MFHA1_MOUSE
ID MFHA1_MOUSE Reviewed; 1048 AA.
AC Q3V1N1; Q3TAN2; Q8C4N5;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Malignant fibrous histiocytoma-amplified sequence 1 homolog {ECO:0000305};
GN Name=Mfhas1 {ECO:0000312|MGI:MGI:1098644};
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 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 73-1048.
RC STRAIN=C57BL/6J, and NOD; TISSUE=Head, and Spleen;
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 FUNCTION.
RX PubMed=20616063; DOI=10.1073/pnas.1000093107;
RA Ng A.C., Eisenberg J.M., Heath R.J., Huett A., Robinson C.M., Nau G.J.,
RA Xavier R.J.;
RT "Human leucine-rich repeat proteins: a genome-wide bioinformatic
RT categorization and functional analysis in innate immunity.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:4631-4638(2011).
RN [4]
RP FUNCTION.
RX PubMed=26599367; DOI=10.1371/journal.pone.0143662;
RA Zhong J., Shi Q.Q., Zhu M.M., Shen J., Wang H.H., Ma D., Miao C.H.;
RT "MFHAS1 is associated with sepsis and stimulates TLR2/NF-kappaB signaling
RT pathway following negative regulation.";
RL PLoS ONE 10:E0143662-E0143662(2015).
RN [5]
RP INDUCTION.
RX PubMed=28609714; DOI=10.1016/j.molimm.2017.06.017;
RA Shi Q., Xiong B., Zhong J., Wang H., Ma D., Miao C.;
RT "MFHAS1 suppresses TLR4 signaling pathway via induction of PP2A C subunit
RT cytoplasm translocation and inhibition of c-Jun dephosphorylation at
RT Thr239.";
RL Mol. Immunol. 88:79-88(2017).
CC -!- FUNCTION: Probable GTP-binding protein (By similarity). Functions in
CC innate immunity and more specifically the inflammatory response as a
CC regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways
CC (PubMed:20616063, PubMed:26599367). Negatively regulates the part of
CC the TLR4 signaling pathway that leads to the activation of the
CC transcription factor AP-1. By retaining the phosphatase complex PP2A
CC into the cytoplasm, prevents the dephosphorylation of the AP-1 subunit
CC JUN which is required for proper activation of the transcription factor
CC (By similarity). Both inhibits and activates the TLR2-dependent
CC signaling pathway (PubMed:26599367). Positively regulates the TLR2
CC signaling pathway to activate specifically the downstream p38 and JNK
CC MAP kinases and promote the polarization of macrophages toward the pro-
CC inflammatory M1 phenotype. It may also play a role in the regulation of
CC inflammation induced by high glucose through the PKB/AKT signaling
CC pathway. Also involved in erythrocyte differentiation through
CC activation of the ERK1/ERK2 signaling pathway (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y4C4, ECO:0000269|PubMed:20616063,
CC ECO:0000269|PubMed:26599367}.
CC -!- SUBUNIT: Interacts with RAF1. Interacts with HSPD1. Interacts with
CC PPP2CA; retains PPP2CA into the cytoplasm and excludes it from the
CC nucleus. Interacts with PPP2R2A; the interaction is direct. Interacts
CC with PJA2. {ECO:0000250|UniProtKB:Q9Y4C4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y4C4}.
CC -!- INDUCTION: Up-regulated by lipopolysaccharides (LPS) (at protein
CC level). {ECO:0000269|PubMed:28609714}.
CC -!- PTM: Ubiquitinated. Ubiquitination by PJA2 does not lead MFHAS1 to
CC proteasomal degradation but positively regulates its function in
CC polarization of macrophages. {ECO:0000250|UniProtKB:Q9Y4C4}.
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DR EMBL; AC129082; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC129211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK081646; BAC38281.1; -; mRNA.
DR EMBL; AK132349; BAE21119.1; -; mRNA.
DR EMBL; AK171731; BAE42636.1; -; mRNA.
DR CCDS; CCDS40319.1; -.
DR RefSeq; NP_001074748.1; NM_001081279.1.
DR AlphaFoldDB; Q3V1N1; -.
DR SMR; Q3V1N1; -.
DR BioGRID; 206359; 2.
DR STRING; 10090.ENSMUSP00000044135; -.
DR iPTMnet; Q3V1N1; -.
DR PhosphoSitePlus; Q3V1N1; -.
DR EPD; Q3V1N1; -.
DR MaxQB; Q3V1N1; -.
DR PaxDb; Q3V1N1; -.
DR PRIDE; Q3V1N1; -.
DR ProteomicsDB; 252549; -.
DR Antibodypedia; 65867; 18 antibodies from 9 providers.
DR Ensembl; ENSMUST00000037666; ENSMUSP00000044135; ENSMUSG00000070056.
DR GeneID; 52065; -.
DR KEGG; mmu:52065; -.
DR UCSC; uc009lla.1; mouse.
DR CTD; 9258; -.
DR MGI; MGI:1098644; Mfhas1.
DR VEuPathDB; HostDB:ENSMUSG00000070056; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000158928; -.
DR HOGENOM; CLU_320767_0_0_1; -.
DR InParanoid; Q3V1N1; -.
DR OMA; IVCPKNG; -.
DR OrthoDB; 1013039at2759; -.
DR PhylomeDB; Q3V1N1; -.
DR TreeFam; TF351429; -.
DR BioGRID-ORCS; 52065; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Mfhas1; mouse.
DR PRO; PR:Q3V1N1; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q3V1N1; protein.
DR Bgee; ENSMUSG00000070056; Expressed in metanephric cortical collecting duct and 249 other tissues.
DR ExpressionAtlas; Q3V1N1; baseline and differential.
DR Genevisible; Q3V1N1; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006952; P:defense response; IMP:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0034137; P:positive regulation of toll-like receptor 2 signaling pathway; IMP:UniProtKB.
DR GO; GO:0043030; P:regulation of macrophage activation; ISS:UniProtKB.
DR GO; GO:0034121; P:regulation of toll-like receptor signaling pathway; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR020859; ROC_dom.
DR Pfam; PF13855; LRR_8; 3.
DR SMART; SM00369; LRR_TYP; 13.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51450; LRR; 12.
DR PROSITE; PS51424; ROC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; GTP-binding; Immunity; Inflammatory response;
KW Innate immunity; Leucine-rich repeat; Nucleotide-binding;
KW Reference proteome; Repeat; Signal transduction inhibitor; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C4"
FT CHAIN 2..1048
FT /note="Malignant fibrous histiocytoma-amplified sequence 1
FT homolog"
FT /id="PRO_0000308610"
FT REPEAT 60..81
FT /note="LRR 1"
FT REPEAT 84..105
FT /note="LRR 2"
FT REPEAT 108..129
FT /note="LRR 3"
FT REPEAT 132..153
FT /note="LRR 4"
FT REPEAT 155..176
FT /note="LRR 5"
FT REPEAT 178..199
FT /note="LRR 6"
FT REPEAT 201..222
FT /note="LRR 7"
FT REPEAT 224..246
FT /note="LRR 8"
FT REPEAT 247..268
FT /note="LRR 9"
FT REPEAT 270..292
FT /note="LRR 10"
FT REPEAT 293..314
FT /note="LRR 11"
FT REPEAT 316..337
FT /note="LRR 12"
FT REPEAT 339..360
FT /note="LRR 13"
FT DOMAIN 399..645
FT /note="Roc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT REGION 60..645
FT /note="Required for interaction with PPP2R2A"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C4"
FT REGION 60..360
FT /note="Required for interaction with PJA2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C4"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C4"
FT MOD_RES 597
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4C4"
FT CONFLICT 133
FT /note="L -> M (in Ref. 2; BAE42636)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="R -> P (in Ref. 2; BAE42636)"
FT /evidence="ECO:0000305"
FT CONFLICT 635
FT /note="R -> Q (in Ref. 2; BAE42636)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1048 AA; 116599 MW; 9FE71A05E80544C0 CRC64;
MAGQDSGNLK TVRLWRDAAL RARKLRSNLR QLTLSCPGAG GDPLESPDAP QLVLPANIGD
IEVLNLGNNG LEDVPEGLGS ALGSLRVLVL RRNRFARLPP AVAELGHHLT ELDVSHNRLT
ILGAEVVSAL RELRKLNLSH NQLPALPAQL GALAHLEELD VSFNRLAHLP DSFSCLNHLR
TLDVDHNQLT AFPQQLLQLA ALEELDVSSN RLRGLPEDIS ALRALKILWL SGAELGTLPR
GFCELASLES LMLDNNGLQA LPDEFSRLQR LKMLNLSSNL FEEFPAALLP LAGLEELYLS
RNQLTSVPSL IAGLGRLLTL WLDNNRIRYL PDSIVELTGL EELVLQGNQI AVLPDNFGQL
SRVGLWKIKD NPLIQPPYEV CMKGIPYIAA YQKELAHSQP AVQPRLKLLL MGHKAAGKTL
LRHCLTEDKV EGGQGGGDKE KSYLPFPPLG SKGIEVTSWT ADASRGLRFI VYDLAGDESY
EVIQPFFLSP GALYVLVVNL ATYEPRCFPT TVGSFLHRVG ARVPHAVVCI VGTHADLCGE
RELEEKCLDI HRQIALQEKN DAEGLSHLAK VVDEALARDF ELRSASPHAA YYGVSDKNLR
RRKAHFQYLL NHRLQILSPV LPVSCRDPLQ LQRLRDKLLS VAEHREIFPN LHRVLPRSWQ
VLEELHFQPP QAQRLWLSWW DSARLGLQAG LTEDRLQSAL SYLHESGKLL YFEDSPALKE
HVFHNLTRLI DILNVFFQRD ASLLLHKLLL GTNGEGEGEG ESFPTIAVPS PGQDPLRATQ
LHHYVEGFLL HGLLPAHIIR LLLKPHVQAQ QDLQLLLELL EKMGLCYCLN KPKGKPLNGS
AAWYKFPCYV QNEVPHAEAW INGTNLAGQS FVAEQLQIEY SFPFTFPPGL FARYSVQINS
HVVHRSDGKF QIFAYRGKVP VVVSYRPAKG VLQPDTLSIA SHASLPNIWT AWQAITPLVE
ELNVLLQEWP GLHYTVHILC SKCLKRGSPN PHAFPGELLS QPRPEGVAEI ICPKNGSERV
NVALVYPPTP TVISPCSKKN VGEKHRNQ
