PXL2A_HUMAN
ID PXL2A_HUMAN Reviewed; 229 AA.
AC Q9BRX8; B2RD81; Q6UW08; Q8N2K3; Q8NBK9; Q96JR0;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Peroxiredoxin-like 2A {ECO:0000305};
DE AltName: Full=Peroxiredoxin-like 2 activated in M-CSF stimulated monocytes {ECO:0000303|PubMed:19951071, ECO:0000303|PubMed:26438880};
DE Short=Protein PAMM {ECO:0000303|PubMed:19951071, ECO:0000303|PubMed:26438880};
DE AltName: Full=Redox-regulatory protein FAM213A;
GN Name=PRXL2A {ECO:0000312|HGNC:HGNC:28651};
GN Synonyms=C10orf58, FAM213A, PAMM {ECO:0000303|PubMed:19951071,
GN ECO:0000303|PubMed:26438880}; ORFNames=PRO2290, PSEC0139, UNQ611/PRO1198;
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] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Embryo, and Heart;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 63-229 (ISOFORMS 1/2).
RC TISSUE=Fetal liver;
RX PubMed=11483580; DOI=10.1101/gr.175501;
RA Yu Y., Zhang C., Zhou G., Wu S., Qu X., Wei H., Xing G., Dong C., Zhai Y.,
RA Wan J., Ouyang S., Li L., Zhang S., Zhou K., Zhang Y., Wu C., He F.;
RT "Gene expression profiling in human fetal liver and identification of
RT tissue- and developmental-stage-specific genes through compiled expression
RT profiles and efficient cloning of full-length cDNAs.";
RL Genome Res. 11:1392-1403(2001).
RN [7]
RP PROTEIN SEQUENCE OF 90-99; 156-164 AND 192-199, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY CSF1 AND TNFSF11, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF CYS-85 AND CYS-88.
RX PubMed=19951071; DOI=10.1089/ars.2009.2886;
RA Xu Y., Morse L.R., da Silva R.A., Odgren P.R., Sasaki H., Stashenko P.,
RA Battaglino R.A.;
RT "PAMM: a redox regulatory protein that modulates osteoclast
RT differentiation.";
RL Antioxid. Redox Signal. 13:27-37(2010).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-88.
RX PubMed=26438880; DOI=10.1042/bj20150019;
RA Guo F., He H., Fu Z.C., Huang S., Chen T., Papasian C.J., Morse L.R.,
RA Xu Y., Battaglino R.A., Yang X.F., Jiang Z., Xin H.B., Fu M.;
RT "Adipocyte-derived PAMM suppresses macrophage inflammation by inhibiting
RT MAPK signalling.";
RL Biochem. J. 472:309-318(2015).
CC -!- FUNCTION: Involved in redox regulation of the cell (PubMed:26438880,
CC PubMed:19951071). Acts as an antioxidant (PubMed:19951071,
CC PubMed:26438880). Inhibits TNFSF11-induced NFKB1 and JUN activation and
CC osteoclast differentiation (PubMed:19951071). May affect bone
CC resorption and help to maintain bone mass (PubMed:19951071). Acts as a
CC negative regulator of macrophage-mediated inflammation by inhibiting
CC macrophage production of inflammatory cytokines, probably through
CC suppression of the MAPK signaling pathway (PubMed:26438880).
CC {ECO:0000269|PubMed:19951071, ECO:0000269|PubMed:26438880}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19951071}. Secreted
CC {ECO:0000269|PubMed:26438880}. Note=Secreted from mature adipocytes but
CC not from preadipocytes. {ECO:0000269|PubMed:26438880}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BRX8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BRX8-2; Sequence=VSP_042229;
CC -!- TISSUE SPECIFICITY: Expressed in CSF1 and TNFSF11-stimulated CD14(+)
CC peripheral blood mononuclear cells (PBMCs).
CC {ECO:0000269|PubMed:19951071}.
CC -!- INDUCTION: Up-regulated by CSF1 in peripheral blood mononuclear cells
CC (PBMCs). This induction is reduced in the presence of TNFSF11.
CC {ECO:0000269|PubMed:19951071}.
CC -!- MISCELLANEOUS: The active site cysteines correspond to the redox-active
CC cysteines of peroxiredoxins.
CC -!- SIMILARITY: Belongs to the peroxiredoxin-like PRXL2 family. PRXL2A
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK55527.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG37828.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY359059; AAQ89418.1; -; mRNA.
DR EMBL; AK315440; BAG37828.1; ALT_INIT; mRNA.
DR EMBL; AK074643; BAC11108.1; -; mRNA.
DR EMBL; AK075447; BAC11627.1; -; mRNA.
DR EMBL; AC021028; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005871; AAH05871.3; -; mRNA.
DR EMBL; AF305824; AAK55527.1; ALT_INIT; mRNA.
DR CCDS; CCDS58089.1; -. [Q9BRX8-2]
DR CCDS; CCDS7368.1; -. [Q9BRX8-1]
DR RefSeq; NP_001230707.1; NM_001243778.1. [Q9BRX8-1]
DR RefSeq; NP_001230708.1; NM_001243779.1. [Q9BRX8-1]
DR RefSeq; NP_001230709.1; NM_001243780.1. [Q9BRX8-1]
DR RefSeq; NP_001230710.1; NM_001243781.1. [Q9BRX8-2]
DR RefSeq; NP_001230711.1; NM_001243782.1.
DR RefSeq; NP_115709.3; NM_032333.4. [Q9BRX8-1]
DR RefSeq; XP_011538567.1; XM_011540265.2. [Q9BRX8-1]
DR RefSeq; XP_011538568.1; XM_011540266.2. [Q9BRX8-1]
DR AlphaFoldDB; Q9BRX8; -.
DR BioGRID; 124020; 87.
DR IntAct; Q9BRX8; 32.
DR MINT; Q9BRX8; -.
DR STRING; 9606.ENSP00000482445; -.
DR BindingDB; Q9BRX8; -.
DR ChEMBL; CHEMBL3879824; -.
DR iPTMnet; Q9BRX8; -.
DR PhosphoSitePlus; Q9BRX8; -.
DR SwissPalm; Q9BRX8; -.
DR BioMuta; FAM213A; -.
DR DMDM; 73620080; -.
DR EPD; Q9BRX8; -.
DR jPOST; Q9BRX8; -.
DR MassIVE; Q9BRX8; -.
DR MaxQB; Q9BRX8; -.
DR PaxDb; Q9BRX8; -.
DR PeptideAtlas; Q9BRX8; -.
DR PRIDE; Q9BRX8; -.
DR ProteomicsDB; 78849; -. [Q9BRX8-1]
DR ProteomicsDB; 78850; -. [Q9BRX8-2]
DR Antibodypedia; 2394; 75 antibodies from 17 providers.
DR DNASU; 84293; -.
DR Ensembl; ENST00000372181.1; ENSP00000361254.1; ENSG00000122378.14. [Q9BRX8-1]
DR Ensembl; ENST00000372185.5; ENSP00000361259.1; ENSG00000122378.14. [Q9BRX8-2]
DR Ensembl; ENST00000372187.9; ENSP00000361261.5; ENSG00000122378.14. [Q9BRX8-1]
DR Ensembl; ENST00000372188.5; ENSP00000361262.1; ENSG00000122378.14. [Q9BRX8-1]
DR Ensembl; ENST00000606162.6; ENSP00000482445.1; ENSG00000122378.14. [Q9BRX8-1]
DR Ensembl; ENST00000615554.4; ENSP00000478152.1; ENSG00000122378.14. [Q9BRX8-1]
DR GeneID; 84293; -.
DR KEGG; hsa:84293; -.
DR MANE-Select; ENST00000606162.6; ENSP00000482445.1; NM_032333.5; NP_115709.3.
DR UCSC; uc001kcc.5; human. [Q9BRX8-1]
DR CTD; 84293; -.
DR DisGeNET; 84293; -.
DR GeneCards; PRXL2A; -.
DR HGNC; HGNC:28651; PRXL2A.
DR HPA; ENSG00000122378; Tissue enhanced (adipose).
DR MIM; 617165; gene.
DR neXtProt; NX_Q9BRX8; -.
DR OpenTargets; ENSG00000122378; -.
DR PharmGKB; PA134969403; -.
DR VEuPathDB; HostDB:ENSG00000122378; -.
DR eggNOG; KOG4498; Eukaryota.
DR GeneTree; ENSGT00940000161199; -.
DR HOGENOM; CLU_086062_0_0_1; -.
DR InParanoid; Q9BRX8; -.
DR OMA; KFYGPQK; -.
DR OrthoDB; 1442607at2759; -.
DR PhylomeDB; Q9BRX8; -.
DR TreeFam; TF313804; -.
DR PathwayCommons; Q9BRX8; -.
DR SignaLink; Q9BRX8; -.
DR BioGRID-ORCS; 84293; 15 hits in 1081 CRISPR screens.
DR ChiTaRS; FAM213A; human.
DR GeneWiki; C10orf58; -.
DR GenomeRNAi; 84293; -.
DR Pharos; Q9BRX8; Tchem.
DR PRO; PR:Q9BRX8; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9BRX8; protein.
DR Bgee; ENSG00000122378; Expressed in pigmented layer of retina and 190 other tissues.
DR Genevisible; Q9BRX8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016209; F:antioxidant activity; IDA:UniProtKB.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; IDA:UniProtKB.
DR InterPro; IPR032802; PRXL2A.
DR InterPro; IPR032801; PXL2A/B/C.
DR PANTHER; PTHR28630; PTHR28630; 1.
DR PANTHER; PTHR28630:SF3; PTHR28630:SF3; 1.
DR Pfam; PF13911; AhpC-TSA_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antioxidant; Cytoplasm; Direct protein sequencing;
KW Redox-active center; Reference proteome; Secreted.
FT CHAIN 1..229
FT /note="Peroxiredoxin-like 2A"
FT /id="PRO_0000019550"
FT REGION 14..112
FT /note="Thioredoxin fold"
FT /evidence="ECO:0000250"
FT ACT_SITE 85
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT ACT_SITE 88
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..11
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16303743"
FT /id="VSP_042229"
FT MUTAGEN 85
FT /note="C->G: Decrease of about 38% in antioxidant activity
FT in TNFSF11-stimulated osteoclasts and reduced inhibition of
FT TNFSF11-induced osteoclast formation. Does not change anti-
FT inflammatory properties."
FT /evidence="ECO:0000269|PubMed:19951071,
FT ECO:0000269|PubMed:26438880"
FT MUTAGEN 88
FT /note="C->G: Decrease of about 125% in antioxidant activity
FT in TNFSF11-stimulated osteoclasts and reduced inhibition of
FT TNFSF11-induced osteoclast formation."
FT /evidence="ECO:0000269|PubMed:19951071"
FT CONFLICT 201
FT /note="K -> N (in Ref. 2; BAC11108)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="K -> R (in Ref. 3; BAC11627)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 229 AA; 25764 MW; 9ECE72DEF6C338D7 CRC64;
MSFLQDPSFF TMGMWSIGAG ALGAAALALL LANTDVFLSK PQKAALEYLE DIDLKTLEKE
PRTFKAKELW EKNGAVIMAV RRPGCFLCRE EAADLSSLKS MLDQLGVPLY AVVKEHIRTE
VKDFQPYFKG EIFLDEKKKF YGPQRRKMMF MGFIRLGVWY NFFRAWNGGF SGNLEGEGFI
LGGVFVVGSG KQGILLEHRE KEFGDKVNLL SVLEAAKMIK PQTLASEKK
