ANG4_MOUSE
ID ANG4_MOUSE Reviewed; 144 AA.
AC Q3TMQ6; Q3UWE7; Q80XS4; Q80Z85;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Angiogenin-4;
DE EC=3.1.27.-;
DE Flags: Precursor;
GN Name=Ang4;
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], FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=NMRI;
RX PubMed=12548285; DOI=10.1038/ni888;
RA Hooper L.V., Stappenbeck T.S., Hong C.V., Gordon J.I.;
RT "Angiogenins: a new class of microbicidal proteins involved in innate
RT immunity.";
RL Nat. Immunol. 4:269-273(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Colon, and Intestinal mucosa;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Brain, and Colon;
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 X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS), FUNCTION, MUTAGENESIS OF HIS-36;
RP ARG-56; LYS-83; HIS-136 AND GLU-139, AND DISULFIDE BONDS.
RX PubMed=17279775; DOI=10.1021/bi062158n;
RA Crabtree B., Holloway D.E., Baker M.D., Acharya K.R., Subramanian V.;
RT "Biological and structural features of murine angiogenin-4, an angiogenic
RT protein.";
RL Biochemistry 46:2431-2443(2007).
CC -!- FUNCTION: Has bactericidal activity against E.faecalis and
CC L.monocytogenes, but not against L.innocua and E.coli. Promotes
CC angiogenesis (in vitro). Has low ribonuclease activity (in vitro).
CC Promotes proliferation of melanoma cells, but not of endothelial cells
CC or fibroblasts (in vitro). {ECO:0000269|PubMed:12548285,
CC ECO:0000269|PubMed:17279775}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle lumen
CC {ECO:0000269|PubMed:12548285}. Secreted {ECO:0000250|UniProtKB:P10152}.
CC Nucleus, nucleolus {ECO:0000250|UniProtKB:P03950}. Note=Exposure to
CC bacterial lipopolysaccharide (LPS) triggers secretion from intestinal
CC epithelium cells (PubMed:12548285). Rapidly endocytosed by target cells
CC and translocated to the nucleus where it accumulates in the nucleolus
CC and binds to DNA (By similarity). {ECO:0000250|UniProtKB:P03950,
CC ECO:0000269|PubMed:12548285}.
CC -!- TISSUE SPECIFICITY: Detected in small intestine, caecum and colon, with
CC the highest expression in Paneth cells in the intestinal epithelium.
CC {ECO:0000269|PubMed:12548285}.
CC -!- INDUCTION: Up-regulated in small intestine by contact with normal
CC intestinal microflora. Expressed at very low levels in intestine from
CC germ-free mice. {ECO:0000269|PubMed:12548285}.
CC -!- SIMILARITY: Belongs to the pancreatic ribonuclease family.
CC {ECO:0000305}.
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DR EMBL; AY219870; AAO62354.1; -; mRNA.
DR EMBL; AK136415; BAE22968.1; -; mRNA.
DR EMBL; AK165799; BAE38385.1; -; mRNA.
DR EMBL; AC122877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466659; EDL42283.1; -; Genomic_DNA.
DR EMBL; BC042938; AAH42938.2; -; mRNA.
DR EMBL; BC132444; AAI32445.1; -; mRNA.
DR EMBL; BC132448; AAI32449.1; -; mRNA.
DR CCDS; CCDS36911.1; -.
DR RefSeq; NP_808212.2; NM_177544.4.
DR PDB; 2J4T; X-ray; 2.02 A; A/B=1-144.
DR PDBsum; 2J4T; -.
DR AlphaFoldDB; Q3TMQ6; -.
DR SMR; Q3TMQ6; -.
DR STRING; 10090.ENSMUSP00000073525; -.
DR iPTMnet; Q3TMQ6; -.
DR PhosphoSitePlus; Q3TMQ6; -.
DR PaxDb; Q3TMQ6; -.
DR PeptideAtlas; Q3TMQ6; -.
DR PRIDE; Q3TMQ6; -.
DR ProteomicsDB; 281980; -.
DR DNASU; 219033; -.
DR Ensembl; ENSMUST00000073860; ENSMUSP00000073525; ENSMUSG00000060615.
DR GeneID; 219033; -.
DR KEGG; mmu:219033; -.
DR UCSC; uc007tnd.1; mouse.
DR CTD; 219033; -.
DR MGI; MGI:2656551; Ang4.
DR VEuPathDB; HostDB:ENSMUSG00000060615; -.
DR eggNOG; ENOG502S9Q1; Eukaryota.
DR GeneTree; ENSGT00940000162981; -.
DR HOGENOM; CLU_117006_3_1_1; -.
DR InParanoid; Q3TMQ6; -.
DR OMA; ACDEHEH; -.
DR OrthoDB; 1549558at2759; -.
DR PhylomeDB; Q3TMQ6; -.
DR TreeFam; TF333393; -.
DR BioGRID-ORCS; 219033; 2 hits in 69 CRISPR screens.
DR ChiTaRS; Ang4; mouse.
DR PRO; PR:Q3TMQ6; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q3TMQ6; protein.
DR Bgee; ENSMUSG00000060615; Expressed in paneth cell and 29 other tissues.
DR ExpressionAtlas; Q3TMQ6; baseline and differential.
DR Genevisible; Q3TMQ6; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0005604; C:basement membrane; ISO:MGI.
DR GO; GO:0005694; C:chromosome; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0030141; C:secretory granule; IDA:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0005507; F:copper ion binding; ISO:MGI.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; ISO:MGI.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0004540; F:ribonuclease activity; IMP:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0032431; P:activation of phospholipase A2 activity; ISO:MGI.
DR GO; GO:0007202; P:activation of phospholipase C activity; ISO:MGI.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:MGI.
DR GO; GO:0019732; P:antifungal humoral response; ISO:MGI.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IDA:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:MGI.
DR GO; GO:0006651; P:diacylglycerol biosynthetic process; ISO:MGI.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:MGI.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0009725; P:response to hormone; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0001878; P:response to yeast; ISO:MGI.
DR GO; GO:0006401; P:RNA catabolic process; IMP:UniProtKB.
DR GO; GO:0009303; P:rRNA transcription; ISO:MGI.
DR Gene3D; 3.10.130.10; -; 1.
DR InterPro; IPR001427; RNaseA.
DR InterPro; IPR036816; RNaseA-like_dom_sf.
DR InterPro; IPR023411; RNaseA_AS.
DR InterPro; IPR023412; RNaseA_domain.
DR PANTHER; PTHR11437; PTHR11437; 1.
DR Pfam; PF00074; RnaseA; 1.
DR PRINTS; PR00794; RIBONUCLEASE.
DR SMART; SM00092; RNAse_Pc; 1.
DR SUPFAM; SSF54076; SSF54076; 1.
DR PROSITE; PS00127; RNASE_PANCREATIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Angiogenesis; Antibiotic; Antimicrobial; Cytoplasmic vesicle;
KW Disulfide bond; Endonuclease; Hydrolase; Nuclease; Nucleus;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..144
FT /note="Angiogenin-4"
FT /id="PRO_0000415440"
FT MOTIF 54..58
FT /note="Nucleolar localization signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 36
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT ACT_SITE 136
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT BINDING 31
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 63..67
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT DISULFID 49..103
FT /evidence="ECO:0000269|PubMed:17279775"
FT DISULFID 62..114
FT /evidence="ECO:0000269|PubMed:17279775"
FT DISULFID 80..129
FT /evidence="ECO:0000269|PubMed:17279775"
FT MUTAGEN 36
FT /note="H->A: Loss of ribonuclease activity. Loss of
FT angiogenic activity."
FT /evidence="ECO:0000269|PubMed:17279775"
FT MUTAGEN 56
FT /note="R->A: Loss of angiogenic activity. No effect on
FT ribonuclease activity."
FT /evidence="ECO:0000269|PubMed:17279775"
FT MUTAGEN 83
FT /note="K->N: Loss of angiogenic activity. No effect on
FT ribonuclease activity."
FT /evidence="ECO:0000269|PubMed:17279775"
FT MUTAGEN 136
FT /note="H->A: Loss of ribonuclease activity. Loss of
FT angiogenic activity."
FT /evidence="ECO:0000269|PubMed:17279775"
FT MUTAGEN 139
FT /note="E->A: Loss of angiogenic activity. Increased
FT ribonuclease activity."
FT /evidence="ECO:0000269|PubMed:17279775"
FT CONFLICT 42
FT /note="N -> K (in Ref. 1; AAO62354, 4; EDL42283 and 5;
FT AAH42938/AAI32445/AAI32449)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="F -> V (in Ref. 2; BAE22968)"
FT /evidence="ECO:0000305"
FT CONFLICT 107..108
FT /note="GA -> RG (in Ref. 1; AAO62354, 4; EDL42283 and 5;
FT AAH42938/AAI32445/AAI32449)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="R -> W (in Ref. 1; AAO62354, 4; EDL42283 and 5;
FT AAH42938/AAI32445/AAI32449)"
FT /evidence="ECO:0000305"
FT HELIX 27..36
FT /evidence="ECO:0007829|PDB:2J4T"
FT HELIX 46..55
FT /evidence="ECO:0007829|PDB:2J4T"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:2J4T"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:2J4T"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:2J4T"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:2J4T"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:2J4T"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:2J4T"
FT STRAND 88..96
FT /evidence="ECO:0007829|PDB:2J4T"
FT STRAND 98..105
FT /evidence="ECO:0007829|PDB:2J4T"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:2J4T"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:2J4T"
FT STRAND 126..130
FT /evidence="ECO:0007829|PDB:2J4T"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:2J4T"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:2J4T"
SQ SEQUENCE 144 AA; 16425 MW; 0D93DE32A5A4CABA CRC64;
MTMSPCPLLL VFVLGLVVIP PTLAQNERYE KFLRQHYDAK PNGRDDRYCE SMMKERKLTS
PCKDVNTFIH GTKKNIRAIC GKKGSPYGEN FRISNSPFQI TTCTHSGASP RPPCGYRAFK
DFRYIVIACE DGWPVHFDES FISP
