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Q14AX6 (CDK12_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 79. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cdk12
Synonyms:Crk7, Crkrs, Kiaa0904
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1484 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7

Catalytic activity

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

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Interacts with CCNL1 and CCNL2 By similarity. Ref.7

Subcellular location

Nucleus By similarity. Nucleus speckle By similarity. Note: Colocalized with nuclear speckles throughout interphase By similarity. Ref.7

Post-translational modification

Phosphorylation at Thr-889 increases kinase activity By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence CAM21270.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processmRNA processing
mRNA splicing
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA splicing

Inferred from sequence or structural similarity. Source: UniProtKB

mRNA processing

Inferred from electronic annotation. Source: UniProtKB-KW

phosphorylation of RNA polymerase II C-terminal domain

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: HGNC

regulation of MAP kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcyclin K-CDK12 complex

Inferred from electronic annotation. Source: Ensembl

nuclear cyclin-dependent protein kinase holoenzyme complex

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear speck

Inferred from sequence or structural similarity. Source: UniProtKB

nucleolus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase II carboxy-terminal domain kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein kinase activity

Inferred from sequence or structural similarity. Source: HGNC

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14AX6-1)

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.
Isoform 2 (identifier: Q14AX6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1250-1258: ACPPHILPP → GKQTGHESH
     1259-1484: Missing.
Isoform 3 (identifier: Q14AX6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1250-1258: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14841484Cyclin-dependent kinase 12
PRO_0000314470

Regions

Domain723 – 1016294Protein kinase
Nucleotide binding729 – 7379ATP By similarity
Nucleotide binding810 – 8156ATP By similarity
Compositional bias137 – 393257Ser-rich
Compositional bias406 – 4127Poly-Ala
Compositional bias524 – 703180Pro-rich
Compositional bias1234 – 127643Pro-rich

Sites

Active site8551Proton acceptor By similarity
Binding site7521ATP By similarity
Binding site10361ATP By similarity

Amino acid modifications

Modified residue571Phosphothreonine By similarity
Modified residue731Phosphotyrosine By similarity
Modified residue2351Phosphoserine By similarity
Modified residue2481Phosphoserine By similarity
Modified residue2731Phosphoserine By similarity
Modified residue2751Phosphoserine By similarity
Modified residue3001Phosphoserine By similarity
Modified residue3021Phosphoserine By similarity
Modified residue3091Phosphoserine By similarity
Modified residue3111Phosphoserine By similarity
Modified residue3171Phosphoserine By similarity
Modified residue3221Phosphoserine By similarity
Modified residue3241Phosphoserine By similarity
Modified residue3311Phosphoserine By similarity
Modified residue3321Phosphoserine By similarity
Modified residue3331Phosphoserine By similarity
Modified residue3371Phosphoserine By similarity
Modified residue3441Phosphoserine By similarity
Modified residue3821Phosphoserine Ref.5 Ref.6
Modified residue3841Phosphoserine Ref.5 Ref.6
Modified residue3991Phosphoserine By similarity
Modified residue4191Phosphoserine By similarity
Modified residue4221Phosphoserine By similarity
Modified residue5111Phosphothreonine By similarity
Modified residue6771Phosphoserine By similarity
Modified residue6811Phosphoserine By similarity
Modified residue6881Phosphothreonine By similarity
Modified residue8891Phosphothreonine By similarity
Modified residue10491Phosphoserine By similarity
Modified residue10791Phosphoserine Ref.5
Modified residue12401Phosphothreonine By similarity

Natural variations

Alternative sequence1250 – 12589ACPPHILPP → GKQTGHESH in isoform 2.
VSP_030285
Alternative sequence1250 – 12589Missing in isoform 3.
VSP_030286
Alternative sequence1259 – 1484226Missing in isoform 2.
VSP_030287

Experimental info

Sequence conflict3461L → I in AAL69526. Ref.1
Sequence conflict3631R → S in AAL69526. Ref.1
Sequence conflict3771R → H in AAL69526. Ref.1
Sequence conflict425 – 4273ILP → FCL in BAC98047. Ref.4
Sequence conflict4961G → V in AAL69526. Ref.1
Sequence conflict5621L → V in AAL69526. Ref.1
Sequence conflict8541R → Q in AAL69526. Ref.1
Sequence conflict8631L → V in AAL69526. Ref.1
Sequence conflict8701K → R in AAL69526. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: 5FCEE8D1903DF803

FASTA1,484163,681
        10         20         30         40         50         60 
MPNSERHGGK KDGSGGASGT SQPSSGGGSS NSRERHRLVS KHKRHKSKHS KDVGLVTPEA 

        70         80         90        100        110        120 
ASLGTIIKPL VEYDDISSDS DTFSDDTAFK SDRRENEERR GTDRSDRLHR HRHHQHRRSR 

       130        140        150        160        170        180 
DLLKTKQTEK EKNQEVSKSG SMKDRVSGSS KRSVEGSDDY GKAQLSKSGS KESRSSKMHK 

       190        200        210        220        230        240 
EKTRKERELK SGYKDRSKSH RKRETPKSYK TVASPKRRSR SPHRKWSDSS KQDDSPSGAS 

       250        260        270        280        290        300 
YGQDYDLSPP RSHTSSNYDS YKKSPGSTSR RQSISPPYKE PSAYQSSTRS PSPYSRRQRS 

       310        320        330        340        350        360 
VSPYSRRRSS SYERSGSYSG RSPSPYGRRR SSSPFLSKRS LSRSPLPSRK SMKSRSRSPA 

       370        380        390        400        410        420 
YSRHSSSHSK KKRSGSRSRH SSISPVRLPL NSSLGAELSR KKKERAAAAA AAKMDGKESK 

       430        440        450        460        470        480 
SSPIILPKKE KLEVKESGLE SKKLPRSIKS EKSTPDTELV TVAHSNPEVK HCLDTGKVRL 

       490        500        510        520        530        540 
DENLQKHPAK DLKAQGTKDV KPVAPKEVIV TSKETETSEK ETLPPLPTIT SPPPLPATTP 

       550        560        570        580        590        600 
PPQTPPLPPL PPLPAIPLQP PLPPPQPPFS QVPVSSTSIL PSSPHPRTST LSSQTNSQPP 

       610        620        630        640        650        660 
VQVSMKTQVS ITAAIPHLKT STLPPLPLPP LLPGDDDMDS PKETLPSKPA KKEKEQRTRH 

       670        680        690        700        710        720 
LLTDLPLPPE LPGGDPSPPD SPEPKAITPP QQPYKKRPKI CCPRYGERRQ TESDWGKRCV 

       730        740        750        760        770        780 
DKFDIIGIIG EGTYGQVYKA KDKDTGELVA LKKVRLDNEK EGFPITAIRE IKILRQLVHQ 

       790        800        810        820        830        840 
SVVNMKEIVT DKQDALDFKK DKGAFYLVFE YMDHDLMGLL ESGLVHFSED HIKSFMKQLM 

       850        860        870        880        890        900 
EGLDYCHKKN FLHRDIKCSN ILLNNSGQIK LADFGLARLY NSEESRPYTN KVITLWYRPP 

       910        920        930        940        950        960 
ELLLGEERYT PAIDVWSCGC ILGELFTKKP IFQANLELAQ LELISRLCGS PCPAVWPDVI 

       970        980        990       1000       1010       1020 
KLPYFNTMKP KKQYRRRLRE EFSFIPSAAL DLLDHMLTLD PSKRCTAEQT LQSDFLKDVE 

      1030       1040       1050       1060       1070       1080 
LSKMAPPDLP HWQDCHELWS KKRRRQRQSG IVIEDPPPSK ASRKETTSGT TAEPVKNNSP 

      1090       1100       1110       1120       1130       1140 
APPQPAPVKA EPGPGDAVGL GDITQQLNQS ELAVLLNLLQ SQTDLSIPQM AQLLNIHSNP 

      1150       1160       1170       1180       1190       1200 
EMQQQLEALN QSISALTEAS SQQQDSESIA PEESLKEVPS VPVVLPPAEQ TTPEASNTPA 

      1210       1220       1230       1240       1250       1260 
DMQNVLAVLL SQLMKTQEPA GNLEENTNDK NSGPQGPRRT PTMPQEEAAA CPPHILPPEK 

      1270       1280       1290       1300       1310       1320 
RPPEPPGPPP PPPPPPLVEG DLSSAPQELN PAVTAALLQL LSQPEAEPPG HLPHEHQALR 

      1330       1340       1350       1360       1370       1380 
PMEYSTRSHP NRTYGNTDGP ETGFSSADTD ERSSGPALTE SLVQTPVKNR TFSGSVSHLG 

      1390       1400       1410       1420       1430       1440 
ESNSYQGTGS VQFPGDQDLR FTRVPLALHS VVGQPFLKSE GNSNSVVHAE TKLQNYGELG 

      1450       1460       1470       1480 
PGTTGANSSG TTLQWGGPAQ SYGKPYRGAA RVLPRGGRGR GVPY 

« Hide

Isoform 2 [UniParc].

Checksum: F21408B379D9EFB5
Show »

FASTA1,258139,883
Isoform 3 [UniParc].

Checksum: 53626C566777F0CA
Show »

FASTA1,475162,755

References

« Hide 'large scale' references
[1]"Characterization of a putative SR-related protein kinase that is differentially expressed in the embryonic nervous system."
Lin S.-F., Chen H.-H., Fann M.-J.
Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: BALB/c.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 425-1484 (ISOFORM 3).
Tissue: Embryonic tail.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382; SER-384 AND SER-1079, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[6]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382 AND SER-384, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[7]"The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes."
Blazek D., Kohoutek J., Bartholomeeusen K., Johansen E., Hulinkova P., Luo Z., Cimermancic P., Ule J., Peterlin B.M.
Genes Dev. 25:2158-2172(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS25342.1. [Q14AX6-2]
CCDS48901.1. [Q14AX6-1]
CCDS48902.1. [Q14AX6-3]
RefSeqNP_001103096.1. NM_001109626.1. [Q14AX6-1]
NP_001103098.1. NM_001109628.1. [Q14AX6-3]
NP_081228.2. NM_026952.2. [Q14AX6-2]
UniGeneMm.260516.
Mm.486492.
Mm.488484.

3D structure databases

ProteinModelPortalQ14AX6.
SMRQ14AX6. Positions 712-1042.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid213247. 1 interaction.
IntActQ14AX6. 1 interaction.
MINTMINT-4119098.

PTM databases

PhosphoSiteQ14AX6.

Proteomic databases

MaxQBQ14AX6.
PaxDbQ14AX6.
PRIDEQ14AX6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000003203; ENSMUSP00000003203; ENSMUSG00000003119. [Q14AX6-2]
ENSMUST00000107538; ENSMUSP00000103162; ENSMUSG00000003119. [Q14AX6-1]
ENSMUST00000107539; ENSMUSP00000103163; ENSMUSG00000003119. [Q14AX6-3]
GeneID69131.
KEGGmmu:69131.
UCSCuc007lfr.2. mouse. [Q14AX6-1]
uc007lfs.2. mouse. [Q14AX6-2]
uc007lfu.2. mouse. [Q14AX6-3]

Organism-specific databases

CTD51755.
MGIMGI:1098802. Cdk12.
RougeSearch...

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000114964.
HOGENOMHOG000049118.
HOVERGENHBG050852.
InParanoidQ14AX6.
KOK08819.
OMAYSTRSHP.
OrthoDBEOG76DTSM.
PhylomeDBQ14AX6.
TreeFamTF101060.

Gene expression databases

ArrayExpressQ14AX6.
BgeeQ14AX6.
CleanExMM_CRKRS.
GenevestigatorQ14AX6.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio328674.
PROQ14AX6.
SOURCESearch...

Entry information

Entry nameCDK12_MOUSE
AccessionPrimary (citable) accession number: Q14AX6
Secondary accession number(s): A2A530 expand/collapse secondary AC list , A2A531, B1AQH7, Q6ZQ27, Q8R457
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: July 9, 2014
This is version 79 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot