LMLN_HUMAN
ID LMLN_HUMAN Reviewed; 655 AA.
AC Q96KR4; B3LDG9; B3LDH0; C9J796; F8WB28; Q96KR5;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Leishmanolysin-like peptidase {ECO:0000305};
DE EC=3.4.24.- {ECO:0000250|UniProtKB:Q9VH19};
DE AltName: Full=Invadolysin {ECO:0000303|PubMed:19706689};
GN Name=LMLN;
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] (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION,
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=19706689; DOI=10.1242/jcs.044610;
RA Cobbe N., Marshall K.M., Gururaja Rao S., Chang C.W., Di Cara F., Duca E.,
RA Vass S., Kassan A., Heck M.M.;
RT "The conserved metalloprotease invadolysin localizes to the surface of
RT lipid droplets.";
RL J. Cell Sci. 122:3414-3423(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon, and Testis;
RA Chen J.M., Fortunato M., Barrett A.J.;
RT "Cloning and expression of splice variants of leishmanolysin-like protein,
RT a human form of the protozoan leishmanolysin, EC 3.4.24.36.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=15557119; DOI=10.1083/jcb.200405155;
RA McHugh B., Krause S.A., Yu B., Deans A.M., Heasman S., McLaughlin P.,
RA Heck M.M.;
RT "Invadolysin: a novel, conserved metalloprotease links mitotic structural
RT rearrangements with cell migration.";
RL J. Cell Biol. 167:673-686(2004).
CC -!- FUNCTION: Metalloprotease. {ECO:0000250|UniProtKB:Q9VH19}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P08148};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P08148};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15557119}. Lipid
CC droplet {ECO:0000269|PubMed:19706689}. Note=Found in ring-like
CC structures resembling invadopodia. In migrating cells it relocalizes
CC from internal structures to the leading edge of cells.
CC {ECO:0000269|PubMed:19706689}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96KR4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96KR4-2; Sequence=VSP_028002, VSP_028003;
CC Name=3;
CC IsoId=Q96KR4-3; Sequence=VSP_028003;
CC -!- TISSUE SPECIFICITY: Expressed in all cell lines analyzed.
CC {ECO:0000269|PubMed:19706689}.
CC -!- SIMILARITY: Belongs to the peptidase M8 family. {ECO:0000305}.
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DR EMBL; AM920777; CAP49203.1; -; mRNA.
DR EMBL; AM920778; CAP49204.1; -; mRNA.
DR EMBL; AJ312398; CAC42882.1; -; mRNA.
DR EMBL; AJ312399; CAC42883.1; -; mRNA.
DR EMBL; AC135893; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001129521.2; NM_001136049.2. [Q96KR4-3]
DR RefSeq; NP_149018.2; NM_033029.3. [Q96KR4-1]
DR AlphaFoldDB; Q96KR4; -.
DR BioGRID; 124601; 28.
DR IntAct; Q96KR4; 7.
DR STRING; 9606.ENSP00000410926; -.
DR MEROPS; M08.003; -.
DR iPTMnet; Q96KR4; -.
DR PhosphoSitePlus; Q96KR4; -.
DR BioMuta; LMLN; -.
DR DMDM; 296434578; -.
DR EPD; Q96KR4; -.
DR MassIVE; Q96KR4; -.
DR PeptideAtlas; Q96KR4; -.
DR PRIDE; Q96KR4; -.
DR ProteomicsDB; 30667; -.
DR ProteomicsDB; 77106; -. [Q96KR4-1]
DR ProteomicsDB; 77107; -. [Q96KR4-2]
DR Antibodypedia; 2701; 23 antibodies from 8 providers.
DR DNASU; 89782; -.
DR Ensembl; ENST00000330198.8; ENSP00000328829.4; ENSG00000185621.11. [Q96KR4-1]
DR Ensembl; ENST00000420910.6; ENSP00000410926.2; ENSG00000185621.11. [Q96KR4-3]
DR Ensembl; ENST00000482695.5; ENSP00000418324.1; ENSG00000185621.11. [Q96KR4-2]
DR GeneID; 89782; -.
DR KEGG; hsa:89782; -.
DR MANE-Select; ENST00000420910.7; ENSP00000410926.3; NM_001136049.3; NP_001129521.3. [Q96KR4-3]
DR UCSC; uc003fyt.4; human. [Q96KR4-1]
DR CTD; 89782; -.
DR DisGeNET; 89782; -.
DR GeneCards; LMLN; -.
DR HGNC; HGNC:15991; LMLN.
DR HPA; ENSG00000185621; Low tissue specificity.
DR MIM; 609380; gene.
DR neXtProt; NX_Q96KR4; -.
DR OpenTargets; ENSG00000185621; -.
DR PharmGKB; PA30402; -.
DR VEuPathDB; HostDB:ENSG00000185621; -.
DR eggNOG; KOG2556; Eukaryota.
DR GeneTree; ENSGT00390000008796; -.
DR HOGENOM; CLU_023820_1_0_1; -.
DR InParanoid; Q96KR4; -.
DR OMA; HSESMWE; -.
DR PhylomeDB; Q96KR4; -.
DR TreeFam; TF315265; -.
DR PathwayCommons; Q96KR4; -.
DR SignaLink; Q96KR4; -.
DR BioGRID-ORCS; 89782; 14 hits in 1080 CRISPR screens.
DR ChiTaRS; LMLN; human.
DR GenomeRNAi; 89782; -.
DR Pharos; Q96KR4; Tdark.
DR PRO; PR:Q96KR4; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q96KR4; protein.
DR Bgee; ENSG00000185621; Expressed in bronchial epithelial cell and 178 other tissues.
DR ExpressionAtlas; Q96KR4; baseline and differential.
DR Genevisible; Q96KR4; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR001577; Peptidase_M8.
DR PANTHER; PTHR10942; PTHR10942; 1.
DR Pfam; PF01457; Peptidase_M8; 3.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell cycle; Cell division; Cytoplasm; Hydrolase;
KW Lipid droplet; Metal-binding; Metalloprotease; Mitosis; Protease;
KW Reference proteome; Zinc.
FT CHAIN 1..655
FT /note="Leishmanolysin-like peptidase"
FT /id="PRO_0000303076"
FT ACT_SITE 273
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 272
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT VAR_SEQ 1..73
FT /note="MVTTLGPKMAAEWGGGVGYSGSGPGRSRWRWSGSVWVRSVLLLLGGLRASAT
FT STPVSLGSSPPCRHHVPSDTE -> MGRRSGLLGLRPGPEPVALER (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:19706689, ECO:0000303|Ref.2"
FT /id="VSP_028002"
FT VAR_SEQ 411
FT /note="G -> GWYKANYSMAEKLDWGRGMGCDFVRKSCKFWIDQQRQK (in
FT isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:19706689, ECO:0000303|Ref.2"
FT /id="VSP_028003"
FT VARIANT 106
FT /note="E -> D (in dbSNP:rs7373165)"
FT /id="VAR_060158"
FT CONFLICT 539
FT /note="R -> K (in Ref. 1; CAP49203/CAP49204 and 2;
FT CAC42882/CAC42883)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 655 AA; 73568 MW; D6A767CE3FA7A915 CRC64;
MVTTLGPKMA AEWGGGVGYS GSGPGRSRWR WSGSVWVRSV LLLLGGLRAS ATSTPVSLGS
SPPCRHHVPS DTEVINKVHL KANHVVKRDV DEHLRIKTVY DKSVEELLPE KKNLVKNKLF
PQAISYLEKT FQVRRPAGTI LLSRQCATNQ YLRKENDPHR YCTGECAAHT KCGPVIVPEE
HLQQCRVYRG GKWPHGAVGV PDQEGISDAD FVLYVGALAT ERCSHENIIS YAAYCQQEAN
MDRPIAGYAN LCPNMISTQP QEFVGMLSTV KHEVIHALGF SAGLFAFYHD KDGNPLTSRF
ADGLPPFNYS LGLYQWSDKV VRKVERLWDV RDNKIVRHTV YLLVTPRVVE EARKHFDCPV
LEGMELENQG GVGTELNHWE KRLLENEAMT GSHTQNRVLS RITLALMEDT GRQMLSPYCD
TLRSNPLQLT CRQDQRAVAV CNLQKFPKPL PQEYQYFDEL SGIPAEDLPY YGGSVEIADY
CPFSQEFSWH LSGEYQRSSD CRILENQPEI FKNYGAEKYG PHSVCLIQKS AFVMEKCERK
LSYPDWGSGC YQVSCSPQGL KVWVQDTSYL CSRAGQVLPV SIQMNGWIHD GNLLCPSCWD
FCELCPPETD PPATNLTRAL PLDLCSCSSS LVVTLWLLLG NLFPLLAGFL LCIWH
