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FAST kinase domain-containing protein 4 (Cell cycle progression restoration protein 2) (Cell cycle progression protein 2) (Protein TBRG4) (Transforming growth factor beta regulator 4)

 FAKD4_HUMAN             Reviewed;         631 AA.
Q969Z0; A4D2L2; A4D2L3; D3DVL5; D3DVL6; O14710; Q53GI8; Q8NDM4;
Q9BUC6; Q9Y2F6;
23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
01-DEC-2001, sequence version 1.
18-JUL-2018, entry version 138.
RecName: Full=FAST kinase domain-containing protein 4 {ECO:0000303|PubMed:20869947};
AltName: Full=Cell cycle progression restoration protein 2;
Short=Cell cycle progression protein 2;
AltName: Full=Protein TBRG4;
AltName: Full=Transforming growth factor beta regulator 4 {ECO:0000312|HGNC:HGNC:17443};
Flags: Precursor;
Name=TBRG4 {ECO:0000312|HGNC:HGNC:17443};
Synonyms=CPR2 {ECO:0000303|PubMed:9383053},
FASTKD4 {ECO:0000303|PubMed:20869947}, KIAA0948;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Brain;
PubMed=10231032; DOI=10.1093/dnares/6.1.63;
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M.,
Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
"Prediction of the coding sequences of unidentified human genes. XIII.
The complete sequences of 100 new cDNA clones from brain which code
for large proteins in vitro.";
DNA Res. 6:63-70(1999).
[2]
SEQUENCE REVISION.
Ohara O., Nagase T., Kikuno R.;
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Kidney;
Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
Tanaka A., Yokoyama S.;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
SER-22 AND LEU-57.
TISSUE=Mammary cancer;
PubMed=17974005; DOI=10.1186/1471-2164-8-399;
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
"The full-ORF clone resource of the German cDNA consortium.";
BMC Genomics 8:399-399(2007).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12690205; DOI=10.1126/science.1083423;
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
Mural R.J., Adams M.D., Tsui L.-C.;
"Human chromosome 7: DNA sequence and biology.";
Science 300:767-772(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Lung, and Uterus;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
NUCLEOTIDE SEQUENCE [MRNA] OF 172-615 (ISOFORM 1), AND FUNCTION.
TISSUE=Hepatoma;
PubMed=9383053;
Edwards M.C., Liegeois N., Horecka J., DePinho R.A., Sprague G.F. Jr.,
Tyers M., Elledge S.J.;
"Human CPR (cell cycle progression restoration) genes impart a Far-
phenotype on yeast cells.";
Genetics 147:1063-1076(1997).
[9]
TISSUE SPECIFICITY.
TISSUE=Lung;
PubMed=12759187; DOI=10.1016/S0167-4781(03)00051-4;
Rival-Gervier S., Thepot D., Jolivet G., Houdebine L.-M.;
"Pig whey acidic protein gene is surrounded by two ubiquitously
expressed genes.";
Biochim. Biophys. Acta 1627:7-14(2003).
[10]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
Greff Z., Keri G., Stemmann O., Mann M.;
"Kinase-selective enrichment enables quantitative phosphoproteomics of
the kinome across the cell cycle.";
Mol. Cell 31:438-448(2008).
[11]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19608861; DOI=10.1126/science.1175371;
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
Walther T.C., Olsen J.V., Mann M.;
"Lysine acetylation targets protein complexes and co-regulates major
cellular functions.";
Science 325:834-840(2009).
[12]
SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=20869947; DOI=10.1016/j.bbrc.2010.09.075;
Simarro M., Gimenez-Cassina A., Kedersha N., Lazaro J.B.,
Adelmant G.O., Marto J.A., Rhee K., Tisdale S., Danial N.,
Benarafa C., Orduna A., Anderson P.;
"Fast kinase domain-containing protein 3 is a mitochondrial protein
essential for cellular respiration.";
Biochem. Biophys. Res. Commun. 401:440-446(2010).
[13]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[14]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22814378; DOI=10.1073/pnas.1210303109;
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
Aldabe R.;
"N-terminal acetylome analyses and functional insights of the N-
terminal acetyltransferase NatB.";
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
[15]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[16]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=25944712; DOI=10.1002/pmic.201400617;
Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M.,
Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
"N-terminome analysis of the human mitochondrial proteome.";
Proteomics 15:2519-2524(2015).
[17]
SUBCELLULAR LOCATION, FUNCTION, DOMAIN, AND MUTAGENESIS OF ASP-531.
PubMed=28335001; DOI=10.1093/nar/gkx164;
Boehm E., Zaganelli S., Maundrell K., Jourdain A.A., Thore S.,
Martinou J.C.;
"FASTKD1 and FASTKD4 have opposite effects on expression of specific
mitochondrial RNAs, depending upon their endonuclease-like RAP
domain.";
Nucleic Acids Res. 45:6135-6146(2017).
-!- FUNCTION: Plays a role in processing of mitochondrial RNA
precursors and in stabilization of a subset of mature
mitochondrial RNA species, such as MT-CO1, MT-CO2, MT-CYB, MT-CO3,
MT-ND3, MT-ND5 and MT-ATP8/6. May play a role in cell cycle
progression (PubMed:9383053). {ECO:0000269|PubMed:28335001,
ECO:0000269|PubMed:9383053}.
-!- INTERACTION:
Q6RW13:AGTRAP; NbExp=3; IntAct=EBI-702328, EBI-741181;
Q13137:CALCOCO2; NbExp=3; IntAct=EBI-702328, EBI-739580;
Q8IZU0:FAM9B; NbExp=3; IntAct=EBI-702328, EBI-10175124;
Q969L2:MAL2; NbExp=3; IntAct=EBI-702328, EBI-944295;
-!- SUBCELLULAR LOCATION: Mitochondrion matrix
{ECO:0000269|PubMed:20869947, ECO:0000269|PubMed:28335001}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q969Z0-1; Sequence=Displayed;
Name=2;
IsoId=Q969Z0-2; Sequence=VSP_022460;
-!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:12759187).
Expression detected in spleen, thymus, testis, ovary, colon,
heart, smooth muscle, kidney, brain, lung, liver and white adipose
tissue with highest expression in smooth muscle (PubMed:20869947).
{ECO:0000269|PubMed:12759187, ECO:0000269|PubMed:20869947}.
-!- DOMAIN: RAP domain is required for TBRG4 function in mRNA
stability and translation. {ECO:0000269|PubMed:28335001}.
-!- SIMILARITY: Belongs to the FAST kinase family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAB69312.1; Type=Frameshift; Positions=211, 479, 498, 576; Evidence={ECO:0000305};
Sequence=BAA76792.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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EMBL; AB023165; BAA76792.2; ALT_INIT; mRNA.
EMBL; AK222943; BAD96663.1; -; mRNA.
EMBL; AL833840; CAD38700.1; -; mRNA.
EMBL; CH236960; EAL23744.1; -; Genomic_DNA.
EMBL; CH236960; EAL23745.1; -; Genomic_DNA.
EMBL; CH471128; EAW61051.1; -; Genomic_DNA.
EMBL; CH471128; EAW61052.1; -; Genomic_DNA.
EMBL; CH471128; EAW61054.1; -; Genomic_DNA.
EMBL; CH471128; EAW61055.1; -; Genomic_DNA.
EMBL; BC002732; AAH02732.2; -; mRNA.
EMBL; BC014918; AAH14918.1; -; mRNA.
EMBL; BC017235; AAH17235.1; -; mRNA.
EMBL; AF011792; AAB69312.1; ALT_FRAME; mRNA.
CCDS; CCDS5501.1; -. [Q969Z0-1]
CCDS; CCDS5502.1; -. [Q969Z0-2]
RefSeq; NP_004740.2; NM_004749.3. [Q969Z0-1]
RefSeq; NP_112162.1; NM_030900.3. [Q969Z0-2]
RefSeq; NP_954573.1; NM_199122.2. [Q969Z0-2]
UniGene; Hs.231411; -.
UniGene; Hs.741611; -.
ProteinModelPortal; Q969Z0; -.
BioGrid; 114666; 41.
IntAct; Q969Z0; 33.
MINT; Q969Z0; -.
STRING; 9606.ENSP00000258770; -.
iPTMnet; Q969Z0; -.
PhosphoSitePlus; Q969Z0; -.
BioMuta; TBRG4; -.
DMDM; 74731072; -.
EPD; Q969Z0; -.
MaxQB; Q969Z0; -.
PaxDb; Q969Z0; -.
PeptideAtlas; Q969Z0; -.
PRIDE; Q969Z0; -.
ProteomicsDB; 75880; -.
ProteomicsDB; 75881; -. [Q969Z0-2]
DNASU; 9238; -.
Ensembl; ENST00000258770; ENSP00000258770; ENSG00000136270. [Q969Z0-1]
Ensembl; ENST00000361278; ENSP00000354992; ENSG00000136270. [Q969Z0-2]
Ensembl; ENST00000395655; ENSP00000379016; ENSG00000136270. [Q969Z0-2]
Ensembl; ENST00000494076; ENSP00000420597; ENSG00000136270. [Q969Z0-1]
GeneID; 9238; -.
KEGG; hsa:9238; -.
UCSC; uc003tmv.5; human. [Q969Z0-1]
CTD; 9238; -.
DisGeNET; 9238; -.
EuPathDB; HostDB:ENSG00000136270.13; -.
GeneCards; TBRG4; -.
HGNC; HGNC:17443; TBRG4.
HPA; HPA020582; -.
HPA; HPA050430; -.
MIM; 611325; gene.
neXtProt; NX_Q969Z0; -.
OpenTargets; ENSG00000136270; -.
PharmGKB; PA134882196; -.
eggNOG; ENOG410IEJA; Eukaryota.
eggNOG; ENOG4111EYX; LUCA.
GeneTree; ENSGT00530000063266; -.
HOVERGEN; HBG094028; -.
InParanoid; Q969Z0; -.
OMA; MMKVGHL; -.
OrthoDB; EOG091G0WV6; -.
PhylomeDB; Q969Z0; -.
TreeFam; TF324885; -.
ChiTaRS; TBRG4; human.
GeneWiki; TBRG4; -.
GenomeRNAi; 9238; -.
PRO; PR:Q969Z0; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000136270; -.
CleanEx; HS_TBRG4; -.
ExpressionAtlas; Q969Z0; baseline and differential.
Genevisible; Q969Z0; HS.
GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
GO; GO:0007050; P:cell cycle arrest; TAS:UniProtKB.
GO; GO:0045333; P:cellular respiration; ISS:UniProtKB.
GO; GO:0071277; P:cellular response to calcium ion; HEP:ARUK-UCL.
GO; GO:0090615; P:mitochondrial mRNA processing; IMP:UniProtKB.
GO; GO:0016071; P:mRNA metabolic process; IMP:UniProtKB.
GO; GO:0008284; P:positive regulation of cell proliferation; TAS:UniProtKB.
GO; GO:0044528; P:regulation of mitochondrial mRNA stability; IMP:UniProtKB.
InterPro; IPR013579; FAST_2.
InterPro; IPR010622; FAST_Leu-rich.
InterPro; IPR013584; RAP.
Pfam; PF06743; FAST_1; 1.
Pfam; PF08368; FAST_2; 1.
Pfam; PF08373; RAP; 1.
SMART; SM00952; RAP; 1.
PROSITE; PS51286; RAP; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Mitochondrion;
Phosphoprotein; Polymorphism; Reference proteome; Transit peptide.
TRANSIT 1 107 Mitochondrion. {ECO:0000255}.
CHAIN 108 631 FAST kinase domain-containing protein 4.
/FTId=PRO_0000273026.
DOMAIN 561 619 RAP. {ECO:0000255|PROSITE-
ProRule:PRU00619}.
MOD_RES 553 553 Phosphoserine.
{ECO:0000244|PubMed:23186163}.
VAR_SEQ 246 355 Missing (in isoform 2).
{ECO:0000303|PubMed:10231032,
ECO:0000303|Ref.3}.
/FTId=VSP_022460.
VARIANT 22 22 A -> S (in dbSNP:rs2304694).
{ECO:0000269|PubMed:17974005}.
/FTId=VAR_030071.
VARIANT 57 57 P -> L (in dbSNP:rs2304693).
{ECO:0000269|PubMed:17974005}.
/FTId=VAR_030072.
MUTAGEN 531 531 D->A: Does not affect location in
mitochondria; fails to rescue the
increased accumulation of the level of
mature MT-ND3, MT-CO3, MT-CYB or MT-ND5
mRNA in TBRG4-deficient cells; does not
abolish the accumulation of the MT-ND5-
CYB precursor RNA in a TBRG4-deficient
cell line. {ECO:0000269|PubMed:28335001}.
CONFLICT 365 365 T -> A (in Ref. 3; BAD96663).
{ECO:0000305}.
CONFLICT 489 489 V -> E (in Ref. 8; AAB69312).
{ECO:0000305}.
CONFLICT 524 524 A -> S (in Ref. 8; AAB69312).
{ECO:0000305}.
SEQUENCE 631 AA; 70738 MW; 4EFC3AF5D5BBABD3 CRC64;
MAAHLVKRCT CLLREAARQA PAMAPVGRLR LAWVAHKTLT SSATSPISHL PGSLMEPVEK
ERASTPYIEK QVDHLIKKAT RPEELLELLG GSHDLDSNQA AMVLIRLSHL LSEKPEDKGL
LIQDAHFHQL LCLLNSQIAS VWHGTLSKLL GSLYALGIPK ASKELQSVEQ EVRWRMRKLK
YKHLAFLAES CATLSQEQHS QELLAELLTH LERRWTEIED SHTLVTVMMK VGHLSEPLMN
RLEDKCLELV EHFGPNELRK VLVMLAAQSR RSVPLLRAIS YHLVQKPFSL TKDVLLDVAY
AYGKLSFHQT QVSQRLATDL LSLMPSLTSG EVAHCAKSFA LLKWLSLPLF EAFAQHVLNR
AQDITLPHLC SVLLAFARLN FHPDQEDQFF SLVHEKLGSE LPGLEPALQV DLVWALCVLQ
QAREAELQAV LHPEFHIQFL GGKSQKDQNT FQKLLHINAT ALLEYPEYSG PLLPASAVAP
GPSALDRKVT PLQKELQETL KGLLGSADKG SLEVATQYGW VLDAEVLLDS DGEFLPVRDF
VAPHLAQPTG SQSPPPGSKR LAFLRWEFPN FNSRSKDLLG RFVLARRHIV AAGFLIVDVP
FYEWLELKSE WQKGAYLKDK MRKAVAEELA K


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