UniProt functional annotation for Q99459



	UniProt functional annotation for Q99459

UniProt code: Q99459.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:20176811, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) (PubMed:20176811). {ECO:0000269|PubMed:10570151, ECO:0000269|PubMed:11082045, ECO:0000269|PubMed:11101529, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12927788, ECO:0000269|PubMed:18583928, ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:9038199, ECO:0000269|PubMed:9468527, ECO:0000269|PubMed:9632794}.

Subunit: Homodimer. Interacts with DAPK3 (By similarity). Component of the precatalytic, catalytic and postcatalytic spliceosome complexes (PubMed:11991638, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Part of a spliceosomal 'core' complex consisting of CDC5L, PLRG1, SPF27, CCAP1, CCAP3 and CCAP6. Interacts with PLRG1, Lodestar/TTF2, and NIPP1/PPP1R8. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts (via its C-terminus) directly in the complex with PRPF19 and BCAS2. Interacts (via its C-terminus) directly with PRGL1 (via its WD40 repeat domain); the interaction is required for mRNA splicing but not for spliceosome assembly. Also interacts with CTNNBL1. Interacts with PRPF19 (via N-terminus) (By similarity). {ECO:0000250|UniProtKB:O08837, ECO:0000269|PubMed:10827081, ECO:0000269|PubMed:11082045, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12927788, ECO:0000269|PubMed:18583928, ECO:0000269|PubMed:18722174, ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:21385873, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453}.

Subcellular location: Nucleus {ECO:0000269|PubMed:10570151, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:18583928, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:9038199, ECO:0000269|PubMed:9598309}. Nucleus speckle {ECO:0000269|PubMed:10570151, ECO:0000269|PubMed:10827081, ECO:0000269|PubMed:11544257}. Cytoplasm {ECO:0000269|PubMed:9038199}. Note=May shuttle between cytoplasm and nucleus. {ECO:0000269|PubMed:9038199}.

Tissue specificity: Ubiquitously expressed in both fetal and adult tissues. {ECO:0000269|PubMed:9038199, ECO:0000269|PubMed:9598309, ECO:0000269|PubMed:9632794}.

Ptm: Phosphorylated on serine and threonine residues. Phosphorylation on Thr-411 and Thr-438 is required for CDC5L-mediated mRNA splicing. Has no effect on subcellular location nor on homodimerization. Phosphorylated in vitro by CDK2. Phosphorylation enhances interaction with PPP1R8. {ECO:0000269|PubMed:10827081, ECO:0000269|PubMed:18583928, ECO:0000269|PubMed:9038199}.

Disease: Note=A chromosomal aberration involving CDC5L is found in multicystic renal dysplasia. Translocation t(6;19)(p21;q13.1) with USF2.

Similarity: Belongs to the CEF1 family. {ECO:0000305}.

Sequence caution: Sequence=BAA24862.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:20176811, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) (PubMed:20176811). {ECO:0000269\|PubMed:10570151, ECO:0000269\|PubMed:11082045, ECO:0000269\|PubMed:11101529, ECO:0000269\|PubMed:11544257, ECO:0000269\|PubMed:11991638, ECO:0000269\|PubMed:12927788, ECO:0000269\|PubMed:18583928, ECO:0000269\|PubMed:20176811, ECO:0000269\|PubMed:24332808, ECO:0000269\|PubMed:28076346, ECO:0000269\|PubMed:28502770, ECO:0000269\|PubMed:29301961, ECO:0000269\|PubMed:29360106, ECO:0000269\|PubMed:29361316, ECO:0000269\|PubMed:30705154, ECO:0000269\|PubMed:30728453, ECO:0000269\|PubMed:9038199, ECO:0000269\|PubMed:9468527, ECO:0000269\|PubMed:9632794}.


Subunit:		Homodimer. Interacts with DAPK3 (By similarity). Component of the precatalytic, catalytic and postcatalytic spliceosome complexes (PubMed:11991638, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Part of a spliceosomal 'core' complex consisting of CDC5L, PLRG1, SPF27, CCAP1, CCAP3 and CCAP6. Interacts with PLRG1, Lodestar/TTF2, and NIPP1/PPP1R8. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts (via its C-terminus) directly in the complex with PRPF19 and BCAS2. Interacts (via its C-terminus) directly with PRGL1 (via its WD40 repeat domain); the interaction is required for mRNA splicing but not for spliceosome assembly. Also interacts with CTNNBL1. Interacts with PRPF19 (via N-terminus) (By similarity). {ECO:0000250\|UniProtKB:O08837, ECO:0000269\|PubMed:10827081, ECO:0000269\|PubMed:11082045, ECO:0000269\|PubMed:11544257, ECO:0000269\|PubMed:11991638, ECO:0000269\|PubMed:12927788, ECO:0000269\|PubMed:18583928, ECO:0000269\|PubMed:18722174, ECO:0000269\|PubMed:20176811, ECO:0000269\|PubMed:21385873, ECO:0000269\|PubMed:28076346, ECO:0000269\|PubMed:28502770, ECO:0000269\|PubMed:29301961, ECO:0000269\|PubMed:29360106, ECO:0000269\|PubMed:29361316, ECO:0000269\|PubMed:30705154, ECO:0000269\|PubMed:30728453}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:10570151, ECO:0000269\|PubMed:11544257, ECO:0000269\|PubMed:18583928, ECO:0000269\|PubMed:28076346, ECO:0000269\|PubMed:28502770, ECO:0000269\|PubMed:29301961, ECO:0000269\|PubMed:29360106, ECO:0000269\|PubMed:29361316, ECO:0000269\|PubMed:30705154, ECO:0000269\|PubMed:30728453, ECO:0000269\|PubMed:9038199, ECO:0000269\|PubMed:9598309}. Nucleus speckle {ECO:0000269\|PubMed:10570151, ECO:0000269\|PubMed:10827081, ECO:0000269\|PubMed:11544257}. Cytoplasm {ECO:0000269\|PubMed:9038199}. Note=May shuttle between cytoplasm and nucleus. {ECO:0000269\|PubMed:9038199}.
Tissue specificity:		Ubiquitously expressed in both fetal and adult tissues. {ECO:0000269\|PubMed:9038199, ECO:0000269\|PubMed:9598309, ECO:0000269\|PubMed:9632794}.
Ptm:		Phosphorylated on serine and threonine residues. Phosphorylation on Thr-411 and Thr-438 is required for CDC5L-mediated mRNA splicing. Has no effect on subcellular location nor on homodimerization. Phosphorylated in vitro by CDK2. Phosphorylation enhances interaction with PPP1R8. {ECO:0000269\|PubMed:10827081, ECO:0000269\|PubMed:18583928, ECO:0000269\|PubMed:9038199}.
Disease:		Note=A chromosomal aberration involving CDC5L is found in multicystic renal dysplasia. Translocation t(6;19)(p21;q13.1) with USF2.
Similarity:		Belongs to the CEF1 family. {ECO:0000305}.
Sequence caution:		Sequence=BAA24862.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};