LANC1_HUMAN
ID LANC1_HUMAN Reviewed; 399 AA.
AC O43813;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Glutathione S-transferase LANCL1 {ECO:0000250|UniProtKB:O89112};
DE EC=2.5.1.18 {ECO:0000250|UniProtKB:O89112};
DE AltName: Full=40 kDa erythrocyte membrane protein;
DE Short=p40 {ECO:0000250|UniProtKB:Q9QX69};
DE AltName: Full=LanC-like protein 1 {ECO:0000303|PubMed:11474189};
GN Name=LANCL1 {ECO:0000312|HGNC:HGNC:6508};
GN Synonyms=GPR69A {ECO:0000250|UniProtKB:Q9QX69};
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], PROTEIN SEQUENCE OF 5-24; 28-35; 40-50; 198-201
RP AND 392-399, TISSUE SPECIFICITY, AND INTERACTION WITH STOM.
RC TISSUE=Bone marrow, Erythrocyte, and Fetal brain;
RX PubMed=9512664; DOI=10.1016/s0167-4781(97)00178-4;
RA Mayer H., Salzer U., Breuss J., Ziegler S., Marchler-Bauer A., Prohaska R.;
RT "Isolation, molecular characterization, and tissue-specific expression of a
RT novel putative G protein-coupled receptor.";
RL Biochim. Biophys. Acta 1395:301-308(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Brain, and Testis;
RX PubMed=11474189; DOI=10.1159/000056958;
RA Mayer H., Bauer H., Prohaska R.;
RT "Organization and chromosomal localization of the human and mouse genes
RT coding for LanC-like protein 1 (LANCL1).";
RL Cytogenet. Cell Genet. 93:100-104(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10944443; DOI=10.1006/bbrc.2000.3260;
RA Bauer H., Mayer H., Marchler-Bauer A., Salzer U., Prohaska R.;
RT "Characterization of p40/GPR69A as a peripheral membrane protein related to
RT the lantibiotic synthetase component C.";
RL Biochem. Biophys. Res. Commun. 275:69-74(2000).
RN [5]
RP TISSUE SPECIFICITY, INTERACTION WITH P.FALCIPARUM SBP1 (MICROBIAL
RP INFECTION), IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=15811525; DOI=10.1016/j.molbiopara.2005.01.013;
RA Blisnick T., Vincensini L., Barale J.C., Namane A., Braun Breton C.;
RT "LANCL1, an erythrocyte protein recruited to the Maurer's clefts during
RT Plasmodium falciparum development.";
RL Mol. Biochem. Parasitol. 141:39-47(2005).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=16979580; DOI=10.1016/j.bbamem.2006.07.018;
RA Landlinger C., Salzer U., Prohaska R.;
RT "Myristoylation of human LanC-like protein 2 (LANCL2) is essential for the
RT interaction with the plasma membrane and the increase in cellular
RT sensitivity to adriamycin.";
RL Biochim. Biophys. Acta 1758:1759-1767(2006).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE AND ZINC
RP IONS, MUTAGENESIS OF ARG-4; LYS-317; CYS-322 AND ARG-364, INTERACTION WITH
RP EPS8, AND FUNCTION.
RX PubMed=19528316; DOI=10.1101/gad.1789209;
RA Zhang W., Wang L., Liu Y., Xu J., Zhu G., Cang H., Li X., Bartlam M.,
RA Hensley K., Li G., Rao Z., Zhang X.C.;
RT "Structure of human lanthionine synthetase C-like protein 1 and its
RT interaction with Eps8 and glutathione.";
RL Genes Dev. 23:1387-1392(2009).
CC -!- FUNCTION: Functions as glutathione transferase. Catalyzes conjugation
CC of the glutathione (GSH) to artificial substrates 1-chloro-2,4-
CC dinitrobenzene (CDNB) and p-nitrophenyl acetate. Mitigates neuronal
CC oxidative stress during normal postnatal development and in response to
CC oxidative stresses probably through GSH antioxidant defense mechanism
CC (By similarity). May play a role in EPS8 signaling. Binds glutathione
CC (PubMed:19528316). {ECO:0000250|UniProtKB:O89112,
CC ECO:0000269|PubMed:19528316}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + RX = a halide anion + an S-substituted
CC glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:90779; EC=2.5.1.18;
CC Evidence={ECO:0000250|UniProtKB:O89112};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-
CC S-glutathione + chloride + H(+); Xref=Rhea:RHEA:51220,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17996, ChEBI:CHEBI:34718,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:133977; EC=2.5.1.18;
CC Evidence={ECO:0000250|UniProtKB:O89112};
CC -!- SUBUNIT: Interacts with the C-terminal of STOM (PubMed:9512664).
CC Interacts with the EPS8 SH3 domain. Interaction with EPS8 is inhibited
CC by glutathione binding (PubMed:19528316). {ECO:0000269|PubMed:19528316,
CC ECO:0000269|PubMed:9512664}.
CC -!- SUBUNIT: (Microbial infection) Interacts with P.falciparum SBP1.
CC {ECO:0000269|PubMed:15811525}.
CC -!- INTERACTION:
CC O43813; Q9UHR4: BAIAP2L1; NbExp=3; IntAct=EBI-3046631, EBI-2483278;
CC O43813; P42858: HTT; NbExp=10; IntAct=EBI-3046631, EBI-466029;
CC O43813; Q08509: Eps8; Xeno; NbExp=2; IntAct=EBI-3046631, EBI-375596;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15811525}. Cell
CC membrane {ECO:0000269|PubMed:10944443, ECO:0000269|PubMed:16979580};
CC Peripheral membrane protein {ECO:0000269|PubMed:10944443}.
CC -!- TISSUE SPECIFICITY: Detected in erythrocytes, brain, kidney, testis,
CC ovary, heart, lung, placenta and spleen (at protein level). Ubiquitous.
CC Strongly expressed in brain, spinal cord, pituitary gland, kidney,
CC heart, skeletal muscle, pancreas, ovary and testis.
CC {ECO:0000269|PubMed:10944443, ECO:0000269|PubMed:15811525,
CC ECO:0000269|PubMed:9512664}.
CC -!- MISCELLANEOUS: Was originally thought to be a G-protein coupled
CC receptor. {ECO:0000305|PubMed:9512664}.
CC -!- SIMILARITY: Belongs to the LanC-like protein family. {ECO:0000305}.
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DR EMBL; Y11395; CAA72205.1; -; mRNA.
DR EMBL; AJ289236; CAC21950.1; -; Genomic_DNA.
DR EMBL; AJ289237; CAC21950.1; JOINED; Genomic_DNA.
DR EMBL; AJ289238; CAC21950.1; JOINED; Genomic_DNA.
DR EMBL; AJ289239; CAC21950.1; JOINED; Genomic_DNA.
DR EMBL; BC028685; AAH28685.1; -; mRNA.
DR CCDS; CCDS2392.1; -.
DR RefSeq; NP_001130046.1; NM_001136574.1.
DR RefSeq; NP_001130047.1; NM_001136575.1.
DR RefSeq; NP_006046.1; NM_006055.2.
DR PDB; 3E6U; X-ray; 2.60 A; A/B/C/D=1-399.
DR PDB; 3E73; X-ray; 2.80 A; A/B=1-399.
DR PDBsum; 3E6U; -.
DR PDBsum; 3E73; -.
DR AlphaFoldDB; O43813; -.
DR SMR; O43813; -.
DR BioGRID; 115599; 77.
DR IntAct; O43813; 35.
DR MINT; O43813; -.
DR STRING; 9606.ENSP00000388713; -.
DR GlyGen; O43813; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43813; -.
DR PhosphoSitePlus; O43813; -.
DR SwissPalm; O43813; -.
DR BioMuta; LANCL1; -.
DR EPD; O43813; -.
DR jPOST; O43813; -.
DR MassIVE; O43813; -.
DR PaxDb; O43813; -.
DR PeptideAtlas; O43813; -.
DR PRIDE; O43813; -.
DR ProteomicsDB; 49178; -.
DR Antibodypedia; 34207; 115 antibodies from 20 providers.
DR DNASU; 10314; -.
DR Ensembl; ENST00000233714.8; ENSP00000233714.4; ENSG00000115365.12.
DR Ensembl; ENST00000431941.6; ENSP00000397646.2; ENSG00000115365.12.
DR Ensembl; ENST00000441020.7; ENSP00000393323.3; ENSG00000115365.12.
DR Ensembl; ENST00000443314.5; ENSP00000388713.1; ENSG00000115365.12.
DR Ensembl; ENST00000450366.7; ENSP00000393597.2; ENSG00000115365.12.
DR GeneID; 10314; -.
DR KEGG; hsa:10314; -.
DR MANE-Select; ENST00000450366.7; ENSP00000393597.2; NM_006055.3; NP_006046.1.
DR CTD; 10314; -.
DR DisGeNET; 10314; -.
DR GeneCards; LANCL1; -.
DR HGNC; HGNC:6508; LANCL1.
DR HPA; ENSG00000115365; Tissue enhanced (brain).
DR MIM; 604155; gene.
DR neXtProt; NX_O43813; -.
DR OpenTargets; ENSG00000115365; -.
DR PharmGKB; PA30293; -.
DR VEuPathDB; HostDB:ENSG00000115365; -.
DR eggNOG; KOG2787; Eukaryota.
DR GeneTree; ENSGT00530000063186; -.
DR HOGENOM; CLU_036244_0_0_1; -.
DR InParanoid; O43813; -.
DR OMA; YSLVFIN; -.
DR PhylomeDB; O43813; -.
DR TreeFam; TF300068; -.
DR PathwayCommons; O43813; -.
DR SignaLink; O43813; -.
DR BioGRID-ORCS; 10314; 11 hits in 1082 CRISPR screens.
DR ChiTaRS; LANCL1; human.
DR EvolutionaryTrace; O43813; -.
DR GenomeRNAi; 10314; -.
DR Pharos; O43813; Tbio.
DR PRO; PR:O43813; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O43813; protein.
DR Bgee; ENSG00000115365; Expressed in endothelial cell and 210 other tissues.
DR ExpressionAtlas; O43813; baseline and differential.
DR Genevisible; O43813; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc.
DR GO; GO:0043295; F:glutathione binding; IDA:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; ISS:UniProtKB.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IDA:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:1903203; P:regulation of oxidative stress-induced neuron death; ISS:UniProtKB.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR007822; LANC-like.
DR InterPro; IPR020464; LanC-like_prot_euk.
DR Pfam; PF05147; LANC_like; 1.
DR PRINTS; PR01951; LANCEUKARYTE.
DR PRINTS; PR01950; LANCSUPER.
DR SMART; SM01260; LANC_like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Membrane; Metal-binding; Reference proteome;
KW Transferase; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..399
FT /note="Glutathione S-transferase LANCL1"
FT /id="PRO_0000191268"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19528316"
FT BINDING 317
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:19528316"
FT BINDING 322
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19528316"
FT BINDING 323
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19528316"
FT BINDING 364..367
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:19528316"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 142
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MUTAGEN 4
FT /note="R->A: Loss of glutathione binding."
FT /evidence="ECO:0000269|PubMed:19528316"
FT MUTAGEN 317
FT /note="K->A: Loss of glutathione binding."
FT /evidence="ECO:0000269|PubMed:19528316"
FT MUTAGEN 322
FT /note="C->A: Loss of glutathione binding."
FT /evidence="ECO:0000269|PubMed:19528316"
FT MUTAGEN 364
FT /note="R->A,E: Loss of glutathione binding."
FT /evidence="ECO:0000269|PubMed:19528316"
FT HELIX 2..4
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 15..19
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 30..50
FT /evidence="ECO:0007829|PDB:3E6U"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:3E6U"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 65..79
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 82..96
FT /evidence="ECO:0007829|PDB:3E6U"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 111..123
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 127..138
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 139..143
FT /evidence="ECO:0007829|PDB:3E6U"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 155..169
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 176..196
FT /evidence="ECO:0007829|PDB:3E6U"
FT TURN 197..202
FT /evidence="ECO:0007829|PDB:3E6U"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 221..228
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 237..242
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 244..253
FT /evidence="ECO:0007829|PDB:3E6U"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 279..293
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 296..312
FT /evidence="ECO:0007829|PDB:3E6U"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:3E73"
FT HELIX 325..339
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 342..355
FT /evidence="ECO:0007829|PDB:3E6U"
FT TURN 356..359
FT /evidence="ECO:0007829|PDB:3E6U"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 376..386
FT /evidence="ECO:0007829|PDB:3E6U"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:3E6U"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:3E6U"
SQ SEQUENCE 399 AA; 45283 MW; 2664F275F9281AF2 CRC64;
MAQRAFPNPY ADYNKSLAEG YFDAAGRLTP EFSQRLTNKI RELLQQMERG LKSADPRDGT
GYTGWAGIAV LYLHLYDVFG DPAYLQLAHG YVKQSLNCLT KRSITFLCGD AGPLAVAAVL
YHKMNNEKQA EDCITRLIHL NKIDPHAPNE MLYGRIGYIY ALLFVNKNFG VEKIPQSHIQ
QICETILTSG ENLARKRNFT AKSPLMYEWY QEYYVGAAHG LAGIYYYLMQ PSLQVSQGKL
HSLVKPSVDY VCQLKFPSGN YPPCIGDNRD LLVHWCHGAP GVIYMLIQAY KVFREEKYLC
DAYQCADVIW QYGLLKKGYG LCHGSAGNAY AFLTLYNLTQ DMKYLYRACK FAEWCLEYGE
HGCRTPDTPF SLFEGMAGTI YFLADLLVPT KARFPAFEL
