GALC_HUMAN
ID GALC_HUMAN Reviewed; 685 AA.
AC P54803; B4DKE8; B4DYN1; B4DZJ8; B7Z7Z2; J3KN25; J3KPP8; Q8J030;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 08-JUN-2016, sequence version 3.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Galactocerebrosidase {ECO:0000305};
DE Short=GALCERase;
DE EC=3.2.1.46 {ECO:0000269|PubMed:8281145, ECO:0000269|PubMed:8399327};
DE AltName: Full=Galactocerebroside beta-galactosidase;
DE AltName: Full=Galactosylceramidase {ECO:0000303|PubMed:9272171};
DE AltName: Full=Galactosylceramide beta-galactosidase;
DE Flags: Precursor;
GN Name=GALC {ECO:0000312|HGNC:HGNC:4115};
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 [GENOMIC DNA], AND VARIANT THR-562.
RX PubMed=7601472; DOI=10.1016/0888-7543(95)80230-j;
RA Luzi P., Rafi M.A., Wenger D.A.;
RT "Structure and organization of the human galactocerebrosidase (GALC)
RT gene.";
RL Genomics 26:407-409(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9434153; DOI=10.1016/s0167-4781(97)00140-1;
RA Sakai N., Fukushima H., Inui K., Fu L., Nishigaki T., Yanagihara I.,
RA Tatsumi N., Ozono K., Okada S.;
RT "Human galactocerebrosidase gene: promoter analysis of the 5'-flanking
RT region and structural organization.";
RL Biochim. Biophys. Acta 1395:62-67(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 2-685 (ISOFORM 3), AND VARIANTS CYS-184 AND
RP THR-562.
RC TISSUE=Testis, and 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-641.
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-685 (ISOFORM 1), PROTEIN SEQUENCE OF 43-75
RP AND 452-470, CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Testis;
RX PubMed=8281145; DOI=10.1093/hmg/2.11.1841;
RA Chen Y.Q., Rafi M.A., de Gala G., Wenger D.A.;
RT "Cloning and expression of cDNA encoding human galactocerebrosidase, the
RT enzyme deficient in globoid cell leukodystrophy.";
RL Hum. Mol. Genet. 2:1841-1845(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 5-685 (ISOFORM 1), AND PARTIAL PROTEIN
RP SEQUENCE.
RC TISSUE=Placenta, and Skin fibroblast;
RX PubMed=8297359; DOI=10.1006/bbrc.1994.1071;
RA Sakai N., Inui K., Fujii N., Fukushima H., Nishimoto J., Yanagihara I.,
RA Isegawa Y., Iwamatsu A., Okada S.;
RT "Krabbe disease: isolation and characterization of a full-length cDNA for
RT human galactocerebrosidase.";
RL Biochem. Biophys. Res. Commun. 198:485-491(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-685 (ISOFORM 1), AND VARIANT
RP THR-562.
RC TISSUE=Testis;
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 [8]
RP PROTEIN SEQUENCE OF 43-61 AND 452-470, PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Urine;
RX PubMed=8399327; DOI=10.1016/0005-2760(93)90175-9;
RA Chen Y.Q., Wenger D.A.;
RT "Galactocerebrosidase from human urine: purification and partial
RT characterization.";
RL Biochim. Biophys. Acta 1170:53-61(1993).
RN [9]
RP REVIEW ON GLD MUTATIONS.
RX PubMed=9338580;
RX DOI=10.1002/(sici)1098-1004(1997)10:4<268::aid-humu2>3.0.co;2-d;
RA Wenger D.A., Rafi M.A., Luzi P.;
RT "Molecular genetics of Krabbe disease (globoid cell leukodystrophy):
RT diagnostic and clinical implications.";
RL Hum. Mutat. 10:268-279(1997).
RN [10]
RP REVIEW ON VARIANTS.
RX PubMed=10833326; DOI=10.1006/mgme.2000.2990;
RA Wenger D.A., Rafi M.A., Luzi P., Datto J., Costantino-Ceccarini E.;
RT "Krabbe disease: genetic aspects and progress toward therapy.";
RL Mol. Genet. Metab. 70:1-9(2000).
RN [11]
RP VARIANT CYS-184.
RX PubMed=7581365; DOI=10.1093/hmg/4.8.1285;
RA Rafi M.A., Luzi P., Chen Y.Q., Wenger D.A.;
RT "A large deletion together with a point mutation in the GALC gene is a
RT common mutant allele in patients with infantile Krabbe disease.";
RL Hum. Mol. Genet. 4:1285-1289(1995).
RN [12]
RP VARIANTS GLD ALA-318 AND GLY-566.
RX PubMed=8595408; DOI=10.1093/hmg/4.10.1865;
RA Tatsumi N., Inui K., Sakai N., Fukushima H., Nishimoto J., Yanagihara I.,
RA Nishigaki T., Tsukamoto H., Fu L., Taniike M., Okada S.;
RT "Molecular defects in Krabbe disease.";
RL Hum. Mol. Genet. 4:1865-1868(1995).
RN [13]
RP VARIANTS GLD HIS-79; SER-111; LEU-117; THR-250; SER-284 AND CYS-314, AND
RP VARIANT THR-562.
RX PubMed=8940268;
RA De Gasperi R., Gama Sosa M.A., Sartorato E.L., Battistini S.,
RA MacFarlane H., Gusella J.F., Krivit W., Kolodny E.H.;
RT "Molecular heterogeneity of late-onset forms of globoid-cell
RT leukodystrophy.";
RL Am. J. Hum. Genet. 59:1233-1242(1996).
RN [14]
RP ERRATUM OF PUBMED:8940268.
RA De Gasperi R., Gama Sosa M.A., Sartorato E.L., Battistini S.,
RA MacFarlane H., Gusella J.F., Krivit W., Kolodny E.H.;
RL Am. J. Hum. Genet. 60:1264-1264(1997).
RN [15]
RP VARIANTS GLD ASN-544 AND SER-599.
RX PubMed=8786069; DOI=10.1007/bf02185759;
RA Rafi M.A., Luzi P., Zlotogora J., Wenger D.A.;
RT "Two different mutations are responsible for Krabbe disease in the Druze
RT and Moslem Arab populations in Israel.";
RL Hum. Genet. 97:304-308(1996).
RN [16]
RP VARIANTS GLD MET-82; ASP-286 AND SER-634, AND VARIANTS VAL-305 AND THR-562.
RX PubMed=9272171; DOI=10.1007/s004390050532;
RA Furuya H., Kukita Y.-J., Nagano S., Sakai Y., Yamashita Y., Fukuyama H.,
RA Inatomi Y., Saito Y., Koike R., Tsuji S., Fukumaki Y., Hayashi K.,
RA Kobayashi T.;
RT "Adult onset globoid cell leukodystrophy (Krabbe disease): analysis of
RT galactosylceramidase cDNA from four Japanese patients.";
RL Hum. Genet. 100:450-456(1997).
RN [17]
RP VARIANTS GLD ASP-286 AND ARG-553, VARIANT ALA-641, AND CHARACTERIZATION OF
RP VARIANT GLD ASP-286.
RX PubMed=10477434;
RX DOI=10.1002/(sici)1098-1004(1999)14:3<256::aid-humu9>3.0.co;2-6;
RA De Gasperi R., Gama Sosa M.A., Sartorato E.L., Battistini S., Raghavan S.,
RA Kolodny E.H.;
RT "Molecular basis of late-life globoid cell leukodystrophy.";
RL Hum. Mutat. 14:256-262(1999).
RN [18]
RP VARIANTS GLD ARG-59; PHE-68; ILE-278; CYS-335; GLY-426; HIS-531 AND
RP ARG-668.
RX PubMed=10234611; DOI=10.1023/a:1005449919660;
RA Fu L., Inui K., Nishigaki T., Tatsumi N., Tsukamoto H., Kokubu C.,
RA Muramatsu T., Okada S.;
RT "Molecular heterogeneity of Krabbe disease.";
RL J. Inherit. Metab. Dis. 22:155-162(1999).
RN [19]
RP VARIANT GLD SER-41.
RX PubMed=17579360; DOI=10.1002/humu.9500;
RA Lissens W., Arena A., Seneca S., Rafi M., Sorge G., Liebaers I., Wenger D.,
RA Fiumara A.;
RT "A single mutation in the GALC gene is responsible for the majority of late
RT onset Krabbe disease patients in the Catania (Sicily, Italy) region.";
RL Hum. Mutat. 28:742-742(2007).
RN [20]
RP VARIANTS GLD LYS-130; ARG-318; ARG-323; THR-384; LEU-396 AND ASN-490, AND
RP VARIANTS PRO-21; CYS-184; ASN-248; THR-562 AND ALA-641.
RX PubMed=20886637; DOI=10.1002/humu.21367;
RA Tappino B., Biancheri R., Mort M., Regis S., Corsolini F., Rossi A.,
RA Stroppiano M., Lualdi S., Fiumara A., Bembi B., Di Rocco M., Cooper D.N.,
RA Filocamo M.;
RT "Identification and characterization of 15 novel GALC gene mutations
RT causing Krabbe disease.";
RL Hum. Mutat. 31:E1894-E1914(2010).
RN [21]
RP VARIANT GLD MET-681.
RX PubMed=23462331; DOI=10.1016/j.gene.2013.02.010;
RA Yang Y., Ren X., Xu Q., Wang C., Liu H., He X.;
RT "Four novel GALC gene mutations in two Chinese patients with Krabbe
RT disease.";
RL Gene 519:381-384(2013).
CC -!- FUNCTION: Hydrolyzes the galactose ester bonds of glycolipids such as
CC galactosylceramide and galactosylsphingosine (PubMed:8281145,
CC PubMed:8399327). Enzyme with very low activity responsible for the
CC lysosomal catabolism of galactosylceramide, a major lipid in myelin,
CC kidney and epithelial cells of small intestine and colon
CC (PubMed:8281145, PubMed:8399327). {ECO:0000269|PubMed:8281145,
CC ECO:0000269|PubMed:8399327}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine + H2O = an
CC N-acylsphing-4-enine + D-galactose; Xref=Rhea:RHEA:14297,
CC ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:18390,
CC ChEBI:CHEBI:52639; EC=3.2.1.46; Evidence={ECO:0000269|PubMed:8281145,
CC ECO:0000269|PubMed:8399327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14298;
CC Evidence={ECO:0000269|PubMed:8399327, ECO:0000305|PubMed:8281145};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-galactosyl-(1<->1)-sphing-4-enine + H2O = D-galactose +
CC sphing-4-enine; Xref=Rhea:RHEA:43908, ChEBI:CHEBI:4139,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57756, ChEBI:CHEBI:57934;
CC Evidence={ECO:0000269|PubMed:8399327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43909;
CC Evidence={ECO:0000269|PubMed:8399327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a D-galactosylceramide + H2O = an N-acyl-sphingoid base + D-
CC galactose; Xref=Rhea:RHEA:43412, ChEBI:CHEBI:4139, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:36498, ChEBI:CHEBI:83273;
CC Evidence={ECO:0000250|UniProtKB:P54818};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43413;
CC Evidence={ECO:0000250|UniProtKB:P54818};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for N-acyl-beta-D-galactosylsphingosine
CC {ECO:0000305|PubMed:8399327};
CC pH dependence:
CC Optimum pH is 4.0-4.4. {ECO:0000269|PubMed:8399327};
CC Temperature dependence:
CC Activity is lost after heating at 52 degrees Celsius for five
CC minutes.;
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P54803-1; Sequence=Displayed;
CC Name=3;
CC IsoId=P54803-3; Sequence=VSP_036976;
CC Name=4;
CC IsoId=P54803-4; Sequence=VSP_036974;
CC Name=5;
CC IsoId=P54803-5; Sequence=VSP_036975, VSP_036977;
CC -!- TISSUE SPECIFICITY: Detected in urine. Detected in testis, brain and
CC placenta (at protein level). Detected in kidney and liver.
CC {ECO:0000269|PubMed:8399327}.
CC -!- POLYMORPHISM: Polymorphic amino-acid changes are responsible for the
CC wide range of catalytic activities found in the general population.
CC -!- DISEASE: Leukodystrophy, globoid cell (GLD) [MIM:245200]: An autosomal
CC recessive disorder characterized by insufficient catabolism of several
CC galactolipids that are important for normal myelin production. Four
CC clinical forms are recognized. The infantile form accounts for 90% of
CC cases. It manifests before six months of age with irritability,
CC spasticity, arrest of motor and mental development, and bouts of
CC temperature elevation without infection. This is followed by myoclonic
CC jerks of arms and legs, oposthotonus, hypertonic fits, and mental
CC regression, which progresses to a severe decerebrate condition with no
CC voluntary movements and death from respiratory infections or cerebral
CC hyperpyrexia before 2 years of age. Cases with later onset present with
CC unexplained blindness, weakness and sensorimotor peripheral neuropathy,
CC mental deterioration and death. {ECO:0000269|PubMed:10234611,
CC ECO:0000269|PubMed:10477434, ECO:0000269|PubMed:17579360,
CC ECO:0000269|PubMed:20886637, ECO:0000269|PubMed:23462331,
CC ECO:0000269|PubMed:8595408, ECO:0000269|PubMed:8786069,
CC ECO:0000269|PubMed:8940268, ECO:0000269|PubMed:9272171}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 59 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-17 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA16645.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA80975.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH36518.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA04971.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA04972.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA04972.1; Type=Miscellaneous discrepancy; Note=Probable intron retention.; Evidence={ECO:0000305};
CC Sequence=BAA24902.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG59160.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L38559; AAA80975.1; ALT_INIT; Genomic_DNA.
DR EMBL; L38544; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38545; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38546; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38547; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38548; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38549; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38550; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38551; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38552; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38553; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38555; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38556; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38557; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; L38558; AAA80975.1; JOINED; Genomic_DNA.
DR EMBL; D86181; BAA24902.1; ALT_INIT; Genomic_DNA.
DR EMBL; AK296530; BAG59160.1; ALT_INIT; mRNA.
DR EMBL; AK302519; BAG63793.1; -; mRNA.
DR EMBL; AK302683; BAH13778.1; -; mRNA.
DR EMBL; AK302956; BAG64110.1; -; mRNA.
DR EMBL; AL136501; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157955; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L23116; AAA16645.1; ALT_INIT; mRNA.
DR EMBL; D25283; BAA04971.1; ALT_INIT; mRNA.
DR EMBL; D25284; BAA04972.1; ALT_SEQ; mRNA.
DR EMBL; BC036518; AAH36518.1; ALT_INIT; mRNA.
DR CCDS; CCDS55936.1; -. [P54803-3]
DR CCDS; CCDS55937.1; -. [P54803-4]
DR CCDS; CCDS9878.2; -. [P54803-1]
DR PIR; I54205; I54205.
DR RefSeq; NP_000144.2; NM_000153.3. [P54803-1]
DR RefSeq; NP_001188330.1; NM_001201401.1. [P54803-3]
DR RefSeq; NP_001188331.1; NM_001201402.1. [P54803-4]
DR AlphaFoldDB; P54803; -.
DR SMR; P54803; -.
DR BioGRID; 108854; 48.
DR IntAct; P54803; 14.
DR STRING; 9606.ENSP00000261304; -.
DR ChEMBL; CHEMBL3713095; -.
DR SwissLipids; SLP:000000644; -.
DR CAZy; GH59; Glycoside Hydrolase Family 59.
DR GlyGen; P54803; 6 sites.
DR iPTMnet; P54803; -.
DR PhosphoSitePlus; P54803; -.
DR BioMuta; GALC; -.
DR DMDM; 229462868; -.
DR EPD; P54803; -.
DR jPOST; P54803; -.
DR MassIVE; P54803; -.
DR MaxQB; P54803; -.
DR PaxDb; P54803; -.
DR PeptideAtlas; P54803; -.
DR PRIDE; P54803; -.
DR ProteomicsDB; 56722; -. [P54803-1]
DR ProteomicsDB; 56723; -. [P54803-3]
DR ProteomicsDB; 56724; -. [P54803-4]
DR ProteomicsDB; 56725; -. [P54803-5]
DR Antibodypedia; 26266; 239 antibodies from 28 providers.
DR DNASU; 2581; -.
DR Ensembl; ENST00000261304.7; ENSP00000261304.2; ENSG00000054983.17. [P54803-1]
DR Ensembl; ENST00000393568.8; ENSP00000377198.4; ENSG00000054983.17. [P54803-3]
DR Ensembl; ENST00000393569.6; ENSP00000377199.2; ENSG00000054983.17. [P54803-4]
DR Ensembl; ENST00000544807.6; ENSP00000437513.2; ENSG00000054983.17. [P54803-5]
DR GeneID; 2581; -.
DR KEGG; hsa:2581; -.
DR MANE-Select; ENST00000261304.7; ENSP00000261304.2; NM_000153.4; NP_000144.2.
DR UCSC; uc010tvz.2; human. [P54803-1]
DR CTD; 2581; -.
DR DisGeNET; 2581; -.
DR GeneCards; GALC; -.
DR GeneReviews; GALC; -.
DR HGNC; HGNC:4115; GALC.
DR HPA; ENSG00000054983; Low tissue specificity.
DR MalaCards; GALC; -.
DR MIM; 245200; phenotype.
DR MIM; 606890; gene.
DR neXtProt; NX_P54803; -.
DR OpenTargets; ENSG00000054983; -.
DR Orphanet; 206448; Adult Krabbe disease.
DR Orphanet; 206436; Infantile Krabbe disease.
DR Orphanet; 206443; Late-infantile/juvenile Krabbe disease.
DR PharmGKB; PA28530; -.
DR VEuPathDB; HostDB:ENSG00000054983; -.
DR eggNOG; ENOG502QQ1Q; Eukaryota.
DR GeneTree; ENSGT00390000003303; -.
DR HOGENOM; CLU_015456_2_0_1; -.
DR InParanoid; P54803; -.
DR OMA; VASDNLW; -.
DR PhylomeDB; P54803; -.
DR TreeFam; TF312985; -.
DR BRENDA; 3.2.1.46; 2681.
DR PathwayCommons; P54803; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR SignaLink; P54803; -.
DR BioGRID-ORCS; 2581; 14 hits in 1078 CRISPR screens.
DR ChiTaRS; GALC; human.
DR GeneWiki; Galactosylceramidase; -.
DR GenomeRNAi; 2581; -.
DR Pharos; P54803; Tbio.
DR PRO; PR:P54803; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P54803; protein.
DR Bgee; ENSG00000054983; Expressed in adrenal tissue and 207 other tissues.
DR ExpressionAtlas; P54803; baseline and differential.
DR Genevisible; P54803; HS.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0004336; F:galactosylceramidase activity; IDA:UniProtKB.
DR GO; GO:0006683; P:galactosylceramide catabolic process; IDA:UniProtKB.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:0042552; P:myelination; IEA:Ensembl.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR001286; Glyco_hydro_59.
DR InterPro; IPR035394; Glyco_hydro_59_dom.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR15172; PTHR15172; 1.
DR Pfam; PF02057; Glyco_hydro_59; 1.
DR Pfam; PF17387; Glyco_hydro_59M; 1.
DR PRINTS; PR00850; GLHYDRLASE59.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disease variant;
KW Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Leukodystrophy;
KW Lipid degradation; Lipid metabolism; Lysosome; Reference proteome; Signal;
KW Sphingolipid metabolism.
FT SIGNAL 1..42
FT /evidence="ECO:0000269|PubMed:8281145,
FT ECO:0000269|PubMed:8399327"
FT CHAIN 43..685
FT /note="Galactocerebrosidase"
FT /id="PRO_0000012230"
FT ACT_SITE 198
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 274
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 109
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 396
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 403
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 556
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 559
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 287..394
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..65
FT /note="MAEWLLSASWQRRAKAMTAAAGSAGRAAVPLLLCALLAPGGAYVLDDSDGLG
FT REFDGIGAVSGGG -> MLGKSHGRATHGPLPLADLGIHLPCVKVLHQVTPEEKPA
FT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036974"
FT VAR_SEQ 1..65
FT /note="MAEWLLSASWQRRAKAMTAAAGSAGRAAVPLLLCALLAPGGAYVLDDSDGLG
FT REFDGIGAVSGGG -> MGFMVADLW (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036975"
FT VAR_SEQ 66..88
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036976"
FT VAR_SEQ 638..685
FT /note="GHFTSGMLNDKSLWTDIPVNFPKNGWAAIGTHSFEFAQFDNFLVEATR ->
FT VAGRRKKT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036977"
FT VARIANT 21
FT /note="A -> P (in dbSNP:rs111887056)"
FT /evidence="ECO:0000269|PubMed:20886637"
FT /id="VAR_064430"
FT VARIANT 41
FT /note="G -> S (in GLD; dbSNP:rs387906955)"
FT /evidence="ECO:0000269|PubMed:17579360"
FT /id="VAR_064431"
FT VARIANT 59
FT /note="G -> R (in GLD; infantile; significant reduction of
FT activity)"
FT /evidence="ECO:0000269|PubMed:10234611"
FT /id="VAR_013956"
FT VARIANT 68
FT /note="S -> F (in GLD; infantile; significant reduction of
FT activity; dbSNP:rs1555383892)"
FT /evidence="ECO:0000269|PubMed:10234611"
FT /id="VAR_013957"
FT VARIANT 79
FT /note="R -> H (in GLD; dbSNP:rs370117160)"
FT /evidence="ECO:0000269|PubMed:8940268"
FT /id="VAR_013958"
FT VARIANT 82
FT /note="I -> M (in GLD; adult; reduction of activity; when
FT associated with V-2105)"
FT /evidence="ECO:0000269|PubMed:9272171"
FT /id="VAR_013959"
FT VARIANT 111
FT /note="G -> D (in GLD; dbSNP:rs746487628)"
FT /id="VAR_003380"
FT VARIANT 111
FT /note="G -> S (in GLD; dbSNP:rs756690487)"
FT /evidence="ECO:0000269|PubMed:8940268"
FT /id="VAR_003381"
FT VARIANT 112
FT /note="T -> A (in GLD; adult; dbSNP:rs147313927)"
FT /id="VAR_003382"
FT VARIANT 117
FT /note="M -> L (in GLD; adult; dbSNP:rs145580093)"
FT /evidence="ECO:0000269|PubMed:8940268"
FT /id="VAR_003383"
FT VARIANT 130
FT /note="E -> K (in GLD; dbSNP:rs374635469)"
FT /evidence="ECO:0000269|PubMed:20886637"
FT /id="VAR_064432"
FT VARIANT 184
FT /note="R -> C (in dbSNP:rs1805078)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:20886637, ECO:0000269|PubMed:7581365"
FT /id="VAR_013960"
FT VARIANT 187
FT /note="D -> V (in GLD; dbSNP:rs997021099)"
FT /id="VAR_003384"
FT VARIANT 194
FT /note="G -> A (in GLD; dbSNP:rs963756824)"
FT /id="VAR_003385"
FT VARIANT 248
FT /note="D -> N (in dbSNP:rs34362748)"
FT /evidence="ECO:0000269|PubMed:20886637"
FT /id="VAR_003386"
FT VARIANT 250
FT /note="I -> T (in GLD; late infantile; dbSNP:rs886039569)"
FT /evidence="ECO:0000269|PubMed:8940268"
FT /id="VAR_003387"
FT VARIANT 263
FT /note="A -> T (in GLD; dbSNP:rs1308816724)"
FT /id="VAR_003388"
FT VARIANT 278
FT /note="T -> I (in GLD; infantile; significant reduction of
FT activity)"
FT /evidence="ECO:0000269|PubMed:10234611"
FT /id="VAR_013961"
FT VARIANT 284
FT /note="G -> S (in GLD; dbSNP:rs377274761)"
FT /evidence="ECO:0000269|PubMed:8940268"
FT /id="VAR_003389"
FT VARIANT 286
FT /note="G -> D (in GLD; significant reduction of activity;
FT dbSNP:rs199847983)"
FT /evidence="ECO:0000269|PubMed:10477434,
FT ECO:0000269|PubMed:9272171"
FT /id="VAR_003390"
FT VARIANT 295
FT /note="N -> T (in GLD; dbSNP:rs746922378)"
FT /id="VAR_003391"
FT VARIANT 303
FT /note="S -> F (in GLD; infantile; dbSNP:rs756352952)"
FT /id="VAR_003392"
FT VARIANT 305
FT /note="I -> V (in dbSNP:rs74887188)"
FT /evidence="ECO:0000269|PubMed:9272171"
FT /id="VAR_013962"
FT VARIANT 314
FT /note="Y -> C (in GLD; dbSNP:rs1595215209)"
FT /evidence="ECO:0000269|PubMed:8940268"
FT /id="VAR_013963"
FT VARIANT 318
FT /note="P -> A (in GLD; dbSNP:rs1057516642)"
FT /evidence="ECO:0000269|PubMed:8595408"
FT /id="VAR_003393"
FT VARIANT 318
FT /note="P -> R (in GLD; dbSNP:rs387906954)"
FT /evidence="ECO:0000269|PubMed:20886637"
FT /id="VAR_064433"
FT VARIANT 323
FT /note="G -> R (in GLD; dbSNP:rs1472207768)"
FT /evidence="ECO:0000269|PubMed:20886637"
FT /id="VAR_064434"
FT VARIANT 335
FT /note="Y -> C (in GLD; infantile; significant reduction of
FT activity; dbSNP:rs757407613)"
FT /evidence="ECO:0000269|PubMed:10234611"
FT /id="VAR_013964"
FT VARIANT 384
FT /note="I -> T (in GLD; dbSNP:rs1376496659)"
FT /evidence="ECO:0000269|PubMed:20886637"
FT /id="VAR_064435"
FT VARIANT 396
FT /note="R -> L (in GLD)"
FT /evidence="ECO:0000269|PubMed:20886637"
FT /id="VAR_064436"
FT VARIANT 396
FT /note="R -> W (in GLD; bilateral cherry red spots;
FT dbSNP:rs770485731)"
FT /id="VAR_003394"
FT VARIANT 400
FT /note="P -> L (in GLD; dbSNP:rs771232832)"
FT /id="VAR_003395"
FT VARIANT 426
FT /note="W -> G (in GLD; infantile; significant reduction of
FT activity)"
FT /evidence="ECO:0000269|PubMed:10234611"
FT /id="VAR_013965"
FT VARIANT 468
FT /note="T -> S (in GLD; unknown pathological significance;
FT dbSNP:rs34134328)"
FT /evidence="ECO:0000269|PubMed:9338580"
FT /id="VAR_003396"
FT VARIANT 490
FT /note="Y -> N (in GLD; dbSNP:rs202135871)"
FT /evidence="ECO:0000269|PubMed:20886637"
FT /id="VAR_064437"
FT VARIANT 514
FT /note="F -> S (in GLD; dbSNP:rs375867319)"
FT /id="VAR_003397"
FT VARIANT 529
FT /note="T -> M (in GLD; infantile; dbSNP:rs200960659)"
FT /id="VAR_003398"
FT VARIANT 531
FT /note="R -> C (in GLD; dbSNP:rs749893889)"
FT /id="VAR_003399"
FT VARIANT 531
FT /note="R -> H (in GLD; infantile; significant reduction of
FT activity; dbSNP:rs200378205)"
FT /evidence="ECO:0000269|PubMed:10234611"
FT /id="VAR_013966"
FT VARIANT 544
FT /note="D -> N (in GLD; Arab patients; dbSNP:rs387906952)"
FT /evidence="ECO:0000269|PubMed:8786069"
FT /id="VAR_003400"
FT VARIANT 553
FT /note="G -> R (in GLD; loss of activity;
FT dbSNP:rs748573754)"
FT /evidence="ECO:0000269|PubMed:10477434"
FT /id="VAR_013967"
FT VARIANT 562
FT /note="I -> T (in dbSNP:rs398607)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:20886637,
FT ECO:0000269|PubMed:7601472, ECO:0000269|PubMed:8940268,
FT ECO:0000269|PubMed:9272171"
FT /id="VAR_003401"
FT VARIANT 566
FT /note="V -> G (in GLD)"
FT /evidence="ECO:0000269|PubMed:8595408"
FT /id="VAR_003402"
FT VARIANT 567
FT /note="Y -> S (in GLD; dbSNP:rs752537626)"
FT /id="VAR_003403"
FT VARIANT 592
FT /note="A -> S (in GLD; dbSNP:rs1360345372)"
FT /id="VAR_003404"
FT VARIANT 599
FT /note="I -> S (in GLD; infantile; Druze patients;
FT dbSNP:rs387906953)"
FT /evidence="ECO:0000269|PubMed:8786069"
FT /id="VAR_003405"
FT VARIANT 634
FT /note="L -> S (in GLD; adult; dbSNP:rs138577661)"
FT /evidence="ECO:0000269|PubMed:9272171"
FT /id="VAR_013968"
FT VARIANT 641
FT /note="T -> A (in dbSNP:rs421262)"
FT /evidence="ECO:0000269|PubMed:10477434,
FT ECO:0000269|PubMed:12508121, ECO:0000269|PubMed:20886637"
FT /id="VAR_003406"
FT VARIANT 645
FT /note="L -> R (in GLD; adult; dbSNP:rs780593419)"
FT /id="VAR_003407"
FT VARIANT 668
FT /note="T -> R (in GLD; infantile; significant reduction of
FT activity)"
FT /evidence="ECO:0000269|PubMed:10234611"
FT /id="VAR_013969"
FT VARIANT 681
FT /note="V -> M (in GLD; dbSNP:rs200607029)"
FT /evidence="ECO:0000269|PubMed:23462331"
FT /id="VAR_069512"
FT CONFLICT 78
FT /note="Y -> H (in Ref. 1; BAH13778)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="I -> T (in Ref. 3; BAG64110)"
FT /evidence="ECO:0000305"
FT CONFLICT 422
FT /note="E -> G (in Ref. 3; BAG64110)"
FT /evidence="ECO:0000305"
FT CONFLICT P54803-4:17
FT /note="A -> T (in Ref. 3; BAG64110)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 685 AA; 77063 MW; 03F3D223381AD5B1 CRC64;
MAEWLLSASW QRRAKAMTAA AGSAGRAAVP LLLCALLAPG GAYVLDDSDG LGREFDGIGA
VSGGGATSRL LVNYPEPYRS QILDYLFKPN FGASLHILKV EIGGDGQTTD GTEPSHMHYA
LDENYFRGYE WWLMKEAKKR NPNITLIGLP WSFPGWLGKG FDWPYVNLQL TAYYVVTWIV
GAKRYHDLDI DYIGIWNERS YNANYIKILR KMLNYQGLQR VKIIASDNLW ESISASMLLD
AELFKVVDVI GAHYPGTHSA KDAKLTGKKL WSSEDFSTLN SDMGAGCWGR ILNQNYINGY
MTSTIAWNLV ASYYEQLPYG RCGLMTAQEP WSGHYVVESP VWVSAHTTQF TQPGWYYLKT
VGHLEKGGSY VALTDGLGNL TIIIETMSHK HSKCIRPFLP YFNVSQQFAT FVLKGSFSEI
PELQVWYTKL GKTSERFLFK QLDSLWLLDS DGSFTLSLHE DELFTLTTLT TGRKGSYPLP
PKSQPFPSTY KDDFNVDYPF FSEAPNFADQ TGVFEYFTNI EDPGEHHFTL RQVLNQRPIT
WAADASNTIS IIGDYNWTNL TIKCDVYIET PDTGGVFIAG RVNKGGILIR SARGIFFWIF
ANGSYRVTGD LAGWIIYALG RVEVTAKKWY TLTLTIKGHF TSGMLNDKSL WTDIPVNFPK
NGWAAIGTHS FEFAQFDNFL VEATR
