Overview
| Uniprot ID | Q96FZ2 |
|---|
| Protein Name | Abasic site processing protein HMCES |
|---|
| Gene Name | HMCES |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 89 |
FKESDPSKLQFNTTN |
Function
Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites (PubMed:30554877, PubMed:31235913, PubMed:31235915, PubMed:32307824, PubMed:32492421). Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue (PubMed:30554877, PubMed:31235913). Promotes error-free repair by protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks (PubMed:30554877). The HMCES DNA-protein cross-link is then either reversed or degraded (PubMed:30554877, PubMed:36608669, PubMed:37519246, PubMed:37950866). HMCES is able to catalyze the reversal of its thiazolidine cross-link and cycle between a cross-link and a non-cross-linked state depending on DNA context: mediates self-reversal of the thiazolidine cross-link in double stranded DNA, allowing APEX1 to initiate downstream repair of abasic sites (PubMed:37519246, PubMed:37950866). The HMCES DNA-protein cross-link can also be degraded by the SPRTN metalloprotease following unfolding by the BRIP1/FANCJ helicase (PubMed:36608669). Has preference for ssDNA, but can also accommodate double-stranded DNA with 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (PubMed:31235915, PubMed:31806351). Plays a protective role during somatic hypermutation of immunoglobulin genes in B-cells: acts via its ability to form covalent cross-links with abasic sites, thereby limiting the accumulation of deletions in somatic hypermutation target regions (PubMed:35450882). Also involved in class switch recombination (CSR) in B-cells independently of the formation of a DNA-protein cross-link: acts by binding and protecting ssDNA overhangs to promote DNA double-strand break repair through the microhomology-mediated alternative-end-joining (Alt-EJ) pathway (By similarity). Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine (By similarity)
Protein Sequence
10
MCGRTSCHLP
20
RDVLTRACAY
30
QDRRGQQRLP
40
EWRDPDKYCP
50
SYNKSPQSNS
60
PVLLSRLHFE
70
KDADSSERII
80
APMRWGLVPS
90
WFKESDPSKL
100
QFNTTNCRSD
110
TVMEKRSFKV
120
PLGKGRRCVV
130
LADGFYEWQR
140
CQGTNQRQPY
150
FIYFPQIKTE
160
KSGSIGAADS
170
PENWEKVWDN
180
WRLLTMAGIF
190
DCWEPPEGGD
200
VLYSYTIITV
210
DSCKGLSDIH
220
HRMPAILDGE
230
EAVSKWLDFG
240
EVSTQEALKL
250
IHPTENITFH
260
AVSSVVNNSR
270
NNTPECLAPV
280
DLVVKKELRA
290
SGSSQRMLQW
300
LATKSPKKED
310
SKTPQKEESD
320
VPQWSSQFLQ
330
KSPLPTKRGT
340
AGLLEQWLKR
350
EKEEEPVAKR
PYSQ
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005657 |
replication fork |
| Molecular Function |
GO:0140431 |
DNA-(abasic site) binding |
| Molecular Function |
GO:0008233 |
peptidase activity |
| Molecular Function |
GO:0160129 |
protein-DNA covalent cross-linking activity |
| Molecular Function |
GO:0003697 |
single-stranded DNA binding |
| Biological Process |
GO:0006974 |
DNA damage response |
| Biological Process |
GO:0097681 |
double-strand break repair via alternative nonhomologous end joining |
| Biological Process |
GO:0036297 |
interstrand cross-link repair |
| Biological Process |
GO:0045830 |
positive regulation of isotype switching |
| Biological Process |
GO:0106300 |
protein-DNA covalent cross-linking repair |
| Biological Process |
GO:0006508 |
proteolysis |
| Biological Process |
GO:0016446 |
somatic hypermutation of immunoglobulin genes |
Reference
[1] 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.