CDKAL_MOUSE
ID CDKAL_MOUSE Reviewed; 578 AA.
AC Q91WE6; Q3TE97; Q3V3D2; Q5T0I5; Q8C4B0; Q9CT69;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Threonylcarbamoyladenosine tRNA methylthiotransferase;
DE EC=2.8.4.5 {ECO:0000269|PubMed:20584901};
DE AltName: Full=CDK5 regulatory subunit-associated protein 1-like 1;
DE AltName: Full=tRNA-t(6)A37 methylthiotransferase;
GN Name=Cdkal1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Cerebellum, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20584901; DOI=10.1074/jbc.m110.106831;
RA Arragain S., Handelman S.K., Forouhar F., Wei F.Y., Tomizawa K., Hunt J.F.,
RA Douki T., Fontecave M., Mulliez E., Atta M.;
RT "Identification of eukaryotic and prokaryotic methylthiotransferase for
RT biosynthesis of 2-methylthio-N6-threonylcarbamoyladenosine in tRNA.";
RL J. Biol. Chem. 285:28425-28433(2010).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=23048041; DOI=10.1074/jbc.m112.376558;
RA Brambillasca S., Altkrueger A., Colombo S., Friedrich A., Eickelmann P.,
RA Mark M., Borgese N., Solimena M.;
RT "CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1) is a tail-
RT anchored protein in the endoplasmic reticulum (ER) of insulinoma cells.";
RL J. Biol. Chem. 287:41808-41819(2012).
CC -!- FUNCTION: Catalyzes the methylthiolation of N6-
CC threonylcarbamoyladenosine (t(6)A), leading to the formation of 2-
CC methylthio-N6-threonylcarbamoyladenosine (ms(2)t(6)A) at position 37 in
CC tRNAs that read codons beginning with adenine.
CC {ECO:0000269|PubMed:20584901}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[sulfur carrier]-SH + AH2 + N(6)-L-
CC threonylcarbamoyladenosine(37) in tRNA + 2 S-adenosyl-L-methionine =
CC 2-methylsulfanyl-N(6)-L-threonylcarbamoyladenosine(37) in tRNA + 5'-
CC deoxyadenosine + [sulfur carrier]-H + A + 2 H(+) + L-methionine + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:37075, Rhea:RHEA-COMP:10163,
CC Rhea:RHEA-COMP:11092, Rhea:RHEA-COMP:14737, Rhea:RHEA-COMP:14739,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15378, ChEBI:CHEBI:17319,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:29917, ChEBI:CHEBI:57844,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:64428,
CC ChEBI:CHEBI:74418, ChEBI:CHEBI:74420; EC=2.8.4.5;
CC Evidence={ECO:0000269|PubMed:20584901};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00780};
CC Note=Binds 2 [4Fe-4S] clusters. One cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000255|PROSITE-ProRule:PRU00780};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q5VV42}; Single-pass membrane protein
CC {ECO:0000255}. Note=Is a tail-anchored protein that exploits the TCR40
CC assisted pathway for insertion into the endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:Q5VV42}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q91WE6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91WE6-2; Sequence=VSP_027460;
CC Name=3;
CC IsoId=Q91WE6-3; Sequence=VSP_027457;
CC Name=4;
CC IsoId=Q91WE6-4; Sequence=VSP_027456, VSP_027458, VSP_027459;
CC Name=5;
CC IsoId=Q91WE6-5; Sequence=VSP_027454, VSP_027455;
CC -!- TISSUE SPECIFICITY: Expressed in pancreas, liver and skeletal muscle,
CC especially in white muscle fibers. {ECO:0000269|PubMed:23048041}.
CC -!- SIMILARITY: Belongs to the methylthiotransferase family. CDKAL1
CC subfamily. {ECO:0000305}.
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DR EMBL; AK004490; BAB23330.1; -; mRNA.
DR EMBL; AK041864; BAE20608.1; -; mRNA.
DR EMBL; AK045506; BAE43325.1; -; mRNA.
DR EMBL; AK082629; BAC38554.1; -; mRNA.
DR EMBL; AK169761; BAE41351.1; -; mRNA.
DR EMBL; AL513025; CAI24677.1; -; Genomic_DNA.
DR EMBL; AL512647; CAI24677.1; JOINED; Genomic_DNA.
DR EMBL; AL589701; CAI24677.1; JOINED; Genomic_DNA.
DR EMBL; AL645587; CAI24677.1; JOINED; Genomic_DNA.
DR EMBL; AL512647; CAI25816.1; -; Genomic_DNA.
DR EMBL; AL513025; CAI25816.1; JOINED; Genomic_DNA.
DR EMBL; AL589701; CAI25816.1; JOINED; Genomic_DNA.
DR EMBL; AL645587; CAI25816.1; JOINED; Genomic_DNA.
DR EMBL; AL645587; CAI35144.1; -; Genomic_DNA.
DR EMBL; AL512647; CAI35144.1; JOINED; Genomic_DNA.
DR EMBL; AL513025; CAI35144.1; JOINED; Genomic_DNA.
DR EMBL; AL589701; CAI35144.1; JOINED; Genomic_DNA.
DR EMBL; AL589701; CAI35240.1; -; Genomic_DNA.
DR EMBL; AL512647; CAI35240.1; JOINED; Genomic_DNA.
DR EMBL; AL513025; CAI35240.1; JOINED; Genomic_DNA.
DR EMBL; AL645587; CAI35240.1; JOINED; Genomic_DNA.
DR EMBL; AL513025; CAI24675.1; -; Genomic_DNA.
DR EMBL; BC016073; AAH16073.1; -; mRNA.
DR CCDS; CCDS26412.1; -. [Q91WE6-1]
DR CCDS; CCDS84016.1; -. [Q91WE6-5]
DR RefSeq; NP_001295415.1; NM_001308486.1. [Q91WE6-5]
DR RefSeq; NP_653119.1; NM_144536.3. [Q91WE6-1]
DR AlphaFoldDB; Q91WE6; -.
DR SMR; Q91WE6; -.
DR BioGRID; 213112; 3.
DR IntAct; Q91WE6; 1.
DR STRING; 10090.ENSMUSP00000006353; -.
DR iPTMnet; Q91WE6; -.
DR PhosphoSitePlus; Q91WE6; -.
DR EPD; Q91WE6; -.
DR jPOST; Q91WE6; -.
DR MaxQB; Q91WE6; -.
DR PaxDb; Q91WE6; -.
DR PeptideAtlas; Q91WE6; -.
DR PRIDE; Q91WE6; -.
DR ProteomicsDB; 281145; -. [Q91WE6-1]
DR ProteomicsDB; 281146; -. [Q91WE6-2]
DR ProteomicsDB; 281147; -. [Q91WE6-3]
DR ProteomicsDB; 281148; -. [Q91WE6-4]
DR ProteomicsDB; 281149; -. [Q91WE6-5]
DR Antibodypedia; 2738; 247 antibodies from 32 providers.
DR DNASU; 68916; -.
DR Ensembl; ENSMUST00000006353; ENSMUSP00000006353; ENSMUSG00000006191. [Q91WE6-1]
DR Ensembl; ENSMUST00000091674; ENSMUSP00000089262; ENSMUSG00000006191. [Q91WE6-5]
DR Ensembl; ENSMUST00000137225; ENSMUSP00000117404; ENSMUSG00000006191. [Q91WE6-4]
DR Ensembl; ENSMUST00000140278; ENSMUSP00000122249; ENSMUSG00000006191. [Q91WE6-2]
DR GeneID; 68916; -.
DR KEGG; mmu:68916; -.
DR UCSC; uc007pyn.1; mouse. [Q91WE6-1]
DR CTD; 54901; -.
DR MGI; MGI:1921765; Cdkal1.
DR VEuPathDB; HostDB:ENSMUSG00000006191; -.
DR eggNOG; KOG4355; Eukaryota.
DR GeneTree; ENSGT00940000155952; -.
DR HOGENOM; CLU_018697_4_1_1; -.
DR InParanoid; Q91WE6; -.
DR OMA; HYAYPTG; -.
DR OrthoDB; 835984at2759; -.
DR PhylomeDB; Q91WE6; -.
DR TreeFam; TF317476; -.
DR BioGRID-ORCS; 68916; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Cdkal1; mouse.
DR PRO; PR:Q91WE6; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q91WE6; protein.
DR Bgee; ENSMUSG00000006191; Expressed in spermatocyte and 211 other tissues.
DR ExpressionAtlas; Q91WE6; baseline and differential.
DR Genevisible; Q91WE6; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:MGI.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035598; F:N6-threonylcarbomyladenosine methylthiotransferase activity; IMP:MGI.
DR GO; GO:0061712; F:tRNA (N(6)-L-threonylcarbamoyladenosine(37)-C(2))-methylthiotransferase; IEA:UniProtKB-EC.
DR GO; GO:1990145; P:maintenance of translational fidelity; IMP:MGI.
DR GO; GO:0035600; P:tRNA methylthiolation; IMP:MGI.
DR Gene3D; 3.40.50.12160; -; 1.
DR Gene3D; 3.80.30.20; -; 1.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR005839; Methylthiotransferase.
DR InterPro; IPR020612; Methylthiotransferase_CS.
DR InterPro; IPR013848; Methylthiotransferase_N.
DR InterPro; IPR038135; Methylthiotransferase_N_sf.
DR InterPro; IPR006466; MiaB-like_B.
DR InterPro; IPR007197; rSAM.
DR InterPro; IPR023404; rSAM_horseshoe.
DR InterPro; IPR002792; TRAM_dom.
DR Pfam; PF04055; Radical_SAM; 1.
DR Pfam; PF01938; TRAM; 1.
DR Pfam; PF00919; UPF0004; 1.
DR SFLD; SFLDS00029; Radical_SAM; 1.
DR SMART; SM00729; Elp3; 1.
DR TIGRFAMs; TIGR01578; MiaB-like-B; 1.
DR TIGRFAMs; TIGR00089; TIGR00089; 1.
DR PROSITE; PS51449; MTTASE_N; 1.
DR PROSITE; PS01278; MTTASE_RADICAL; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
DR PROSITE; PS50926; TRAM; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Alternative splicing; Endoplasmic reticulum; Iron; Iron-sulfur;
KW Membrane; Metal-binding; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Transmembrane; Transmembrane helix;
KW tRNA processing.
FT CHAIN 1..578
FT /note="Threonylcarbamoyladenosine tRNA
FT methylthiotransferase"
FT /id="PRO_0000298671"
FT TRANSMEM 553..570
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 63..171
FT /note="MTTase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT DOMAIN 199..430
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT DOMAIN 430..492
FT /note="TRAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00208"
FT BINDING 72
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 108
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 137
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 213
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 217
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT BINDING 220
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00780"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5VV42"
FT MOD_RES 498
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5VV42"
FT VAR_SEQ 95..135
FT /note="ENASDADLWLLNSCTVKNPAEDHFRNSIKKAQEENKKVVLA -> AQSGTES
FT SLGAMELIHHPVRTVLHSVRCRVLKTPLILLVVWW (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027454"
FT VAR_SEQ 136..578
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027455"
FT VAR_SEQ 213..360
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027456"
FT VAR_SEQ 352..578
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027457"
FT VAR_SEQ 366
FT /note="P -> L (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027458"
FT VAR_SEQ 367..578
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027459"
FT VAR_SEQ 516..578
FT /note="EFRNRLGNHPNGTSDTCPATQHGSAYSRMVLQMSQYDCALKVATGLALLALL
FT LHFWPDSLLTM -> ALDYL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027460"
SQ SEQUENCE 578 AA; 65289 MW; 293F451812B51D50 CRC64;
MPSASCDVLL DDIEDIISQE DSKPQDRQFS RKHVFPKVRR RNTQKYLQEE PRPPSDSTIP
GIQKIWIRTW GCSHNNSDGE YMAGQLAAYG YKITENASDA DLWLLNSCTV KNPAEDHFRN
SIKKAQEENK KVVLAGCVPQ AQPRQDYLKG LSIIGVQQID RVVEVVEETI KGHSVRLLGQ
KKDNGKRLGG ARLDLPKIRK NPLIEIISIN TGCLNACTYC KTKHARGNLA SYPIDELVER
AKQSFQEGVC EIWLTSEDTG AYGRDIGTDL PTLLWKLVEV IPEGAMLRLG MTNPPYILEH
LEEMAKILNH PRVYAFLHIP VQSASDSVLM DMKREYCVAD FKRVVDFLKE KVPGITIATD
IICGFPGETD QDFQETVKLV EEYKFPSLFI NQFYPRPGTP AAKAEQVPAH VKKQRTKDLS
RVFHSYNPYD HKIGERQQVL VTEESFDSKF YVAHNRFYEQ VLVPKNPAFM GKMVEVDIYE
SGKHFLKGQP VSETRVYTPS ISKPLAKGEV SGLTKEFRNR LGNHPNGTSD TCPATQHGSA
YSRMVLQMSQ YDCALKVATG LALLALLLHF WPDSLLTM
