CDK5RAP3
entrez
80279
canonical
uniprot
Q96JB5
canonical
ensembl
ENSG00000108465
resolver
ensp
ENSP00000344683
resolver
ensp
ENSP00000438886
resolver
genesymbol
CDK5RAP3
resolver
genesymbol_syn
IC53
resolver
genesymbol_syn
LZAP
resolver
hgnc
HGNC:18673
resolver
uniprot
B7Z6N4
resolver
uniprot
D3DTU1
resolver
uniprot
D3DTU2
resolver
uniprot
F5H3I5
resolver
uniprot
Q53FA2
resolver
uniprot
Q9H3F8
resolver
uniprot
Q9H8G0
resolver
uniprot
Q9HBR9
resolver
uniprot_entry
CK5P3_HUMAN
resolver
uniprot_sec
B7Z6N4
resolver
uniprot_sec
D3DTU1
resolver
uniprot_sec
D3DTU2
resolver
uniprot_sec
F5H3I5
resolver
uniprot_sec
Q53FA2
resolver
uniprot_sec
Q9H3F8
resolver
uniprot_sec
Q9H8G0
resolver
uniprot_sec
Q9HBR9
resolver
amino_acid_sequence
MEDHQHVPIDIQTSKLLDWLVDRRHCSLKWQSLVLTIREKINAAIQDMPESEEIAQLLSGSYIHYFHCLRILDLLKGTEASTKNIFGRYSSQRMKDWQEIIALYEKDNTYLVELSSLLVRNVNYEIPSLKKQIAKCQQLQQEYSRKEEECQAGAAEMREQFYHSCKQYGITGENVRGELLALVKDLPSQLAEIGAAAQQSLGEAIDVYQASVGFVCESPTEQVLPMLRFVQKRGNSTVYEWRTGTEPSVVERPHLEELPEQVAEDAIDWGDFGVEAVSEGTDSGISAEAAGIDWGIFPESDSKDPGGDGIDWGDDAVALQITVLEAGTQAPEGVARGPDALTLLEYTETRNQFLDELMELEIFLAQRAVELSEEADVLSVSQFQLAPAILQGQTKEKMVTMVSVLEDLIGKLTSLQLQHLFMILASPRYVDRVTEFLQQKLKQSQLLALKKELMVQKQQEALEEQAALEPKLDLLLEKTKELQKLIEADISKRYSGRPVNLMGTSL
uniprot
proteins
function
FUNCTION: Substrate adapter of E3 ligase complexes mediating ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, and which is involved in various processes, such as ribosome recycling and reticulophagy (also called ER-phagy) (PubMed:23152784, PubMed:30635284, PubMed:32851973, PubMed:36121123, PubMed:36543799, PubMed:37595036, PubMed:38383785, PubMed:38383789). As part of the UREL complex, plays a key role in ribosome recycling by promoting mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 occurs on free 60S ribosomes following ribosome dissociation: it weakens the junction between post-termination 60S subunits and SEC61 translocons, promoting release and recycling of the large ribosomal subunit from the endoplasmic reticulum membrane (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 and subsequent 60S ribosome recycling either take place after normal termination of translation or after ribosome stalling during cotranslational translocation at the endoplasmic reticulum (PubMed:32851973, PubMed:37595036, PubMed:38383785, PubMed:38383789). Within the UREL complex, CDK5RAP3 acts as a substrate adapter that constrains UFL1 ligase activity to mono-ufmylate RPL26/uL24 at 'Lys-134' (PubMed:36121123, PubMed:38383785, PubMed:38383789). The UREL complex is also involved in reticulophagy in response to endoplasmic reticulum stress by promoting ufmylation of proteins such as CYB5R3, thereby promoting lysosomal degradation of ufmylated proteins (PubMed:36543799). Also acts as a regulator of transcription: negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation (PubMed:17785205, PubMed:20228063). Also regulates mitotic G2/M transition checkpoint and mitotic G2 DNA damage checkpoint (PubMed:15790566, PubMed:19223857). Through its interaction with CDKN2A/ARF and MDM2 may induce MDM2-dependent p53/TP53 ubiquitination, stabilization and activation in the nucleus, thereby promoting G1 cell cycle arrest and inhibition of cell proliferation (PubMed:16173922). May also play a role in the rupture of the nuclear envelope during apoptosis (PubMed:23478299). May regulate MAPK14 activity by regulating its dephosphorylation by PPM1D/WIP1 (PubMed:21283629). Required for liver development (By similarity). {ECO:0000250|UniProtKB:Q99LM2, ECO:0000269|PubMed:15790566, ECO:0000269|PubMed:16173922, ECO:0000269|PubMed:17785205, ECO:0000269|PubMed:19223857, ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:21283629, ECO:0000269|PubMed:23152784, ECO:0000269|PubMed:23478299, ECO:0000269|PubMed:30635284, ECO:0000269|PubMed:32851973, ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}.; FUNCTION: (Microbial infection) May be negatively regulated by hepatitis B virus large envelope protein mutant pre-s2 to promote mitotic entry. {ECO:0000269|PubMed:21971960}.
uniprot
proteins
mass_dalton
56921
uniprot
proteins
mutagenesis
MUTAGEN 217; /note="E->A: Abolished interaction with UFL1; when associated with A-355, A-359, A-373 and A-432."; /evidence="ECO:0000269|PubMed:37595036"; MUTAGEN 268; /note="D->E: Alters cleavage by CASP3 in vitro. Prevents apoptosis-induced cleavage in vivo; when associated with E-282 and E-311."; /evidence="ECO:0000269|PubMed:23478299"; MUTAGEN 269; /note="W->A: Abolished interaction with ATG8 family proteins; when associated with A-294 and A-312."; /evidence="ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:36762703"; MUTAGEN 282; /note="D->E: Alters cleavage by CASP3 in vitro. Prevents apoptosis-induced cleavage in vivo; when associated with E-268 and E-311."; /evidence="ECO:0000269|PubMed:23478299"; MUTAGEN 294; /note="W->A: Abolished interaction with ATG8 family proteins; when associated with A-269 and A-312."; /evidence="ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:36762703"; MUTAGEN 311; /note="D->E: Alters cleavage by CASP3 in vitro. Prevents apoptosis-induced cleavage in vivo; when associated with E-268 and E-282."; /evidence="ECO:0000269|PubMed:23478299"; MUTAGEN 312; /note="W->A: Abolished interaction with ATG8 family proteins; when associated with A-269 and A-294."; /evidence="ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:36762703"; MUTAGEN 355; /note="D->A: Abolished interaction with UFL1; when associated with A-355, A-359, A-373 and A-432."; /evidence="ECO:0000269|PubMed:37595036"; MUTAGEN 359; /note="E->A: Abolished interaction with UFL1; when associated with A-217, A-355, A-373 and A-432."; /evidence="ECO:0000269|PubMed:37595036"; MUTAGEN 373; /note="E->A: Abolished interaction with UFL1; when associated with A-217, A-355, A-359 and A-432."; /evidence="ECO:0000269|PubMed:37595036"; MUTAGEN 432; /note="R->A: Abolished interaction with UFL1; when associated with A-217, A-355, A-359 and A-373."; /evidence="ECO:0000269|PubMed:37595036
uniprot
proteins
post_translational_modification
PTM: May be phosphorylated by CDK5. {ECO:0000250|UniProtKB:Q9JLH7}.; PTM: Ubiquitinated. Probably triggers proteasomal degradation and is negatively regulated by UFL1. {ECO:0000269|PubMed:20228063}.; PTM: May be ufmylated. {ECO:0000250|UniProtKB:Q99LM2}.; PTM: Cleaved by caspases early during apoptosis, the resulting peptides may play a role in rupture of the nuclear envelope. {ECO:0000269|PubMed:23478299}.
uniprot
proteins
protein_family
CDK5RAP3 family
uniprot
proteins
pubmed
10721722
uniprot
proteins
pubmed
12054757
uniprot
proteins
pubmed
12737517
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15790566
uniprot
proteins
pubmed
16173922
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17785205
uniprot
proteins
pubmed
19223857
uniprot
proteins
pubmed
20164180
uniprot
proteins
pubmed
20228063
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21283629
uniprot
proteins
pubmed
21465471
uniprot
proteins
pubmed
21971960
uniprot
proteins
pubmed
23152784
uniprot
proteins
pubmed
23478299
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25772364
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
30635284
uniprot
proteins
pubmed
32851973
uniprot
proteins
pubmed
36121123
uniprot
proteins
pubmed
36543799
uniprot
proteins
pubmed
36762703
uniprot
proteins
pubmed
37595036
uniprot
proteins
pubmed
38383785
uniprot
proteins
pubmed
38383789
uniprot
proteins
sequence_length
506
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}. Cytoplasm {ECO:0000269|PubMed:15790566, ECO:0000269|PubMed:16173922, ECO:0000269|PubMed:19223857}. Nucleus {ECO:0000269|PubMed:16173922}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:19223857}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:23478299}. Note=Tethered to the endoplasmic reticulum membrane as part of the UFM1 ribosome E3 ligase (UREL) complex (PubMed:38383785, PubMed:38383789). Colocalizes and associates with microtubules (PubMed:23478299). {ECO:0000269|PubMed:23478299, ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}.
uniprot
proteins