SG3A2_MOUSE
ID SG3A2_MOUSE Reviewed; 91 AA.
AC Q920H1; Q5D060; Q920H2; Q920H3;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2017, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Secretoglobin family 3A member 2;
DE AltName: Full=Pneumo secretory protein 1;
DE Short=PnSP-1;
DE AltName: Full=Uteroglobin-related protein 1;
DE Flags: Precursor;
GN Name=Scgb3a2; Synonyms=Pnsp1, Ugrp1;
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 [MRNA] (ISOFORMS A; B AND C), SUBUNIT, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Lung;
RX PubMed=11682631; DOI=10.1210/mend.15.11.0728;
RA Niimi T., Keck-Waggoner C.L., Popescu N.C., Zhou Y., Levitt R.C.,
RA Kimura S.;
RT "UGRP1, a uteroglobin/Clara cell secretory protein-related protein, is a
RT novel lung-enriched downstream target gene for the T/EBP/NKX2.1 homeodomain
RT transcription factor.";
RL Mol. Endocrinol. 15:2021-2036(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC STRAIN=NMRI;
RA Clippe A., Laing I.A., LeSouef P.N., Bernard A., Knoops B.;
RT "Molecular cloning of PnSP-1, a protein of the respiratory tract with
RT potential association to atopy.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE22952.1};
RC TISSUE=Lung {ECO:0000312|EMBL:BAE22952.1};
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 [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
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 TISSUE SPECIFICITY.
RX PubMed=12406855; DOI=10.1164/rccm.200204-285oc;
RA Reynolds S.D., Reynolds P.R., Pryhuber G.S., Finder J.D., Stripp B.R.;
RT "Secretoglobins SCGB3A1 and SCGB3A2 define secretory cell subsets in mouse
RT and human airways.";
RL Am. J. Respir. Crit. Care Med. 166:1498-1509(2002).
RN [7]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12175512; DOI=10.1016/s0925-4773(02)00056-4;
RA Porter D., Lahti-Domenici J., Torres-Arzayus M., Chin L., Polyak K.;
RT "Expression of high in normal-1 (HIN-1) and uteroglobin related protein-1
RT (UGRP-1) in adult and developing tissues.";
RL Mech. Dev. 114:201-204(2002).
RN [8]
RP FUNCTION.
RX PubMed=16456148; DOI=10.1164/rccm.200503-456oc;
RA Chiba Y., Kurotani R., Kusakabe T., Miura T., Link B.W., Misawa M.,
RA Kimura S.;
RT "Uteroglobin-related protein 1 expression suppresses allergic airway
RT inflammation in mice.";
RL Am. J. Respir. Crit. Care Med. 173:958-964(2006).
RN [9]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=18535256; DOI=10.1164/rccm.200707-1104oc;
RA Kurotani R., Tomita T., Yang Q., Carlson B.A., Chen C., Kimura S.;
RT "Role of secretoglobin 3A2 in lung development.";
RL Am. J. Respir. Crit. Care Med. 178:389-398(2008).
RN [10]
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF CYS-68.
RX PubMed=24213919; DOI=10.1152/ajplung.00037.2013;
RA Cai Y., Winn M.E., Zehmer J.K., Gillette W.K., Lubkowski J.T., Pilon A.L.,
RA Kimura S.;
RT "Preclinical evaluation of human secretoglobin 3A2 in mouse models of lung
RT development and fibrosis.";
RL Am. J. Physiol. 306:L10-L22(2014).
RN [11]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=24514953; DOI=10.1007/s00441-014-1794-z;
RA Miyano Y., Tahara S., Sakata I., Sakai T., Abe H., Kimura S., Kurotani R.;
RT "Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse
RT pituitary gland.";
RL Cell Tissue Res. 356:253-260(2014).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=25242865; DOI=10.1155/2014/216465;
RA Kido T., Yoneda M., Cai Y., Matsubara T., Ward J.M., Kimura S.;
RT "Secretoglobin superfamily protein SCGB3A2 deficiency potentiates
RT ovalbumin-induced allergic pulmonary inflammation.";
RL Mediators Inflamm. 2014:216465-216465(2014).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26559674; DOI=10.1371/journal.pone.0142497;
RA Cai Y., Kimura S.;
RT "Secretoglobin 3A2 exhibits anti-fibrotic activity in bleomycin-induced
RT pulmonary fibrosis model mice.";
RL PLoS ONE 10:E0142497-E0142497(2015).
CC -!- FUNCTION: Secreted cytokine-like protein (By similarity). Binds to the
CC scavenger receptor MARCO (By similarity). Can also bind to pathogens
CC including the Gram-positive bacterium L.monocytogenes, the Gram-
CC negative bacterium P.aeruginosa, and yeast (By similarity). Strongly
CC inhibits phospholipase A2 (PLA2G1B) activity (PubMed:24213919). Seems
CC to have anti-inflammatory effects in respiratory epithelium
CC (PubMed:16456148, PubMed:25242865). Also has anti-fibrotic activity in
CC lung (PubMed:24213919, PubMed:26559674). May play a role in fetal lung
CC development and maturation (PubMed:18535256). Promotes branching
CC morphogenesis during early stages of lung development
CC (PubMed:18535256). In the pituitary, may inhibit production of
CC follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
CC (PubMed:24514953). {ECO:0000250|UniProtKB:Q96PL1,
CC ECO:0000269|PubMed:16456148, ECO:0000269|PubMed:18535256,
CC ECO:0000269|PubMed:24213919, ECO:0000269|PubMed:24514953,
CC ECO:0000269|PubMed:25242865, ECO:0000269|PubMed:26559674}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:11682631,
CC PubMed:24213919). Monomer (PubMed:11682631, PubMed:24213919). Interacts
CC with APOA1 (By similarity). {ECO:0000250|UniProtKB:Q96PL1,
CC ECO:0000269|PubMed:11682631, ECO:0000269|PubMed:24213919}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11682631}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A {ECO:0000303|PubMed:11682631};
CC IsoId=Q920H1-2; Sequence=Displayed;
CC Name=B {ECO:0000303|PubMed:11682631};
CC IsoId=Q920H1-3; Sequence=VSP_059182;
CC Name=C {ECO:0000303|PubMed:11682631};
CC IsoId=Q920H1-1; Sequence=VSP_059183;
CC -!- TISSUE SPECIFICITY: Highly expressed in lung where it localizes to
CC epithelial cells of the trachea, bronchus and bronchioles (at protein
CC level) (PubMed:11682631, PubMed:12406855, PubMed:12175512,
CC PubMed:25242865). Expressed in club/Clara cells of the bronchioles
CC (PubMed:12406855). Also detected in the anterior and posterior lobes of
CC the pituitary gland where it may localize to gonadotropic cells (at
CC protein level) (PubMed:24514953). Not detected in other tissues tested
CC (PubMed:11682631, PubMed:12175512). {ECO:0000269|PubMed:11682631,
CC ECO:0000269|PubMed:12175512, ECO:0000269|PubMed:12406855,
CC ECO:0000269|PubMed:24514953, ECO:0000269|PubMed:25242865}.
CC -!- DEVELOPMENTAL STAGE: Detected in the pituitary gland from postnatal day
CC 1 onwards (at protein level) (PubMed:24514953). Weakly expressed in
CC embryonic lung at stages 11.5 dpc and 12.5 dpc (PubMed:11682631,
CC PubMed:18535256). Seems to localize most strongly to the growing tips
CC of bronchi at stage 13.5 dpc (PubMed:18535256). Highly expressed in
CC developing lung at stages 16.5 dpc and 18.5 dpc, where it localizes to
CC airway epithelia (PubMed:11682631, PubMed:12406855, PubMed:12175512,
CC PubMed:24514953). During gestation, detected in the mammary gland at
CC 6.5 days post coitum (dpc), but expression declines at 8.5 dpc and is
CC absent at later stages (PubMed:12175512). {ECO:0000269|PubMed:11682631,
CC ECO:0000269|PubMed:12175512, ECO:0000269|PubMed:12406855,
CC ECO:0000269|PubMed:18535256, ECO:0000269|PubMed:24514953}.
CC -!- DISRUPTION PHENOTYPE: Viable and fertile, with no gross abnormalities.
CC Lung tissue appears normal (PubMed:25242865). In a C57BL/6NCr strain
CC background, animals show a mild increase in ovalbumin-induced
CC inflammatory response in lung (PubMed:25242865). However, in a mixed
CC genetic background, there is a reduced ovalbumin-induced inflammatory
CC response, possibly due to the presence of modifier genes
CC (PubMed:25242865). Animals have a more severe response to bleomycin-
CC induced pulmonary fibrosis characterized by increased weight loss, more
CC extensive fibrosis in lung tissue, increased expression of collagen
CC genes, higher numbers of lymphocyte, monocyte and neutrophil cells in
CC bronchoalveolar lavage fluid, and increased cytokine levels
CC (PubMed:26559674). {ECO:0000269|PubMed:25242865,
CC ECO:0000269|PubMed:26559674}.
CC -!- MISCELLANEOUS: [Isoform A]: Major isoform.
CC {ECO:0000269|PubMed:11682631}.
CC -!- SIMILARITY: Belongs to the secretoglobin family. UGRP subfamily.
CC {ECO:0000305}.
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DR EMBL; AF274959; AAL25708.1; -; mRNA.
DR EMBL; AF274960; AAL25709.1; -; mRNA.
DR EMBL; AF274961; AAL25710.1; -; mRNA.
DR EMBL; AF439546; AAQ04561.1; -; mRNA.
DR EMBL; AK136373; BAE22952.1; -; mRNA.
DR EMBL; AK136396; BAE22961.1; -; mRNA.
DR EMBL; CH466528; EDL10011.1; -; Genomic_DNA.
DR EMBL; BC061046; AAH61046.1; -; mRNA.
DR CCDS; CCDS79640.1; -. [Q920H1-2]
DR CCDS; CCDS79641.1; -. [Q920H1-3]
DR RefSeq; NP_001276572.1; NM_001289643.1. [Q920H1-3]
DR RefSeq; NP_001276573.1; NM_001289644.1. [Q920H1-2]
DR RefSeq; XP_011245113.1; XM_011246811.1.
DR AlphaFoldDB; Q920H1; -.
DR SMR; Q920H1; -.
DR BioGRID; 228174; 1.
DR STRING; 10090.ENSMUSP00000038872; -.
DR PhosphoSitePlus; Q920H1; -.
DR MaxQB; Q920H1; -.
DR PaxDb; Q920H1; -.
DR PRIDE; Q920H1; -.
DR ProteomicsDB; 261331; -. [Q920H1-2]
DR ProteomicsDB; 261332; -. [Q920H1-3]
DR ProteomicsDB; 261333; -. [Q920H1-1]
DR Antibodypedia; 27663; 51 antibodies from 16 providers.
DR Ensembl; ENSMUST00000043803; ENSMUSP00000038872; ENSMUSG00000038791. [Q920H1-1]
DR Ensembl; ENSMUST00000187157; ENSMUSP00000140476; ENSMUSG00000038791. [Q920H1-2]
DR Ensembl; ENSMUST00000189750; ENSMUSP00000140375; ENSMUSG00000038791. [Q920H1-3]
DR GeneID; 117158; -.
DR KEGG; mmu:117158; -.
DR UCSC; uc008eum.2; mouse. [Q920H1-2]
DR UCSC; uc008eun.2; mouse.
DR UCSC; uc012bck.2; mouse. [Q920H1-3]
DR CTD; 117156; -.
DR MGI; MGI:2153470; Scgb3a2.
DR VEuPathDB; HostDB:ENSMUSG00000038791; -.
DR eggNOG; ENOG502SVJM; Eukaryota.
DR GeneTree; ENSGT00420000029848; -.
DR HOGENOM; CLU_146812_0_0_1; -.
DR InParanoid; Q920H1; -.
DR OMA; NSVLPFM; -.
DR OrthoDB; 1615937at2759; -.
DR PhylomeDB; Q920H1; -.
DR TreeFam; TF336928; -.
DR Reactome; R-MMU-3000480; Scavenging by Class A Receptors.
DR BioGRID-ORCS; 117158; 1 hit in 70 CRISPR screens.
DR ChiTaRS; Scgb3a2; mouse.
DR PRO; PR:Q920H1; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q920H1; protein.
DR Bgee; ENSMUSG00000038791; Expressed in right lung lobe and 43 other tissues.
DR Genevisible; Q920H1; MM.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR InterPro; IPR040301; Secretoglobin_3A.
DR PANTHER; PTHR34829; PTHR34829; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000250|UniProtKB:Q96PL1"
FT CHAIN 22..91
FT /note="Secretoglobin family 3A member 2"
FT /id="PRO_0000036382"
FT DISULFID 68
FT /note="Interchain"
FT /evidence="ECO:0000305|PubMed:24213919"
FT VAR_SEQ 84
FT /note="L -> LVIIICSYFPGRSLCYVNNLPSF (in isoform B)"
FT /evidence="ECO:0000305|PubMed:11682631"
FT /id="VSP_059182"
FT VAR_SEQ 85..91
FT /note="EALSHLV -> VIIICSYFPGRSLCYVNNLPSFVSVLFLPMICAYPRDSKKQ
FT TFAFIERVFEQSKL (in isoform C)"
FT /evidence="ECO:0000305|PubMed:11682631"
FT /id="VSP_059183"
FT MUTAGEN 68
FT /note="C->S: Fails to homodimerize."
FT /evidence="ECO:0000269|PubMed:24213919"
SQ SEQUENCE 91 AA; 9819 MW; 2B5C4D39E6A4EE14 CRC64;
MKLVSIFLLV TIGICGYSAT ALLINRLPVV DKLPVPLDDI IPSFDPLKML LKTLGISVEH
LVTGLKKCVD ELGPEASEAV KKLLEALSHL V
