HMCES_XENTR
ID HMCES_XENTR Reviewed; 335 AA.
AC Q6P7N4; Q28G29;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Abasic site processing protein HMCES {ECO:0000250|UniProtKB:Q96FZ2};
DE AltName: Full=Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein;
DE Short=ES cell-specific 5hmC-binding protein {ECO:0000250|UniProtKB:Q96FZ2};
DE AltName: Full=Peptidase HMCES {ECO:0000250|UniProtKB:Q8R1M0};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q8R1M0};
DE AltName: Full=SRAP domain-containing protein 1 {ECO:0000250|UniProtKB:Q96FZ2};
GN Name=hmces {ECO:0000250|UniProtKB:Q96FZ2};
GN Synonyms=srapd1 {ECO:0000250|UniProtKB:Q96FZ2}; ORFNames=TGas027m07.1;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastrula;
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Sensor of abasic sites in single-stranded DNA (ssDNA)
CC required to preserve genome integrity by promoting error-free repair of
CC abasic sites. Acts as an enzyme that recognizes and binds abasic sites
CC in ssDNA at replication forks and chemically modifies the lesion by
CC forming a covalent cross-link with DNA: forms a stable thiazolidine
CC linkage between a ring-opened abasic site and the alpha-amino and
CC sulfhydryl substituents of its N-terminal catalytic cysteine residue.
CC The HMCES DNA-protein cross-link is then degraded by the proteasome.
CC Promotes error-free repair of abasic sites by acting as a 'suicide'
CC enzyme that is degraded, thereby protecting abasic sites from
CC translesion synthesis (TLS) polymerases and endonucleases that are
CC error-prone and would generate mutations and double-strand breaks. Has
CC preference for ssDNA, but can also accommodate double-stranded DNA with
CC 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (By similarity).
CC Acts as a protease: mediates autocatalytic processing of its N-terminal
CC methionine in order to expose the catalytic cysteine (By similarity).
CC {ECO:0000250|UniProtKB:Q8R1M0, ECO:0000250|UniProtKB:Q96FZ2}.
CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:Q96FZ2}.
CC Note=Recruited to chromatin following DNA damage. Localizes to
CC replication forks. {ECO:0000250|UniProtKB:Q96FZ2}.
CC -!- DOMAIN: Glu-129 is involved in sensing abasic sites in single-stranded
CC DNA (ssDNA). His-203 stabilizes the abasic sites by forming a hydrogen
CC bond with the O4' hydroxyl group. {ECO:0000250|UniProtKB:P76318}.
CC -!- SIMILARITY: Belongs to the SOS response-associated peptidase family.
CC {ECO:0000305}.
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DR EMBL; CR761600; CAJ81530.1; -; mRNA.
DR EMBL; BC061596; AAH61596.1; -; mRNA.
DR RefSeq; NP_989149.1; NM_203818.1.
DR RefSeq; XP_012816213.1; XM_012960759.2.
DR AlphaFoldDB; Q6P7N4; -.
DR SMR; Q6P7N4; -.
DR STRING; 8364.ENSXETP00000019823; -.
DR PaxDb; Q6P7N4; -.
DR DNASU; 394754; -.
DR GeneID; 394754; -.
DR KEGG; xtr:394754; -.
DR CTD; 56941; -.
DR Xenbase; XB-GENE-964491; hmces.
DR eggNOG; KOG2618; Eukaryota.
DR HOGENOM; CLU_035990_1_0_1; -.
DR InParanoid; Q6P7N4; -.
DR OrthoDB; 1487237at2759; -.
DR PhylomeDB; Q6P7N4; -.
DR Proteomes; UP000008143; Chromosome 4.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000024746; Expressed in egg cell and 14 other tissues.
DR GO; GO:0005657; C:replication fork; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0045830; P:positive regulation of isotype switching; ISS:UniProtKB.
DR GO; GO:0018142; P:protein-DNA covalent cross-linking; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.90.1680.10; -; 1.
DR InterPro; IPR003738; SRAP.
DR InterPro; IPR036590; SRAP-like.
DR PANTHER; PTHR13604; PTHR13604; 1.
DR Pfam; PF02586; SRAP; 1.
DR SUPFAM; SSF143081; SSF143081; 1.
PE 2: Evidence at transcript level;
KW Autocatalytic cleavage; Chromosome; Covalent protein-DNA linkage;
KW DNA damage; DNA-binding; Hydrolase; Protease; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8R1M0"
FT CHAIN 2..335
FT /note="Abasic site processing protein HMCES"
FT /id="PRO_0000164400"
FT REGION 24..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 284..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT SITE 129
FT /note="Required for sensing abasic sites"
FT /evidence="ECO:0000250|UniProtKB:P76318"
FT SITE 203
FT /note="Required to stabilize abasic sites"
FT /evidence="ECO:0000250|UniProtKB:P76318"
FT MOD_RES 2
FT /note="Thiazolidine linkage to a ring-opened DNA abasic
FT site"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
SQ SEQUENCE 335 AA; 38164 MW; 1AAF4816421F3247 CRC64;
MCGRTACTLA PDDVRKACTY RDKQGGRKWP NWRDGDSDKY QPSYNKSPQS NSPVLLSLKH
FQKDADSSER VLAAMRWGLI PSWFNEPDPS KMQYKTNNCR SDTMTEKALY KASLFKGKRC
VVLADGFYEW QRQNSEKQPY YIYFPQIKAE KSPAEQDITD WNGQRLLTMA GLFDCWEPPN
GGETLYSYTV ITVDSSKTMN WIHDRMPAIL DGDEAVRKWL DFGEVPTKDA LKLIHPIENI
TYHPVSTVVN NSRNNTPECM AAIILTQKKG PALSASSKKM LDWLQNKSPK KEESHSIQSP
KLSQFGAPPK KTSAGLMQQW LKKEDGEPSP KRAKK
