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Q14AX6

- CDK12_MOUSE

UniProt

Q14AX6 - CDK12_MOUSE

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Protein
Cyclin-dependent kinase 12
Gene
Cdk12, Crk7, Crkrs, Kiaa0904
Organism
Mus musculus (Mouse)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei752 – 7521ATP By similarity
Active sitei855 – 8551Proton acceptor By similarity
Binding sitei1036 – 10361ATP By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi729 – 7379ATP By similarity
Nucleotide bindingi810 – 8156ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB
  3. cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB-EC
  4. protein kinase activity Source: HGNC

GO - Biological processi

  1. RNA splicing Source: UniProtKB
  2. mRNA processing Source: UniProtKB-KW
  3. phosphorylation of RNA polymerase II C-terminal domain Source: UniProtKB
  4. protein autophosphorylation Source: HGNC
  5. regulation of MAP kinase activity Source: UniProtKB
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

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
ProteomesiUP000000589: 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.1 Publication

GO - Cellular componenti

  1. cyclin K-CDK12 complex Source: Ensembl
  2. nuclear cyclin-dependent protein kinase holoenzyme complex Source: UniProtKB
  3. nuclear speck Source: UniProtKB
  4. nucleolus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14841484Cyclin-dependent kinase 12
PRO_0000314470Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei57 – 571Phosphothreonine By similarity
Modified residuei73 – 731Phosphotyrosine By similarity
Modified residuei235 – 2351Phosphoserine By similarity
Modified residuei248 – 2481Phosphoserine By similarity
Modified residuei273 – 2731Phosphoserine By similarity
Modified residuei275 – 2751Phosphoserine By similarity
Modified residuei300 – 3001Phosphoserine By similarity
Modified residuei302 – 3021Phosphoserine By similarity
Modified residuei309 – 3091Phosphoserine By similarity
Modified residuei311 – 3111Phosphoserine By similarity
Modified residuei317 – 3171Phosphoserine By similarity
Modified residuei322 – 3221Phosphoserine By similarity
Modified residuei324 – 3241Phosphoserine By similarity
Modified residuei331 – 3311Phosphoserine By similarity
Modified residuei332 – 3321Phosphoserine By similarity
Modified residuei333 – 3331Phosphoserine By similarity
Modified residuei337 – 3371Phosphoserine By similarity
Modified residuei344 – 3441Phosphoserine By similarity
Modified residuei382 – 3821Phosphoserine2 Publications
Modified residuei384 – 3841Phosphoserine2 Publications
Modified residuei399 – 3991Phosphoserine By similarity
Modified residuei419 – 4191Phosphoserine By similarity
Modified residuei422 – 4221Phosphoserine By similarity
Modified residuei511 – 5111Phosphothreonine By similarity
Modified residuei677 – 6771Phosphoserine By similarity
Modified residuei681 – 6811Phosphoserine By similarity
Modified residuei688 – 6881Phosphothreonine By similarity
Modified residuei889 – 8891Phosphothreonine By similarity
Modified residuei1049 – 10491Phosphoserine By similarity
Modified residuei1079 – 10791Phosphoserine1 Publication
Modified residuei1240 – 12401Phosphothreonine By similarity

Post-translational modificationi

Phosphorylation at Thr-889 increases kinase activity By similarity.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ14AX6.
PaxDbiQ14AX6.
PRIDEiQ14AX6.

PTM databases

PhosphoSiteiQ14AX6.

Expressioni

Gene expression databases

ArrayExpressiQ14AX6.
BgeeiQ14AX6.
CleanExiMM_CRKRS.
GenevestigatoriQ14AX6.

Interactioni

Subunit structurei

Interacts with CCNL1 and CCNL2 By similarity.1 Publication

Protein-protein interaction databases

BioGridi213247. 1 interaction.
IntActiQ14AX6. 1 interaction.
MINTiMINT-4119098.

Structurei

3D structure databases

ProteinModelPortaliQ14AX6.
SMRiQ14AX6. Positions 712-1042.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini723 – 1016294Protein kinase
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi137 – 393257Ser-rich
Add
BLAST
Compositional biasi406 – 4127Poly-Ala
Compositional biasi524 – 703180Pro-rich
Add
BLAST
Compositional biasi1234 – 127643Pro-rich
Add
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00740000114964.
HOGENOMiHOG000049118.
HOVERGENiHBG050852.
InParanoidiQ14AX6.
KOiK08819.
OMAiYSTRSHP.
OrthoDBiEOG76DTSM.
PhylomeDBiQ14AX6.
TreeFamiTF101060.

Family and domain databases

InterProiIPR011009. 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]
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. Align

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

MPNSERHGGK KDGSGGASGT SQPSSGGGSS NSRERHRLVS KHKRHKSKHS     50
KDVGLVTPEA ASLGTIIKPL VEYDDISSDS DTFSDDTAFK SDRRENEERR 100
GTDRSDRLHR HRHHQHRRSR DLLKTKQTEK EKNQEVSKSG SMKDRVSGSS 150
KRSVEGSDDY GKAQLSKSGS KESRSSKMHK EKTRKERELK SGYKDRSKSH 200
RKRETPKSYK TVASPKRRSR SPHRKWSDSS KQDDSPSGAS YGQDYDLSPP 250
RSHTSSNYDS YKKSPGSTSR RQSISPPYKE PSAYQSSTRS PSPYSRRQRS 300
VSPYSRRRSS SYERSGSYSG RSPSPYGRRR SSSPFLSKRS LSRSPLPSRK 350
SMKSRSRSPA YSRHSSSHSK KKRSGSRSRH SSISPVRLPL NSSLGAELSR 400
KKKERAAAAA AAKMDGKESK SSPIILPKKE KLEVKESGLE SKKLPRSIKS 450
EKSTPDTELV TVAHSNPEVK HCLDTGKVRL DENLQKHPAK DLKAQGTKDV 500
KPVAPKEVIV TSKETETSEK ETLPPLPTIT SPPPLPATTP PPQTPPLPPL 550
PPLPAIPLQP PLPPPQPPFS QVPVSSTSIL PSSPHPRTST LSSQTNSQPP 600
VQVSMKTQVS ITAAIPHLKT STLPPLPLPP LLPGDDDMDS PKETLPSKPA 650
KKEKEQRTRH LLTDLPLPPE LPGGDPSPPD SPEPKAITPP QQPYKKRPKI 700
CCPRYGERRQ TESDWGKRCV DKFDIIGIIG EGTYGQVYKA KDKDTGELVA 750
LKKVRLDNEK EGFPITAIRE IKILRQLVHQ SVVNMKEIVT DKQDALDFKK 800
DKGAFYLVFE YMDHDLMGLL ESGLVHFSED HIKSFMKQLM EGLDYCHKKN 850
FLHRDIKCSN ILLNNSGQIK LADFGLARLY NSEESRPYTN KVITLWYRPP 900
ELLLGEERYT PAIDVWSCGC ILGELFTKKP IFQANLELAQ LELISRLCGS 950
PCPAVWPDVI KLPYFNTMKP KKQYRRRLRE EFSFIPSAAL DLLDHMLTLD 1000
PSKRCTAEQT LQSDFLKDVE LSKMAPPDLP HWQDCHELWS KKRRRQRQSG 1050
IVIEDPPPSK ASRKETTSGT TAEPVKNNSP APPQPAPVKA EPGPGDAVGL 1100
GDITQQLNQS ELAVLLNLLQ SQTDLSIPQM AQLLNIHSNP EMQQQLEALN 1150
QSISALTEAS SQQQDSESIA PEESLKEVPS VPVVLPPAEQ TTPEASNTPA 1200
DMQNVLAVLL SQLMKTQEPA GNLEENTNDK NSGPQGPRRT PTMPQEEAAA 1250
CPPHILPPEK RPPEPPGPPP PPPPPPLVEG DLSSAPQELN PAVTAALLQL 1300
LSQPEAEPPG HLPHEHQALR PMEYSTRSHP NRTYGNTDGP ETGFSSADTD 1350
ERSSGPALTE SLVQTPVKNR TFSGSVSHLG ESNSYQGTGS VQFPGDQDLR 1400
FTRVPLALHS VVGQPFLKSE GNSNSVVHAE TKLQNYGELG PGTTGANSSG 1450
TTLQWGGPAQ SYGKPYRGAA RVLPRGGRGR GVPY 1484
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.

Show »
Length:1,475
Mass (Da):162,755
Checksum:i53626C566777F0CA
GO

Sequence cautioni

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1250 – 12589ACPPHILPP → GKQTGHESH in isoform 2.
VSP_030285
Alternative sequencei1250 – 12589Missing in isoform 3.
VSP_030286
Alternative sequencei1259 – 1484226Missing in isoform 2.
VSP_030287Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti346 – 3461L → I in AAL69526. 1 Publication
Sequence conflicti363 – 3631R → S in AAL69526. 1 Publication
Sequence conflicti377 – 3771R → H in AAL69526. 1 Publication
Sequence conflicti425 – 4273ILP → FCL in BAC98047. 1 Publication
Sequence conflicti496 – 4961G → V in AAL69526. 1 Publication
Sequence conflicti562 – 5621L → V in AAL69526. 1 Publication
Sequence conflicti854 – 8541R → Q in AAL69526. 1 Publication
Sequence conflicti863 – 8631L → V in AAL69526. 1 Publication
Sequence conflicti870 – 8701K → R in AAL69526. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS25342.1. [Q14AX6-2 ]
CCDS48901.1. [Q14AX6-1 ]
CCDS48902.1. [Q14AX6-3 ]
RefSeqi NP_001103096.1. NM_001109626.1. [Q14AX6-1 ]
NP_001103098.1. NM_001109628.1. [Q14AX6-3 ]
NP_081228.2. NM_026952.2. [Q14AX6-2 ]
UniGenei Mm.260516.
Mm.486492.
Mm.488484.

3D structure databases

ProteinModelPortali Q14AX6.
SMRi Q14AX6. Positions 712-1042.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 213247. 1 interaction.
IntActi Q14AX6. 1 interaction.
MINTi MINT-4119098.

PTM databases

PhosphoSitei Q14AX6.

Proteomic databases

MaxQBi Q14AX6.
PaxDbi Q14AX6.
PRIDEi Q14AX6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000003203 ; ENSMUSP00000003203 ; ENSMUSG00000003119 . [Q14AX6-2 ]
ENSMUST00000107538 ; ENSMUSP00000103162 ; ENSMUSG00000003119 . [Q14AX6-1 ]
ENSMUST00000107539 ; ENSMUSP00000103163 ; ENSMUSG00000003119 . [Q14AX6-3 ]
GeneIDi 69131.
KEGGi mmu:69131.
UCSCi uc007lfr.2. mouse. [Q14AX6-1 ]
uc007lfs.2. mouse. [Q14AX6-2 ]
uc007lfu.2. mouse. [Q14AX6-3 ]

Organism-specific databases

CTDi 51755.
MGIi MGI:1098802. Cdk12.
Rougei Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00740000114964.
HOGENOMi HOG000049118.
HOVERGENi HBG050852.
InParanoidi Q14AX6.
KOi K08819.
OMAi YSTRSHP.
OrthoDBi EOG76DTSM.
PhylomeDBi Q14AX6.
TreeFami TF101060.

Miscellaneous databases

NextBioi 328674.
PROi Q14AX6.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q14AX6.
Bgeei Q14AX6.
CleanExi MM_CRKRS.
Genevestigatori Q14AX6.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

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: July 9, 2014
This is version 79 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

External Data

Dasty 3

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