FCSK_HUMAN
ID FCSK_HUMAN Reviewed; 1084 AA.
AC Q8N0W3; Q5PSM3; Q5XKL6; Q6ZRA0; Q96MT9;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=L-fucose kinase {ECO:0000305};
DE Short=Fucokinase;
DE EC=2.7.1.52 {ECO:0000269|PubMed:30503518};
GN Name=FCSK {ECO:0000312|HGNC:HGNC:29500};
GN Synonyms=FUK {ECO:0000312|HGNC:HGNC:29500};
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 [MRNA] (ISOFORM 1).
RX PubMed=12056818; DOI=10.1016/s0006-291x(02)00541-7;
RA Hinderlich S., Berger M., Blume A., Chen H., Ghaderi D., Bauer C.;
RT "Identification of human L-fucose kinase amino acid sequence.";
RL Biochem. Biophys. Res. Commun. 294:650-654(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Neuron, and Thymus;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-146; THR-521; HIS-571;
RP LEU-701; THR-858; MET-861; TRP-901; GLN-939 AND TRP-939.
RG SeattleSNPs variation discovery resource;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Uterus;
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 [5]
RP INVOLVEMENT IN CDGF2, FUNCTION, CATALYTIC ACTIVITY, VARIANTS CDGF2 PRO-223;
RP CYS-683 AND GLN-994, AND TISSUE SPECIFICITY.
RX PubMed=30503518; DOI=10.1016/j.ajhg.2018.10.021;
RG Undiagnosed Diseases Network;
RA Ng B.G., Rosenfeld J.A., Emrick L., Jain M., Burrage L.C., Lee B.,
RA Craigen W.J., Bearden D.R., Graham B.H., Freeze H.H.;
RT "Pathogenic Variants in Fucokinase Cause a Congenital Disorder of
RT Glycosylation.";
RL Am. J. Hum. Genet. 103:1030-1037(2018).
CC -!- FUNCTION: Takes part in the salvage pathway for reutilization of fucose
CC from the degradation of oligosaccharides.
CC {ECO:0000269|PubMed:30503518}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-fucose = ADP + beta-L-fucose 1-phosphate + H(+);
CC Xref=Rhea:RHEA:13241, ChEBI:CHEBI:2181, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57268, ChEBI:CHEBI:456216;
CC EC=2.7.1.52; Evidence={ECO:0000269|PubMed:30503518};
CC -!- INTERACTION:
CC Q8N0W3; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-4291312, EBI-1389308;
CC Q8N0W3; O43711: TLX3; NbExp=3; IntAct=EBI-4291312, EBI-3939165;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N0W3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N0W3-2; Sequence=VSP_015422, VSP_015423;
CC -!- TISSUE SPECIFICITY: Expressed in fibroblasts.
CC {ECO:0000269|PubMed:30503518}.
CC -!- DISEASE: Congenital disorder of glycosylation with defective
CC fucosylation 2 (CDGF2) [MIM:618324]: A form of congenital disorder of
CC glycosylation, a genetically heterogeneous group of multisystem
CC disorders caused by a defect in glycoprotein biosynthesis and
CC characterized by under-glycosylated serum glycoproteins. Congenital
CC disorders of glycosylation result in a wide variety of clinical
CC features, such as defects in the nervous system development,
CC psychomotor retardation, dysmorphic features, hypotonia, coagulation
CC disorders, and immunodeficiency. CDGF2 is an autosomal recessive
CC disorder, apparent from birth, characterized by hypotonia, poor
CC feeding, severely impaired intellectual and psychomotor development,
CC seizures with epileptic encephalopathy, visual impairment and other
CC ocular features, respiratory difficulty with frequent infections, as
CC well as contractures. Brain imaging shows cerebellar and brainstem
CC atrophy, hypoplasia or agenesis of the corpus callosum, and white
CC matter abnormalities including periventricular leukomalacia.
CC {ECO:0000269|PubMed:30503518}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB71190.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAD29647.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/fuk/";
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DR EMBL; AJ441184; CAD29647.1; ALT_FRAME; mRNA.
DR EMBL; AK056456; BAB71190.1; ALT_FRAME; mRNA.
DR EMBL; AK128387; BAC87413.1; -; mRNA.
DR EMBL; AY829643; AAV67949.1; -; Genomic_DNA.
DR EMBL; BC013735; AAH13735.1; -; mRNA.
DR EMBL; BC032542; AAH32542.2; -; mRNA.
DR CCDS; CCDS10891.2; -. [Q8N0W3-1]
DR PIR; JC7878; JC7878.
DR RefSeq; NP_659496.2; NM_145059.2. [Q8N0W3-1]
DR RefSeq; XP_011521230.1; XM_011522928.1. [Q8N0W3-1]
DR RefSeq; XP_011521231.1; XM_011522929.1. [Q8N0W3-1]
DR RefSeq; XP_016878501.1; XM_017023012.1. [Q8N0W3-1]
DR AlphaFoldDB; Q8N0W3; -.
DR BioGRID; 128243; 87.
DR IntAct; Q8N0W3; 5.
DR STRING; 9606.ENSP00000288078; -.
DR iPTMnet; Q8N0W3; -.
DR PhosphoSitePlus; Q8N0W3; -.
DR BioMuta; FUK; -.
DR DMDM; 73915340; -.
DR EPD; Q8N0W3; -.
DR jPOST; Q8N0W3; -.
DR MassIVE; Q8N0W3; -.
DR MaxQB; Q8N0W3; -.
DR PaxDb; Q8N0W3; -.
DR PeptideAtlas; Q8N0W3; -.
DR PRIDE; Q8N0W3; -.
DR ProteomicsDB; 71470; -. [Q8N0W3-1]
DR ProteomicsDB; 71471; -. [Q8N0W3-2]
DR Antibodypedia; 29979; 160 antibodies from 27 providers.
DR DNASU; 197258; -.
DR Ensembl; ENST00000288078.11; ENSP00000288078.6; ENSG00000157353.17. [Q8N0W3-1]
DR Ensembl; ENST00000378912.6; ENSP00000368192.2; ENSG00000157353.17. [Q8N0W3-2]
DR GeneID; 197258; -.
DR KEGG; hsa:197258; -.
DR MANE-Select; ENST00000288078.11; ENSP00000288078.6; NM_145059.3; NP_659496.2.
DR UCSC; uc002eyy.4; human. [Q8N0W3-1]
DR CTD; 197258; -.
DR DisGeNET; 197258; -.
DR GeneCards; FCSK; -.
DR HGNC; HGNC:29500; FCSK.
DR HPA; ENSG00000157353; Low tissue specificity.
DR MalaCards; FCSK; -.
DR MIM; 608675; gene.
DR MIM; 618324; phenotype.
DR neXtProt; NX_Q8N0W3; -.
DR OpenTargets; ENSG00000157353; -.
DR PharmGKB; PA134863646; -.
DR VEuPathDB; HostDB:ENSG00000157353; -.
DR eggNOG; KOG4644; Eukaryota.
DR GeneTree; ENSGT00390000002251; -.
DR HOGENOM; CLU_006983_0_0_1; -.
DR InParanoid; Q8N0W3; -.
DR OMA; QRWREAW; -.
DR OrthoDB; 135001at2759; -.
DR PhylomeDB; Q8N0W3; -.
DR TreeFam; TF314554; -.
DR BRENDA; 2.7.1.52; 2681.
DR PathwayCommons; Q8N0W3; -.
DR Reactome; R-HSA-6787639; GDP-fucose biosynthesis.
DR SignaLink; Q8N0W3; -.
DR BioGRID-ORCS; 197258; 13 hits in 1081 CRISPR screens.
DR ChiTaRS; FUK; human.
DR GenomeRNAi; 197258; -.
DR Pharos; Q8N0W3; Tbio.
DR PRO; PR:Q8N0W3; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8N0W3; protein.
DR Bgee; ENSG00000157353; Expressed in right hemisphere of cerebellum and 145 other tissues.
DR ExpressionAtlas; Q8N0W3; baseline and differential.
DR Genevisible; Q8N0W3; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0050201; F:fucokinase activity; IMP:UniProtKB.
DR GO; GO:0046835; P:carbohydrate phosphorylation; IEA:Ensembl.
DR GO; GO:0042352; P:GDP-L-fucose salvage; IMP:UniProtKB.
DR GO; GO:1903350; P:response to dopamine; IEA:Ensembl.
DR InterPro; IPR012887; Fucokinase.
DR InterPro; IPR013750; GHMP_kinase_C_dom.
DR InterPro; IPR036554; GHMP_kinase_C_sf.
DR InterPro; IPR006204; GHMP_kinase_N_dom.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR Pfam; PF07959; Fucokinase; 1.
DR Pfam; PF08544; GHMP_kinases_C; 1.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55060; SSF55060; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Congenital disorder of glycosylation;
KW Disease variant; Kinase; Nucleotide-binding; Reference proteome;
KW Transferase.
FT CHAIN 1..1084
FT /note="L-fucose kinase"
FT /id="PRO_0000156672"
FT BINDING 834..845
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT VAR_SEQ 78
FT /note="T -> TWICVGVSLWIRGCHPPGRLPEASVHRAFPLLQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015422"
FT VAR_SEQ 816..841
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015423"
FT VARIANT 146
FT /note="V -> M (in dbSNP:rs17881323)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021327"
FT VARIANT 223
FT /note="S -> P (in CDGF2; unknown pathological significance;
FT dbSNP:rs769009456)"
FT /evidence="ECO:0000269|PubMed:30503518"
FT /id="VAR_081646"
FT VARIANT 521
FT /note="A -> T (in dbSNP:rs17881069)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021328"
FT VARIANT 571
FT /note="R -> H (in dbSNP:rs17886171)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021329"
FT VARIANT 683
FT /note="R -> C (in CDGF2; unknown pathological significance;
FT dbSNP:rs755169246)"
FT /evidence="ECO:0000269|PubMed:30503518"
FT /id="VAR_081647"
FT VARIANT 701
FT /note="P -> L (in dbSNP:rs17883716)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021330"
FT VARIANT 858
FT /note="A -> T (in dbSNP:rs17884050)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021331"
FT VARIANT 861
FT /note="V -> M (in dbSNP:rs17878599)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021332"
FT VARIANT 901
FT /note="R -> W (in dbSNP:rs17881635)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021333"
FT VARIANT 939
FT /note="R -> Q (in dbSNP:rs17886060)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021334"
FT VARIANT 939
FT /note="R -> W (in dbSNP:rs17883248)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021335"
FT VARIANT 994
FT /note="K -> Q (in CDGF2; unknown pathological significance;
FT dbSNP:rs199515460)"
FT /evidence="ECO:0000269|PubMed:30503518"
FT /id="VAR_081648"
FT CONFLICT 400
FT /note="L -> S (in Ref. 2; BAB71190)"
FT /evidence="ECO:0000305"
FT CONFLICT 609
FT /note="C -> R (in Ref. 2; BAB71190)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1084 AA; 117623 MW; 153F91882F4B143C CRC64;
MEQPKGVDWT VIILTCQYKD SVQVFQRELE VRQKREQIPA GTLLLAVEDP EKRVGSGGAT
LNALLVAAEH LSARAGFTVV TSDVLHSAWI LILHMGRDFP FDDCGRAFTC LPVENPEAPV
EALVCNLDCL LDIMTYRLGP GSPPGVWVCS TDMLLSVPAN PGISWDSFRG ARVIALPGSP
AYAQNHGVYL TDPQGLVLDI YYQGTEAEIQ RCVRPDGRVP LVSGVVFFSV ETAERLLATH
VSPPLDACTY LGLDSGARPV QLSLFFDILH CMAENVTRED FLVGRPPELG QGDADVAGYL
QSARAQLWRE LRDQPLTMAY VSSGSYSYMT SSASEFLLSL TLPGAPGAQI VHSQVEEQQL
LAAGSSVVSC LLEGPVQLGP GSVLQHCHLQ GPIHIGAGCL VTGLDTAHSK ALHGRELRDL
VLQGHHTRLH GSPGHAFTLV GRLDSWERQG AGTYLNVPWS EFFKRTGVRA WDLWDPETLP
AEYCLPSARL FPVLHPSREL GPQDLLWMLD HQEDGGEALR AWRASWRLSW EQLQPCLDRA
ATLASRRDLF FRQALHKARH VLEARQDLSL RPLIWAAVRE GCPGPLLATL DQVAAGAGDP
GVAARALACV ADVLGCMAEG RGGLRSGPAA NPEWMRPFSY LECGDLAAGV EALAQERDKW
LSRPALLVRA ARHYEGAGQI LIRQAVMSAQ HFVSTEQVEL PGPGQWVVAE CPARVDFSGG
WSDTPPLAYE LGGAVLGLAV RVDGRRPIGA RARRIPEPEL WLAVGPRQDE MTVKIVCRCL
ADLRDYCQPH APGALLKAAF ICAGIVHVHS ELQLSEQLLR TFGGGFELHT WSELPHGSGL
GTSSILAGTA LAALQRAAGR VVGTEALIHA VLHLEQVLTT GGGWQDQVGG LMPGIKVGRS
RAQLPLKVEV EEVTVPEGFV QKLNDHLLLV YTGKTRLARN LLQDVLRSWY ARLPAVVQNA
HSLVRQTEEC AEGFRQGSLP LLGQCLTSYW EQKKLMAPGC EPLTVRRMMD VLAPHVHGQS
LAGAGGGGFL YLLTKEPQQK EALEAVLAKT EGLGNYSIHL VEVDTQGLSL KLLGTEASTC
CPFP
