DCLRE1B
entrez
64858
canonical
uniprot
Q9H816
canonical
ensembl
ENSG00000118655
resolver
ensp
ENSP00000498042
resolver
ensp
ENSP00000640575
resolver
enst
ENST00000650450
resolver
enst
ENST00000970516
resolver
genesymbol
DCLRE1B
resolver
genesymbol_syn
SNM1B
resolver
hgnc
HGNC:17641
resolver
uniprot
Q9H9E5
resolver
uniprot_entry
DCR1B_HUMAN
resolver
uniprot_sec
Q9H9E5
resolver
activity_regulation
ACTIVITY REGULATION: Beta-lactamase activity is inhibited by sulbactam. {ECO:0000269|PubMed:31434986}.
uniprot
proteins
amino_acid_sequence
MNGVLIPHTPIAVDFWSLRRAGTARLFFLSHMHSDHTVGLSSTWARPLYCSPITAHLLHRHLQVSKQWIQALEVGESHVLPLDEIGQETMTVTLLDANHCPGSVMFLFEGYFGTILYTGDFRYTPSMLKEPALTLGKQIHTLYLDNTNCNPALVLPSRQEAAHQIVQLIRKHPQHNIKIGLYSLGKESLLEQLALEFQTWVVLSPRRLELVQLLGLADVFTVEEKAGRIHAVDHMEICHSNMLRWNQTHPTIAILPTSRKIHSSHPDIHVIPYSDHSSYSELRAFVAALKPCQVVPIVSRRPCGGFQDSLSPRISVPLIPDSVQQYMSSSSRKPSLLWLLERRLKRPRTQGVVFESPEESADQSQADRDSKKAKKEKLSPWPADLEKQPSHHPLRIKKQLFPDLYSKEWNKAVPFCESQKRVTMLTAPLGFSVHLRSTDEEFISQKTREEIGLGSPLVPMGDDDGGPEATGNQSAWMGHGSPLSHSSKGTPLLATEFRGLALKYLLTPVNFFQAGYSSRRFDQQVEKYHKPC
uniprot
proteins
disease_involvement
DISEASE: Dyskeratosis congenita, autosomal recessive, 8 (DKCB8) [MIM:620133]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. Additional DKCB8 features include microcephaly, intrauterine growth retardation, and developmental anomalies in some patients. DKCB8 patients exhibit normal global telemore length, although there is evidence of telomere instability. {ECO:0000269|PubMed:20479256, ECO:0000269|PubMed:35007328}. Note=The disease is caused by variants affecting the gene represented in this entry. In addition to missense and stop-gain variants, an aberrant splice variant of DCLRE1B, designated Apollo-Delta, has been found in a patient with severe dyskeratosis congenita and features of Hoyeraal-Hreidarsson syndrome (PubMed:20479256). Apollo-Delta hampers the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence, but maintains its DNA interstrand cross-link repair function in the whole genome. {ECO:0000269|PubMed:20479256}.
uniprot
proteins
ec_number
3.1.-.-
uniprot
proteins
ec_number
3.5.2.6
uniprot
proteins
function
FUNCTION: 5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint. Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin (PubMed:31434986). Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem) (PubMed:31434986). {ECO:0000269|PubMed:15467758, ECO:0000269|PubMed:15572677, ECO:0000269|PubMed:16730175, ECO:0000269|PubMed:16730176, ECO:0000269|PubMed:18468965, ECO:0000269|PubMed:18469862, ECO:0000269|PubMed:19197158, ECO:0000269|PubMed:19411856, ECO:0000269|PubMed:20655466, ECO:0000269|PubMed:31434986}.
uniprot
proteins
mass_dalton
60002
uniprot
proteins
mutagenesis
MUTAGEN 14; /note="D->N: In Apm3; abolishes exonuclease activity and function on telomere maintenance. Impairs interaction with SPAG5."; /evidence="ECO:0000269|PubMed:19197158, ECO:0000269|PubMed:20655466"; MUTAGEN 33; /note="H->A: In Apm1; abolishes exonuclease activity and function on telomere maintenance; when associated with N-35."; /evidence="ECO:0000269|PubMed:20655466"; MUTAGEN 35; /note="D->N: In Apm2; abolishes exonuclease activity and function on telomere maintenance. In Apm1; abolishes exonuclease activity and function on telomere maintenance; when associated with A-33."; /evidence="ECO:0000269|PubMed:20655466"; MUTAGEN 276; /note="H->A: Slightly affects interaction with SPAG5."; /evidence="ECO:0000269|PubMed:19197158"; MUTAGEN 504; /note="Y->A: Abolishes interaction with TERF2."; /evidence="ECO:0000269|PubMed:18202258"; MUTAGEN 506; /note="L->A: Abolishes interaction with TERF2."; /evidence="ECO:0000269|PubMed:18202258"; MUTAGEN 508; /note="P->A: Abolishes interaction with TERF2."; /evidence="ECO:0000269|PubMed:18202258
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated, leading to its degradation. Interaction with TERF2 protects it from ubiquitination. {ECO:0000269|PubMed:18593705}.
uniprot
proteins
protein_family
DNA repair metallo-beta-lactamase (DRMBL) family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15467758
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15572677
uniprot
proteins
pubmed
16606622
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16730175
uniprot
proteins
pubmed
16730176
uniprot
proteins
pubmed
18202258
uniprot
proteins
pubmed
18468965
uniprot
proteins
pubmed
18469862
uniprot
proteins
pubmed
18593705
uniprot
proteins
pubmed
19197158
uniprot
proteins
pubmed
19411856
uniprot
proteins
pubmed
20479256
uniprot
proteins
pubmed
20655466
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
31434986
uniprot
proteins
pubmed
35007328
uniprot
proteins
sequence_length
532
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Chromosome, telomere. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Mainly localizes to telomeres, recruited via its interaction with TERF2. During mitosis, localizes to the centrosome.
uniprot
proteins