SIMC1_HUMAN
ID SIMC1_HUMAN Reviewed; 872 AA.
AC Q8NDZ2; F6R0L0; J3KQQ8; Q6NXN8; Q6ZTU4; Q8IZ15; R9TJD7;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 3.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=SUMO-interacting motif-containing protein 1;
DE AltName: Full=Platform element for inhibition of autolytic degradation {ECO:0000303|PubMed:23707407};
GN Name=SIMC1; Synonyms=C5orf25, PLEIAD {ECO:0000303|PubMed:23707407};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), ALTERNATIVE SPLICING (ISOFORM 1),
RP VARIANTS ARG-463 AND ARG-772, FUNCTION (ISOFORMS 1 AND 5), SUBCELLULAR
RP LOCATION (ISOFORM 5), INTERACTION WITH CAPN3 AND CTBP1 (ISOFORMS 1 AND 5),
RP AND TISSUE SPECIFICITY (ISOFORM 5).
RC TISSUE=Skeletal muscle;
RX PubMed=23707407; DOI=10.1016/j.jmb.2013.05.009;
RA Ono Y., Iemura S., Novak S.M., Doi N., Kitamura F., Natsume T.,
RA Gregorio C.C., Sorimachi H.;
RT "PLEIAD/SIMC1/C5orf25, a novel autolysis regulator for a skeletal-muscle-
RT specific calpain, CAPN3, scaffolds a CAPN3 substrate, CTBP1.";
RL J. Mol. Biol. 425:2955-2972(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4), AND VARIANTS
RP ARG-463 AND ARG-772.
RC TISSUE=Testis;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [7]
RP IDENTIFICATION OF REPEAT SUMO-INTERACTING MOTIF, AND INTERACTION WITH SUMO1
RP AND SUMO2.
RX PubMed=23086935; DOI=10.1074/jbc.m112.410985;
RA Sun H., Hunter T.;
RT "PolySUMO-binding proteins identified through a string search.";
RL J. Biol. Chem. 287:42071-42083(2012).
CC -!- FUNCTION: [Isoform 1]: Inhibits the protease activity of CAPN3.
CC {ECO:0000269|PubMed:23707407}.
CC -!- FUNCTION: [Isoform 5]: Inhibits the protease activity of CAPN3.
CC {ECO:0000269|PubMed:23707407}.
CC -!- SUBUNIT: [Isoform 1]: Interacts (via SIM domains) with SUMO1 and SUMO2
CC (PubMed:23086935). Interacts with CAPN3 and CTBP1 (PubMed:23707407).
CC {ECO:0000269|PubMed:23086935, ECO:0000269|PubMed:23707407}.
CC -!- SUBUNIT: [Isoform 5]: Interacts with CAPN3 and CTBP1.
CC {ECO:0000269|PubMed:23707407}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm
CC {ECO:0000269|PubMed:23707407}. Cytoplasm, myofibril, sarcomere
CC {ECO:0000269|PubMed:23707407}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=PLEIADa {ECO:0000303|PubMed:23707407};
CC IsoId=Q8NDZ2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NDZ2-2; Sequence=VSP_020673, VSP_020674, VSP_020675;
CC Name=3;
CC IsoId=Q8NDZ2-3; Sequence=VSP_020672, VSP_020676;
CC Name=4;
CC IsoId=Q8NDZ2-4; Sequence=VSP_020671, VSP_020677;
CC Name=5; Synonyms=PLEIADf {ECO:0000303|PubMed:23707407};
CC IsoId=Q8NDZ2-5; Sequence=VSP_060886;
CC -!- TISSUE SPECIFICITY: [Isoform 5]: Skeletal muscle.
CC {ECO:0000269|PubMed:23707407}.
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DR EMBL; KF151170; AGN32860.1; -; mRNA.
DR EMBL; AK126204; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC138956; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC139493; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC073880; AAH73880.1; -; mRNA.
DR EMBL; BC037298; AAH37298.1; -; mRNA.
DR EMBL; BC032390; AAH32390.1; -; mRNA.
DR EMBL; BC066980; AAH66980.1; -; mRNA.
DR CCDS; CCDS4398.2; -. [Q8NDZ2-3]
DR CCDS; CCDS78088.1; -. [Q8NDZ2-5]
DR CCDS; CCDS78089.1; -. [Q8NDZ2-1]
DR CCDS; CCDS78090.1; -. [Q8NDZ2-4]
DR RefSeq; NP_001295124.1; NM_001308195.1. [Q8NDZ2-5]
DR RefSeq; NP_001295125.1; NM_001308196.1. [Q8NDZ2-1]
DR RefSeq; NP_001295129.1; NM_001308200.1. [Q8NDZ2-4]
DR RefSeq; NP_940969.3; NM_198567.5. [Q8NDZ2-3]
DR RefSeq; XP_016864943.1; XM_017009454.1. [Q8NDZ2-1]
DR AlphaFoldDB; Q8NDZ2; -.
DR BioGRID; 131981; 33.
DR IntAct; Q8NDZ2; 17.
DR MINT; Q8NDZ2; -.
DR STRING; 9606.ENSP00000342075; -.
DR GlyGen; Q8NDZ2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NDZ2; -.
DR PhosphoSitePlus; Q8NDZ2; -.
DR BioMuta; SIMC1; -.
DR DMDM; 449081288; -.
DR EPD; Q8NDZ2; -.
DR jPOST; Q8NDZ2; -.
DR MassIVE; Q8NDZ2; -.
DR MaxQB; Q8NDZ2; -.
DR PaxDb; Q8NDZ2; -.
DR PeptideAtlas; Q8NDZ2; -.
DR PRIDE; Q8NDZ2; -.
DR ProteomicsDB; 73096; -. [Q8NDZ2-1]
DR ProteomicsDB; 73097; -. [Q8NDZ2-2]
DR ProteomicsDB; 73098; -. [Q8NDZ2-3]
DR ProteomicsDB; 73099; -. [Q8NDZ2-4]
DR Antibodypedia; 60845; 52 antibodies from 12 providers.
DR DNASU; 375484; -.
DR Ensembl; ENST00000332772.4; ENSP00000331311.4; ENSG00000170085.18. [Q8NDZ2-4]
DR Ensembl; ENST00000341199.10; ENSP00000342075.6; ENSG00000170085.18. [Q8NDZ2-3]
DR Ensembl; ENST00000429602.7; ENSP00000410552.3; ENSG00000170085.18. [Q8NDZ2-5]
DR Ensembl; ENST00000430704.6; ENSP00000409287.2; ENSG00000170085.18. [Q8NDZ2-3]
DR Ensembl; ENST00000443967.5; ENSP00000406571.1; ENSG00000170085.18. [Q8NDZ2-1]
DR GeneID; 375484; -.
DR KEGG; hsa:375484; -.
DR MANE-Select; ENST00000429602.7; ENSP00000410552.3; NM_001308195.2; NP_001295124.1. [Q8NDZ2-5]
DR UCSC; uc003mdr.4; human. [Q8NDZ2-1]
DR CTD; 375484; -.
DR DisGeNET; 375484; -.
DR GeneCards; SIMC1; -.
DR HGNC; HGNC:24779; SIMC1.
DR HPA; ENSG00000170085; Tissue enhanced (ovary).
DR MIM; 618102; gene.
DR neXtProt; NX_Q8NDZ2; -.
DR OpenTargets; ENSG00000170085; -.
DR PharmGKB; PA144596506; -.
DR VEuPathDB; HostDB:ENSG00000170085; -.
DR eggNOG; ENOG502RR6K; Eukaryota.
DR GeneTree; ENSGT00940000153451; -.
DR HOGENOM; CLU_011688_1_0_1; -.
DR InParanoid; Q8NDZ2; -.
DR OMA; GDAIQSP; -.
DR OrthoDB; 117288at2759; -.
DR PhylomeDB; Q8NDZ2; -.
DR TreeFam; TF332523; -.
DR PathwayCommons; Q8NDZ2; -.
DR SignaLink; Q8NDZ2; -.
DR BioGRID-ORCS; 375484; 13 hits in 1076 CRISPR screens.
DR ChiTaRS; SIMC1; human.
DR GenomeRNAi; 375484; -.
DR Pharos; Q8NDZ2; Tbio.
DR PRO; PR:Q8NDZ2; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q8NDZ2; protein.
DR Bgee; ENSG00000170085; Expressed in ileal mucosa and 183 other tissues.
DR ExpressionAtlas; Q8NDZ2; baseline and differential.
DR Genevisible; Q8NDZ2; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0030017; C:sarcomere; IDA:UniProtKB.
DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0032184; F:SUMO polymer binding; IDA:UniProtKB.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Protease inhibitor; Reference proteome.
FT CHAIN 1..872
FT /note="SUMO-interacting motif-containing protein 1"
FT /id="PRO_0000250581"
FT REGION 1..367
FT /note="Interaction with CTBP1"
FT /evidence="ECO:0000269|PubMed:23707407"
FT REGION 163..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 246..387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..872
FT /note="Required for inhibition of CAPN3 protease activity"
FT /evidence="ECO:0000269|PubMed:23707407"
FT REGION 625..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 26..30
FT /note="SUMO interaction motif 1 (SIM); mediates the binding
FT to polysumoylated substrates"
FT /evidence="ECO:0000269|PubMed:23086935"
FT MOTIF 45..49
FT /note="SUMO interaction motif 2 (SIM); mediates the binding
FT to polysumoylated substrates"
FT /evidence="ECO:0000269|PubMed:23086935"
FT COMPBIAS 163..188
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..386
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 626..655
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..539
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020671"
FT VAR_SEQ 1..415
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020672"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020673"
FT VAR_SEQ 1..24
FT /note="MAPASASGEDLRKLPTMAEVNGEQ -> MEDFIVISDDSGSESSGGARPGRS
FT RRPRRALSRTSGALPRRTV (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:23707407"
FT /id="VSP_060886"
FT VAR_SEQ 377..415
FT /note="SPSPQSETPLEKVPWLSVMETPARKEISLSEPAKPGSAH -> TPAWGTEQD
FT SVSKKKKKKKRKEIPPNFLLFNLYRTRVKN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020674"
FT VAR_SEQ 416..872
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020675"
FT VAR_SEQ 416..458
FT /note="VQSRTPQGGLYNRPCLHRLKYFLRPPVHHLFFQTLIPDKDTRE -> MEDFI
FT VISDDSGSESSGGARPGRSRRPRRALSRTSGALPRRTV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020676"
FT VAR_SEQ 540..559
FT /note="ANAKTVEWDWKLLTYVMEEE -> MPRSFEQVIILKKWFLKPYK (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020677"
FT VARIANT 221
FT /note="S -> F (in dbSNP:rs2001605)"
FT /id="VAR_027568"
FT VARIANT 463
FT /note="K -> R (in dbSNP:rs17857141)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:23707407"
FT /id="VAR_027569"
FT VARIANT 636
FT /note="S -> F (in dbSNP:rs2001605)"
FT /id="VAR_059603"
FT VARIANT 772
FT /note="H -> R (in dbSNP:rs17853733)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:23707407"
FT /id="VAR_027570"
FT CONFLICT 336
FT /note="D -> G (in Ref. 2; AK126204)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="S -> R (in Ref. 4; AAH37298 and 1; AGN32860)"
FT /evidence="ECO:0000305"
FT CONFLICT 693
FT /note="F -> L (in Ref. 3; AAH66980)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 872 AA; 96838 MW; D056ACDB8DD23805 CRC64;
MAPASASGED LRKLPTMAEV NGEQDFIDLT RETRPRTKDR SGLYVIDLTR AEGENRPIAT
LDLTLEPVTP SQKEPTSLQT CASLSGKAVM EGHVDRSSQP TARRIINSDP VDLDLVEENT
FVGPPPATSI SGGSVYPTEP NCSSATFTGN LSFLASLQLS SDVSSLSPTS NNSRSSSSSS
NQKAPLPCPQ QDVSRPPQAL PCPLRPLPCP PRASPCPPRA SSCPPRALSC PSQTMQCQLP
ALTHPPQEVP CPRQNIPGPP QDSLGLPQDV PGLPQSILHP QDVAYLQDMP RSPGDVPQSP
SDVSPSPDAP QSPGGMPHLP GDVLHSPGDM PHSSGDVTHS PRDIPHLPGD RPDFTQNDVQ
NRDMPMDISA LSSPSCSPSP QSETPLEKVP WLSVMETPAR KEISLSEPAK PGSAHVQSRT
PQGGLYNRPC LHRLKYFLRP PVHHLFFQTL IPDKDTRENK GQKLEPIPHR RLRMVTNTIE
ENFPLGTVQF LMDFVSPQHY PPREIVAHII QKILLSGSET VDVLKEAYML LMKIQQLHPA
NAKTVEWDWK LLTYVMEEEG QTLPGRVLFL RYVVQTLEDD FQQTLRRQRQ HLQQSIANMV
LSCDKQPHNV RDVIKWLVKA VTEDGLTQPP NGNQTSSGTG ILKASSSHPS SQPNLTKNTN
QLIVCQLQRM LSIAVEVDRT PTCSSNKIAE MMFGFVLDIP ERSQREMFFT TMESHLLRCK
VLEIIFLHSC ETPTRLPLSL AQALYFLNNS TSLLKCQSDK SQWQTWDELV EHLQFLLSSY
QHVLREHLRS SVIDRKDLII KRIKPKPQQG DDITVVDVEK QIEAFRSRLI QMLGEPLVPQ
LQDKVHLLKL LLFYAADLNP DAEPFQKGWS GS
