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Protein

Cyclin-dependent kinase 12

Gene

Cdk12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors.1 Publication

Catalytic activityi

ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei752ATPPROSITE-ProRule annotation1
Active sitei855Proton acceptorPROSITE-ProRule annotation1
Binding sitei1036ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi729 – 737ATPPROSITE-ProRule annotation9
Nucleotide bindingi810 – 815ATPPROSITE-ProRule annotation6

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

mRNA processing, mRNA splicing

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-6796648. TP53 Regulates Transcription of DNA Repair Genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 12 (EC:2.7.11.22, EC:2.7.11.23)
Alternative name(s):
Cdc2-related kinase, arginine/serine-rich
Short name:
CrkRS
Cell division cycle 2-related protein kinase 7
Short name:
CDC2-related protein kinase 7
Cell division protein kinase 12
Gene namesi
Name:Cdk12
Synonyms:Crk7, Crkrs, Kiaa0904
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1098802. Cdk12.

Subcellular locationi

  • Nucleus By similarity
  • Nucleus speckle By similarity

  • Note: Colocalized with nuclear speckles throughout interphase.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003144701 – 1484Cyclin-dependent kinase 12Add BLAST1484

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57PhosphothreonineBy similarity1
Modified residuei73PhosphotyrosineBy similarity1
Modified residuei235PhosphoserineCombined sources1
Modified residuei248PhosphoserineCombined sources1
Modified residuei264PhosphoserineBy similarity1
Modified residuei273PhosphoserineBy similarity1
Modified residuei275PhosphoserineBy similarity1
Modified residuei300PhosphoserineBy similarity1
Modified residuei302PhosphoserineBy similarity1
Modified residuei309PhosphoserineBy similarity1
Modified residuei311PhosphoserineBy similarity1
Modified residuei317PhosphoserineBy similarity1
Modified residuei322PhosphoserineBy similarity1
Modified residuei324PhosphoserineBy similarity1
Modified residuei331PhosphoserineBy similarity1
Modified residuei332PhosphoserineBy similarity1
Modified residuei333PhosphoserineBy similarity1
Modified residuei337PhosphoserineBy similarity1
Modified residuei340PhosphoserineBy similarity1
Modified residuei342PhosphoserineBy similarity1
Modified residuei344PhosphoserineBy similarity1
Modified residuei382PhosphoserineCombined sources1
Modified residuei384PhosphoserineCombined sources1
Modified residuei399PhosphoserineBy similarity1
Modified residuei419PhosphoserineBy similarity1
Modified residuei422PhosphoserineBy similarity1
Modified residuei511PhosphothreonineBy similarity1
Modified residuei610PhosphoserineBy similarity1
Modified residuei640PhosphoserineBy similarity1
Modified residuei677PhosphoserineCombined sources1
Modified residuei681PhosphoserineCombined sources1
Modified residuei688PhosphothreonineBy similarity1
Modified residuei885PhosphoserineBy similarity1
Modified residuei889PhosphothreonineCombined sources1
Modified residuei1049PhosphoserineBy similarity1
Modified residuei1079PhosphoserineCombined sources1
Modified residuei1240PhosphothreonineCombined sources1
Modified residuei1242PhosphothreonineCombined sources1
Isoform 3 (identifier: Q14AX6-3)
Modified residuei1240PhosphothreonineCombined sources1
Modified residuei1242PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylation at Thr-889 increases kinase activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ14AX6.
PaxDbiQ14AX6.
PeptideAtlasiQ14AX6.
PRIDEiQ14AX6.

PTM databases

iPTMnetiQ14AX6.
PhosphoSitePlusiQ14AX6.

Expressioni

Gene expression databases

BgeeiENSMUSG00000003119.
CleanExiMM_CRKRS.
GenevisibleiQ14AX6. MM.

Interactioni

Subunit structurei

Interacts with CCNL1 and CCNL2.By similarity

GO - Molecular functioni

  • cyclin binding Source: MGI
  • protein kinase binding Source: MGI

Protein-protein interaction databases

BioGridi213247. 1 interactor.
IntActiQ14AX6. 1 interactor.
MINTiMINT-4119098.
STRINGi10090.ENSMUSP00000103162.

Structurei

3D structure databases

ProteinModelPortaliQ14AX6.
SMRiQ14AX6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini723 – 1016Protein kinasePROSITE-ProRule annotationAdd BLAST294

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi137 – 393Ser-richAdd BLAST257
Compositional biasi406 – 412Poly-Ala7
Compositional biasi524 – 703Pro-richAdd BLAST180
Compositional biasi1234 – 1276Pro-richAdd BLAST43

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0600. Eukaryota.
ENOG410XPIR. LUCA.
GeneTreeiENSGT00860000133755.
HOGENOMiHOG000049118.
HOVERGENiHBG050852.
InParanoidiQ14AX6.
KOiK08819.
OMAiXCILGEL.
OrthoDBiEOG091G08Z8.
PhylomeDBiQ14AX6.
TreeFamiTF101060.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14AX6-1) [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
MPNSERHGGK KDGSGGASGT SQPSSGGGSS NSRERHRLVS KHKRHKSKHS
60 70 80 90 100
KDVGLVTPEA ASLGTIIKPL VEYDDISSDS DTFSDDTAFK SDRRENEERR
110 120 130 140 150
GTDRSDRLHR HRHHQHRRSR DLLKTKQTEK EKNQEVSKSG SMKDRVSGSS
160 170 180 190 200
KRSVEGSDDY GKAQLSKSGS KESRSSKMHK EKTRKERELK SGYKDRSKSH
210 220 230 240 250
RKRETPKSYK TVASPKRRSR SPHRKWSDSS KQDDSPSGAS YGQDYDLSPP
260 270 280 290 300
RSHTSSNYDS YKKSPGSTSR RQSISPPYKE PSAYQSSTRS PSPYSRRQRS
310 320 330 340 350
VSPYSRRRSS SYERSGSYSG RSPSPYGRRR SSSPFLSKRS LSRSPLPSRK
360 370 380 390 400
SMKSRSRSPA YSRHSSSHSK KKRSGSRSRH SSISPVRLPL NSSLGAELSR
410 420 430 440 450
KKKERAAAAA AAKMDGKESK SSPIILPKKE KLEVKESGLE SKKLPRSIKS
460 470 480 490 500
EKSTPDTELV TVAHSNPEVK HCLDTGKVRL DENLQKHPAK DLKAQGTKDV
510 520 530 540 550
KPVAPKEVIV TSKETETSEK ETLPPLPTIT SPPPLPATTP PPQTPPLPPL
560 570 580 590 600
PPLPAIPLQP PLPPPQPPFS QVPVSSTSIL PSSPHPRTST LSSQTNSQPP
610 620 630 640 650
VQVSMKTQVS ITAAIPHLKT STLPPLPLPP LLPGDDDMDS PKETLPSKPA
660 670 680 690 700
KKEKEQRTRH LLTDLPLPPE LPGGDPSPPD SPEPKAITPP QQPYKKRPKI
710 720 730 740 750
CCPRYGERRQ TESDWGKRCV DKFDIIGIIG EGTYGQVYKA KDKDTGELVA
760 770 780 790 800
LKKVRLDNEK EGFPITAIRE IKILRQLVHQ SVVNMKEIVT DKQDALDFKK
810 820 830 840 850
DKGAFYLVFE YMDHDLMGLL ESGLVHFSED HIKSFMKQLM EGLDYCHKKN
860 870 880 890 900
FLHRDIKCSN ILLNNSGQIK LADFGLARLY NSEESRPYTN KVITLWYRPP
910 920 930 940 950
ELLLGEERYT PAIDVWSCGC ILGELFTKKP IFQANLELAQ LELISRLCGS
960 970 980 990 1000
PCPAVWPDVI KLPYFNTMKP KKQYRRRLRE EFSFIPSAAL DLLDHMLTLD
1010 1020 1030 1040 1050
PSKRCTAEQT LQSDFLKDVE LSKMAPPDLP HWQDCHELWS KKRRRQRQSG
1060 1070 1080 1090 1100
IVIEDPPPSK ASRKETTSGT TAEPVKNNSP APPQPAPVKA EPGPGDAVGL
1110 1120 1130 1140 1150
GDITQQLNQS ELAVLLNLLQ SQTDLSIPQM AQLLNIHSNP EMQQQLEALN
1160 1170 1180 1190 1200
QSISALTEAS SQQQDSESIA PEESLKEVPS VPVVLPPAEQ TTPEASNTPA
1210 1220 1230 1240 1250
DMQNVLAVLL SQLMKTQEPA GNLEENTNDK NSGPQGPRRT PTMPQEEAAA
1260 1270 1280 1290 1300
CPPHILPPEK RPPEPPGPPP PPPPPPLVEG DLSSAPQELN PAVTAALLQL
1310 1320 1330 1340 1350
LSQPEAEPPG HLPHEHQALR PMEYSTRSHP NRTYGNTDGP ETGFSSADTD
1360 1370 1380 1390 1400
ERSSGPALTE SLVQTPVKNR TFSGSVSHLG ESNSYQGTGS VQFPGDQDLR
1410 1420 1430 1440 1450
FTRVPLALHS VVGQPFLKSE GNSNSVVHAE TKLQNYGELG PGTTGANSSG
1460 1470 1480
TTLQWGGPAQ SYGKPYRGAA RVLPRGGRGR GVPY
Length:1,484
Mass (Da):163,681
Last modified:January 15, 2008 - v2
Checksum:i5FCEE8D1903DF803
GO
Isoform 2 (identifier: Q14AX6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1250-1258: ACPPHILPP → GKQTGHESH
     1259-1484: Missing.

Show »
Length:1,258
Mass (Da):139,883
Checksum:iF21408B379D9EFB5
GO
Isoform 3 (identifier: Q14AX6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1250-1258: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:1,475
Mass (Da):162,755
Checksum:i53626C566777F0CA
GO

Sequence cautioni

The sequence CAM21270 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti346L → I in AAL69526 (Ref. 1) Curated1
Sequence conflicti363R → S in AAL69526 (Ref. 1) Curated1
Sequence conflicti377R → H in AAL69526 (Ref. 1) Curated1
Sequence conflicti425 – 427ILP → FCL in BAC98047 (PubMed:14621295).Curated3
Sequence conflicti496G → V in AAL69526 (Ref. 1) Curated1
Sequence conflicti562L → V in AAL69526 (Ref. 1) Curated1
Sequence conflicti854R → Q in AAL69526 (Ref. 1) Curated1
Sequence conflicti863L → V in AAL69526 (Ref. 1) Curated1
Sequence conflicti870K → R in AAL69526 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0302851250 – 1258ACPPHILPP → GKQTGHESH in isoform 2. 2 Publications9
Alternative sequenceiVSP_0302861250 – 1258Missing in isoform 3. 1 Publication9
Alternative sequenceiVSP_0302871259 – 1484Missing in isoform 2. 2 PublicationsAdd BLAST226

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY072295 mRNA. Translation: AAL69526.1.
AL591205 Genomic DNA. Translation: CAM21267.1.
AL591205 Genomic DNA. Translation: CAM21268.1.
AL591205 Genomic DNA. Translation: CAM21269.1.
AL591205 Genomic DNA. Translation: CAM21270.1. Sequence problems.
BC116645 mRNA. Translation: AAI16646.1.
AK129237 mRNA. Translation: BAC98047.1.
CCDSiCCDS25342.1. [Q14AX6-2]
CCDS48901.1. [Q14AX6-1]
CCDS48902.1. [Q14AX6-3]
RefSeqiNP_001103096.1. NM_001109626.1. [Q14AX6-1]
NP_001103098.1. NM_001109628.1. [Q14AX6-3]
NP_081228.2. NM_026952.2. [Q14AX6-2]
UniGeneiMm.260516.
Mm.486492.
Mm.488484.

Genome annotation databases

EnsembliENSMUST00000003203; ENSMUSP00000003203; ENSMUSG00000003119. [Q14AX6-2]
ENSMUST00000107538; ENSMUSP00000103162; ENSMUSG00000003119. [Q14AX6-1]
ENSMUST00000107539; ENSMUSP00000103163; ENSMUSG00000003119. [Q14AX6-3]
GeneIDi69131.
KEGGimmu:69131.
UCSCiuc007lfr.2. mouse. [Q14AX6-1]
uc007lfs.2. mouse. [Q14AX6-2]
uc007lfu.2. mouse. [Q14AX6-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY072295 mRNA. Translation: AAL69526.1.
AL591205 Genomic DNA. Translation: CAM21267.1.
AL591205 Genomic DNA. Translation: CAM21268.1.
AL591205 Genomic DNA. Translation: CAM21269.1.
AL591205 Genomic DNA. Translation: CAM21270.1. Sequence problems.
BC116645 mRNA. Translation: AAI16646.1.
AK129237 mRNA. Translation: BAC98047.1.
CCDSiCCDS25342.1. [Q14AX6-2]
CCDS48901.1. [Q14AX6-1]
CCDS48902.1. [Q14AX6-3]
RefSeqiNP_001103096.1. NM_001109626.1. [Q14AX6-1]
NP_001103098.1. NM_001109628.1. [Q14AX6-3]
NP_081228.2. NM_026952.2. [Q14AX6-2]
UniGeneiMm.260516.
Mm.486492.
Mm.488484.

3D structure databases

ProteinModelPortaliQ14AX6.
SMRiQ14AX6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi213247. 1 interactor.
IntActiQ14AX6. 1 interactor.
MINTiMINT-4119098.
STRINGi10090.ENSMUSP00000103162.

PTM databases

iPTMnetiQ14AX6.
PhosphoSitePlusiQ14AX6.

Proteomic databases

MaxQBiQ14AX6.
PaxDbiQ14AX6.
PeptideAtlasiQ14AX6.
PRIDEiQ14AX6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003203; ENSMUSP00000003203; ENSMUSG00000003119. [Q14AX6-2]
ENSMUST00000107538; ENSMUSP00000103162; ENSMUSG00000003119. [Q14AX6-1]
ENSMUST00000107539; ENSMUSP00000103163; ENSMUSG00000003119. [Q14AX6-3]
GeneIDi69131.
KEGGimmu:69131.
UCSCiuc007lfr.2. mouse. [Q14AX6-1]
uc007lfs.2. mouse. [Q14AX6-2]
uc007lfu.2. mouse. [Q14AX6-3]

Organism-specific databases

CTDi51755.
MGIiMGI:1098802. Cdk12.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0600. Eukaryota.
ENOG410XPIR. LUCA.
GeneTreeiENSGT00860000133755.
HOGENOMiHOG000049118.
HOVERGENiHBG050852.
InParanoidiQ14AX6.
KOiK08819.
OMAiXCILGEL.
OrthoDBiEOG091G08Z8.
PhylomeDBiQ14AX6.
TreeFamiTF101060.

Enzyme and pathway databases

ReactomeiR-MMU-6796648. TP53 Regulates Transcription of DNA Repair Genes.

Miscellaneous databases

ChiTaRSiCdk12. mouse.
PROiQ14AX6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003119.
CleanExiMM_CRKRS.
GenevisibleiQ14AX6. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDK12_MOUSE
AccessioniPrimary (citable) accession number: Q14AX6
Secondary accession number(s): A2A530
, A2A531, B1AQH7, Q6ZQ27, Q8R457
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: November 30, 2016
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.