Search Results

Overview

Uniprot IDQ9Y3Z3
Protein NameDeoxynucleoside triphosphate triphosphohydrolase SAMHD1
Gene NameSAMHD1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
11 ADSEQPSKRPRCDDS
534 NRAIRITKNQVSQLL
560 YCKKVDRKSLYAARQ
596 PLITPQKKEWNDSTS
622 KSRVQLFKDDPM***

Function

Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:22056990, PubMed:23601106, PubMed:23602554, PubMed:24336198, PubMed:26294762, PubMed:26431200, PubMed:28229507, PubMed:28834754, PubMed:29670289). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:22056990, PubMed:23364794, PubMed:23601106, PubMed:23602554, PubMed:24336198, PubMed:25038827, PubMed:26101257, PubMed:26294762, PubMed:26431200, PubMed:28229507). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:24035396, PubMed:24217394, PubMed:29610582). Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (PubMed:21613998, PubMed:21720370). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (PubMed:23858451). Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks (PubMed:23601106, PubMed:23602554, PubMed:29610582, PubMed:29670289). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication (PubMed:29670289). Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (PubMed:27477283, PubMed:29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:29670289). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity)

Protein Sequence

10 MQRADSEQPS 20 KRPRCDDSPR 30 TPSNTPSAEA 40 DWSPGLELHP 50 DYKTWGPEQV 60 CSFLRRGGFE 70 EPVLLKNIRE 80 NEITGALLPC 90 LDESRFENLG 100 VSSLGERKKL 110 LSYIQRLVQI 120 HVDTMKVIND 130 PIHGHIELHP 140 LLVRIIDTPQ 150 FQRLRYIKQL 160 GGGYYVFPGA 170 SHNRFEHSLG 180 VGYLAGCLVH 190 ALGEKQPELQ 200 ISERDVLCVQ 210 IAGLCHDLGH 220 GPFSHMFDGR 230 FIPLARPEVK 240 WTHEQGSVMM 250 FEHLINSNGI 260 KPVMEQYGLI 270 PEEDICFIKE 280 QIVGPLESPV 290 EDSLWPYKGR 300 PENKSFLYEI 310 VSNKRNGIDV 320 DKWDYFARDC 330 HHLGIQNNFD 340 YKRFIKFARV 350 CEVDNELRIC 360 ARDKEVGNLY 370 DMFHTRNSLH 380 RRAYQHKVGN 390 IIDTMITDAF 400 LKADDYIEIT 410 GAGGKKYRIS 420 TAIDDMEAYT 430 KLTDNIFLEI 440 LYSTDPKLKD 450 AREILKQIEY 460 RNLFKYVGET 470 QPTGQIKIKR 480 EDYESLPKEV 490 ASAKPKVLLD 500 VKLKAEDFIV 510 DVINMDYGMQ 520 EKNPIDHVSF 530 YCKTAPNRAI 540 RITKNQVSQL 550 LPEKFAEQLI 560 RVYCKKVDRK 570 SLYAARQYFV 580 QWCADRNFTK 590 PQDGDVIAPL 600 ITPQKKEWND 610 STSVQNPTRL 620 REASKSRVQL FKDDPM

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0035861 site of double-strand break
Cellular Component GO:0097197 tetraspanin-enriched microdomain
Molecular Function GO:0106375 deoxynucleoside triphosphate hydrolase activity
Molecular Function GO:0032567 dGTP binding
Molecular Function GO:0008832 dGTPase activity
Molecular Function GO:0005525 GTP binding
Molecular Function GO:0003676 nucleic acid binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0004540 RNA nuclease activity
Molecular Function GO:0003697 single-stranded DNA binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0046061 dATP catabolic process
Biological Process GO:0051607 defense response to virus
Biological Process GO:0009264 deoxyribonucleotide catabolic process
Biological Process GO:0006203 dGTP catabolic process
Biological Process GO:0006974 DNA damage response
Biological Process GO:0110025 DNA strand resection involved in replication fork processing
Biological Process GO:0000724 double-strand break repair via homologous recombination
Biological Process GO:0006955 immune response
Biological Process GO:0045087 innate immune response
Biological Process GO:0060339 negative regulation of type I interferon-mediated signaling pathway
Biological Process GO:0051289 protein homotetramerization
Biological Process GO:0045088 regulation of innate immune response
Biological Process GO:0016446 somatic hypermutation of immunoglobulin genes

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[4] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[5] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[6] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[7] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.