SP2A3_MOUSE
ID SP2A3_MOUSE Reviewed; 83 AA.
AC Q4KL71;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Small proline-rich protein 2A3 {ECO:0000305};
GN Name=Sprr2a3 {ECO:0000303|PubMed:34735226, ECO:0000312|MGI:MGI:3845028};
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=Amnion;
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] {ECO:0000312|EMBL:EDL00710.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAH99393.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6NCr {ECO:0000312|EMBL:AAH99393.1};
RC TISSUE=Placenta {ECO:0000312|EMBL:AAH99393.1};
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=34735226; DOI=10.1126/science.abe6723;
RA Hu Z., Zhang C., Sifuentes-Dominguez L., Zarek C.M., Propheter D.C.,
RA Kuang Z., Wang Y., Pendse M., Ruhn K.A., Hassell B., Behrendt C.L.,
RA Zhang B., Raj P., Harris-Tryon T.A., Reese T.A., Hooper L.V.;
RT "Small proline-rich protein 2A is a gut bactericidal protein deployed
RT during helminth infection.";
RL Science 374:eabe6723-eabe6723(2021).
CC -!- FUNCTION: Gut bactericidal protein that selectively kills Gram-positive
CC bacteria by binding to negatively charged lipids on bacterial
CC membranes, leading to bacterial membrane permeabilization and
CC disruption (PubMed:34735226). Specifically binds lipids bearing
CC negatively charged headgroups, such as phosphatidic acid,
CC phosphatidylserine (PS), cardiolipin (CL), and phosphatidylinositol
CC phosphates, but not to zwitterionic or neutral lipids (By similarity).
CC Induced by type-2 cytokines in response to helminth infection and is
CC required to protect against helminth-induced bacterial invasion of
CC intestinal tissue (PubMed:34735226). May also be involved in the
CC development of the cornified envelope of squamous epithelia; however,
CC additional evidences are required to confirm this result in vivo (By
CC similarity). {ECO:0000250|UniProtKB:P35326,
CC ECO:0000269|PubMed:34735226}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:34735226}. Secreted,
CC extracellular space {ECO:0000269|PubMed:34735226}. Cytoplasmic vesicle,
CC secretory vesicle {ECO:0000269|PubMed:34735226}. Note=Present in
CC intestinal secretory epithelial cells and is secreted into the
CC intestinal lumen. {ECO:0000269|PubMed:34735226}.
CC -!- INDUCTION: By type-2 cytokines IL4 and IL13 in response to helminth
CC infection. {ECO:0000269|PubMed:34735226}.
CC -!- PTM: Forms five pairs of intrachain disulfide bonds.
CC {ECO:0000250|UniProtKB:P35326}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Sprr2a1, Sprr2a2 and Sprr2a3 show an
CC expansion of Gram-positive bacteria in the small intestinal lumen and
CC mucus layer (PubMed:34735226). Mice were born in normal Mendelian
CC ratios, are healthy and show normal intestinal morphology with no signs
CC of inflammation in normal conditions (PubMed:34735226). They however
CC show an increased abundance of Gram-positive bacteria in the small
CC intestinal lumen, with a marked increase in the relative abundance of
CC Lactobacillus, Turicibacter, and C.Arthromitus (PubMed:34735226). At
CC the same time, a reduction in the abundance of Bacteroidetes, a class
CC of Gram-negative bacteria is observed (PubMed:34735226). Mice are more
CC susceptible to L. monocytogenes infection (PubMed:34735226).
CC {ECO:0000269|PubMed:34735226}.
CC -!- SIMILARITY: Belongs to the cornifin (SPRR) family. {ECO:0000305}.
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DR EMBL; AK147183; BAE27745.1; -; mRNA.
DR EMBL; AK168529; BAE40407.1; -; mRNA.
DR EMBL; CH466656; EDL00710.1; -; Genomic_DNA.
DR EMBL; BC099393; AAH99393.1; -; mRNA.
DR CCDS; CCDS17548.1; -.
DR RefSeq; NP_001158259.1; NM_001164787.1.
DR RefSeq; NP_001296311.1; NM_001309382.1.
DR RefSeq; NP_035598.2; NM_011468.4.
DR AlphaFoldDB; Q4KL71; -.
DR PaxDb; Q4KL71; -.
DR PRIDE; Q4KL71; -.
DR Ensembl; ENSMUST00000071805; ENSMUSP00000102950; ENSMUSG00000068893.
DR Ensembl; ENSMUST00000074449; ENSMUSP00000083330; ENSMUSG00000078664.
DR Ensembl; ENSMUST00000090871; ENSMUSP00000088386; ENSMUSG00000068893.
DR Ensembl; ENSMUST00000090872; ENSMUSP00000088387; ENSMUSG00000074445.
DR Ensembl; ENSMUST00000193337; ENSMUSP00000142110; ENSMUSG00000074445.
DR GeneID; 100042514; -.
DR GeneID; 100303744; -.
DR GeneID; 20755; -.
DR KEGG; mmu:100042514; -.
DR KEGG; mmu:100303744; -.
DR KEGG; mmu:20755; -.
DR UCSC; uc008qdq.1; mouse.
DR CTD; 100042514; -.
DR CTD; 100303744; -.
DR CTD; 20755; -.
DR MGI; MGI:3845028; Sprr2a3.
DR VEuPathDB; HostDB:ENSMUSG00000068893; -.
DR VEuPathDB; HostDB:ENSMUSG00000074445; -.
DR VEuPathDB; HostDB:ENSMUSG00000078664; -.
DR HOGENOM; CLU_192372_0_0_1; -.
DR OMA; VCPPPEC; -.
DR OrthoDB; 1843068at2759; -.
DR BioGRID-ORCS; 100042514; 0 hits in 3 CRISPR screens.
DR BioGRID-ORCS; 100303744; 4 hits in 32 CRISPR screens.
DR BioGRID-ORCS; 20755; 3 hits in 32 CRISPR screens.
DR ChiTaRS; Sprr2a3; mouse.
DR PRO; PR:Q4KL71; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q4KL71; protein.
DR Bgee; ENSMUSG00000068893; Expressed in ileum and 33 other tissues.
DR ExpressionAtlas; Q4KL71; baseline and differential.
DR Genevisible; Q4KL71; MM.
DR GO; GO:0001533; C:cornified envelope; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0008289; F:lipid binding; ISS:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEA:UniProt.
DR InterPro; IPR029142; SPRR2.
DR Pfam; PF14820; SPRR2; 1.
PE 2: Evidence at transcript level;
KW Antibiotic; Antimicrobial; Cytoplasmic vesicle; Disulfide bond;
KW Lipid-binding; Reference proteome; Repeat; Secreted.
FT CHAIN 1..83
FT /note="Small proline-rich protein 2A3"
FT /id="PRO_0000425580"
FT REPEAT 21..29
FT /note="1"
FT /evidence="ECO:0000255"
FT REPEAT 30..38
FT /note="2"
FT /evidence="ECO:0000255"
FT REPEAT 39..47
FT /note="3"
FT /evidence="ECO:0000255"
FT REPEAT 48..56
FT /note="4"
FT /evidence="ECO:0000255"
FT REPEAT 57..65
FT /note="5"
FT /evidence="ECO:0000255"
FT REGION 21..65
FT /note="5 X 9 AA approximate tandem repeats"
FT /evidence="ECO:0000255"
SQ SEQUENCE 83 AA; 9408 MW; 7CF13DF8DE397D46 CRC64;
MSYYQQQCNQ PCRPPPVCPP PKCPEPCPPQ VWPGPCRPVM CFEPCLPSVW PGPCRPVVCY
EQCPPQPWQS TCPPVQFPPC QQK
