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Q3MJK5 (CDK12_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 82. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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
Protein kinase for splicing component
Gene names
Name:Cdk12
Synonyms:Crk7, Crkrs, Pksc
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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'. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors By similarity. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Ref.1

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. Ref.1

Subcellular location

Nucleus. Nucleus speckle. Note: Colocalized with nuclear speckles throughout interphase. Ref.1

Tissue specificity

Expressed in embryonic tissues such as brain, spinal cord, heart, lung, liver, gut and limb. Levels are lower in adult tissues. Ref.1

Developmental stage

Expressed at E10.5 and E14.5. Ref.1

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.

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 mutant phenotype Ref.1. 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 electronic annotation. Source: Ensembl

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 direct assay Ref.1. Source: UniProtKB

nuclear speck

Inferred from direct assay Ref.1. 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 binding

Inferred from physical interaction Ref.1. Source: UniProtKB

cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q3MJK5-1)

Also known as: CDK12(L);

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: Q3MJK5-2)

Also known as: CDK12(S);

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14841484Cyclin-dependent kinase 12
PRO_0000314471

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 By similarity
Modified residue3841Phosphoserine By similarity
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 By similarity
Modified residue12401Phosphothreonine By similarity

Natural variations

Alternative sequence1250 – 12589ACPPHILPP → GKQTGHESQ in isoform 2.
VSP_030288
Alternative sequence1259 – 1484226Missing in isoform 2.
VSP_030289

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CDK12(L)) [UniParc].

Last modified October 25, 2005. Version 1.
Checksum: E3B346EA6A587D7B

FASTA1,484163,790
        10         20         30         40         50         60 
MPNSERHGGK KDGSGGASGT SQPSSGGGSS NSRERHRLVS KHKRHKSKHS KDMGLVTPEA 

        70         80         90        100        110        120 
ASLGTIIKPL VEYDDISSDS DTFSDDMAFK SDRRENDERR GTDRSDRLHR HRHHQHRRSR 

       130        140        150        160        170        180 
DLLKTKQTEK EKNQEVSKSG SMKDRLSGSS KRSVEGNDDY GKAQLSKSSS KESRSSKMHK 

       190        200        210        220        230        240 
EKTRKERELK SGHKDRSKSH RKRETPKSYK TVDSPKRRSR SPHRKWSDSS KQDDSPSGAS 

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

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

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

       430        440        450        460        470        480 
GSPIILPKKE KFEVKESGLE SKKLPRGIKS EKSTPDTELV NVAHSNTEVK NCLDTGKVKL 

       490        500        510        520        530        540 
DENLQKHPVK DLKAQGTKDT KPVALKEVIV TSKETETSEK EALPPLPTIT SPPPLPSTTP 

       550        560        570        580        590        600 
PPQTPPLPPL PPLPAVPLQP PLPPPQPPFS QVPVSNTSTL PSSPHPRTST LSSQTNSQPL 

       610        620        630        640        650        660 
VQVSMKTQLS VTAAIPHLKT STLPPLPLPP LLPGDDDMDS PKEMLPSKPA 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 IVIEEQPPSK ASRKETTSGT AAEPVKNSSP 

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

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

      1210       1220       1230       1240       1250       1260 
DMQNMLAVLL SQLMKTQEPA GNLEENTSDK NSGPQGPRRT PTMPQEEAAA CPPHILPPEK 

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

      1330       1340       1350       1360       1370       1380 
PMEYSTRSHP NRTYGNTDGP ETGFSATDTD ERSSGPALTE SLVQTLVKNR TFSGSVSHLG 

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

      1450       1460       1470       1480 
PGTTGANSSG TTLQWGGPAQ SFGKPYRGAA RVPPRGGRGR GVPY 

« Hide

Isoform 2 (CDK12(S)) [UniParc].

Checksum: 9CF659A276E67FAE
Show »

FASTA1,258139,985

References

[1]"Identification and characterization of the CDK12/cyclin L1 complex involved in alternative splicing regulation."
Chen H.-H., Wang Y.-C., Fann M.-J.
Mol. Cell. Biol. 26:2736-2745(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH CCNL1 AND CCNL2, SUBCELLULAR LOCATION, FUNCTION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY072294 mRNA. Translation: AAL69525.1.
AY962568 mRNA. Translation: AAY41734.1.
RefSeqNP_001029039.1. NM_001033867.1. [Q3MJK5-1]
NP_620271.1. NM_138916.2. [Q3MJK5-2]
UniGeneRn.48817.

3D structure databases

ProteinModelPortalQ3MJK5.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000008256.

PTM databases

PhosphoSiteQ3MJK5.

Proteomic databases

PaxDbQ3MJK5.
PRIDEQ3MJK5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000008256; ENSRNOP00000008256; ENSRNOG00000006000. [Q3MJK5-1]
GeneID192350.
KEGGrno:192350.
UCSCRGD:621111. rat. [Q3MJK5-1]

Organism-specific databases

CTD51755.
RGD621111. Cdk12.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000114964.
HOGENOMHOG000049118.
HOVERGENHBG050852.
InParanoidQ3MJK5.
KOK08819.
OMAYSTRSHP.
OrthoDBEOG76DTSM.
PhylomeDBQ3MJK5.
TreeFamTF101060.

Gene expression databases

GenevestigatorQ3MJK5.

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

NextBio623019.
PROQ3MJK5.

Entry information

Entry nameCDK12_RAT
AccessionPrimary (citable) accession number: Q3MJK5
Secondary accession number(s): Q8R458
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: October 25, 2005
Last modified: June 11, 2014
This is version 82 of the entry and version 1 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