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Protein

CDK5 regulatory subunit-associated protein 3

Gene

CDK5RAP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable tumor suppressor initially identified as a CDK5R1 interactor controlling cell proliferation (PubMed:12054757, PubMed:12737517). 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 play a role in the unfolded protein response, mediating the ufmylation of multiple proteins in response to endoplasmic reticulum stress (PubMed:23152784). 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).10 Publications
(Microbial infection) May be negatively regulated by hepatitis B virus large envelope protein mutant pre-s2 to promote mitotic entry.

GO - Molecular functioni

  • cyclin binding Source: UniProtKB
  • MDM2/MDM4 family protein binding Source: UniProtKB
  • mitogen-activated protein kinase binding Source: UniProtKB
  • NF-kappaB binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • ubiquitin-like protein ligase binding Source: MGI

GO - Biological processi

  • apoptotic nuclear changes Source: UniProtKB
  • brain development Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • endoplasmic reticulum unfolded protein response Source: UniProtKB
  • mitotic G2/M transition checkpoint Source: UniProtKB
  • mitotic G2 DNA damage checkpoint Source: UniProtKB
  • negative regulation of cellular protein catabolic process Source: UniProtKB
  • negative regulation of MAP kinase activity Source: UniProtKB
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • negative regulation of protein kinase activity by regulation of protein phosphorylation Source: UniProtKB
  • negative regulation of protein phosphorylation Source: UniProtKB
  • negative regulation of protein serine/threonine kinase activity Source: UniProtKB
  • positive regulation of protein localization to nucleus Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
  • positive regulation of signal transduction by p53 class mediator Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • protein ufmylation Source: MGI
  • regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
  • regulation of neuron differentiation Source: UniProtKB
  • regulation of phosphatase activity Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
CDK5 regulatory subunit-associated protein 3Imported
Alternative name(s):
CDK5 activator-binding protein C531 Publication
LXXLL/leucine-zipper-containing ARF-binding protein1 Publication
Protein HSF-27Imported
Gene namesi
Name:CDK5RAP3Imported
Synonyms:IC531 Publication, LZAP1 Publication
ORF Names:MSTP016, OK/SW-cl.114, PP1553
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:18673. CDK5RAP3.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • endomembrane system Source: GO_Central
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi268D → E: Alters cleavage by CASP3 in vitro. Prevents apoptosis-induced cleavage in vivo; when associated with E-282 and E-311. 1 Publication1
Mutagenesisi282D → E: Alters cleavage by CASP3 in vitro. Prevents apoptosis-induced cleavage in vivo; when associated with E-268 and E-311. 1 Publication1
Mutagenesisi311D → E: Alters cleavage by CASP3 in vitro. Prevents apoptosis-induced cleavage in vivo; when associated with E-268 and E-282. 1 Publication1

Organism-specific databases

DisGeNETi80279.
OpenTargetsiENSG00000108465.
PharmGKBiPA38633.

Polymorphism and mutation databases

DMDMi32129444.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002205161 – 506CDK5 regulatory subunit-associated protein 3Add BLAST506

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki450Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

May be phosphorylated by CDK5.By similarity
Ubiquitinated. Probably triggers proteasomal degradation and is negatively regulated by UFL1.1 Publication
May be ufmylated.By similarity
Cleaved by caspases early during apoptosis, the resulting peptides may play a role in rupture of the nuclear envelope.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96JB5.
MaxQBiQ96JB5.
PaxDbiQ96JB5.
PeptideAtlasiQ96JB5.
PRIDEiQ96JB5.

PTM databases

iPTMnetiQ96JB5.
PhosphoSitePlusiQ96JB5.
SwissPalmiQ96JB5.

Expressioni

Tissue specificityi

Ubiquitously expressed (PubMed:12054757, PubMed:10721722). Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform 3 is expressed in kidney, liver, skeletal muscle and placenta (PubMed:12737517).3 Publications

Gene expression databases

BgeeiENSG00000108465.
CleanExiHS_CDK5RAP3.
ExpressionAtlasiQ96JB5. baseline and differential.
GenevisibleiQ96JB5. HS.

Organism-specific databases

HPAiHPA022141.
HPA022882.
HPA027883.

Interactioni

Subunit structurei

Interacts with CDK5R1; competes with CDK5RAP1 and CDK5RAP2 (PubMed:12737517). Interacts with RELA (PubMed:17785205). Interacts with CHEK1; may negatively regulate CHEK1 and thereby stimulate entry into mitosis (PubMed:19223857). Interacts with CDKN2A/ARF and MDM2; forms a ternary complex involved in regulation of p53/TP53 (PubMed:16173922). Interacts with UFL1; the interaction is direct (PubMed:20164180, PubMed:20228063). Interacts with DDRGK1 (PubMed:20228063). Interacts with MAPK14 (PubMed:21283629). Interacts with CCNB1 (PubMed:15790566). Interacts with TUBG1; may regulate CDK5RAP3 in mitotic G2/M transition checkpoint (PubMed:21465471).9 Publications
(Microbial infection) Interacts with hepatitis B virus large envelope protein mutant pre-s2; promotes mitotic entry.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FKBP6O753445EBI-718818,EBI-744771
RELAQ042064EBI-718818,EBI-73886
TSPYL4Q9UJ045EBI-718818,EBI-308511

GO - Molecular functioni

  • cyclin binding Source: UniProtKB
  • MDM2/MDM4 family protein binding Source: UniProtKB
  • mitogen-activated protein kinase binding Source: UniProtKB
  • NF-kappaB binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • ubiquitin-like protein ligase binding Source: MGI

Protein-protein interaction databases

BioGridi123213. 48 interactors.
IntActiQ96JB5. 21 interactors.
MINTiMINT-1410069.
STRINGi9606.ENSP00000344683.

Structurei

3D structure databases

ProteinModelPortaliQ96JB5.
SMRiQ96JB5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni269 – 506Required for interaction with UFL1 and mediates interaction with CHEK12 PublicationsAdd BLAST238

Sequence similaritiesi

Belongs to the CDK5RAP3 family.Curated

Phylogenomic databases

eggNOGiKOG2607. Eukaryota.
ENOG410XSWB. LUCA.
GeneTreeiENSGT00390000000713.
HOGENOMiHOG000231047.
HOVERGENiHBG050978.
InParanoidiQ96JB5.
OMAiPGVRKQM.
OrthoDBiEOG091G11PB.
PhylomeDBiQ96JB5.

Family and domain databases

InterProiIPR008491. DUF773.
[Graphical view]
PANTHERiPTHR14894. PTHR14894. 1 hit.
PfamiPF05600. DUF773. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96JB5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEDHQHVPID IQTSKLLDWL VDRRHCSLKW QSLVLTIREK INAAIQDMPE
60 70 80 90 100
SEEIAQLLSG SYIHYFHCLR ILDLLKGTEA STKNIFGRYS SQRMKDWQEI
110 120 130 140 150
IALYEKDNTY LVELSSLLVR NVNYEIPSLK KQIAKCQQLQ QEYSRKEEEC
160 170 180 190 200
QAGAAEMREQ FYHSCKQYGI TGENVRGELL ALVKDLPSQL AEIGAAAQQS
210 220 230 240 250
LGEAIDVYQA SVGFVCESPT EQVLPMLRFV QKRGNSTVYE WRTGTEPSVV
260 270 280 290 300
ERPHLEELPE QVAEDAIDWG DFGVEAVSEG TDSGISAEAA GIDWGIFPES
310 320 330 340 350
DSKDPGGDGI DWGDDAVALQ ITVLEAGTQA PEGVARGPDA LTLLEYTETR
360 370 380 390 400
NQFLDELMEL EIFLAQRAVE LSEEADVLSV SQFQLAPAIL QGQTKEKMVT
410 420 430 440 450
MVSVLEDLIG KLTSLQLQHL FMILASPRYV DRVTEFLQQK LKQSQLLALK
460 470 480 490 500
KELMVQKQQE ALEEQAALEP KLDLLLEKTK ELQKLIEADI SKRYSGRPVN

LMGTSL
Length:506
Mass (Da):56,921
Last modified:June 16, 2003 - v2
Checksum:iA21E59A79E1F87E0
GO
Isoform 2 (identifier: Q96JB5-2) [UniParc]FASTAAdd to basket
Also known as: IC53

The sequence of this isoform differs from the canonical sequence as follows:
     1-87: Missing.
     88-111: RYSSQRMKDWQEIIALYEKDNTYL → MCVHPGACLPHVGVSWAEFPGHFS

Note: Due to an intron retention.
Show »
Length:419
Mass (Da):46,351
Checksum:iDA15DED087A5A795
GO
Isoform 3 (identifier: Q96JB5-3) [UniParc]FASTAAdd to basket
Also known as: IC53-2

The sequence of this isoform differs from the canonical sequence as follows:
     1-225: Missing.

Note: Due to intron retention. No experimental confirmation available.
Show »
Length:281
Mass (Da):31,200
Checksum:iBDC6C94A65DF078C
GO
Isoform 4 (identifier: Q96JB5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: ME → MRRQSMTSATRDLHTALDGKATQGGKK

Note: No experimental confirmation available.
Show »
Length:531
Mass (Da):59,589
Checksum:iAE71C7A39A36A358
GO

Sequence cautioni

The sequence AAK69655 differs from that shown. Reason: Frameshift at position 410.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti98Q → R in BAH13320 (PubMed:14702039).Curated1
Sequence conflicti113E → V in BAD97107 (Ref. 6) Curated1
Sequence conflicti406E → K in AAK69655 (Ref. 3) Curated1
Sequence conflicti443Q → E in BAD97107 (Ref. 6) Curated1
Sequence conflicti479T → A in BAH13320 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048688324L → V.Corresponds to variant rs35054799dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0075681 – 225Missing in isoform 3. 1 PublicationAdd BLAST225
Alternative sequenceiVSP_0075661 – 87Missing in isoform 2. 1 PublicationAdd BLAST87
Alternative sequenceiVSP_0556461 – 2ME → MRRQSMTSATRDLHTALDGK ATQGGKK in isoform 4. 1 Publication2
Alternative sequenceiVSP_00756788 – 111RYSSQ…DNTYL → MCVHPGACLPHVGVSWAEFP GHFS in isoform 2. 1 PublicationAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110322 mRNA. Translation: AAG39277.1.
AF217982 mRNA. Translation: AAG17225.1.
AF343090 mRNA. Translation: AAK69655.1. Frameshift.
AB062433 mRNA. Translation: BAB93496.1.
AK023722 mRNA. Translation: BAB14657.1.
AK300643 mRNA. Translation: BAH13320.1.
AK223387 mRNA. Translation: BAD97107.1.
AC018521 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94772.1.
CH471109 Genomic DNA. Translation: EAW94774.1.
CH471109 Genomic DNA. Translation: EAW94775.1.
CH471109 Genomic DNA. Translation: EAW94778.1.
BC009957 mRNA. Translation: AAH09957.1.
BC072435 mRNA. Translation: AAH72435.1.
CCDSiCCDS42356.1. [Q96JB5-1]
CCDS62232.1. [Q96JB5-4]
PIRiJC7863.
RefSeqiNP_001265126.1. NM_001278197.1. [Q96JB5-4]
NP_001265127.1. NM_001278198.1.
NP_001265145.1. NM_001278216.1. [Q96JB5-3]
NP_001265146.1. NM_001278217.1. [Q96JB5-2]
NP_788276.1. NM_176096.2. [Q96JB5-1]
XP_011523599.1. XM_011525297.1. [Q96JB5-4]
XP_016880653.1. XM_017025164.1. [Q96JB5-2]
XP_016880654.1. XM_017025165.1. [Q96JB5-2]
UniGeneiHs.20157.

Genome annotation databases

EnsembliENST00000338399; ENSP00000344683; ENSG00000108465. [Q96JB5-1]
ENST00000536708; ENSP00000438886; ENSG00000108465. [Q96JB5-4]
GeneIDi80279.
KEGGihsa:80279.
UCSCiuc002imr.5. human. [Q96JB5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110322 mRNA. Translation: AAG39277.1.
AF217982 mRNA. Translation: AAG17225.1.
AF343090 mRNA. Translation: AAK69655.1. Frameshift.
AB062433 mRNA. Translation: BAB93496.1.
AK023722 mRNA. Translation: BAB14657.1.
AK300643 mRNA. Translation: BAH13320.1.
AK223387 mRNA. Translation: BAD97107.1.
AC018521 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94772.1.
CH471109 Genomic DNA. Translation: EAW94774.1.
CH471109 Genomic DNA. Translation: EAW94775.1.
CH471109 Genomic DNA. Translation: EAW94778.1.
BC009957 mRNA. Translation: AAH09957.1.
BC072435 mRNA. Translation: AAH72435.1.
CCDSiCCDS42356.1. [Q96JB5-1]
CCDS62232.1. [Q96JB5-4]
PIRiJC7863.
RefSeqiNP_001265126.1. NM_001278197.1. [Q96JB5-4]
NP_001265127.1. NM_001278198.1.
NP_001265145.1. NM_001278216.1. [Q96JB5-3]
NP_001265146.1. NM_001278217.1. [Q96JB5-2]
NP_788276.1. NM_176096.2. [Q96JB5-1]
XP_011523599.1. XM_011525297.1. [Q96JB5-4]
XP_016880653.1. XM_017025164.1. [Q96JB5-2]
XP_016880654.1. XM_017025165.1. [Q96JB5-2]
UniGeneiHs.20157.

3D structure databases

ProteinModelPortaliQ96JB5.
SMRiQ96JB5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123213. 48 interactors.
IntActiQ96JB5. 21 interactors.
MINTiMINT-1410069.
STRINGi9606.ENSP00000344683.

PTM databases

iPTMnetiQ96JB5.
PhosphoSitePlusiQ96JB5.
SwissPalmiQ96JB5.

Polymorphism and mutation databases

DMDMi32129444.

Proteomic databases

EPDiQ96JB5.
MaxQBiQ96JB5.
PaxDbiQ96JB5.
PeptideAtlasiQ96JB5.
PRIDEiQ96JB5.

Protocols and materials databases

DNASUi80279.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338399; ENSP00000344683; ENSG00000108465. [Q96JB5-1]
ENST00000536708; ENSP00000438886; ENSG00000108465. [Q96JB5-4]
GeneIDi80279.
KEGGihsa:80279.
UCSCiuc002imr.5. human. [Q96JB5-1]

Organism-specific databases

CTDi80279.
DisGeNETi80279.
GeneCardsiCDK5RAP3.
H-InvDBHIX0013932.
HGNCiHGNC:18673. CDK5RAP3.
HPAiHPA022141.
HPA022882.
HPA027883.
MIMi608202. gene.
neXtProtiNX_Q96JB5.
OpenTargetsiENSG00000108465.
PharmGKBiPA38633.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2607. Eukaryota.
ENOG410XSWB. LUCA.
GeneTreeiENSGT00390000000713.
HOGENOMiHOG000231047.
HOVERGENiHBG050978.
InParanoidiQ96JB5.
OMAiPGVRKQM.
OrthoDBiEOG091G11PB.
PhylomeDBiQ96JB5.

Miscellaneous databases

ChiTaRSiCDK5RAP3. human.
GeneWikiiCDK5RAP3.
GenomeRNAii80279.
PROiQ96JB5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108465.
CleanExiHS_CDK5RAP3.
ExpressionAtlasiQ96JB5. baseline and differential.
GenevisibleiQ96JB5. HS.

Family and domain databases

InterProiIPR008491. DUF773.
[Graphical view]
PANTHERiPTHR14894. PTHR14894. 1 hit.
PfamiPF05600. DUF773. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCK5P3_HUMAN
AccessioniPrimary (citable) accession number: Q96JB5
Secondary accession number(s): B7Z6N4
, D3DTU1, D3DTU2, F5H3I5, Q53FA2, Q9H3F8, Q9H8G0, Q9HBR9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: June 16, 2003
Last modified: November 30, 2016
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.