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Description:
Cell division protein kinase 7 (EC 2.7.1.37) (CDK-activating kinase)(CAK) (TFIIH basal transcription factor complex kinase subunit) (39kDa protein kinase) (P39 Mo15) (STK1) (CAK1).
Molecular weight: 39038
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 )
Important dates:
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 1.
07-MAR-2006, entry version 67.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein CDK7_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | X79193 | CAA55785.1 | - |
| EMBL | L20320 | AAA36657.1 | - |
| EMBL | X77743 | CAA54793.1 | - |
| EMBL | X77303 | CAA54508.1 | - |
| EMBL | Y13120 | CAA73587.1 | - |
| EMBL | AY130859 | AAM77799.1 | - |
| EMBL | BC000834 | AAH00834.1 | - |
| EMBL | BC005298 | AAH05298.1 | - |
| PIR | A54820 | A54820. | |
| PIR | I37215 | I37215. | |
| PDB | 1LG3 | Model | A=1-307. |
| PDB | 1PA8 | Model | A=181-346. |
| PDB | 1UA2 | X-ray | A/B/C/D=1-346. |
| TRANSFAC | T02186 | -. | |
| Ensembl | ENSG00000134058 | Homo sapiens.1 | |
| H-InvDB | HIX0004919 | -.1 | |
| HGNC | HGNC:1778 | CDK7.1 | |
| MIM | 601955 | gene. | |
| Reactome | P50613 | -.1 | |
| LinkHub | P50613 | -.1 | |
| GO | GO:0005634 | C:nucleus | TAS. |
| GO | GO:0050681 | F:androgen receptor binding | NAS. |
| GO | GO:0004693 | F:cyclin-dependent protein kinase activity | TAS. |
| GO | GO:0004672 | F:protein kinase activity | TAS. |
| GO | GO:0003713 | F:transcription coactivator activity | NAS. |
| GO | GO:0030521 | P:androgen receptor signaling pathway | NAS. |
| GO | GO:0008283 | P:cell proliferation | TAS. |
| GO | GO:0045893 | P:positive regulation of transcription, DNA-d... | NAS. |
| GO | GO:0000079 | P:regulation of cyclin dependent protein kina... | TAS. |
| GO | GO:0006367 | P:transcription initiation from RNA polymeras... | TAS. |
| InterPro | IPR000719 | Prot_kinase. | |
| InterPro | IPR008271 | Ser_thr_pkin_AS. | |
| InterPro | IPR002290 | Ser_thr_pkinase. | |
| InterPro | IPR001245 | Tyr_pkinase. | |
| Pfam | PF00069 | Pkinase | 1. |
| ProDom | PD000001 | Prot_kinase | 1. |
| SMART | SM00220 | S_TKc | 1. |
| PROSITE | PS00107 | PROTEIN_KINASE_ATP | 1. |
| PROSITE | PS50011 | PROTEIN_KINASE_DOM | 1. |
| PROSITE | PS00108 | PROTEIN_KINASE_ST | 1. |
Keywords:
3D-structure; ATP-binding; Cell cycle; Cell division; DNA damage; DNA repair; Kinase; Nuclear protein; Nucleotide-binding; Phosphorylation; Polymorphism; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Placenta;
RX MEDLINE=95014737; PubMed=7929589; DOI=10.1083/jcb.127.2.467;
RA Tassan J.-P., Schultz S.J., Bartek J., Nigg E.A.;
RT "Cell cycle analysis of the activity, subcellular localization, and
RT subunit composition of human CAK (CDK-activating kinase).";
RL J. Cell Biol. 127:467-478(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Mammary gland;
RX MEDLINE=94268838; PubMed=8208544;
RA Levedakou E.N., He M., Baptist E.W., Craven R.J., Cance W.G.,
RA Welcsh P.L., Simmons A., Naylor S.L., Leach R.J., Lewis T.B.,
RA Bowcock A., Liu E.T.;
RT "Two novel human serine/threonine kinases with homologies to the cell
RT cycle regulating Xenopus MO15, and NIMA kinases: cloning and
RT characterization of their expression pattern.";
RL Oncogene 9:1977-1988(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RX MEDLINE=95022621; PubMed=7936635;
RA Darbon J.-M., Devault A., Taviaux S., Fesquet D., Martinez A.M.,
RA Galas S., Cavadore J.-C., Doree M., Blanchard J.-M.;
RT "Cloning, expression and subcellular localization of the human homolog
RT of p40MO15 catalytic subunit of cdk-activating kinase.";
RL Oncogene 9:3127-3138(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Fibroblast;
RX MEDLINE=94268852; PubMed=8208556;
RA Wu L., Yee A., Liu L., Carbonaro-Hall D., Venkatesan N., Tolo T.,
RA Hall F.L.;
RT "Molecular cloning of the human CAK1 gene encoding a cyclin-dependent
RT kinase-activating kinase.";
RL Oncogene 9:2089-2096(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Lung, and Thymus;
RA Kobelt D., Karn T., Hock B., Holtrich U., Braeuninger A., Wolf G.,
RA Strebhardt K., Ruebsamen-Waigmann H.;
RT "Human and Xenopus MO15 mRNA are highly conserved but show different
RT patterns of expression in adult tissues.";
RL Oncol. Rep. 1:1269-1275(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-163 AND MET-285.
RA Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W.,
RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and Urinary bladder;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [8]
RP MUTAGENESIS OF THR-170.
RX MEDLINE=94349374; PubMed=8069918; DOI=10.1016/0092-8674(94)90535-5;
RA Fisher R.P., Morgan D.O.;
RT "A novel cyclin associates with MO15/CDK7 to form the CDK-activating
RT kinase.";
RL Cell 78:713-724(1994).
RN [9]
RP FUNCTION.
RX MEDLINE=99149021; PubMed=10024882; DOI=10.1016/S1097-2765(00)80177-X;
RA Tirode F., Busso D., Coin F., Egly J.-M.;
RT "Reconstitution of the transcription factor TFIIH: assignment of
RT functions for the three enzymatic subunits, XPB, XPD, and cdk7.";
RL Mol. Cell 3:87-95(1999).
RN [10]
RP PHOSPHORYLATION SITES SER-164 AND THR-170, AND MUTAGENESIS OF SER-164
RP AND THR-170.
RX MEDLINE=99051317; PubMed=9832506;
RA Akoulitchev S., Reinberg D.;
RT "The molecular mechanism of mitotic inhibition of TFIIH is mediated by
RT phosphorylation of CDK7.";
RL Genes Dev. 12:3541-3550(1998).
Feature:
CHAIN 1 346 Cell division protein kinase 7.
/FTId=PRO_0000085791.
DOMAIN 12 295 Protein kinase.
NP_BIND 18 26 ATP (By similarity).
ACT_SITE 137 137 Proton acceptor (By similarity).
BINDING 41 41 ATP (By similarity).
MOD_RES 164 164 Phosphoserine.
MOD_RES 170 170 Phosphothreonine (By similarity).
VARIANT 163 163 G -> A.
/FTId=VAR_023118.
VARIANT 285 285 T -> M.
/FTId=VAR_023119.
MUTAGEN 41 41 K->A: Total loss of activity.
MUTAGEN 164 164 S->A: No mitotic repression of
transcriptional activity of the
reconstituted TFIIH complex.
MUTAGEN 170 170 T->A: Total loss of activity.
MUTAGEN 170 170 T->A: Total loss of transcriptional
activity of the reconstituted TFIIH
complex.
CONFLICT 130 130 Q -> R (in Ref. 7; AAH05298).
CONFLICT 249 249 F -> C (in Ref. 5).
CONFLICT 321 321 S -> A (in Ref. 5).
STRAND 14 21
TURN 22 23
STRAND 24 30
STRAND 32 33
STRAND 36 42
TURN 57 57
HELIX 58 68
TURN 72 73
STRAND 74 74
STRAND 77 81
TURN 84 85
STRAND 88 92
STRAND 95 97
HELIX 98 102
TURN 103 104
STRAND 107 108
STRAND 111 112
HELIX 113 130
TURN 131 132
HELIX 140 142
STRAND 143 145
TURN 147 148
STRAND 151 153
HELIX 157 159
STRAND 160 160
TURN 161 163
STRAND 164 164
STRAND 172 172
TURN 177 178
HELIX 181 184
TURN 185 186
STRAND 188 188
HELIX 192 208
STRAND 209 210
STRAND 212 213
STRAND 216 217
HELIX 218 229
TURN 234 236
STRAND 237 239
TURN 240 241
STRAND 242 243
TURN 244 245
HELIX 257 260
TURN 262 263
HELIX 266 276
STRAND 278 279
TURN 280 282
STRAND 283 283
HELIX 286 290
TURN 291 291
STRAND 292 292
HELIX 293 295
TURN 296 296
STRAND 297 299
STRAND 304 307
Comments:
-!- FUNCTION: Cyclin-dependent kinases (CDKs) are activated by the
binding to a cyclin and mediate the progression through the cell
cycle. Each different complex controls a specific transition
between two subsequent phases in the cell cycle. CDK7 is the
catalytic subunit of the CDK-activating kinase (CAK) complex, a
serine-threonine kinase. CAK activates the cyclin-associated
kinases CDC2/CDK1, CDK2, CDK4 and CDK6 by threonine
phosphorylation. CAK complexed to the core-TFIIH basal
transcription factor activates RNA polymerase II by serine
phosphorylation of the repetitive C-terminus domain (CTD) of its
large subunit (POLR2A), allowing its escape from the promoter and
elongation of the transcripts. Involved in cell cycle control and
in RNA transcription by RNA polymerase II. Its expression and
activity are constant throughout the cell cycle.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- ENZYME REGULATION: Inactivated by phosphorylation.
-!- SUBUNIT: Associates primarily with cyclin H and MAT1 to form the
CAK complex. CAK can further associate with the core-TFIIH to form
the TFIIH basal transcription factor.
-!- SUBCELLULAR LOCATION: Nucleus.
-!- TISSUE SPECIFICITY: Ubiquitous.
-!- PTM: Phosphorylation of Ser-164 during mitosis inactivates the
enzyme.
-!- PTM: Phosphorylation of Thr-170 is required for activity.
-!- SIMILARITY: Belongs to the Ser/Thr protein kinase family.
CDC2/CDKX subfamily.
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Sequence length: 346
MALDVKSRAK RYEKLDFLGE GQFATVYKAR DKNTNQIVAI KKIKLGHRSE AKDGINRTAL
REIKLLQELS HPNIIGLLDA FGHKSNISLV FDFMETDLEV IIKDNSLVLT PSHIKAYMLM
TLQGLEYLHQ HWILHRDLKP NNLLLDENGV LKLADFGLAK SFGSPNRAYT HQVVTRWYRA
PELLFGARMY GVGVDMWAVG CILAELLLRV PFLPGDSDLD QLTRIFETLG TPTEEQWPDM
CSLPDYVTFK SFPGIPLHHI FSAAGDDLLD LIQGLFLFNP CARITATQAL KMKYFSNRPG
PTPGCQLPRP NCPVETLKEQ SNPALAIKRK RTEALEQGGL PKKLIF