UniProtKB - Q96FZ2 (HMCES_HUMAN)
Protein
Abasic site processing protein HMCES
Gene
HMCES
Organism
Homo sapiens (Human)
Status
Functioni
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:31235915, PubMed:31235913). 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). The HMCES DNA-protein cross-link is then degraded by the proteasome (PubMed:30554877). Promotes error-free repair of abasic sites by acting as a 'suicide' enzyme that is degraded, thereby protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks (PubMed:30554877). 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). 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).By similarity4 Publications
Caution
Was initially reported to specifically bind 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells (By similarity). It was later suggested to act as an endonuclease that specifically cleaves 5hmC-containing DNA (By similarity). However, the endonuclease activity on 5hmC-containing DNA could not be confirmed by another report (PubMed:30554877).By similarity1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 2 | Nucleophile1 Publication1 Publication | 1 | |
Sitei | 127 | Required for sensing abasic sitesBy similarity | 1 | |
Sitei | 210 | Required to stabilize abasic sitesBy similarity | 1 |
GO - Molecular functioni
- peptidase activity Source: UniProtKB-KW
- single-stranded DNA binding Source: UniProtKB
GO - Biological processi
- cellular response to DNA damage stimulus Source: UniProtKB
- double-strand break repair via alternative nonhomologous end joining Source: Ensembl
- positive regulation of isotype switching Source: UniProtKB
- protein-DNA covalent cross-linking Source: UniProtKB
Keywordsi
Molecular function | DNA-binding, Hydrolase, Protease |
Biological process | DNA damage |
Enzyme and pathway databases
PathwayCommonsi | Q96FZ2 |
Names & Taxonomyi
Protein namesi | Recommended name: Abasic site processing protein HMCESCuratedAlternative name(s): Embryonic stem cell-specific 5-hydroxymethylcytosine-binding proteinImported Short name: ES cell-specific 5hmC-binding proteinImported Peptidase HMCESCurated (EC:3.4.-.-By similarity) SRAP domain-containing protein 1By similarity |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:24446, HMCES |
MIMi | 618288, gene |
neXtProti | NX_Q96FZ2 |
VEuPathDBi | HostDB:ENSG00000183624.13 |
Subcellular locationi
Other locations
- Chromosome 1 Publication
Note: Recruited to chromatin following DNA damage (PubMed:30554877). Localizes to replication forks (PubMed:30554877).1 Publication
Other locations
- replication fork Source: UniProtKB
Keywords - Cellular componenti
ChromosomePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2 | 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. 2 Publications | 1 | |
Mutagenesisi | 4 | R → A: Strongly reduced binding to single-stranded DNA. 1 Publication | 1 | |
Mutagenesisi | 81 | W → E: Strongly reduced binding to single-stranded DNA. 1 Publication | 1 | |
Mutagenesisi | 98 | 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). 1 Publication | 1 | |
Mutagenesisi | 212 | R → A: Abolished ability to bind DNA and abolished ability to promote class switch recombination (CSR) in B-cells. 1 Publication | 1 | |
Mutagenesisi | 337 – 338 | WL → AA: Abolished interaction with PCNA. Cells are hypersensitive to ionizing radiations. 1 Publication | 2 |
Organism-specific databases
DisGeNETi | 56941 |
OpenTargetsi | ENSG00000183624 |
PharmGKBi | PA142672398 |
Miscellaneous databases
Pharosi | Q96FZ2, Tbio |
Genetic variation databases
BioMutai | HMCES |
DMDMi | 74731769 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000164394 | 2 – 354 | Abasic site processing protein HMCESAdd BLAST | 353 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | Thiazolidine linkage to a ring-opened DNA abasic site1 Publication | 1 | |
Cross-linki | 148 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 151 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 160 | PhosphoserineCombined sources | 1 | |
Cross-linki | 275 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 276 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 295 | PhosphoserineCombined sources | 1 | |
Cross-linki | 306 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 322 | PhosphoserineCombined sources | 1 | |
Cross-linki | 339 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 342 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources |
Post-translational modificationi
Ubiquitinated; the covalent HMCES DNA-protein cross-link is ubiquitinated, leading to its degradation by the proteasome.1 Publication
Keywords - PTMi
Autocatalytic cleavage, Covalent protein-DNA linkage, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q96FZ2 |
jPOSTi | Q96FZ2 |
MassIVEi | Q96FZ2 |
MaxQBi | Q96FZ2 |
PaxDbi | Q96FZ2 |
PeptideAtlasi | Q96FZ2 |
PRIDEi | Q96FZ2 |
ProteomicsDBi | 76573 |
PTM databases
iPTMneti | Q96FZ2 |
PhosphoSitePlusi | Q96FZ2 |
SwissPalmi | Q96FZ2 |
Expressioni
Developmental stagei
Expressed at higher level in S-phase than in quiescent cells.1 Publication
Gene expression databases
Bgeei | ENSG00000183624, Expressed in tonsil and 234 other tissues |
ExpressionAtlasi | Q96FZ2, baseline and differential |
Genevisiblei | Q96FZ2, HS |
Organism-specific databases
HPAi | ENSG00000183624, Low tissue specificity |
Interactioni
Subunit structurei
Interacts (via PIP-box motif) with PCNA.
1 PublicationProtein-protein interaction databases
BioGRIDi | 121265, 27 interactors |
IntActi | Q96FZ2, 19 interactors |
STRINGi | 9606.ENSP00000372955 |
Miscellaneous databases
RNActi | Q96FZ2, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96FZ2 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 332 – 338 | PIP-box1 Publication | 7 |
Domaini
Glu-127 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-210 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group.By similarity
Sequence similaritiesi
Belongs to the SOS response-associated peptidase family.Curated
Phylogenomic databases
eggNOGi | KOG2618, Eukaryota |
GeneTreei | ENSGT00390000018439 |
InParanoidi | Q96FZ2 |
OMAi | HEKPSYR |
OrthoDBi | 1487237at2759 |
PhylomeDBi | Q96FZ2 |
TreeFami | TF324343 |
Family and domain databases
Gene3Di | 3.90.1680.10, 1 hit |
InterProi | View protein in InterPro IPR003738, SRAP IPR036590, SRAP-like |
PANTHERi | PTHR13604, PTHR13604, 1 hit |
Pfami | View protein in Pfam PF02586, SRAP, 1 hit |
SUPFAMi | SSF143081, SSF143081, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All
Q96FZ2-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MCGRTSCHLP RDVLTRACAY QDRRGQQRLP EWRDPDKYCP SYNKSPQSNS
60 70 80 90 100
PVLLSRLHFE KDADSSERII APMRWGLVPS WFKESDPSKL QFNTTNCRSD
110 120 130 140 150
TVMEKRSFKV PLGKGRRCVV LADGFYEWQR CQGTNQRQPY FIYFPQIKTE
160 170 180 190 200
KSGSIGAADS PENWEKVWDN WRLLTMAGIF DCWEPPEGGD VLYSYTIITV
210 220 230 240 250
DSCKGLSDIH HRMPAILDGE EAVSKWLDFG EVSTQEALKL IHPTENITFH
260 270 280 290 300
AVSSVVNNSR NNTPECLAPV DLVVKKELRA SGSSQRMLQW LATKSPKKED
310 320 330 340 350
SKTPQKEESD VPQWSSQFLQ KSPLPTKRGT AGLLEQWLKR EKEEEPVAKR
PYSQ
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE7EMP6 | E7EMP6_HUMAN | Abasic site processing protein HMCE... | HMCES | 312 | Annotation score: | ||
D6R9T3 | D6R9T3_HUMAN | Abasic site processing protein HMCE... | HMCES | 282 | Annotation score: | ||
D6RAI0 | D6RAI0_HUMAN | Abasic site processing protein HMCE... | HMCES | 140 | Annotation score: | ||
D6RAZ3 | D6RAZ3_HUMAN | Abasic site processing protein HMCE... | HMCES | 233 | Annotation score: | ||
D6RGK7 | D6RGK7_HUMAN | Abasic site processing protein HMCE... | HMCES | 183 | Annotation score: |
Sequence cautioni
The sequence AAF86870 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 60 | E → D in AAH09993 (PubMed:15489334).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF201934 mRNA Translation: AAF86870.1 Frameshift. AC137695 Genomic DNA No translation available. CH471052 Genomic DNA Translation: EAW79266.1 BC009993 mRNA Translation: AAH09993.1 BC010125 mRNA Translation: AAH10125.1 BC050686 mRNA Translation: AAH50686.1 BC088363 mRNA Translation: AAH88363.1 |
CCDSi | CCDS33852.1 |
RefSeqi | NP_001006109.1, NM_001006109.1 NP_064572.2, NM_020187.2 XP_005247693.1, XM_005247636.3 XP_016862366.1, XM_017006877.1 |
Genome annotation databases
Ensembli | ENST00000383463; ENSP00000372955; ENSG00000183624 ENST00000389735; ENSP00000374385; ENSG00000183624 ENST00000502878; ENSP00000426215; ENSG00000183624 |
GeneIDi | 56941 |
KEGGi | hsa:56941 |
UCSCi | uc003elt.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Protein Spotlight Integrity - Issue 226 of June 2020 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF201934 mRNA Translation: AAF86870.1 Frameshift. AC137695 Genomic DNA No translation available. CH471052 Genomic DNA Translation: EAW79266.1 BC009993 mRNA Translation: AAH09993.1 BC010125 mRNA Translation: AAH10125.1 BC050686 mRNA Translation: AAH50686.1 BC088363 mRNA Translation: AAH88363.1 |
CCDSi | CCDS33852.1 |
RefSeqi | NP_001006109.1, NM_001006109.1 NP_064572.2, NM_020187.2 XP_005247693.1, XM_005247636.3 XP_016862366.1, XM_017006877.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5KO9 | X-ray | 1.50 | A | 1-270 | [»] | |
6OE7 | X-ray | 2.20 | A | 2-270 | [»] | |
6OEA | X-ray | 2.10 | A | 2-270 | [»] | |
6OEB | X-ray | 2.10 | A | 2-270 | [»] | |
6OOV | X-ray | 2.20 | A/B | 2-270 | [»] | |
SMRi | Q96FZ2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121265, 27 interactors |
IntActi | Q96FZ2, 19 interactors |
STRINGi | 9606.ENSP00000372955 |
PTM databases
iPTMneti | Q96FZ2 |
PhosphoSitePlusi | Q96FZ2 |
SwissPalmi | Q96FZ2 |
Genetic variation databases
BioMutai | HMCES |
DMDMi | 74731769 |
Proteomic databases
EPDi | Q96FZ2 |
jPOSTi | Q96FZ2 |
MassIVEi | Q96FZ2 |
MaxQBi | Q96FZ2 |
PaxDbi | Q96FZ2 |
PeptideAtlasi | Q96FZ2 |
PRIDEi | Q96FZ2 |
ProteomicsDBi | 76573 |
Protocols and materials databases
Antibodypediai | 55718, 135 antibodies |
DNASUi | 56941 |
Genome annotation databases
Ensembli | ENST00000383463; ENSP00000372955; ENSG00000183624 ENST00000389735; ENSP00000374385; ENSG00000183624 ENST00000502878; ENSP00000426215; ENSG00000183624 |
GeneIDi | 56941 |
KEGGi | hsa:56941 |
UCSCi | uc003elt.4, human |
Organism-specific databases
CTDi | 56941 |
DisGeNETi | 56941 |
GeneCardsi | HMCES |
HGNCi | HGNC:24446, HMCES |
HPAi | ENSG00000183624, Low tissue specificity |
MIMi | 618288, gene |
neXtProti | NX_Q96FZ2 |
OpenTargetsi | ENSG00000183624 |
PharmGKBi | PA142672398 |
VEuPathDBi | HostDB:ENSG00000183624.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2618, Eukaryota |
GeneTreei | ENSGT00390000018439 |
InParanoidi | Q96FZ2 |
OMAi | HEKPSYR |
OrthoDBi | 1487237at2759 |
PhylomeDBi | Q96FZ2 |
TreeFami | TF324343 |
Enzyme and pathway databases
PathwayCommonsi | Q96FZ2 |
Miscellaneous databases
BioGRID-ORCSi | 56941, 14 hits in 862 CRISPR screens |
ChiTaRSi | HMCES, human |
GenomeRNAii | 56941 |
Pharosi | Q96FZ2, Tbio |
PROi | PR:Q96FZ2 |
RNActi | Q96FZ2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000183624, Expressed in tonsil and 234 other tissues |
ExpressionAtlasi | Q96FZ2, baseline and differential |
Genevisiblei | Q96FZ2, HS |
Family and domain databases
Gene3Di | 3.90.1680.10, 1 hit |
InterProi | View protein in InterPro IPR003738, SRAP IPR036590, SRAP-like |
PANTHERi | PTHR13604, PTHR13604, 1 hit |
Pfami | View protein in Pfam PF02586, SRAP, 1 hit |
SUPFAMi | SSF143081, SSF143081, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HMCES_HUMAN | |
Accessioni | Q96FZ2Primary (citable) accession number: Q96FZ2 Secondary accession number(s): A6NJR9, Q96G34, Q9NRP3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 24, 2006 |
Last sequence update: | December 1, 2001 | |
Last modified: | February 10, 2021 | |
This is version 133 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries