ID   CK5P3_RAT               Reviewed;         504 AA.
AC   Q9JLH7;
DT   16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   03-AUG-2022, entry version 98.
DE   RecName: Full=CDK5 regulatory subunit-associated protein 3 {ECO:0000305};
DE   AltName: Full=CDK5 activator-binding protein C53 {ECO:0000303|PubMed:10721722};
GN   Name=Cdk5rap3 {ECO:0000312|RGD:620002};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CDK5R1, AND PHOSPHORYLATION.
RX   PubMed=10721722; DOI=10.1016/s0378-1119(99)00499-0;
RA   Ching Y.-P., Qi Z., Wang J.H.;
RT   "Cloning of three novel neuronal Cdk5 activator binding proteins.";
RL   Gene 242:285-294(2000).
RN   [2]
RP   TISSUE SPECIFICITY.
RX   PubMed=12054757; DOI=10.1016/s0006-291x(02)00446-1;
RA   Chen J., Liu B., Liu Y.Q., Han Y., Yu H., Zhang Y., Lu L., Zhen Y.,
RA   Hui R.T.;
RT   "A novel gene IC53 stimulates ECV304 cell proliferation and is upregulated
RT   in failing heart.";
RL   Biochem. Biophys. Res. Commun. 294:161-166(2002).
RN   [3]
RP   INTERACTION WITH UFL1.
RX   PubMed=20531390; DOI=10.1038/emboj.2010.116;
RA   Shiwaku H., Yoshimura N., Tamura T., Sone M., Ogishima S., Watase K.,
RA   Tagawa K., Okazawa H.;
RT   "Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman
RT   glia contributes to non-cell-autonomous toxicity.";
RL   EMBO J. 29:2446-2460(2010).
CC   -!- FUNCTION: Substrate adapter for ufmylation, the covalent attachment of
CC       the ubiquitin-like modifier UFM1 to substrate proteins, in response to
CC       endoplasmic reticulum stress (By similarity). Negatively regulates NF-
CC       kappa-B-mediated gene transcription through the control of RELA
CC       phosphorylation. Probable tumor suppressor initially identified as a
CC       CDK5R1 interactor controlling cell proliferation. Also regulates
CC       mitotic G2/M transition checkpoint and mitotic G2 DNA damage
CC       checkpoint. Through its interaction with CDKN2A/ARF and MDM2 may induce
CC       MDM2-dependent p53/TP53 ubiquitination, stabilization and activation in
CC       the nucleus, thereby promoting G1 cell cycle arrest and inhibition of
CC       cell proliferation. May also play a role in the rupture of the nuclear
CC       envelope during apoptosis. May regulate MAPK14 activity by regulating
CC       its dephosphorylation by PPM1D/WIP1 (By similarity). Required for liver
CC       development (By similarity). {ECO:0000250|UniProtKB:Q96JB5,
CC       ECO:0000250|UniProtKB:Q99LM2}.
CC   -!- SUBUNIT: Interacts with CDK5R1; competes with CDK5RAP1 and CDK5RAP2
CC       (PubMed:10721722). Interacts with RELA (By similarity). Interacts with
CC       CHEK1; may negatively regulate CHEK1 and thereby stimulate entry into
CC       mitosis (By similarity). Interacts with CDKN2A/ARF and MDM2; forms a
CC       ternary complex involved in regulation of p53/TP53 (By similarity).
CC       Interacts with UFL1; the interaction is direct (PubMed:20531390).
CC       Interaction with UFL1 anchors CDK5RAP3 in the cytoplasm, preventing its
CC       translocation to the nucleus which allows expression of the CCND1
CC       cyclin and progression of cells through the G1/S transition
CC       (PubMed:20531390). Interacts with DDRGK1 (By similarity). Interacts
CC       with MAPK14 (By similarity). Interacts with CCNB1 (By similarity).
CC       Interacts with TUBG1; may regulate CDK5RAP3 in mitotic G2/M transition
CC       checkpoint (By similarity). {ECO:0000250|UniProtKB:Q96JB5,
CC       ECO:0000269|PubMed:10721722, ECO:0000269|PubMed:20531390}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96JB5}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q96JB5}. Cytoplasm, cytoskeleton, microtubule
CC       organizing center, centrosome {ECO:0000250|UniProtKB:Q96JB5}.
CC       Note=Colocalizes and associates with microtubules.
CC       {ECO:0000250|UniProtKB:Q96JB5}.
CC   -!- TISSUE SPECIFICITY: Expressed in vascular endothelium. Up-regulated in
CC       failing heart. Highly expressed in the ventricular section in subacute
CC       and chronic ischemic heart failure. {ECO:0000269|PubMed:12054757}.
CC   -!- PTM: May be phosphorylated by CDK5. {ECO:0000269|PubMed:10721722}.
CC   -!- PTM: May be ufmylated. {ECO:0000250|UniProtKB:Q99LM2}.
CC   -!- PTM: Ubiquitinated. Probably triggers proteasomal degradation and is
CC       negatively regulated by UFL1. {ECO:0000250|UniProtKB:Q96JB5}.
CC   -!- PTM: Cleaved by caspases early during apoptosis, the resulting peptides
CC       may play a role in rupture of the nuclear envelope.
CC       {ECO:0000250|UniProtKB:Q96JB5}.
CC   -!- SIMILARITY: Belongs to the CDK5RAP3 family. {ECO:0000305}.
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DR   EMBL; AF177476; AAF60222.1; -; mRNA.
DR   AlphaFoldDB; Q9JLH7; -.
DR   SMR; Q9JLH7; -.
DR   BioGRID; 249477; 1.
DR   IntAct; Q9JLH7; 3.
DR   STRING; 10116.ENSRNOP00000065240; -.
DR   jPOST; Q9JLH7; -.
DR   PaxDb; Q9JLH7; -.
DR   PRIDE; Q9JLH7; -.
DR   RGD; 620002; Cdk5rap3.
DR   eggNOG; KOG2607; Eukaryota.
DR   InParanoid; Q9JLH7; -.
DR   PhylomeDB; Q9JLH7; -.
DR   PRO; PR:Q9JLH7; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR   GO; GO:0030332; F:cyclin binding; ISO:RGD.
DR   GO; GO:0097371; F:MDM2/MDM4 family protein binding; ISO:RGD.
DR   GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:RGD.
DR   GO; GO:0051059; F:NF-kappaB binding; ISO:RGD.
DR   GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISS:UniProtKB.
DR   GO; GO:0030262; P:apoptotic nuclear changes; ISS:UniProtKB.
DR   GO; GO:0007420; P:brain development; TAS:RGD.
DR   GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR   GO; GO:0060318; P:definitive erythrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR   GO; GO:0001889; P:liver development; ISS:UniProtKB.
DR   GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR   GO; GO:0044818; P:mitotic G2/M transition checkpoint; ISS:UniProtKB.
DR   GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:RGD.
DR   GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR   GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; ISS:UniProtKB.
DR   GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISS:UniProtKB.
DR   GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR   GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0071569; P:protein ufmylation; ISS:UniProtKB.
DR   GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0007346; P:regulation of mitotic cell cycle; IBA:GO_Central.
DR   GO; GO:0010921; P:regulation of phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR   InterPro; IPR008491; CDK5RAP3.
DR   PANTHER; PTHR14894; PTHR14894; 1.
DR   Pfam; PF05600; DUF773; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Cytoskeleton; Isopeptide bond; Nucleus; Phosphoprotein;
KW   Reference proteome; Ubl conjugation.
FT   CHAIN           1..504
FT                   /note="CDK5 regulatory subunit-associated protein 3"
FT                   /id="PRO_0000220519"
FT   REGION          268..504
FT                   /note="Required for interaction with UFL1 and mediates
FT                   interaction with CHEK1"
FT                   /evidence="ECO:0000250|UniProtKB:Q96JB5"
FT   CROSSLNK        448
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q96JB5"
SQ   SEQUENCE   504 AA;  57045 MW;  5283EF7DA2D7042E CRC64;
     MQDHQHVPID IQTSKLLDWL VDRRHCNLKW QSLVLTIREK INTAIQDMPE SQEIAQLLSG
     SYIHYFHCLR IVDLLKGTEA STKNIFGRYS SQRMKDWQEI ISLYEKDNTY LVELSSLLVR
     NVNYEIPSLK KQIAKCQQLQ QDYSRKEEEG QAGAAEMREQ FYHSCKQYGI TGDNVRRELL
     ALVKDLPSQL AEIGAGAQSL GEAIDLYQAC VEFVCDSPTE QVLPMLRYVQ PKGNSTVYEW
     RTGTEPSVVE RPQLEDPPEQ VQEDEIDWGD FGLEAVSDSG NIISAETPGI DWGISLESES
     KDAGADKIDW GDNAVASEIT VLETGTEAPE GVARGSDALT LLEYPETRNQ FIDELMELEI
     FLSQRAVEMS EEADILSVSQ FQLAPAILQG QTKEKMLSLV STLQHLIGQL TSLDLQHLFM
     ILASPRYVDR VTELLQQKLK QSQLLALKKD LMVEKQQEAL QEQAALEPKL DLLLEKTREL
     QKLIEADISK RYNGRPVNLM GTSV