FAKD1_HUMAN
ID FAKD1_HUMAN Reviewed; 847 AA.
AC Q53R41; Q8N583; Q8TEA9; Q96JM5; Q96N71; Q9H6T4;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=FAST kinase domain-containing protein 1, mitochondrial;
DE Flags: Precursor;
GN Name=FASTKD1; Synonyms=KIAA1800;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 166-847 (ISOFORM 1), AND VARIANT VAL-467.
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 93-847 (ISOFORM 1), AND VARIANT
RP VAL-467.
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 142-847 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-360, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20869947; DOI=10.1016/j.bbrc.2010.09.075;
RA Simarro M., Gimenez-Cassina A., Kedersha N., Lazaro J.B., Adelmant G.O.,
RA Marto J.A., Rhee K., Tisdale S., Danial N., Benarafa C., Orduna A.,
RA Anderson P.;
RT "Fast kinase domain-containing protein 3 is a mitochondrial protein
RT essential for cellular respiration.";
RL Biochem. Biophys. Res. Commun. 401:440-446(2010).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=28238724; DOI=10.1016/j.chembiol.2017.02.002;
RA Han S., Udeshi N.D., Deerinck T.J., Svinkina T., Ellisman M.H., Carr S.A.,
RA Ting A.Y.;
RT "Proximity biotinylation as a method for mapping proteins associated with
RT mtDNA in living cells.";
RL Cell Chem. Biol. 24:404-414(2017).
RN [8]
RP SUBCELLULAR LOCATION, FUNCTION, AND DOMAIN.
RX PubMed=28335001; DOI=10.1093/nar/gkx164;
RA Boehm E., Zaganelli S., Maundrell K., Jourdain A.A., Thore S.,
RA Martinou J.C.;
RT "FASTKD1 and FASTKD4 have opposite effects on expression of specific
RT mitochondrial RNAs, depending upon their endonuclease-like RAP domain.";
RL Nucleic Acids Res. 45:6135-6146(2017).
CC -!- FUNCTION: Involved in the down-regulation of mitochondrial MT-ND3 mRNA
CC levels which leads to decreased respiratory complex I abundance and
CC activity. {ECO:0000269|PubMed:28238724, ECO:0000269|PubMed:28335001}.
CC -!- INTERACTION:
CC Q53R41; P41091: EIF2S3; NbExp=3; IntAct=EBI-3957005, EBI-1054228;
CC Q53R41; P14136: GFAP; NbExp=3; IntAct=EBI-3957005, EBI-744302;
CC Q53R41; P28799: GRN; NbExp=3; IntAct=EBI-3957005, EBI-747754;
CC Q53R41; P54652: HSPA2; NbExp=3; IntAct=EBI-3957005, EBI-356991;
CC Q53R41; P42858: HTT; NbExp=9; IntAct=EBI-3957005, EBI-466029;
CC Q53R41; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-3957005, EBI-1055254;
CC Q53R41; O60333-2: KIF1B; NbExp=3; IntAct=EBI-3957005, EBI-10975473;
CC Q53R41; P07196: NEFL; NbExp=3; IntAct=EBI-3957005, EBI-475646;
CC Q53R41; P07237: P4HB; NbExp=3; IntAct=EBI-3957005, EBI-395883;
CC Q53R41; Q9P1I4: ST13; NbExp=3; IntAct=EBI-3957005, EBI-25892254;
CC Q53R41; O76024: WFS1; NbExp=3; IntAct=EBI-3957005, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:20869947,
CC ECO:0000269|PubMed:28238724, ECO:0000269|PubMed:28335001}.
CC Note=Preferentially localizes to mitochondrial RNA granules, platforms
CC for post-transcriptional RNA modification and ribosome assembly
CC (PubMed:28335001). {ECO:0000269|PubMed:28335001}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q53R41-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q53R41-2; Sequence=VSP_024617;
CC -!- TISSUE SPECIFICITY: Expression detected in spleen, thymus, testis,
CC ovary, colon, heart, smooth muscle, kidney, brain, lung, liver and
CC white adipose tissue with highest expression in heart.
CC {ECO:0000269|PubMed:20869947}.
CC -!- DOMAIN: The RAP domain is essential to regulate MT-ND3 mRNA levels.
CC {ECO:0000269|PubMed:28335001}.
CC -!- SIMILARITY: Belongs to the FAST kinase family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-15 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32687.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB15168.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK025554; BAB15168.1; ALT_INIT; mRNA.
DR EMBL; AK055892; BAB71037.1; -; mRNA.
DR EMBL; AK074302; BAB85043.1; -; mRNA.
DR EMBL; AC093899; AAY24118.1; -; Genomic_DNA.
DR EMBL; BC032687; AAH32687.1; ALT_INIT; mRNA.
DR EMBL; AB058703; BAB47429.1; -; mRNA.
DR CCDS; CCDS33318.1; -. [Q53R41-1]
DR CCDS; CCDS63051.1; -. [Q53R41-2]
DR RefSeq; NP_001268405.1; NM_001281476.2. [Q53R41-2]
DR RefSeq; NP_001308975.1; NM_001322046.1. [Q53R41-1]
DR RefSeq; NP_001308977.1; NM_001322048.1.
DR RefSeq; NP_001308978.1; NM_001322049.1.
DR RefSeq; NP_078898.3; NM_024622.5. [Q53R41-1]
DR RefSeq; XP_016860400.1; XM_017004911.1.
DR AlphaFoldDB; Q53R41; -.
DR BioGRID; 122800; 117.
DR IntAct; Q53R41; 37.
DR MINT; Q53R41; -.
DR STRING; 9606.ENSP00000400513; -.
DR iPTMnet; Q53R41; -.
DR PhosphoSitePlus; Q53R41; -.
DR BioMuta; FASTKD1; -.
DR DMDM; 74726532; -.
DR EPD; Q53R41; -.
DR jPOST; Q53R41; -.
DR MassIVE; Q53R41; -.
DR MaxQB; Q53R41; -.
DR PaxDb; Q53R41; -.
DR PeptideAtlas; Q53R41; -.
DR PRIDE; Q53R41; -.
DR ProteomicsDB; 62517; -. [Q53R41-1]
DR ProteomicsDB; 62518; -. [Q53R41-2]
DR Antibodypedia; 33812; 142 antibodies from 22 providers.
DR DNASU; 79675; -.
DR Ensembl; ENST00000453153.7; ENSP00000400513.2; ENSG00000138399.18. [Q53R41-1]
DR Ensembl; ENST00000453929.6; ENSP00000403229.2; ENSG00000138399.18. [Q53R41-2]
DR GeneID; 79675; -.
DR KEGG; hsa:79675; -.
DR MANE-Select; ENST00000453153.7; ENSP00000400513.2; NM_024622.6; NP_078898.3.
DR UCSC; uc002uev.6; human. [Q53R41-1]
DR CTD; 79675; -.
DR DisGeNET; 79675; -.
DR GeneCards; FASTKD1; -.
DR HGNC; HGNC:26150; FASTKD1.
DR HPA; ENSG00000138399; Low tissue specificity.
DR MalaCards; FASTKD1; -.
DR MIM; 617529; gene.
DR neXtProt; NX_Q53R41; -.
DR OpenTargets; ENSG00000138399; -.
DR PharmGKB; PA145148834; -.
DR VEuPathDB; HostDB:ENSG00000138399; -.
DR eggNOG; ENOG502QQ64; Eukaryota.
DR GeneTree; ENSGT01030000234607; -.
DR HOGENOM; CLU_017819_0_0_1; -.
DR InParanoid; Q53R41; -.
DR OMA; HWESNTQ; -.
DR OrthoDB; 352329at2759; -.
DR PhylomeDB; Q53R41; -.
DR TreeFam; TF324885; -.
DR PathwayCommons; Q53R41; -.
DR SignaLink; Q53R41; -.
DR BioGRID-ORCS; 79675; 12 hits in 1081 CRISPR screens.
DR ChiTaRS; FASTKD1; human.
DR GenomeRNAi; 79675; -.
DR Pharos; Q53R41; Tbio.
DR PRO; PR:Q53R41; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q53R41; protein.
DR Bgee; ENSG00000138399; Expressed in secondary oocyte and 202 other tissues.
DR ExpressionAtlas; Q53R41; baseline and differential.
DR Genevisible; Q53R41; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0035770; C:ribonucleoprotein granule; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000959; P:mitochondrial RNA metabolic process; IMP:UniProtKB.
DR GO; GO:0000963; P:mitochondrial RNA processing; IBA:GO_Central.
DR GO; GO:0044528; P:regulation of mitochondrial mRNA stability; IMP:UniProtKB.
DR InterPro; IPR013579; FAST_2.
DR InterPro; IPR010622; FAST_Leu-rich.
DR InterPro; IPR013584; RAP.
DR Pfam; PF06743; FAST_1; 1.
DR Pfam; PF08368; FAST_2; 1.
DR Pfam; PF08373; RAP; 1.
DR SMART; SM00952; RAP; 1.
DR PROSITE; PS51286; RAP; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Mitochondrion; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000305"
FT CHAIN ?..847
FT /note="FAST kinase domain-containing protein 1,
FT mitochondrial"
FT /id="PRO_0000284710"
FT DOMAIN 777..837
FT /note="RAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00619"
FT MOD_RES 360
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 649..692
FT /note="ILSPSRSARVQFHLMELNRSVCLECPEFQIPWFHDRFCQQYNKG -> S
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024617"
FT VARIANT 384
FT /note="E -> Q (in dbSNP:rs12618227)"
FT /id="VAR_031806"
FT VARIANT 446
FT /note="C -> G (in dbSNP:rs35106223)"
FT /id="VAR_031807"
FT VARIANT 467
FT /note="M -> V (in dbSNP:rs2253680)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_031808"
FT CONFLICT 213
FT /note="V -> M (in Ref. 1; BAB85043)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="V -> A (in Ref. 1; BAB85043)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="M -> T (in Ref. 1; BAB15168)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="L -> P (in Ref. 1; BAB85043)"
FT /evidence="ECO:0000305"
FT CONFLICT 756
FT /note="E -> EMPWESNIEIVGSRLPPGAERIALEFLDSKA (in Ref. 4;
FT BAB47429)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 847 AA; 97411 MW; 5026A635048EB0B3 CRC64;
MKKTPVFLES LVTNMLRLRA ICPFSWRVFQ FRPISCEPLI IQMNKCTDEE QMFGFIERNK
AILSEKQVGC AFDMLWKLQK QKTSLLKNAE YVRDHPQFLT LHNLATNKFK LMNDDTLVNV
LYVTQQFAGE AHDPLVEALV TEAWRRLERF DIKLLSEFSS CLADQHLYFS PLMGKIADIV
HRNLETTQDL SSLSVLMVNI SSLISRHFQQ QLVNKTELLF DTIDSSEVNV AKSIAKFLRN
VRYRYQPLLE RCNNVFLSNV DHLDLDSISK ILSVYKFLQF NSFEFIIMAK KKLTEMIPLC
NHPASFVKLF VALGPIAGPE EKKQLKSTML LMSEDLTGEQ ALAVLGAMGD MESRNSCLIK
RVTSVLHKHL DGYKPLELLK ITQELTFLHF QRKEFFAKLR ELLLSYLKNS FIPTEVSVLV
RAISLLPSPH LDEVGISRIE AVLPQCDLNN LSSFATSVLR WIQHDHMYLD NMTAKQLKLL
QKLDHYGRQR LQHSNSLDLL RKELKSLKGN TFPESLLEEM IATLQHFMDD INYINVGEIA
SFISSTDYLS TLLLDRIASV AVQQIEKIHP FTIPAIIRPF SVLNYDPPQR DEFLGTCVQH
LNSYLGILDP FILVFLGFSL ATLEYFPEDL LKAIFNIKFL ARLDSQLEIL SPSRSARVQF
HLMELNRSVC LECPEFQIPW FHDRFCQQYN KGIGGMDGTQ QQIFKMLAEV LGGINCVKAS
VLTPYYHKVD FECILDKRKK PLPYGSHNIA LGQLPEMPWE SNIEIVGSRL PPGAERIALE
FLDSKALCRN IPHMKGKSAM KKRHLEILGY RVIQISQFEW NSMALSTKDA RMDYLRECIF
GEVKSCL
