FUCO2_HUMAN
ID FUCO2_HUMAN Reviewed; 467 AA.
AC Q9BTY2; E9PEB6; Q7Z6V1; Q7Z6Y2; Q8NBK4;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Plasma alpha-L-fucosidase;
DE EC=3.2.1.51;
DE AltName: Full=Alpha-L-fucoside fucohydrolase 2;
DE Short=Alpha-L-fucosidase 2;
DE Flags: Precursor;
GN Name=FUCA2; ORFNames=PSEC0151, UNQ227/PRO260;
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 1), AND VARIANTS VAL-356
RP AND TYR-371.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thalamus;
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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-356
RP AND TYR-371.
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-356
RP AND TYR-371.
RC TISSUE=B-cell, and Placenta;
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 [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-239.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
RP PHOSPHORYLATION AT SER-301.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
CC -!- FUNCTION: Alpha-L-fucosidase is responsible for hydrolyzing the alpha-
CC 1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the
CC carbohydrate moieties of glycoproteins.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an alpha-L-fucoside + H2O = an alcohol + L-fucose;
CC Xref=Rhea:RHEA:12288, ChEBI:CHEBI:2181, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28349, ChEBI:CHEBI:30879; EC=3.2.1.51;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10054};
CC -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9BTY2; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-9050116, EBI-11978177;
CC Q9BTY2; P49639: HOXA1; NbExp=3; IntAct=EBI-9050116, EBI-740785;
CC Q9BTY2; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-9050116, EBI-739863;
CC Q9BTY2; Q701N4: KRTAP5-2; NbExp=3; IntAct=EBI-9050116, EBI-11958178;
CC Q9BTY2; Q6L8H2: KRTAP5-3; NbExp=3; IntAct=EBI-9050116, EBI-11974251;
CC Q9BTY2; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-9050116, EBI-11962058;
CC Q9BTY2; Q5T7P3: LCE1B; NbExp=3; IntAct=EBI-9050116, EBI-10245913;
CC Q9BTY2; Q5T753: LCE1E; NbExp=3; IntAct=EBI-9050116, EBI-11955335;
CC Q9BTY2; Q5TA78: LCE4A; NbExp=3; IntAct=EBI-9050116, EBI-10246358;
CC Q9BTY2; P50222: MEOX2; NbExp=4; IntAct=EBI-9050116, EBI-748397;
CC Q9BTY2; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-9050116, EBI-1210753;
CC Q9BTY2; Q13526: PIN1; NbExp=3; IntAct=EBI-9050116, EBI-714158;
CC Q9BTY2; O14787-2: TNPO2; NbExp=3; IntAct=EBI-9050116, EBI-12076664;
CC Q9BTY2; Q2TAL6: VWC2; NbExp=3; IntAct=EBI-9050116, EBI-11957238;
CC Q9BTY2; O96014: WNT11; NbExp=3; IntAct=EBI-9050116, EBI-8058160;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BTY2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BTY2-2; Sequence=VSP_057004, VSP_057005;
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 29 family. {ECO:0000305}.
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DR EMBL; AY358551; AAQ88915.1; -; mRNA.
DR EMBL; AK296485; BAG59123.1; -; mRNA.
DR EMBL; AK075458; BAC11633.1; -; mRNA.
DR EMBL; AL031320; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003060; AAH03060.1; -; mRNA.
DR EMBL; BC051268; AAH51268.1; -; mRNA.
DR CCDS; CCDS5200.1; -. [Q9BTY2-1]
DR RefSeq; NP_114409.2; NM_032020.4. [Q9BTY2-1]
DR AlphaFoldDB; Q9BTY2; -.
DR SMR; Q9BTY2; -.
DR BioGRID; 108795; 50.
DR IntAct; Q9BTY2; 34.
DR MINT; Q9BTY2; -.
DR STRING; 9606.ENSP00000002165; -.
DR BindingDB; Q9BTY2; -.
DR ChEMBL; CHEMBL2271; -.
DR CAZy; GH29; Glycoside Hydrolase Family 29.
DR GlyConnect; 1608; 3 N-Linked glycans (1 site).
DR GlyGen; Q9BTY2; 4 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q9BTY2; -.
DR PhosphoSitePlus; Q9BTY2; -.
DR BioMuta; FUCA2; -.
DR DMDM; 254763296; -.
DR EPD; Q9BTY2; -.
DR jPOST; Q9BTY2; -.
DR MassIVE; Q9BTY2; -.
DR MaxQB; Q9BTY2; -.
DR PaxDb; Q9BTY2; -.
DR PeptideAtlas; Q9BTY2; -.
DR PRIDE; Q9BTY2; -.
DR ProteomicsDB; 69462; -.
DR ProteomicsDB; 79030; -. [Q9BTY2-1]
DR Antibodypedia; 33149; 352 antibodies from 28 providers.
DR DNASU; 2519; -.
DR Ensembl; ENST00000002165.11; ENSP00000002165.5; ENSG00000001036.14. [Q9BTY2-1]
DR GeneID; 2519; -.
DR KEGG; hsa:2519; -.
DR MANE-Select; ENST00000002165.11; ENSP00000002165.5; NM_032020.5; NP_114409.2.
DR UCSC; uc003qjm.4; human. [Q9BTY2-1]
DR CTD; 2519; -.
DR DisGeNET; 2519; -.
DR GeneCards; FUCA2; -.
DR HGNC; HGNC:4008; FUCA2.
DR HPA; ENSG00000001036; Tissue enhanced (parathyroid).
DR MIM; 136820; gene+phenotype.
DR neXtProt; NX_Q9BTY2; -.
DR OpenTargets; ENSG00000001036; -.
DR PharmGKB; PA28424; -.
DR VEuPathDB; HostDB:ENSG00000001036; -.
DR eggNOG; KOG3340; Eukaryota.
DR GeneTree; ENSGT00440000035378; -.
DR HOGENOM; CLU_002934_1_1_1; -.
DR InParanoid; Q9BTY2; -.
DR OMA; PDFTYQE; -.
DR OrthoDB; 929780at2759; -.
DR PhylomeDB; Q9BTY2; -.
DR TreeFam; TF313034; -.
DR BRENDA; 3.2.1.51; 2681.
DR PathwayCommons; Q9BTY2; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SABIO-RK; Q9BTY2; -.
DR SignaLink; Q9BTY2; -.
DR BioGRID-ORCS; 2519; 9 hits in 1079 CRISPR screens.
DR ChiTaRS; FUCA2; human.
DR GeneWiki; FUCA2; -.
DR GenomeRNAi; 2519; -.
DR Pharos; Q9BTY2; Tchem.
DR PRO; PR:Q9BTY2; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9BTY2; protein.
DR Bgee; ENSG00000001036; Expressed in decidua and 165 other tissues.
DR ExpressionAtlas; Q9BTY2; baseline and differential.
DR Genevisible; Q9BTY2; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0004560; F:alpha-L-fucosidase activity; IDA:UniProtKB.
DR GO; GO:0006004; P:fucose metabolic process; IDA:UniProtKB.
DR GO; GO:0016139; P:glycoside catabolic process; IDA:UniProtKB.
DR GO; GO:2000535; P:regulation of entry of bacterium into host cell; IMP:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IMP:UniProtKB.
DR Gene3D; 2.60.40.1180; -; 1.
DR InterPro; IPR016286; FUC_metazoa-typ.
DR InterPro; IPR031919; Fucosidase_C.
DR InterPro; IPR000933; Glyco_hydro_29.
DR InterPro; IPR018526; Glyco_hydro_29_CS.
DR InterPro; IPR013780; Glyco_hydro_b.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR10030; PTHR10030; 1.
DR Pfam; PF01120; Alpha_L_fucos; 1.
DR Pfam; PF16757; Fucosidase_C; 1.
DR PIRSF; PIRSF001092; Alpha-L-fucosidase; 1.
DR PRINTS; PR00741; GLHYDRLASE29.
DR SMART; SM00812; Alpha_L_fucos; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
DR PROSITE; PS00385; ALPHA_L_FUCOSIDASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycoprotein; Glycosidase; Hydrolase; Phosphoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..467
FT /note="Plasma alpha-L-fucosidase"
FT /id="PRO_0000010312"
FT SITE 294
FT /note="May be important for catalysis"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10054"
FT MOD_RES 301
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 138..165
FT /note="GFTLWGSEYSWNWNAIDEGPKRDIVKEL -> ATCRDSFMWRKSFDEYWAHT
FT RWHHFCSF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057004"
FT VAR_SEQ 166..467
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057005"
FT VARIANT 233
FT /note="A -> E (in dbSNP:rs11155297)"
FT /id="VAR_055822"
FT VARIANT 356
FT /note="M -> V (in dbSNP:rs3762002)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16303743"
FT /id="VAR_022444"
FT VARIANT 371
FT /note="H -> Y (in dbSNP:rs3762001)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16303743"
FT /id="VAR_022445"
FT CONFLICT 400
FT /note="L -> P (in Ref. 3; BAC11633)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 467 AA; 54067 MW; A42AA6B369A3AC39 CRC64;
MRPQELPRLA FPLLLLLLLL LPPPPCPAHS ATRFDPTWES LDARQLPAWF DQAKFGIFIH
WGVFSVPSFG SEWFWWYWQK EKIPKYVEFM KDNYPPSFKY EDFGPLFTAK FFNANQWADI
FQASGAKYIV LTSKHHEGFT LWGSEYSWNW NAIDEGPKRD IVKELEVAIR NRTDLRFGLY
YSLFEWFHPL FLEDESSSFH KRQFPVSKTL PELYELVNNY QPEVLWSDGD GGAPDQYWNS
TGFLAWLYNE SPVRGTVVTN DRWGAGSICK HGGFYTCSDR YNPGHLLPHK WENCMTIDKL
SWGYRREAGI SDYLTIEELV KQLVETVSCG GNLLMNIGPT LDGTISVVFE ERLRQMGSWL
KVNGEAIYET HTWRSQNDTV TPDVWYTSKP KEKLVYAIFL KWPTSGQLFL GHPKAILGAT
EVKLLGHGQP LNWISLEQNG IMVELPQLTI HQMPCKWGWA LALTNVI
