HMCES
entrez
56941
canonical
uniprot
Q96FZ2
canonical
ensembl
ENSG00000183624
resolver
ensp
ENSP00000372955
resolver
ensp
ENSP00000374385
resolver
ensp
ENSP00000392966
resolver
ensp
ENSP00000423132
resolver
ensp
ENSP00000426215
resolver
ensp
ENSP00000527434
resolver
ensp
ENSP00000527436
resolver
ensp
ENSP00000527437
resolver
ensp
ENSP00000527438
resolver
ensp
ENSP00000527440
resolver
ensp
ENSP00000527441
resolver
ensp
ENSP00000527444
resolver
ensp
ENSP00000527446
resolver
ensp
ENSP00000527448
resolver
ensp
ENSP00000619887
resolver
enst
ENST00000383463
resolver
enst
ENST00000389735
resolver
enst
ENST00000417226
resolver
enst
ENST00000502878
resolver
enst
ENST00000857375
resolver
enst
ENST00000857377
resolver
enst
ENST00000857378
resolver
enst
ENST00000857379
resolver
enst
ENST00000857381
resolver
enst
ENST00000857382
resolver
enst
ENST00000857385
resolver
enst
ENST00000857387
resolver
enst
ENST00000857389
resolver
enst
ENST00000949828
resolver
genesymbol
HMCES
resolver
genesymbol_syn
C3orf37
resolver
genesymbol_syn
DC12
resolver
genesymbol_syn
SRAPD1
resolver
hgnc
HGNC:24446
resolver
uniprot
A6NJR9
resolver
uniprot
E7EMP6
resolver
uniprot
Q96G34
resolver
uniprot
Q9NRP3
resolver
uniprot_entry
E7EMP6_HUMAN
resolver
uniprot_entry
HMCES_HUMAN
resolver
uniprot_sec
A6NJR9
resolver
uniprot_sec
Q96G34
resolver
uniprot_sec
Q9NRP3
resolver
activity_regulation
ACTIVITY REGULATION: Formation and reversal of DNA-protein cross-link depends on DNA context (PubMed:37519246, PubMed:37950866). Catalyzes formation of the thiazolidine linkage in presence of abasic sites in single-stranded DNA (PubMed:30554877, PubMed:31235913). Mediates the reversal of the thiazolidine cross-link in presence of double stranded DNA (PubMed:37519246, PubMed:37950866). {ECO:0000269|PubMed:30554877, ECO:0000269|PubMed:31235913, ECO:0000269|PubMed:37519246, ECO:0000269|PubMed:37950866}.
uniprot
proteins
amino_acid_sequence
MCGRTSCHLPRDVLTRACAYQDRRGQQRLPEWRDPDKYCPSYNKSPQSNSPVLLSRLHFEKDADSSERIIAPMRWGLVPSWFKESDPSKLQFNTTNCRSDTVMEKRSFKVPLGKGRRCVVLADGFYEWQRCQGTNQRQPYFIYFPQIKTEKSGSIGAADSPENWEKVWDNWRLLTMAGIFDCWEPPEGGDVLYSYTIITVDSCKGLSDIHHRMPAILDGEEAVSKWLDFGEVSTQEALKLIHPTENITFHAVSSVVNNSRNNTPECLAPVDLVVKKELRASGSSQRMLQWLATKSPKKEDSKTPQKEESDVPQWSSQFLQKSPLPTKRGTAGLLEQWLKREKEEEPVAKRPYSQ
uniprot
proteins
ec_number
3.4.-.-
uniprot
proteins
ec_number
4.-.-.-
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q8R1M0, ECO:0000269|PubMed:30554877, ECO:0000269|PubMed:31235913, ECO:0000269|PubMed:31235915, ECO:0000269|PubMed:31806351, ECO:0000269|PubMed:32307824, ECO:0000269|PubMed:32492421, ECO:0000269|PubMed:35450882, ECO:0000269|PubMed:36608669, ECO:0000269|PubMed:37519246, ECO:0000269|PubMed:37950866}.
uniprot
proteins
mass_dalton
40575
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="C->A: Cells are hypersensitive to ionizing radiations. Abolished ability to form a covalent cross-link with DNA. Does not affect single-stranded DNA (ssDNA)-binding. Does not affect ability to promote class switch recombination (CSR) in B-cells."; /evidence="ECO:0000269|PubMed:30554877, ECO:0000269|PubMed:31806351"; MUTAGEN 4; /note="R->A: Strongly reduced binding to single-stranded DNA."; /evidence="ECO:0000269|PubMed:31235913"; MUTAGEN 81; /note="W->E: Strongly reduced binding to single-stranded DNA."; /evidence="ECO:0000269|PubMed:31235913"; MUTAGEN 98; /note="R->A: Cells are hypersensitive to ionizing radiations. Abolished ability to form a covalent cross-link with DNA. Abolished binding to single-stranded DNA (ssDNA)."; /evidence="ECO:0000269|PubMed:30554877"; MUTAGEN 127; /note="E->A: Abolished ability to mediate self-reversal of covalent cross-link with DNA in presence of double-stranded DNA."; /evidence="ECO:0000269|PubMed:37519246"; MUTAGEN 127; /note="E->Q: Abolished ability to mediate self-reversal of covalent cross-link with DNA in presence of double-stranded DNA."; /evidence="ECO:0000269|PubMed:37950866"; MUTAGEN 210; /note="H->A: Decreased ability to mediate self-reversal of covalent cross-link with DNA in presence of double-stranded DNA."; /evidence="ECO:0000269|PubMed:37519246"; MUTAGEN 212; /note="R->A: Abolished ability to bind DNA and abolished ability to promote class switch recombination (CSR) in B-cells."; /evidence="ECO:0000269|PubMed:31806351"; MUTAGEN 337..338; /note="WL->AA: Abolished interaction with PCNA. Cells are hypersensitive to ionizing radiations."; /evidence="ECO:0000269|PubMed:30554877
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated; the covalent HMCES DNA-protein cross-link is ubiquitinated, leading to its degradation by the proteasome. {ECO:0000269|PubMed:30554877}.
uniprot
proteins
protein_family
SOS response-associated peptidase family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23945014
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
30554877
uniprot
proteins
pubmed
31235913
uniprot
proteins
pubmed
31235915
uniprot
proteins
pubmed
31806351
uniprot
proteins
pubmed
32307824
uniprot
proteins
pubmed
32492421
uniprot
proteins
pubmed
35450882
uniprot
proteins
pubmed
36608669
uniprot
proteins
pubmed
37519246
uniprot
proteins
pubmed
37950866
uniprot
proteins
sequence_length
354
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:30554877}. Note=Recruited to chromatin following DNA damage (PubMed:30554877). Localizes to replication forks (PubMed:30554877). {ECO:0000269|PubMed:30554877}.
uniprot
proteins