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 27-MAR-2024, entry version 205. 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 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 [10] 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 [11] RP VARIANTS KRB 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 [12] RP VARIANTS KRB 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 [13] 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 [14] RP VARIANTS KRB ALA-112 AND VAL-187. RX PubMed=8687180; DOI=10.1002/ana.410400119; RA Luzi P., Rafi M.A., Wenger D.A.; RT "Multiple mutations in the GALC gene in a patient with adult-onset Krabbe RT disease."; RL Ann. Neurol. 40:116-119(1996). RN [15] RP VARIANTS KRB 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 KRB 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 KRB ASP-111; ALA-194; THR-263; THR-295; PHE-303; TRP-396; LEU-400; RP SER-468; SER-514; MET-529; CYS-531; SER-567; SER-592 AND ARG-645. 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 [18] RP VARIANTS KRB ASP-286 AND ARG-553, VARIANT ALA-641, AND CHARACTERIZATION OF RP VARIANT KRB 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 [19] RP VARIANTS KRB 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 [20] RP VARIANT KRB 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 [21] RP VARIANTS KRB 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 [22] RP VARIANT KRB 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). RN [23] RP VARIANTS KRB ASP-111; ALA-112; ASP-286; PHE-303; TRP-396; MET-529; SER-567 RP AND SER-634. RX PubMed=34449528; DOI=10.3390/ijns7030057; RA Wenger D.A., Luzi P., Rafi M.A.; RT "Advances in the Diagnosis and Treatment of Krabbe Disease."; RL Int. J. Neonatal Screen. 7:0-0(2021). 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: Krabbe disease (KRB) [MIM:245200]: An autosomal recessive CC 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:34449528, ECO:0000269|PubMed:8595408, CC ECO:0000269|PubMed:8687180, ECO:0000269|PubMed:8786069, CC ECO:0000269|PubMed:8940268, ECO:0000269|PubMed:9272171, CC ECO:0000269|PubMed:9338580}. Note=The disease is caused by variants CC affecting the gene represented in this 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 50. DR IntAct; P54803; 14. DR STRING; 9606.ENSP00000261304; -. DR ChEMBL; CHEMBL3713095; -. DR SwissLipids; SLP:000000644; -. DR CAZy; GH59; Glycoside Hydrolase Family 59. DR GlyCosmos; P54803; 6 sites, No reported glycans. DR GlyGen; P54803; 7 sites, 1 O-linked glycan (1 site). 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; 9606-ENSP00000261304; -. DR PeptideAtlas; P54803; -. DR ProteomicsDB; 56722; -. [P54803-1] DR ProteomicsDB; 56723; -. [P54803-3] DR ProteomicsDB; 56724; -. [P54803-4] DR ProteomicsDB; 56725; -. [P54803-5] DR Pumba; P54803; -. DR Antibodypedia; 26266; 278 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 AGR; HGNC:4115; -. 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; KYPKNGW; -. DR OrthoDB; 5487508at2759; -. DR PhylomeDB; P54803; -. DR TreeFam; TF312985; -. DR BRENDA; 3.2.1.46; 2681. DR PathwayCommons; P54803; -. DR Reactome; R-HSA-9840310; Glycosphingolipid catabolism. DR SignaLink; P54803; -. DR BioGRID-ORCS; 2581; 16 hits in 1158 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 209 other cell types or tissues. DR ExpressionAtlas; P54803; baseline and differential. 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:0046479; P:glycosphingolipid catabolic process; TAS:Reactome. DR GO; GO:0042552; P:myelination; IEA:Ensembl. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR Gene3D; 3.20.20.80; Glycosidases; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR049162; GH59_C. DR InterPro; IPR049161; GH59_cat. DR InterPro; IPR001286; Glyco_hydro_59. DR InterPro; IPR035394; Glyco_hydro_59_dom. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR PANTHER; PTHR15172; GALACTOCEREBROSIDASE; 1. DR PANTHER; PTHR15172:SF1; GALACTOCEREBROSIDASE; 1. DR Pfam; PF02057; Glyco_hydro_59; 1. DR Pfam; PF21708; Glyco_hydro_59_C; 1. DR Pfam; PF17387; Glyco_hydro_59M; 1. DR PRINTS; PR00850; GLHYDRLASE59. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR Genevisible; P54803; HS. 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 KRB; dbSNP:rs387906955)" FT /evidence="ECO:0000269|PubMed:17579360" FT /id="VAR_064431" FT VARIANT 59 FT /note="G -> R (in KRB; infantile; significant reduction of FT activity)" FT /evidence="ECO:0000269|PubMed:10234611" FT /id="VAR_013956" FT VARIANT 68 FT /note="S -> F (in KRB; 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 KRB; dbSNP:rs370117160)" FT /evidence="ECO:0000269|PubMed:8940268" FT /id="VAR_013958" FT VARIANT 82 FT /note="I -> M (in KRB; adult; reduction of activity; when FT associated with V-305)" FT /evidence="ECO:0000269|PubMed:9272171" FT /id="VAR_013959" FT VARIANT 111 FT /note="G -> D (in KRB; dbSNP:rs746487628)" FT /evidence="ECO:0000269|PubMed:34449528, FT ECO:0000269|PubMed:9338580" FT /id="VAR_003380" FT VARIANT 111 FT /note="G -> S (in KRB; dbSNP:rs756690487)" FT /evidence="ECO:0000269|PubMed:8940268" FT /id="VAR_003381" FT VARIANT 112 FT /note="T -> A (in KRB; dbSNP:rs147313927)" FT /evidence="ECO:0000269|PubMed:34449528, FT ECO:0000269|PubMed:8687180" FT /id="VAR_003382" FT VARIANT 117 FT /note="M -> L (in KRB; adult; dbSNP:rs145580093)" FT /evidence="ECO:0000269|PubMed:8940268" FT /id="VAR_003383" FT VARIANT 130 FT /note="E -> K (in KRB; 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 KRB; dbSNP:rs997021099)" FT /evidence="ECO:0000269|PubMed:8687180" FT /id="VAR_003384" FT VARIANT 194 FT /note="G -> A (in KRB; dbSNP:rs963756824)" FT /evidence="ECO:0000269|PubMed:9338580" 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 KRB; late infantile; dbSNP:rs886039569)" FT /evidence="ECO:0000269|PubMed:8940268" FT /id="VAR_003387" FT VARIANT 263 FT /note="A -> T (in KRB; dbSNP:rs1308816724)" FT /evidence="ECO:0000269|PubMed:9338580" FT /id="VAR_003388" FT VARIANT 278 FT /note="T -> I (in KRB; infantile; significant reduction of FT activity)" FT /evidence="ECO:0000269|PubMed:10234611" FT /id="VAR_013961" FT VARIANT 284 FT /note="G -> S (in KRB; dbSNP:rs377274761)" FT /evidence="ECO:0000269|PubMed:8940268" FT /id="VAR_003389" FT VARIANT 286 FT /note="G -> D (in KRB; significant reduction of activity; FT dbSNP:rs199847983)" FT /evidence="ECO:0000269|PubMed:10477434, FT ECO:0000269|PubMed:34449528, ECO:0000269|PubMed:9272171" FT /id="VAR_003390" FT VARIANT 295 FT /note="N -> T (in KRB; dbSNP:rs746922378)" FT /evidence="ECO:0000269|PubMed:9338580" FT /id="VAR_003391" FT VARIANT 303 FT /note="S -> F (in KRB; dbSNP:rs756352952)" FT /evidence="ECO:0000269|PubMed:34449528, FT ECO:0000269|PubMed:9338580" FT /id="VAR_003392" FT VARIANT 305 FT /note="I -> V (reduction of activity; when associated with FT M-82; dbSNP:rs74887188)" FT /evidence="ECO:0000269|PubMed:9272171" FT /id="VAR_013962" FT VARIANT 314 FT /note="Y -> C (in KRB; dbSNP:rs1595215209)" FT /evidence="ECO:0000269|PubMed:8940268" FT /id="VAR_013963" FT VARIANT 318 FT /note="P -> A (in KRB; dbSNP:rs1057516642)" FT /evidence="ECO:0000269|PubMed:8595408" FT /id="VAR_003393" FT VARIANT 318 FT /note="P -> R (in KRB; dbSNP:rs387906954)" FT /evidence="ECO:0000269|PubMed:20886637" FT /id="VAR_064433" FT VARIANT 323 FT /note="G -> R (in KRB; dbSNP:rs1472207768)" FT /evidence="ECO:0000269|PubMed:20886637" FT /id="VAR_064434" FT VARIANT 335 FT /note="Y -> C (in KRB; 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 KRB; dbSNP:rs1376496659)" FT /evidence="ECO:0000269|PubMed:20886637" FT /id="VAR_064435" FT VARIANT 396 FT /note="R -> L (in KRB)" FT /evidence="ECO:0000269|PubMed:20886637" FT /id="VAR_064436" FT VARIANT 396 FT /note="R -> W (in KRB; dbSNP:rs770485731)" FT /evidence="ECO:0000269|PubMed:34449528, FT ECO:0000269|PubMed:9338580" FT /id="VAR_003394" FT VARIANT 400 FT /note="P -> L (in KRB; dbSNP:rs771232832)" FT /evidence="ECO:0000269|PubMed:9338580" FT /id="VAR_003395" FT VARIANT 426 FT /note="W -> G (in KRB; infantile; significant reduction of FT activity)" FT /evidence="ECO:0000269|PubMed:10234611" FT /id="VAR_013965" FT VARIANT 468 FT /note="T -> S (in KRB; uncertain significance; FT dbSNP:rs34134328)" FT /evidence="ECO:0000269|PubMed:9338580" FT /id="VAR_003396" FT VARIANT 490 FT /note="Y -> N (in KRB; dbSNP:rs202135871)" FT /evidence="ECO:0000269|PubMed:20886637" FT /id="VAR_064437" FT VARIANT 514 FT /note="F -> S (in KRB; dbSNP:rs375867319)" FT /evidence="ECO:0000269|PubMed:9338580" FT /id="VAR_003397" FT VARIANT 529 FT /note="T -> M (in KRB; dbSNP:rs200960659)" FT /evidence="ECO:0000269|PubMed:34449528, FT ECO:0000269|PubMed:9338580" FT /id="VAR_003398" FT VARIANT 531 FT /note="R -> C (in KRB; dbSNP:rs749893889)" FT /evidence="ECO:0000269|PubMed:9338580" FT /id="VAR_003399" FT VARIANT 531 FT /note="R -> H (in KRB; 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 KRB; Arab patients; dbSNP:rs387906952)" FT /evidence="ECO:0000269|PubMed:8786069" FT /id="VAR_003400" FT VARIANT 553 FT /note="G -> R (in KRB; 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 KRB)" FT /evidence="ECO:0000269|PubMed:8595408" FT /id="VAR_003402" FT VARIANT 567 FT /note="Y -> S (in KRB; dbSNP:rs752537626)" FT /evidence="ECO:0000269|PubMed:34449528, FT ECO:0000269|PubMed:9338580" FT /id="VAR_003403" FT VARIANT 592 FT /note="A -> S (in KRB; dbSNP:rs1360345372)" FT /evidence="ECO:0000269|PubMed:9338580" FT /id="VAR_003404" FT VARIANT 599 FT /note="I -> S (in KRB; infantile; Druze patients; FT dbSNP:rs387906953)" FT /evidence="ECO:0000269|PubMed:8786069" FT /id="VAR_003405" FT VARIANT 634 FT /note="L -> S (in KRB; dbSNP:rs138577661)" FT /evidence="ECO:0000269|PubMed:34449528, FT 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 KRB; adult; dbSNP:rs780593419)" FT /evidence="ECO:0000269|PubMed:9338580" FT /id="VAR_003407" FT VARIANT 668 FT /note="T -> R (in KRB; infantile; significant reduction of FT activity)" FT /evidence="ECO:0000269|PubMed:10234611" FT /id="VAR_013969" FT VARIANT 681 FT /note="V -> M (in KRB; 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 //