LACC1_HUMAN
ID LACC1_HUMAN Reviewed; 430 AA.
AC Q8IV20; A2A3Z6; Q8N8X5;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Purine nucleoside phosphorylase LACC1 {ECO:0000305};
DE EC=2.4.2.1 {ECO:0000269|PubMed:31978345};
DE AltName: Full=Adenosine deaminase LACC1 {ECO:0000305};
DE EC=3.5.4.4 {ECO:0000269|PubMed:31978345};
DE AltName: Full=Fatty acid metabolism-immunity nexus {ECO:0000303|PubMed:27478939, ECO:0000303|PubMed:31978345};
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:0000269|PubMed:31978345};
GN Name=LACC1 {ECO:0000303|PubMed:25220867, ECO:0000312|HGNC:HGNC:26789};
GN Synonyms=C13orf31 {ECO:0000312|HGNC:HGNC:26789},
GN FAMIN {ECO:0000303|PubMed:27478939, ECO:0000303|PubMed:31978345};
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 [LARGE SCALE MRNA], AND VARIANT VAL-254.
RC TISSUE=Kidney;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [5]
RP INVOLVEMENT IN JUVAR, AND VARIANT JUVAR ARG-284.
RX PubMed=25220867; DOI=10.1002/art.38877;
RA Wakil S.M., Monies D.M., Abouelhoda M., Al-Tassan N., Al-Dusery H.,
RA Naim E.A., Al-Younes B., Shinwari J., Al-Mohanna F.A., Meyer B.F.,
RA Al-Mayouf S.;
RT "Association of a mutation in LACC1 with a monogenic form of systemic
RT juvenile idiopathic arthritis.";
RL Arthritis Rheum. 67:288-295(2015).
RN [6]
RP SUBCELLULAR LOCATION, INTERACTION WITH FASN, AND CHARACTERIZATION OF
RP VARIANT VAL-254.
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=27959965; DOI=10.1371/journal.pone.0168276;
RA Assadi G., Vesterlund L., Bonfiglio F., Mazzurana L., Cordeddu L.,
RA Schepis D., Mjoesberg J., Ruhrmann S., Fabbri A., Vukojevic V.,
RA Percipalle P., Salomons F.A., Laurencikiene J., Toerkvist L.,
RA Halfvarson J., D'Amato M.;
RT "Functional Analyses of the Crohn's Disease Risk Gene LACC1.";
RL PLoS ONE 11:E0168276-E0168276(2016).
RN [8]
RP INVOLVEMENT IN JUVAR.
RX PubMed=27881174; DOI=10.1186/s12969-016-0124-2;
RA Kallinich T., Thorwarth A., von Stuckrad S.L., Roesen-Wolff A., Luksch H.,
RA Hundsdoerfer P., Minden K., Krawitz P.;
RT "Juvenile arthritis caused by a novel FAMIN (LACC1) mutation in two
RT children with systemic and extended oligoarticular course.";
RL Pediatr. Rheumatol. Online J. 14:63-63(2016).
RN [9]
RP FUNCTION, INTERACTION WITH SDHA, PHOSPHORYLATION, ACETYLATION AT LYS-247,
RP TISSUE SPECIFICITY, INDUCTION, CHARACTERIZATION OF VARIANT VAL-254, AND
RP MUTAGENESIS OF TYR-52; TYR-89; LYS-247; 249-HIS-HIS-250 AND TYR-265.
RX PubMed=28593945; DOI=10.1038/ncomms15614;
RA Lahiri A., Hedl M., Yan J., Abraham C.;
RT "Human LACC1 increases innate receptor-induced responses and a LACC1
RT disease-risk variant modulates these outcomes.";
RL Nat. Commun. 8:15614-15614(2017).
RN [10]
RP INVOLVEMENT IN JUVAR, VARIANT VAL-254, AND VARIANT JUVAR 414-ARG--GLU-430
RP DEL.
RX PubMed=29717096; DOI=10.3899/jrheum.170834;
RA Karacan I., Ugurlu S., Sahin S., Everest E., Kasapcopur O., Tolun A.,
RA Oezdogan H., Turanli E.T.;
RT "LACC1 gene defects in familial form of juvenile arthritis.";
RL J. Rheumatol. 45:726-728(2018).
RN [11]
RP INVOLVEMENT IN JUVAR, AND VARIANT JUVAR PRO-278.
RX PubMed=31811059; DOI=10.1136/annrheumdis-2019-216263;
RA Singh A., Suri D., Vignesh P., Anjani G., Jacob P., Girisha K.M.;
RT "LACC1 gene mutation in three sisters with polyarthritis without systemic
RT features.";
RL Ann. Rheum. Dis. 79:425-426(2020).
RN [12]
RP INVOLVEMENT IN JUVAR.
RX PubMed=30872671; DOI=10.1038/s41598-019-40874-2;
RA Rabionet R., Remesal A., Mensa-Vilaro A., Murias S., Alcobendas R.,
RA Gonzalez-Roca E., Ruiz-Ortiz E., Anton J., Iglesias E., Modesto C.,
RA Comas D., Puig A., Drechsel O., Ossowski S., Yaguee J., Merino R.,
RA Estivill X., Arostegui J.I.;
RT "Biallelic loss-of-function LACC1/FAMIN mutations presenting as rheumatoid
RT factor-negative polyarticular juvenile idiopathic arthritis.";
RL Sci. Rep. 9:4579-4579(2019).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CHARACTERIZATION OF VARIANT VAL-254.
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).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATF6; EIF2AK3 AND ERN1,
RP CHARACTERIZATION OF VARIANT VAL-254, AND CHARACTERIZATION OF VARIANT JUVAR
RP ARG-284.
RX PubMed=31875558; DOI=10.1016/j.celrep.2019.11.105;
RA Huang C., Hedl M., Ranjan K., Abraham C.;
RT "LACC1 required for NOD2-induced, ER stress-mediated innate immune outcomes
RT in human macrophages and LACC1 risk variants modulate these outcomes.";
RL Cell Rep. 29:4525-4539(2019).
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 (PubMed:31978345). Also catalyzes the phosphorolysis of S-
CC methyl-5'-thioadenosine into adenine and S-methyl-5-thio-alpha-D-ribose
CC 1-phosphate (PubMed:31978345). Also has adenosine deaminase activity
CC (PubMed:31978345). Acts as a regulator of innate immunity in
CC macrophages by modulating the purine nucleotide metabolism, thereby
CC regulating the metabolic function and bioenergetic state of macrophages
CC (PubMed:31978345). Enables a purine nucleotide cycle between adenosine
CC and inosine monophosphate and adenylosuccinate that prevents
CC cytoplasmic acidification and balances the cytoplasmic-mitochondrial
CC redox interface (PubMed:31978345). The purine nucleotide cycle consumes
CC aspartate and releases fumarate in a manner involving fatty acid
CC oxidation and ATP-citrate lyase activity (PubMed:31978345).
CC Participates in pattern recognition receptor (PRR)-induced cytokines in
CC macrophages: associates with the NOD2-signaling complex and promotes
CC optimal NOD2-induced signaling, cytokine secretion and bacterial
CC clearance (PubMed:28593945, PubMed:31875558). Localizes to the
CC endoplasmic reticulum upon PRR stimulation of macrophages and
CC associates with endoplasmic reticulum-stress sensors, promoting the
CC endoplasmic reticulum unfolded protein response (UPR)
CC (PubMed:31875558). Does not show laccase activity (PubMed:27959965,
CC PubMed:31978345). {ECO:0000269|PubMed:27959965,
CC ECO:0000269|PubMed:28593945, ECO:0000269|PubMed:31875558,
CC 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:0000269|PubMed:31978345};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27643;
CC Evidence={ECO:0000269|PubMed:31978345};
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:0000269|PubMed:31978345};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27647;
CC Evidence={ECO:0000269|PubMed:31978345};
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:0000269|PubMed:31978345};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13234;
CC Evidence={ECO:0000269|PubMed:31978345};
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:0000269|PubMed:31978345};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11853;
CC Evidence={ECO:0000269|PubMed:31978345};
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:0000269|PubMed:31978345};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24409;
CC Evidence={ECO:0000269|PubMed:31978345};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=36 uM for adenosine (for adenosine phosphorylase activity)
CC {ECO:0000269|PubMed:31978345};
CC KM=11 uM for adenosine (for adenosine deaminase activity)
CC {ECO:0000269|PubMed:31978345};
CC KM=41 uM for inosine {ECO:0000269|PubMed:31978345};
CC KM=1 uM for S-methyl-5'-thioadenosine {ECO:0000269|PubMed:31978345};
CC Vmax=4409 pmol/min/mg enzyme with adenosine as substrate (for
CC adenosine phosphorylase activity) {ECO:0000269|PubMed:31978345};
CC Vmax=541 pmol/min/mg enzyme with adenosine as substrate (for
CC adenosine deaminase activity) {ECO:0000269|PubMed:31978345};
CC Vmax=4187 pmol/min/mg enzyme with inosine as substrate
CC {ECO:0000269|PubMed:31978345};
CC Vmax=2639 pmol/min/mg enzyme with S-methyl-5'-thioadenosine as
CC substrate {ECO:0000269|PubMed:31978345};
CC -!- SUBUNIT: Interacts with FASN (PubMed:27478939). Interacts with SDHA
CC (PubMed:28593945). Interacts with ATF6, EIF2AK3 and ERN1
CC (PubMed:31875558). {ECO:0000269|PubMed:27478939,
CC ECO:0000269|PubMed:28593945, ECO:0000269|PubMed:31875558}.
CC -!- INTERACTION:
CC Q8IV20; P49327: FASN; NbExp=8; IntAct=EBI-12508070, EBI-356658;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BZT9}. Nucleus
CC {ECO:0000250|UniProtKB:Q8BZT9}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:31875558}. Peroxisome {ECO:0000269|PubMed:27478939,
CC ECO:0000269|PubMed:27959965}. Note=Upon stimulation of the pattern-
CC recognition receptor (PRR) NOD2, localizes to the endoplasmic
CC reticulum. {ECO:0000269|PubMed:31875558}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with higher expression
CC levels in immune-related tissues such as lymph nodes and spleen
CC (PubMed:27959965). Expressed in both intestinal and peripheral myeloid-
CC derived cells (PubMed:28593945). {ECO:0000269|PubMed:27959965,
CC ECO:0000269|PubMed:28593945}.
CC -!- INDUCTION: Up-regulated by phorbol 12-myristate 13-acetate (PMA)
CC (PubMed:27959965). Down-regulated by PPAR ligands (PubMed:27959965).
CC Up-regulated upon pattern recognition receptor (PRR) stimulation
CC (PubMed:28593945). {ECO:0000269|PubMed:27959965,
CC ECO:0000269|PubMed:28593945}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000269|PubMed:28593945}.
CC -!- DISEASE: Juvenile arthritis (JUVAR) [MIM:618795]: A rare, familial form
CC of juvenile arthritis characterized by autosomal recessive inheritance
CC and onset in early childhood of symmetric, chronic joint inflammation.
CC It causes joint swelling, pain, stiffness and restricted joint
CC movement. JUVAR has high clinical variability. Some patients exhibit
CC systemic symptoms, including quotidian fever, erythematous rash,
CC generalized lymphadenopathy, hepatomegaly, and/or splenomegaly. Others
CC display polyarthritis without systemic inflammation.
CC {ECO:0000269|PubMed:25220867, ECO:0000269|PubMed:27881174,
CC ECO:0000269|PubMed:29717096, ECO:0000269|PubMed:30872671,
CC ECO:0000269|PubMed:31811059, ECO:0000269|PubMed:31875558}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the purine nucleoside phosphorylase YfiH/LACC1
CC family. {ECO:0000305}.
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DR EMBL; AK096044; BAC04686.1; -; mRNA.
DR EMBL; AL512506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08701.1; -; Genomic_DNA.
DR EMBL; BC035749; AAH35749.1; -; mRNA.
DR CCDS; CCDS9391.1; -.
DR RefSeq; NP_001121775.1; NM_001128303.1.
DR RefSeq; NP_694950.2; NM_153218.2.
DR RefSeq; XP_005266318.1; XM_005266261.3.
DR RefSeq; XP_006719829.1; XM_006719766.3.
DR RefSeq; XP_011533235.1; XM_011534933.2.
DR RefSeq; XP_011533236.1; XM_011534934.2.
DR RefSeq; XP_016875883.1; XM_017020394.1.
DR AlphaFoldDB; Q8IV20; -.
DR SMR; Q8IV20; -.
DR BioGRID; 126879; 48.
DR IntAct; Q8IV20; 65.
DR STRING; 9606.ENSP00000391747; -.
DR iPTMnet; Q8IV20; -.
DR PhosphoSitePlus; Q8IV20; -.
DR BioMuta; LACC1; -.
DR DMDM; 32171848; -.
DR EPD; Q8IV20; -.
DR jPOST; Q8IV20; -.
DR MassIVE; Q8IV20; -.
DR MaxQB; Q8IV20; -.
DR PaxDb; Q8IV20; -.
DR PeptideAtlas; Q8IV20; -.
DR PRIDE; Q8IV20; -.
DR ProteomicsDB; 70644; -.
DR Antibodypedia; 23539; 64 antibodies from 18 providers.
DR DNASU; 144811; -.
DR Ensembl; ENST00000325686.7; ENSP00000317619.5; ENSG00000179630.11.
DR Ensembl; ENST00000441843.5; ENSP00000391747.1; ENSG00000179630.11.
DR GeneID; 144811; -.
DR KEGG; hsa:144811; -.
DR MANE-Select; ENST00000325686.7; ENSP00000317619.5; NM_153218.4; NP_694950.2.
DR UCSC; uc001uzf.4; human.
DR CTD; 144811; -.
DR DisGeNET; 144811; -.
DR GeneCards; LACC1; -.
DR HGNC; HGNC:26789; LACC1.
DR HPA; ENSG00000179630; Tissue enhanced (brain).
DR MalaCards; LACC1; -.
DR MIM; 604302; phenotype.
DR MIM; 613409; gene.
DR MIM; 618795; phenotype.
DR neXtProt; NX_Q8IV20; -.
DR OpenTargets; ENSG00000179630; -.
DR Orphanet; 85414; Systemic-onset juvenile idiopathic arthritis.
DR PharmGKB; PA147358522; -.
DR VEuPathDB; HostDB:ENSG00000179630; -.
DR eggNOG; ENOG502QUMA; Eukaryota.
DR GeneTree; ENSGT00390000000693; -.
DR HOGENOM; CLU_637703_0_0_1; -.
DR InParanoid; Q8IV20; -.
DR OMA; TFIHGFT; -.
DR OrthoDB; 1186116at2759; -.
DR PhylomeDB; Q8IV20; -.
DR TreeFam; TF328389; -.
DR PathwayCommons; Q8IV20; -.
DR SignaLink; Q8IV20; -.
DR BioGRID-ORCS; 144811; 15 hits in 1062 CRISPR screens.
DR GenomeRNAi; 144811; -.
DR Pharos; Q8IV20; Tbio.
DR PRO; PR:Q8IV20; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q8IV20; protein.
DR Bgee; ENSG00000179630; Expressed in corpus callosum and 173 other tissues.
DR ExpressionAtlas; Q8IV20; baseline and differential.
DR Genevisible; Q8IV20; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0004000; F:adenosine deaminase activity; IDA:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IBA:GO_Central.
DR GO; GO:0047975; F:guanosine phosphorylase activity; IDA:UniProtKB.
DR GO; GO:0004731; F:purine-nucleoside phosphorylase activity; IDA:UniProtKB.
DR GO; GO:0017061; F:S-methyl-5-thioadenosine phosphorylase activity; IDA: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; IDA:UniProtKB.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IDA:UniProtKB.
DR GO; GO:0030641; P:regulation of cellular pH; IDA:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:1900542; P:regulation of purine nucleotide metabolic process; ISS: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_0000163187"
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:0000305|PubMed:28593945"
FT VARIANT 254
FT /note="I -> V (may influence susceptibility to juvenile
FT rheumatoid arthritis; increased adenosine deaminase
FT activity and decreased adenosine phosphorylase activity;
FT reduced ability to promote pattern recognition receptor
FT (PRR)-induced cytokines; reduced NOD2-induced signaling;
FT does not change interaction with FASN; dbSNP:rs3764147)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:27478939, ECO:0000269|PubMed:28593945,
FT ECO:0000269|PubMed:29717096, ECO:0000269|PubMed:31875558,
FT ECO:0000269|PubMed:31978345"
FT /id="VAR_052943"
FT VARIANT 278
FT /note="A -> P (in JUVAR; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:31811059"
FT /id="VAR_083278"
FT VARIANT 284
FT /note="C -> R (in JUVAR; reduced NOD2-induced signaling;
FT dbSNP:rs730880295)"
FT /evidence="ECO:0000269|PubMed:25220867,
FT ECO:0000269|PubMed:31875558"
FT /id="VAR_073274"
FT VARIANT 414..430
FT /note="Missing (in JUVAR; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29717096"
FT /id="VAR_083279"
FT MUTAGEN 52
FT /note="Y->A: Does not affect ability to promote pattern
FT recognition receptor (PRR)-induced cytokines in
FT macrophages; when associated with A-89 and A-265."
FT /evidence="ECO:0000269|PubMed:28593945"
FT MUTAGEN 89
FT /note="Y->A: Does not affect ability to promote pattern
FT recognition receptor (PRR)-induced cytokines in
FT macrophages; when associated with A-52 and A-265."
FT /evidence="ECO:0000269|PubMed:28593945"
FT MUTAGEN 247
FT /note="K->A: Decreased acetylation; does not affect ability
FT to promote pattern recognition receptor (PRR)-induced
FT cytokines in macrophages."
FT /evidence="ECO:0000269|PubMed:28593945"
FT MUTAGEN 249..250
FT /note="HH->AA: Impaired ability to promote pattern
FT recognition receptor (PRR)-induced cytokines in
FT macrophages."
FT /evidence="ECO:0000269|PubMed:28593945"
FT MUTAGEN 265
FT /note="Y->A: Does not affect ability to promote pattern
FT recognition receptor (PRR)-induced cytokines in
FT macrophages; when associated with A-52 and A-89."
FT /evidence="ECO:0000269|PubMed:28593945"
SQ SEQUENCE 430 AA; 47780 MW; 369324C4B4A685A4 CRC64;
MAEAVLIDLF GLKLNSQKNC HQTLLKTLNA VQYHHAAKAK FLCIMCCSNI SYERDGEQDN
CEIETSNGLS ALLEEFEIVS CPSMAATLYT IKQKIDEKNL SSIKVIVPRH RKTLMKAFID
QLFTDVYNFE FEDLQVTFRG GLFKQSIEIN VITAQELRGI QNEIETFLRS LPALRGKLTI
ITSSLIPDIF IHGFTTRTGG ISYIPTLSSF NLFSSSKRRD PKVVVQENLR RLANAAGFNV
EKFYRIKTHH SNDIWIMGRK EPDSYDGITT NQRGVTIAAL GADCIPIVFA DPVKKACGVA
HAGWKGTLLG VAMATVNAMI AEYGCSLEDI VVVLGPSVGP CCFTLPRESA EAFHNLHPAC
VQLFDSPNPC IDIRKATRIL LEQGGILPQN IQDQNQDLNL CTSCHPDKFF SHVRDGLNFG
TQIGFISIKE
