LACC1_MOUSE
ID LACC1_MOUSE Reviewed; 430 AA.
AC Q8BZT9; Q14AQ3; Q3U600;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Purine nucleoside phosphorylase LACC1 {ECO:0000305};
DE EC=2.4.2.1 {ECO:0000250|UniProtKB:Q8IV20};
DE AltName: Full=Adenosine deaminase LACC1 {ECO:0000305};
DE EC=3.5.4.4 {ECO:0000250|UniProtKB:Q8IV20};
DE AltName: Full=Fatty acid metabolism-immunity nexus {ECO:0000303|PubMed:27478939};
DE AltName: Full=Guanosine phosphorylase LACC1 {ECO:0000305};
DE AltName: Full=Laccase domain-containing protein 1 {ECO:0000305};
DE AltName: Full=S-methyl-5'-thioadenosine phosphorylase LACC1 {ECO:0000305};
DE EC=2.4.2.28 {ECO:0000250|UniProtKB:Q8IV20};
GN Name=Lacc1 {ECO:0000312|MGI:MGI:2445077};
GN Synonyms=Famin {ECO:0000303|PubMed:27478939};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Colon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP FUNCTION, AND MUTAGENESIS OF VAL-254 AND CYS-284.
RX PubMed=27478939; DOI=10.1038/ni.3532;
RA Cader M.Z., Boroviak K., Zhang Q., Assadi G., Kempster S.L., Sewell G.W.,
RA Saveljeva S., Ashcroft J.W., Clare S., Mukhopadhyay S., Brown K.P.,
RA Tschurtschenthaler M., Raine T., Doe B., Chilvers E.R., Griffin J.L.,
RA Kaneider N.C., Floto R.A., D'Amato M., Bradley A., Wakelam M.J., Dougan G.,
RA Kaser A.;
RT "C13orf31 (FAMIN) is a central regulator of immunometabolic function.";
RL Nat. Immunol. 17:1046-1056(2016).
RN [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30510070; DOI=10.4049/jimmunol.1800636;
RA Skon-Hegg C., Zhang J., Wu X., Sagolla M., Ota N., Wuster A., Tom J.,
RA Doran E., Ramamoorthi N., Caplazi P., Monroe J., Lee W.P., Behrens T.W.;
RT "LACC1 regulates TNF and IL-17 in mouse models of arthritis and
RT inflammation.";
RL J. Immunol. 202:183-193(2019).
RN [5]
RP FUNCTION.
RX PubMed=31978345; DOI=10.1016/j.cell.2019.12.017;
RA Cader M.Z., de Almeida Rodrigues R.P., West J.A., Sewell G.W.,
RA Md-Ibrahim M.N., Reikine S., Sirago G., Unger L.W., Inglesias-Romero A.B.,
RA Ramshorn K., Haag L.M., Saveljeva S., Ebel J.F., Rosenstiel P.,
RA Kaneider N.C., Lee J.C., Lawley T.D., Bradley A., Dougan G., Modis Y.,
RA Griffin J.L., Kaser A.;
RT "FAMIN is a multifunctional purine enzyme enabling the purine nucleotide
RT cycle.";
RL Cell 180:278-295(2020).
CC -!- FUNCTION: Purine nucleoside enzyme that catalyzes the phosphorolysis of
CC adenosine, guanosine and inosine nucleosides, yielding D-ribose 1-
CC phosphate and the respective free bases, adenine, guanine and
CC hypoxanthine (By similarity). Also catalyzes the phosphorolysis of S-
CC methyl-5'-thioadenosine into adenine and S-methyl-5-thio-alpha-D-ribose
CC 1-phosphate (By similarity). Also has adenosine deaminase activity (By
CC similarity). Acts as a regulator of innate immunity in macrophages by
CC modulating the purine nucleotide metabolism, thereby regulating the
CC metabolic function and bioenergetic state of macrophages
CC (PubMed:27478939, PubMed:31978345). Enables a purine nucleotide cycle
CC between adenosine and inosine monophosphate and adenylosuccinate that
CC prevents cytoplasmic acidification and balances the cytoplasmic-
CC mitochondrial redox interface (PubMed:31978345). The purine nucleotide
CC cycle consumes aspartate and releases fumarate in a manner involving
CC fatty acid oxidation and ATP-citrate lyase activity (PubMed:31978345).
CC Participates in pattern recognition receptor-induced cytokines in
CC macrophages: associates with the NOD2-signaling complex and promotes
CC optimal NOD2-induced signaling, cytokine secretion and bacterial
CC clearance (By similarity). Localizes to the endoplasmic reticulum upon
CC PRR stimulation of macrophages and associates with endoplasmic
CC reticulum-stress sensors, promoting the endoplasmic reticulum unfolded
CC protein response (UPR) (By similarity). Does not show laccase activity
CC (By similarity). {ECO:0000250|UniProtKB:Q8IV20,
CC ECO:0000269|PubMed:27478939, ECO:0000269|PubMed:31978345}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + phosphate = adenine + alpha-D-ribose 1-phosphate;
CC Xref=Rhea:RHEA:27642, ChEBI:CHEBI:16335, ChEBI:CHEBI:16708,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27643;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=inosine + phosphate = alpha-D-ribose 1-phosphate +
CC hypoxanthine; Xref=Rhea:RHEA:27646, ChEBI:CHEBI:17368,
CC ChEBI:CHEBI:17596, ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27647;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine + phosphate = alpha-D-ribose 1-phosphate + guanine;
CC Xref=Rhea:RHEA:13233, ChEBI:CHEBI:16235, ChEBI:CHEBI:16750,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13234;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=phosphate + S-methyl-5'-thioadenosine = adenine + S-methyl-5-
CC thio-alpha-D-ribose 1-phosphate; Xref=Rhea:RHEA:11852,
CC ChEBI:CHEBI:16708, ChEBI:CHEBI:17509, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58533; EC=2.4.2.28;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11853;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine + H(+) + H2O = inosine + NH4(+);
CC Xref=Rhea:RHEA:24408, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16335, ChEBI:CHEBI:17596, ChEBI:CHEBI:28938; EC=3.5.4.4;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24409;
CC Evidence={ECO:0000250|UniProtKB:Q8IV20};
CC -!- SUBUNIT: Interacts with FASN. Interacts with SDHA. Interacts with ATF6,
CC EIF2AK3 and ERN1. {ECO:0000250|UniProtKB:Q8IV20}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:30510070}. Nucleus
CC {ECO:0000269|PubMed:30510070}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q8IV20}. Peroxisome
CC {ECO:0000250|UniProtKB:Q8IV20}. Note=Upon stimulation of the pattern-
CC recognition receptor (PRR) NOD2, localizes to the endoplasmic
CC reticulum. {ECO:0000250|UniProtKB:Q8IV20}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in myeloid cells
CC (PubMed:30510070). Highly expressed in primary macrophages and
CC dendritic cells sorted from the peritoneum or spleen, respectively (at
CC protein level) (PubMed:30510070). {ECO:0000269|PubMed:30510070}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000250|UniProtKB:Q8IV20}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype in normal conditions
CC (PubMed:30510070). Mice show increased inflammatory response in mouse
CC models of arthritis and inflammation (PubMed:30510070).
CC {ECO:0000269|PubMed:30510070}.
CC -!- SIMILARITY: Belongs to the purine nucleoside phosphorylase YfiH/LACC1
CC family. {ECO:0000305}.
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DR EMBL; AK033565; BAC28363.1; -; mRNA.
DR EMBL; AK152154; BAE30989.1; -; mRNA.
DR EMBL; AK153349; BAE31925.1; -; mRNA.
DR EMBL; BC116748; AAI16749.1; -; mRNA.
DR EMBL; BC119140; AAI19141.1; -; mRNA.
DR CCDS; CCDS27287.1; -.
DR RefSeq; NP_766076.1; NM_172488.2.
DR AlphaFoldDB; Q8BZT9; -.
DR SMR; Q8BZT9; -.
DR BioGRID; 229184; 1.
DR STRING; 10090.ENSMUSP00000059173; -.
DR PhosphoSitePlus; Q8BZT9; -.
DR MaxQB; Q8BZT9; -.
DR PaxDb; Q8BZT9; -.
DR PRIDE; Q8BZT9; -.
DR ProteomicsDB; 290006; -.
DR DNASU; 210808; -.
DR Ensembl; ENSMUST00000062789; ENSMUSP00000059173; ENSMUSG00000044350.
DR GeneID; 210808; -.
DR KEGG; mmu:210808; -.
DR UCSC; uc007urq.1; mouse.
DR CTD; 144811; -.
DR MGI; MGI:2445077; Lacc1.
DR VEuPathDB; HostDB:ENSMUSG00000044350; -.
DR eggNOG; ENOG502QUMA; Eukaryota.
DR GeneTree; ENSGT00390000000693; -.
DR HOGENOM; CLU_637703_0_0_1; -.
DR InParanoid; Q8BZT9; -.
DR OMA; TFIHGFT; -.
DR OrthoDB; 1186116at2759; -.
DR PhylomeDB; Q8BZT9; -.
DR TreeFam; TF328389; -.
DR BioGRID-ORCS; 210808; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Lacc1; mouse.
DR PRO; PR:Q8BZT9; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8BZT9; protein.
DR Bgee; ENSMUSG00000044350; Expressed in lens of camera-type eye and 124 other tissues.
DR ExpressionAtlas; Q8BZT9; baseline and differential.
DR Genevisible; Q8BZT9; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0004000; F:adenosine deaminase activity; ISS:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IBA:GO_Central.
DR GO; GO:0047975; F:guanosine phosphorylase activity; ISS:UniProtKB.
DR GO; GO:0004731; F:purine-nucleoside phosphorylase activity; ISS:UniProtKB.
DR GO; GO:0017061; F:S-methyl-5-thioadenosine phosphorylase activity; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; ISO:MGI.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; ISO:MGI.
DR GO; GO:0030641; P:regulation of cellular pH; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:1900542; P:regulation of purine nucleotide metabolic process; IMP:UniProtKB.
DR CDD; cd16833; YfiH; 1.
DR Gene3D; 3.60.140.10; -; 1.
DR InterPro; IPR003730; Cu_polyphenol_OxRdtase.
DR InterPro; IPR038371; Cu_polyphenol_OxRdtase_sf.
DR InterPro; IPR011324; Cytotoxic_necrot_fac-like_cat.
DR PANTHER; PTHR30616; PTHR30616; 1.
DR Pfam; PF02578; Cu-oxidase_4; 1.
DR SUPFAM; SSF64438; SSF64438; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Endoplasmic reticulum; Hydrolase; Immunity;
KW Inflammatory response; Innate immunity; Metal-binding; Nucleus; Peroxisome;
KW Phosphoprotein; Reference proteome; Transferase; Zinc.
FT CHAIN 1..430
FT /note="Purine nucleoside phosphorylase LACC1"
FT /id="PRO_0000163188"
FT BINDING 250
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P84138"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P84138"
FT BINDING 301
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P84138"
FT MOD_RES 247
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8IV20"
FT MUTAGEN 254
FT /note="V->I: Reduced function."
FT /evidence="ECO:0000269|PubMed:27478939"
FT MUTAGEN 284
FT /note="C->R: Complete loss of function."
FT /evidence="ECO:0000269|PubMed:27478939"
SQ SEQUENCE 430 AA; 47514 MW; 4F73BC343D9F3414 CRC64;
MAEAVLIDLS GLQLNAQKNC HETLLETLDG IHYHHAPKAK FLCIICCRNA SKEKDGEYGL
CELEAGNGFS RLAGKFETVS HPCLAASLYT IKQKIDEENL SCIKVIVPEH RKLLMKAYVG
QLFTEVYEFE FEDLQGAWRD SLLKPSTGIN VTTTQELEDI QHEIETYLRS LPALKGDLTI
VTSPLIPDNF LHGFTTRTGG ISSVPTLSSL NLFSSSKRRD PKVVVQENVR RLANAAGFNA
EKFYRIKTDH ASEVWVMGKK EPESYDGIVT NQRGVTITAL GADCIPIVFA DPVKKACGVA
HSGWKGTLLG VAMATVNAMI AEYGCDVEDI IVVLGPSVGS CCFTLPKESA VSFHSLHPSC
VRHFDSPRPY VDIRKATRIL LERGGILPQN IQDQKEDLDL CTSCHPEKFF SHVRDGLNFG
TQIGFISLRE
