ID   CK5P3_PONAB             Reviewed;         506 AA.
AC   Q5REX6;
DT   21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   03-AUG-2022, entry version 46.
DE   RecName: Full=CDK5 regulatory subunit-associated protein 3 {ECO:0000305};
GN   Name=CDK5RAP3 {ECO:0000250|UniProtKB:Q96JB5};
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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       Interacts with RELA. Interacts with CHEK1; may negatively regulate
CC       CHEK1 and thereby stimulate entry into mitosis. Interacts with
CC       CDKN2A/ARF and MDM2; forms a ternary complex involved in regulation of
CC       p53/TP53. Interacts with UFL1; the interaction is direct. Interaction
CC       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. Interacts
CC       with DDRGK1. Interacts with MAPK14. Interacts with CCNB1. Interacts
CC       with TUBG1; may regulate CDK5RAP3 in mitotic G2/M transition
CC       checkpoint. {ECO:0000250|UniProtKB:Q96JB5,
CC       ECO:0000250|UniProtKB:Q9JLH7}.
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   -!- PTM: Ubiquitinated. Probably triggers proteasomal degradation and is
CC       negatively regulated by UFL1. {ECO:0000250|UniProtKB:Q96JB5}.
CC   -!- PTM: May be ufmylated. {ECO:0000250|UniProtKB:Q99LM2}.
CC   -!- PTM: May be phosphorylated by CDK5. {ECO:0000250|UniProtKB:Q9JLH7}.
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; CR857387; CAH89681.1; -; mRNA.
DR   AlphaFoldDB; Q5REX6; -.
DR   SMR; Q5REX6; -.
DR   STRING; 9601.ENSPPYP00000009966; -.
DR   eggNOG; KOG2607; Eukaryota.
DR   InParanoid; Q5REX6; -.
DR   Proteomes; UP000001595; 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:0044389; F:ubiquitin-like protein ligase binding; ISS:UniProtKB.
DR   GO; GO:0030262; P:apoptotic nuclear changes; ISS:UniProtKB.
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: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:0071569; P:protein ufmylation; ISS:UniProtKB.
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   2: Evidence at transcript level;
KW   Cytoplasm; Cytoskeleton; Isopeptide bond; Nucleus; Phosphoprotein;
KW   Reference proteome; Ubl conjugation.
FT   CHAIN           1..506
FT                   /note="CDK5 regulatory subunit-associated protein 3"
FT                   /id="PRO_0000220518"
FT   REGION          269..506
FT                   /note="Required for interaction with UFL1 and mediates
FT                   interaction with CHEK1"
FT                   /evidence="ECO:0000250|UniProtKB:Q96JB5"
FT   CROSSLNK        450
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:Q96JB5"
SQ   SEQUENCE   506 AA;  56946 MW;  E756A359FE5437D6 CRC64;
     MEDHQHVPID IQTSKLLDWL VDRRHCSLKW QSLVLTIREK INAAIQDMPE SEEIAQLLSG
     SYIHYFHCLR ILDLLKGTEA STKNIFGRYS SQRMKDWQEI IALYEKDNTY LVELSSLLVR
     NVNYEIPSLK KQIAKCQQLQ QEYSRKEEEC QAGAAEMREQ FYHSCKQYGI TGENVRGELL
     ALVKDLPSQL AETGAAARQS LGEAIDVYQA SVGFVCESHT EQVLPMLQFV QKRGNSTVYE
     WRTGTEPSVV ERPHLEELPE QVAEDAIDWG DFGVEAVSEG TDSGISAKAA GIDWGIFPES
     DSKDPGGDGI DWGDDAVALQ ITVLEAGTQA PEGVARGPDA LTLLEYTETR NQFLDELMEL
     EIFLARRAVE LSEEADVLSV SQFQLAPAIL QGQTKEKTVT MVSVLEDLIG KLTSLQLQHL
     FMILASPRYV DRVTEFLQQK LKQSQLLALK KELMVQKQQE ALEEQAALEP KLDLLLEKTK
     ELQKLIEADI SKRYSGRPVN LMGTSL