LIPN_HUMAN
ID LIPN_HUMAN Reviewed; 398 AA.
AC Q5VXI9; A7KIH9;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Lipase member N;
DE EC=3.1.1.-;
DE AltName: Full=Lipase-like abhydrolase domain-containing protein 4;
DE Flags: Precursor;
GN Name=LIPN; Synonyms=LIPL4;
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], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Keratinocyte;
RX PubMed=17562024; DOI=10.1186/gb-2007-8-6-r107;
RA Toulza E., Mattiuzzo N.R., Galliano M.F., Jonca N., Dossat C., Jacob D.,
RA de Daruvar A., Wincker P., Serre G., Guerrin M.;
RT "Large-scale identification of human genes implicated in epidermal barrier
RT function.";
RL Genome Biol. 8:R107.1-R107.23(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP INVOLVEMENT IN ARCI8, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=21439540; DOI=10.1016/j.ajhg.2011.02.011;
RA Israeli S., Khamaysi Z., Fuchs-Telem D., Nousbeck J., Bergman R., Sarig O.,
RA Sprecher E.;
RT "A mutation in LIPN, encoding epidermal lipase N, causes a late-onset form
RT of autosomal-recessive congenital ichthyosis.";
RL Am. J. Hum. Genet. 88:482-487(2011).
CC -!- FUNCTION: Plays a highly specific role in the last step of keratinocyte
CC differentiation. May have an essential function in lipid metabolism of
CC the most differentiated epidermal layers.
CC {ECO:0000269|PubMed:17562024}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the epidermis in the granular
CC keratinocytes. Also detected in other tissues, although at much lower
CC levels, including lung and spleen. {ECO:0000269|PubMed:17562024,
CC ECO:0000269|PubMed:21439540}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during epidermal differentiation.
CC {ECO:0000269|PubMed:21439540}.
CC -!- DISEASE: Ichthyosis, congenital, autosomal recessive 8 (ARCI8)
CC [MIM:613943]: A form of autosomal recessive congenital ichthyosis, a
CC disorder of keratinization with abnormal differentiation and
CC desquamation of the epidermis, resulting in abnormal skin scaling over
CC the whole body. The main skin phenotypes are lamellar ichthyosis (LI)
CC and non-bullous congenital ichthyosiform erythroderma (NCIE), although
CC phenotypic overlap within the same patient or among patients from the
CC same family can occur. Lamellar ichthyosis is a condition often
CC associated with an embedment in a collodion-like membrane at birth;
CC skin scales later develop, covering the entire body surface. Non-
CC bullous congenital ichthyosiform erythroderma characterized by fine
CC whitish scaling on an erythrodermal background; larger brownish scales
CC are present on the buttocks, neck and legs.
CC {ECO:0000269|PubMed:21439540}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; EF426483; ABR08388.1; -; mRNA.
DR EMBL; AL358532; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS44456.1; -.
DR RefSeq; NP_001095939.1; NM_001102469.1.
DR RefSeq; XP_005270106.1; XM_005270049.3.
DR RefSeq; XP_011538385.1; XM_011540083.2.
DR RefSeq; XP_011538386.1; XM_011540084.2.
DR AlphaFoldDB; Q5VXI9; -.
DR SMR; Q5VXI9; -.
DR STRING; 9606.ENSP00000383923; -.
DR ESTHER; human-LIPN; Acidic_Lipase.
DR GlyGen; Q5VXI9; 1 site.
DR BioMuta; LIPN; -.
DR DMDM; 147647785; -.
DR MassIVE; Q5VXI9; -.
DR PaxDb; Q5VXI9; -.
DR PeptideAtlas; Q5VXI9; -.
DR PRIDE; Q5VXI9; -.
DR Antibodypedia; 48305; 72 antibodies from 12 providers.
DR DNASU; 643418; -.
DR Ensembl; ENST00000404459.2; ENSP00000383923.1; ENSG00000204020.6.
DR GeneID; 643418; -.
DR KEGG; hsa:643418; -.
DR MANE-Select; ENST00000404459.2; ENSP00000383923.1; NM_001102469.2; NP_001095939.1.
DR UCSC; uc010qmw.2; human.
DR CTD; 643418; -.
DR DisGeNET; 643418; -.
DR GeneCards; LIPN; -.
DR GeneReviews; LIPN; -.
DR HGNC; HGNC:23452; LIPN.
DR HPA; ENSG00000204020; Tissue enriched (skin).
DR MalaCards; LIPN; -.
DR MIM; 613924; gene.
DR MIM; 613943; phenotype.
DR neXtProt; NX_Q5VXI9; -.
DR OpenTargets; ENSG00000204020; -.
DR Orphanet; 313; Lamellar ichthyosis.
DR PharmGKB; PA162394123; -.
DR VEuPathDB; HostDB:ENSG00000204020; -.
DR eggNOG; KOG2624; Eukaryota.
DR GeneTree; ENSGT00940000161695; -.
DR HOGENOM; CLU_010974_0_0_1; -.
DR InParanoid; Q5VXI9; -.
DR OMA; MFGTKGF; -.
DR OrthoDB; 651396at2759; -.
DR PhylomeDB; Q5VXI9; -.
DR TreeFam; TF315485; -.
DR PathwayCommons; Q5VXI9; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR BioGRID-ORCS; 643418; 11 hits in 1072 CRISPR screens.
DR GenomeRNAi; 643418; -.
DR Pharos; Q5VXI9; Tbio.
DR PRO; PR:Q5VXI9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q5VXI9; protein.
DR Bgee; ENSG00000204020; Expressed in monocyte and 64 other tissues.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0004465; F:lipoprotein lipase activity; TAS:Reactome.
DR GO; GO:0070268; P:cornification; TAS:Reactome.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR025483; Lipase_euk.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR PIRSF; PIRSF000862; Steryl_ester_lip; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Hydrolase; Ichthyosis; Lipid degradation;
KW Lipid metabolism; Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..398
FT /note="Lipase member N"
FT /id="PRO_0000286831"
FT DOMAIN 79..379
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT ACT_SITE 173
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 344
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 373
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 247..256
FT /evidence="ECO:0000250"
FT VARIANT 244
FT /note="T -> N (in dbSNP:rs10788611)"
FT /id="VAR_032192"
SQ SEQUENCE 398 AA; 45534 MW; 0EE99ED08A5F5978 CRC64;
MMWLLLTTTC LICGTLNAGG FLDLENEVNP EVWMNTSEII IYNGYPSEEY EVTTEDGYIL
LVNRIPYGRT HARSTGPRPV VYMQHALFAD NAYWLENYAN GSLGFLLADA GYDVWMGNSR
GNTWSRRHKT LSETDEKFWA FSFDEMAKYD LPGVIDFIVN KTGQEKLYFI GHSLGTTIGF
VAFSTMPELA QRIKMNFALG PTISFKYPTG IFTRFFLLPN SIIKAVFGTK GFFLEDKKTK
IASTKICNNK ILWLICSEFM SLWAGSNKKN MNQSRMDVYM SHAPTGSSVH NILHIKQLYH
SDEFRAYDWG NDADNMKHYN QSHPPIYDLT AMKVPTAIWA GGHDVLVTPQ DVARILPQIK
SLHYFKLLPD WNHFDFVWGL DAPQRMYSEI IALMKAYS
