INTS11
entrez
54973
canonical
uniprot
Q5TA45
canonical
ensembl
ENSG00000127054
resolver
ensp
ENSP00000404886
resolver
ensp
ENSP00000413493
resolver
ensp
ENSP00000444672
resolver
ensp
ENSP00000445001
resolver
ensp
ENSP00000481821
resolver
ensp
ENSP00000702473
resolver
enst
ENST00000620829
resolver
genesymbol
INTS11
resolver
genesymbol_syn
CPSF3L
resolver
genesymbol_syn
RC68
resolver
hgnc
HGNC:26052
resolver
uniprot
A0A087WYI0
resolver
uniprot
A8K5S2
resolver
uniprot
B3KPR3
resolver
uniprot
B4DM87
resolver
uniprot
G3V1S5
resolver
uniprot
Q5TA46
resolver
uniprot
Q5TA48
resolver
uniprot
Q5TA52
resolver
uniprot
Q5TA53
resolver
uniprot
Q5TA54
resolver
uniprot
Q7L3D7
resolver
uniprot
Q96HY1
resolver
uniprot
Q9BW36
resolver
uniprot
Q9H0F9
resolver
uniprot
Q9H8R5
resolver
uniprot
Q9HAA6
resolver
uniprot
Q9NWX9
resolver
uniprot_entry
A0A087WYI0_HUMAN
resolver
uniprot_entry
INT11_HUMAN
resolver
uniprot_sec
A8K5S2
resolver
uniprot_sec
B3KPR3
resolver
uniprot_sec
B4DM87
resolver
uniprot_sec
G3V1S5
resolver
uniprot_sec
Q5TA46
resolver
uniprot_sec
Q5TA48
resolver
uniprot_sec
Q5TA52
resolver
uniprot_sec
Q5TA53
resolver
uniprot_sec
Q5TA54
resolver
uniprot_sec
Q7L3D7
resolver
uniprot_sec
Q96HY1
resolver
uniprot_sec
Q9BW36
resolver
uniprot_sec
Q9H0F9
resolver
uniprot_sec
Q9H8R5
resolver
uniprot_sec
Q9HAA6
resolver
uniprot_sec
Q9NWX9
resolver
activity_regulation
ACTIVITY REGULATION: The RNA endonuclease activity is inhibited by BRAT1 that forms hydrogen bond and hydrophobic interactions with the active site. {ECO:0000269|PubMed:39032489, ECO:0000269|PubMed:39032490}.
uniprot
proteins
amino_acid_sequence
MPEIRVTPLGAGQDVGRSCILVSIAGKNVMLDCGMHMGFNDDRRFPDFSYITQNGRLTDFLDCVIISHFHLDHCGALPYFSEMVGYDGPIYMTHPTQAICPILLEDYRKIAVDKKGEANFFTSQMIKDCMKKVVAVHLHQTVQVDDELEIKAYYAGHVLGAAMFQIKVGSESVVYTGDYNMTPDRHLGAAWIDKCRPNLLITESTYATTIRDSKRCRERDFLKKVHETVERGGKVLIPVFALGRAQELCILLETFWERMNLKVPIYFSTGLTEKANHYYKLFIPWTNQKIRKTFVQRNMFEFKHIKAFDRAFADNPGPMVVFATPGMLHAGQSLQIFRKWAGNEKNMVIMPGYCVQGTVGHKILSGQRKLEMEGRQVLEVKMQVEYMSFSAHADAKGIMQLVGQAEPESVLLVHGEAKKMEFLKQKIEQELRVNCYMPANGETVTLPTSPSIPVGISLGLLKREMAQGLLPEAKKPRLLHGTLIMKDSNFRLVSSEQALKELGLAEHQLRFTCRVHLHDTRKEQETALRVYSHLKSVLKDHCVQHLPDGSVTVESVLLQAAAPSEDPGTKVLLVSWTYQDEELGSFLTSLLKKGLPQAPS
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities (NEDMLOB) [MIM:620428]: An autosomal recessive disorder apparent from infancy or early childhood, and characterized by global developmental delay, intellectual disability, motor and speech impairment, and brain abnormalities. Specifically, brain imaging shows progressive cortical atrophy, cortical gyral simplification, and delayed myelination affecting cerebrum and cerebellum. Ocular defects can include optic atrophy, nystagmus, strabismus, and retinal dystrophy. Disease severity is variable and some patients may die in childhood. {ECO:0000269|PubMed:37054711, ECO:0000269|PubMed:39032489}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.27.-
uniprot
proteins
function
FUNCTION: RNA endonuclease component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:16239144, PubMed:25201415, PubMed:28396433, PubMed:32697989, PubMed:33243860, PubMed:33548203, PubMed:34762484, PubMed:37080207, PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:32697989, PubMed:33243860, PubMed:33548203, PubMed:34762484, PubMed:37080207, PubMed:38570683). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144, PubMed:22252320, PubMed:26308897, PubMed:30737432). Within the integrator complex, INTS11 constitutes the RNA endonuclease subunit that degrades exiting nascent RNA transcripts (PubMed:28396433, PubMed:32697989, PubMed:33243860, PubMed:33548203, PubMed:34762484, PubMed:37080207, PubMed:38570683). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex (PubMed:23904267). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:22252320, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:25201415, ECO:0000269|PubMed:26308897, ECO:0000269|PubMed:28396433, ECO:0000269|PubMed:30737432, ECO:0000269|PubMed:32697989, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:33548203, ECO:0000269|PubMed:34762484, ECO:0000269|PubMed:37080207, ECO:0000269|PubMed:38570683}.
uniprot
proteins
mass_dalton
67663
uniprot
proteins
mutagenesis
MUTAGEN 38..43; /note="GFNDDR->EFNDDE: In GR2E mutant; abolished interaction with BRAT1."; /evidence="ECO:0000269|PubMed:36869814"; MUTAGEN 72..73; /note="DH->KA: Abolished RNA endonuclease activity."; /evidence="ECO:0000269|PubMed:38570683"; MUTAGEN 127..131; /note="KDCMK->ERCME: Abolished interaction with BRAT1."; /evidence="ECO:0000269|PubMed:36869814"; MUTAGEN 203; /note="E->Q: Abolished RNA endonuclease activity. Abolishes the ability of the Integrator complex to process U1 and U2 snRNA genes. Does not affect interaction with INTS9."; /evidence="ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:28396433, ECO:0000269|PubMed:32697989, ECO:0000269|PubMed:33548203"; MUTAGEN 210; /note="I->E: Decreased nuclear localization of BRAT1."; /evidence="ECO:0000269|PubMed:39032489"; MUTAGEN 381; /note="K->R: Abolished sumoylation, leading to impaired integrator complex integrity; when associated with R-462 and R-475."; /evidence="ECO:0000269|PubMed:36454007"; MUTAGEN 449..502; /note="Missing: In CTD1-delta mutant; decreased processing activity of the Integrator complex."; /evidence="ECO:0000269|PubMed:33548203"; MUTAGEN 462; /note="K->E: Decreased processing activity of the Integrator complex."; /evidence="ECO:0000269|PubMed:33548203"; MUTAGEN 462; /note="K->R: Abolished sumoylation, leading to impaired integrator complex integrity; when associated with R-381 and R-475."; /evidence="ECO:0000269|PubMed:36454007"; MUTAGEN 474..475; /note="KK->SS: Decreased localization in the nucleus."; /evidence="ECO:0000269|PubMed:39032489"; MUTAGEN 475; /note="K->R: Abolished sumoylation, leading to impaired integrator complex integrity; when associated with R-381 and R-462."; /evidence="ECO:0000269|PubMed:36454007"; MUTAGEN 503..600; /note="Missing: In CTD2-delta mutant; decreased processing activity of the Integrator complex."; /evidence="ECO:0000269|PubMed:33548203"; MUTAGEN 509..511; /note="LRF->ARA: Abolished interaction with INTS9."; /evidence="ECO:0000269|PubMed:28396433"; MUTAGEN 510..512; /note="RFT->PFP: Abolished interaction with INTS9."; /evidence="ECO:0000269|PubMed:28396433
uniprot
proteins
post_translational_modification
PTM: Sumoylated; sumoylation regulates its subcellular location and is required for integrator complex integrity. {ECO:0000269|PubMed:36454007}.
uniprot
proteins
protein_family
INTS11 subfamily
uniprot
proteins
protein_family
Metallo-beta-lactamase superfamily
uniprot
proteins
protein_family
RNA-metabolizing metallo-beta-lactamase-like family
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15684398
uniprot
proteins
pubmed
16239144
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22252320
uniprot
proteins
pubmed
23904267
uniprot
proteins
pubmed
25201415
uniprot
proteins
pubmed
26308897
uniprot
proteins
pubmed
28396433
uniprot
proteins
pubmed
29471365
uniprot
proteins
pubmed
30737432
uniprot
proteins
pubmed
32697989
uniprot
proteins
pubmed
33243860
uniprot
proteins
pubmed
33385327
uniprot
proteins
pubmed
33548203
uniprot
proteins
pubmed
33686175
uniprot
proteins
pubmed
34762484
uniprot
proteins
pubmed
36454007
uniprot
proteins
pubmed
36869814
uniprot
proteins
pubmed
37054711
uniprot
proteins
pubmed
37080207
uniprot
proteins
pubmed
38570683
uniprot
proteins
pubmed
39032489
uniprot
proteins
pubmed
39032490
uniprot
proteins
sequence_length
600
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15684398, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:29471365, ECO:0000269|PubMed:36454007, ECO:0000269|PubMed:39032489, ECO:0000269|PubMed:39032490}. Cytoplasm {ECO:0000269|PubMed:15684398, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:29471365, ECO:0000269|PubMed:36454007, ECO:0000269|PubMed:39032489}.
uniprot
proteins