{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9JLH7","uniProtkbId":"CK5P3_RAT","entryAudit":{"firstPublicDate":"2003-06-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2000-10-01","entryVersion":111,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Rattus norvegicus","commonName":"Rat","taxonId":10116,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Rattus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"CDK5 regulatory subunit-associated protein 3"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"10721722"}],"value":"CDK5 activator-binding protein C53"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"RGD","id":"620002"}],"value":"Cdk5rap3"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q99LM2"}],"value":"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) (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). Within the UREL complex, CDK5RAP3 acts as a substrate adapter that constrains UFL1 ligase activity to mono-ufmylate RPL26/uL24 at 'Lys-134' (By similarity). 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 (By similarity). Also acts as a regulator of transcription: negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation (By similarity). Also regulates mitotic G2/M transition checkpoint and mitotic G2 DNA damage checkpoint (By similarity). 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 (By similarity). May also play a role in the rupture of the nuclear envelope during apoptosis (By similarity). May regulate MAPK14 activity by regulating its dephosphorylation by PPM1D/WIP1 (By similarity). Required for liver development (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10721722"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20531390"}],"value":"Substrate adapter component of the UFM1 ribosome E3 ligase (UREL) complex, composed of UFL1, DDRGK1 and CDK5RAP3 (By similarity). Interaction with UFL1 anchors CDK5RAP3 in the cytoplasm, preventing its translocation to the nucleus which allows expression of the CCND1 cyclin and progression of cells through the G1/S transition (PubMed:20531390). Interacts with ATG8 family proteins MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2 (By similarity). Interacts with CDK5R1; competes with CDK5RAP1 and CDK5RAP2 (PubMed:10721722). Interacts with RELA (By similarity). Interacts with CHEK1; may negatively regulate CHEK1 and thereby stimulate entry into mitosis (By similarity). Interacts with CDKN2A/ARF and MDM2; forms a ternary complex involved in regulation of p53/TP53 (By similarity). Interacts with MAPK14 (By similarity). Interacts with CCNB1 (By similarity). Interacts with TUBG1; may regulate CDK5RAP3 in mitotic G2/M transition checkpoint (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"Tethered to the endoplasmic reticulum membrane as part of the UFM1 ribosome E3 ligase (UREL) complex. Colocalizes and associates with microtubules"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","id":"SL-0048"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"Cytoplasm, cytoskeleton","id":"SL-0090"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12054757"}],"value":"Expressed in vascular endothelium. Up-regulated in failing heart. Highly expressed in the ventricular section in subacute and chronic ischemic heart failure"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"The shuffled ATG8-binding motifs mediate interaction with both ATG8 family protein and UFM1"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"The RPL10a-binding domain (RBD) anchors the UREL complex onto the ribosome via association with RPL10a/ul1"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10721722"}],"value":"May be phosphorylated by CDK5"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"Ubiquitinated. Probably triggers proteasomal degradation and is negatively regulated by UFL1"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q99LM2"}],"value":"May be ufmylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}],"value":"Cleaved by caspases early during apoptosis, the resulting peptides may play a role in rupture of the nuclear envelope"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the CDK5RAP3 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":504,"modifier":"EXACT"}},"description":"CDK5 regulatory subunit-associated protein 3","featureId":"PRO_0000220519"},{"type":"Region","location":{"start":{"value":268,"modifier":"EXACT"},"end":{"value":504,"modifier":"EXACT"}},"description":"Required for interaction with UFL1 and mediates interaction with CHEK1","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}]},{"type":"Region","location":{"start":{"value":353,"modifier":"EXACT"},"end":{"value":368,"modifier":"EXACT"}},"description":"RPL10a-binding domain (RBD)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}]},{"type":"Motif","location":{"start":{"value":266,"modifier":"EXACT"},"end":{"value":269,"modifier":"EXACT"}},"description":"Shuffled ATG8-binding motif 1","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}]},{"type":"Motif","location":{"start":{"value":290,"modifier":"EXACT"},"end":{"value":293,"modifier":"EXACT"}},"description":"Shuffled ATG8-binding motif 2","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}]},{"type":"Motif","location":{"start":{"value":308,"modifier":"EXACT"},"end":{"value":311,"modifier":"EXACT"}},"description":"Shuffled ATG8-binding motif 3","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}]},{"type":"Cross-link","location":{"start":{"value":448,"modifier":"EXACT"},"end":{"value":448,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q96JB5"}]}],"keywords":[{"id":"KW-0963","category":"Cellular component","name":"Cytoplasm"},{"id":"KW-0206","category":"Cellular component","name":"Cytoskeleton"},{"id":"KW-0256","category":"Cellular component","name":"Endoplasmic reticulum"},{"id":"KW-1017","category":"PTM","name":"Isopeptide bond"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0539","category":"Cellular component","name":"Nucleus"},{"id":"KW-0597","category":"PTM","name":"Phosphoprotein"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0832","category":"PTM","name":"Ubl conjugation"},{"id":"KW-0833","category":"Biological process","name":"Ubl conjugation pathway"}],"references":[{"referenceNumber":1,"citation":{"id":"10721722","citationType":"journal article","authors":["Ching Y.-P.","Qi Z.","Wang J.H."],"citationCrossReferences":[{"database":"PubMed","id":"10721722"},{"database":"DOI","id":"10.1016/s0378-1119(99)00499-0"}],"title":"Cloning of three novel neuronal Cdk5 activator binding proteins.","publicationDate":"2000","journal":"Gene","firstPage":"285","lastPage":"294","volume":"242"},"referencePositions":["NUCLEOTIDE SEQUENCE [MRNA]","INTERACTION WITH CDK5R1","PHOSPHORYLATION"]},{"referenceNumber":2,"citation":{"id":"12054757","citationType":"journal article","authors":["Chen J.","Liu B.","Liu Y.Q.","Han Y.","Yu H.","Zhang Y.","Lu L.","Zhen Y.","Hui R.T."],"citationCrossReferences":[{"database":"PubMed","id":"12054757"},{"database":"DOI","id":"10.1016/s0006-291x(02)00446-1"}],"title":"A novel gene IC53 stimulates ECV304 cell proliferation and is upregulated in failing heart.","publicationDate":"2002","journal":"Biochem. 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