SMAD5_MOUSE
ID SMAD5_MOUSE Reviewed; 465 AA.
AC P97454; P70341; Q810K0;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 04-MAY-2001, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Mothers against decapentaplegic homolog 5;
DE Short=MAD homolog 5;
DE Short=Mothers against DPP homolog 5;
DE AltName: Full=Dwarfin-C;
DE Short=Dwf-C;
DE AltName: Full=SMAD family member 5;
DE Short=SMAD 5;
DE Short=Smad5;
DE Short=mSmad5;
GN Name=Smad5; Synonyms=Madh5, Msmad5;
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].
RX PubMed=8799132; DOI=10.1073/pnas.93.17.8940;
RA Yingling J.M., Das P., Savage C., Zhang M., Padgett R.W., Wang X.-F.;
RT "Mammalian dwarfins are phosphorylated in response to transforming growth
RT factor beta and are implicated in control of cell growth.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:8940-8944(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9076683; DOI=10.1016/s0925-4773(96)00629-6;
RA Meersseman G., Verschueren K., Nelles L., Blumenstock C., Kraft H.,
RA Wuytens G., Remacle J., Kozak C.A., Tylzanowski P., Niehrs C.,
RA Huylebroeck D.;
RT "The C-terminal domain of Mad-like signal transducers is sufficient for
RT biological activity in the Xenopus embryo and transcriptional activation.";
RL Mech. Dev. 61:127-140(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv;
RA Chang H., Kraft H., Verschueren K., Wang P., Huylebroeck D., Matzuk M.M.;
RT "Genomic organization and expression of mouse Smad5.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Spinal cord;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 REVIEW.
RX PubMed=10708952; DOI=10.1016/s1359-6101(99)00028-3;
RA Weinstein M., Yang X., Deng C.-X.;
RT "Functions of mammalian Smad genes as revealed by targeted gene disruption
RT in mice.";
RL Cytokine Growth Factor Rev. 11:49-58(2000).
RN [7]
RP INTERACTION WITH ZNF8.
RX PubMed=12370310; DOI=10.1128/mcb.22.21.7633-7644.2002;
RA Jiao K., Zhou Y., Hogan B.L.M.;
RT "Identification of mZnf8, a mouse Kruppel-like transcriptional repressor,
RT as a novel nuclear interaction partner of Smad1.";
RL Mol. Cell. Biol. 22:7633-7644(2002).
RN [8]
RP INTERACTION WITH WWP1.
RX PubMed=15221015; DOI=10.1038/sj.onc.1207885;
RA Komuro A., Imamura T., Saitoh M., Yoshida Y., Yamori T., Miyazono K.,
RA Miyazawa K.;
RT "Negative regulation of transforming growth factor-beta (TGF-beta)
RT signaling by WW domain-containing protein 1 (WWP1).";
RL Oncogene 23:6914-6923(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP INTERACTION WITH TMEM119.
RX PubMed=21239498; DOI=10.1074/jbc.m110.179127;
RA Hisa I., Inoue Y., Hendy G.N., Canaff L., Kitazawa R., Kitazawa S.,
RA Komori T., Sugimoto T., Seino S., Kaji H.;
RT "Parathyroid hormone-responsive Smad3-related factor, Tmem119, promotes
RT osteoblast differentiation and interacts with the bone morphogenetic
RT protein-Runx2 pathway.";
RL J. Biol. Chem. 286:9787-9796(2011).
CC -!- FUNCTION: Transcriptional modulator activated by BMP (bone
CC morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-
CC regulated SMAD (R-SMAD) (By similarity). Required for angiogenesis.
CC {ECO:0000250}.
CC -!- SUBUNIT: May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-
CC alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts
CC (via MH2 domain) with LEMD3 (By similarity). Interacts with WWP1.
CC Interacts with TMEM119 (PubMed:21239498). Interacts with ZNF8
CC (PubMed:12370310). Interacts with RANBP3L (By similarity).
CC {ECO:0000250|UniProtKB:Q99717, ECO:0000269|PubMed:12370310,
CC ECO:0000269|PubMed:15221015, ECO:0000269|PubMed:21239498}.
CC -!- INTERACTION:
CC P97454; Q62424: Hoxa13; NbExp=3; IntAct=EBI-7066475, EBI-925160;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=In the cytoplasm in the absence of ligand. Migration to the
CC nucleus when complexed with SMAD4 (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine by BMP (bone morphogenetic proteins) type
CC 1 receptor kinase.
CC -!- PTM: Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin
CC ligase SMURF1. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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DR EMBL; U58993; AAB07871.1; -; mRNA.
DR EMBL; U77638; AAB39737.1; -; mRNA.
DR EMBL; AF063006; AAC83580.1; -; mRNA.
DR EMBL; AK082997; BAC38724.1; -; mRNA.
DR EMBL; BC050001; AAH50001.2; -; mRNA.
DR CCDS; CCDS26565.1; -.
DR RefSeq; NP_001157513.1; NM_001164041.1.
DR RefSeq; NP_001157514.1; NM_001164042.1.
DR RefSeq; NP_032567.1; NM_008541.3.
DR RefSeq; XP_006517180.1; XM_006517117.1.
DR RefSeq; XP_006517181.1; XM_006517118.3.
DR PDB; 5X6G; X-ray; 3.05 A; A/B=1-143.
DR PDB; 5X6H; X-ray; 3.10 A; B=1-143.
DR PDB; 5X6M; X-ray; 3.20 A; A/B/E/F=1-143.
DR PDBsum; 5X6G; -.
DR PDBsum; 5X6H; -.
DR PDBsum; 5X6M; -.
DR AlphaFoldDB; P97454; -.
DR SMR; P97454; -.
DR BioGRID; 201278; 14.
DR IntAct; P97454; 3.
DR MINT; P97454; -.
DR STRING; 10090.ENSMUSP00000105502; -.
DR ChEMBL; CHEMBL3883282; -.
DR iPTMnet; P97454; -.
DR PhosphoSitePlus; P97454; -.
DR MaxQB; P97454; -.
DR PaxDb; P97454; -.
DR PeptideAtlas; P97454; -.
DR PRIDE; P97454; -.
DR ProteomicsDB; 257256; -.
DR Antibodypedia; 7303; 616 antibodies from 41 providers.
DR DNASU; 17129; -.
DR Ensembl; ENSMUST00000069557; ENSMUSP00000065798; ENSMUSG00000021540.
DR Ensembl; ENSMUST00000109874; ENSMUSP00000105500; ENSMUSG00000021540.
DR Ensembl; ENSMUST00000109876; ENSMUSP00000105502; ENSMUSG00000021540.
DR GeneID; 17129; -.
DR KEGG; mmu:17129; -.
DR UCSC; uc007qsw.2; mouse.
DR CTD; 4090; -.
DR MGI; MGI:1328787; Smad5.
DR VEuPathDB; HostDB:ENSMUSG00000021540; -.
DR eggNOG; KOG3701; Eukaryota.
DR GeneTree; ENSGT00940000155437; -.
DR HOGENOM; CLU_026736_0_2_1; -.
DR InParanoid; P97454; -.
DR OMA; PPEEQMG; -.
DR OrthoDB; 608001at2759; -.
DR PhylomeDB; P97454; -.
DR TreeFam; TF314923; -.
DR Reactome; R-MMU-201451; Signaling by BMP.
DR BioGRID-ORCS; 17129; 3 hits in 74 CRISPR screens.
DR PRO; PR:P97454; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P97454; protein.
DR Bgee; ENSMUSG00000021540; Expressed in undifferentiated genital tubercle and 269 other tissues.
DR Genevisible; P97454; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0070411; F:I-SMAD binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
DR GO; GO:0060348; P:bone development; IGI:MGI.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:MGI.
DR GO; GO:0051216; P:cartilage development; IGI:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IGI:BHF-UCL.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:MGI.
DR GO; GO:0007281; P:germ cell development; IMP:MGI.
DR GO; GO:0001880; P:Mullerian duct regression; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0002051; P:osteoblast fate commitment; IGI:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; IGI:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0060395; P:SMAD protein signal transduction; IGI:BHF-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:MGI.
DR GO; GO:0001657; P:ureteric bud development; IEP:UniProtKB.
DR Gene3D; 2.60.200.10; -; 1.
DR Gene3D; 3.90.520.10; -; 1.
DR InterPro; IPR013790; Dwarfin.
DR InterPro; IPR003619; MAD_homology1_Dwarfin-type.
DR InterPro; IPR013019; MAD_homology_MH1.
DR InterPro; IPR017855; SMAD-like_dom_sf.
DR InterPro; IPR001132; SMAD_dom_Dwarfin-type.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR036578; SMAD_MH1_sf.
DR PANTHER; PTHR13703; PTHR13703; 1.
DR Pfam; PF03165; MH1; 1.
DR Pfam; PF03166; MH2; 1.
DR SMART; SM00523; DWA; 1.
DR SMART; SM00524; DWB; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF56366; SSF56366; 1.
DR PROSITE; PS51075; MH1; 1.
DR PROSITE; PS51076; MH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Angiogenesis; Cytoplasm; Developmental protein;
KW Differentiation; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q99717"
FT CHAIN 2..465
FT /note="Mothers against decapentaplegic homolog 5"
FT /id="PRO_0000090866"
FT DOMAIN 13..137
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 271..465
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 163..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 163..184
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..201
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..230
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99717"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99717,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 465
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99717,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT CONFLICT 196
FT /note="S -> P (in Ref. 2; AAB39737)"
FT /evidence="ECO:0000305"
FT HELIX 13..21
FT /evidence="ECO:0007829|PDB:5X6G"
FT HELIX 26..44
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:5X6M"
FT HELIX 48..57
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:5X6G"
FT HELIX 85..93
FT /evidence="ECO:0007829|PDB:5X6G"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:5X6G"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:5X6G"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:5X6G"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:5X6G"
SQ SEQUENCE 465 AA; 52172 MW; D66B638DA76BC20B CRC64;
MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME ELEKALSSPG
QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS HHELKPLDIC EFPFGSKQKE
VCINPYHYKR VESPVLPPVL VPRHNEFNPQ HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP
NNAPFPLSPN SPYPPSPASS TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMAPDNSQP
MDTSSNMIPQ TMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT
DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC
NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF EAVYELTKMC TIRMSFVKGW
GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPLNP ISSVS
