HMCES_PONAB
ID HMCES_PONAB Reviewed; 354 AA.
AC Q5NVR0;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 67.
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};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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 Also involved in class switch recombination (CSR) in B-cells
CC independently of the formation of a DNA-protein cross-link: acts by
CC binding and protecting ssDNA overhangs to promote DNA double-strand
CC break repair through the microhomology-mediated alternative-end-joining
CC (Alt-EJ) pathway. Acts as a protease: mediates autocatalytic processing
CC of its N-terminal methionine in order to expose the catalytic cysteine
CC (By similarity). {ECO:0000250|UniProtKB:Q8R1M0,
CC ECO:0000250|UniProtKB:Q96FZ2}.
CC -!- SUBUNIT: Interacts (via PIP-box motif) with PCNA.
CC {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-127 is involved in sensing abasic sites in single-stranded
CC DNA (ssDNA). His-210 stabilizes the abasic sites by forming a hydrogen
CC bond with the O4' hydroxyl group. {ECO:0000250|UniProtKB:P76318}.
CC -!- PTM: Ubiquitinated; the covalent HMCES DNA-protein cross-link is
CC ubiquitinated, leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q96FZ2}.
CC -!- SIMILARITY: Belongs to the SOS response-associated peptidase family.
CC {ECO:0000305}.
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DR EMBL; CR925946; CAI29603.1; -; mRNA.
DR RefSeq; NP_001127070.1; NM_001133598.1.
DR AlphaFoldDB; Q5NVR0; -.
DR SMR; Q5NVR0; -.
DR STRING; 9601.ENSPPYP00000015009; -.
DR GeneID; 100174100; -.
DR KEGG; pon:100174100; -.
DR CTD; 56941; -.
DR eggNOG; KOG2618; Eukaryota.
DR OrthoDB; 1487237at2759; -.
DR Proteomes; UP000001595; Unplaced.
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; Isopeptide bond; Phosphoprotein;
KW Protease; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8R1M0"
FT CHAIN 2..354
FT /note="Abasic site processing protein HMCES"
FT /id="PRO_0000164396"
FT REGION 292..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 332..338
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT COMPBIAS 293..307
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 308..324
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..354
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT SITE 127
FT /note="Required for sensing abasic sites"
FT /evidence="ECO:0000250|UniProtKB:P76318"
FT SITE 210
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"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT MOD_RES 322
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT CROSSLNK 148
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT CROSSLNK 151
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT CROSSLNK 276
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT CROSSLNK 306
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT CROSSLNK 339
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT CROSSLNK 342
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
SQ SEQUENCE 354 AA; 40513 MW; 24DFA6ADA32EFCD4 CRC64;
MCGRTSCHLP RDVLTRACAY QDRRGQQRLP EWRDPDKYCP SYNKSPQSNS PVLLSRLHFV
KDADSSERII APMRWGLVPS WFKESDPSKL QFNTTNCRND TIMEKRSFKV PLGKGRRCVV
LADGFYEWQR CQGTNQRQPY FIYFPQIKTE KSGSIGAADS PENWGKVWDN WRLLTMAGIF
DCWEPPEGGD VLYSYTIITV DSCKGLSDIH HRMPAILDGE EAVSKWLDFG KVSTQEALKL
IHPTENITFH AVSSVVNNSR NNTPECLAPV DLVVRKELKA SGSSQRMLQW LATKSPKKED
SKTPQKEESD VPQWSSQFLQ KSPLPTKRGT AGLLEQWLKR EKEEEPVAKR PYSQ
