCCCCCHHHHCCCCC | 23000965 | ||
| 808 | Phosphorylation | RALGMSESLFKRLEQ HHCCCCHHHHHHHHH | 24719451 | ||
| 811 | Ubiquitination | GMSESLFKRLEQNKS CCCHHHHHHHHHCCC | - | ||
| 832 | Ubiquitination | VQYRMNSKIMSLSNK EEECCCCHHHHHCCC | - | ||
| 835 | Phosphorylation | RMNSKIMSLSNKLTY CCCCHHHHHCCCCEE | 23403867 | ||
| 839 | Ubiquitination | KIMSLSNKLTYEGKL HHHHHCCCCEECCEE | 29967540 | ||
| 845 | Ubiquitination | NKLTYEGKLECGSDK CCCEECCEECCCCHH | 33845483 | ||
| 852 | Ubiquitination | KLECGSDKVANAVIN EECCCCHHHHHEEEE | 29967540 | ||
| 908 | Ubiquitination | PAPEQVEKGGVSNVT CCHHHHHCCCCCCCC | 29967540 | ||
| 948 | Ubiquitination | APYRQQLKIINDLLA CCHHHHHHHHHHHHH | - | ||
| 968 | Ubiquitination | VEVNTVDKYQGRDKS EEEECCHHHCCCCCE | 21890473 | ||
| 974 | Ubiquitination | DKYQGRDKSIVLVSF HHHCCCCCEEEEEEE | 23000965 | ||
| 975 | Phosphorylation | KYQGRDKSIVLVSFV HHCCCCCEEEEEEEE | - | ||
| 984 | Phosphorylation | VLVSFVRSNKDGTVG EEEEEEECCCCCCHH | - | ||
| 989 | Phosphorylation | VRSNKDGTVGELLKD EECCCCCCHHHHHHH | - | ||
| 994 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 995 | Ubiquitination | GTVGELLKDWRRLNV CCHHHHHHHHHHHCH | 29967540 | ||
| 998 | Ubiquitination | GELLKDWRRLNVAIT HHHHHHHHHHCHHHH | 21890473 | ||
| 1004 | Ubiquitination | WRRLNVAITRAKHKL HHHHCHHHHHHCCCE | 23000965 | ||
| 1035 | Phosphorylation | KLLNHLNSEKLIIDL HHHHHCCCCCEEEEC | 26699800 | ||
| 1037 | Ubiquitination | LNHLNSEKLIIDLPS HHHCCCCCEEEECCC | 29967540 | ||
| 1044 | Phosphorylation | KLIIDLPSREHESLC CEEEECCCCCHHHHH | - | ||
| 1054 (in isoform 1) | Ubiquitination | - | 21890473 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
Oops, there are no upstream regulatory protein records of DNA2_HUMAN !! | ||||||
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of DNA2_HUMAN !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of DNA2_HUMAN !! | ||||||
| Interacting Protein | Gene Name | Interaction Type | PPI Reference | Domain-Domain Interactions |
|---|---|---|---|---|
| EP300_HUMAN | EP300 | physical | 20019387 | |
| FEN1_HUMAN | FEN1 | physical | 20019387 | |
| CTIP_HUMAN | RBBP8 | physical | 25909997 | |
| SMG7_HUMAN | SMG7 | physical | 28514442 | |
| WAC2A_HUMAN | FAM21A | physical | 28514442 | |
| NOB1_HUMAN | NOB1 | physical | 28514442 | |
| FAT4_HUMAN | FAT4 | physical | 28514442 | |
| BUB1_HUMAN | BUB1 | physical | 28514442 | |
| MMS19_HUMAN | MMS19 | physical | 28514442 | |
| SYTC2_HUMAN | TARSL2 | physical | 28514442 | |
| BORA_HUMAN | BORA | physical | 28514442 | |
| GSH0_HUMAN | GCLM | physical | 28514442 | |
| MSTO1_HUMAN | MSTO1 | physical | 28514442 | |
| HAUS7_HUMAN | HAUS7 | physical | 28514442 | |
| NRBP_HUMAN | NRBP1 | physical | 28514442 | |
| RAD51_HUMAN | RAD51 | physical | 28514442 | |
| CIAO1_HUMAN | CIAO1 | physical | 28514442 | |
| AKA11_HUMAN | AKAP11 | physical | 28514442 | |
| KAPCB_HUMAN | PRKACB | physical | 28514442 | |
| HMDH_HUMAN | HMGCR | physical | 28514442 | |
| FACD2_HUMAN | FANCD2 | physical | 22987153 | |
| EXO1_HUMAN | EXO1 | genetic | 22987153 |
| Kegg Drug | ||||||
|---|---|---|---|---|---|---|
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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