STAC3_MOUSE
ID STAC3_MOUSE Reviewed; 360 AA.
AC Q8BZ71;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=SH3 and cysteine-rich domain-containing protein 3;
GN Name=Stac3;
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 MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Jaw, and Limb;
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 [3]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=23626854; DOI=10.1371/journal.pone.0062760;
RA Reinholt B.M., Ge X., Cong X., Gerrard D.E., Jiang H.;
RT "Stac3 is a novel regulator of skeletal muscle development in mice.";
RL PLoS ONE 8:E62760-E62760(2013).
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP AND TISSUE SPECIFICITY.
RX PubMed=23818578; DOI=10.1073/pnas.1310571110;
RA Nelson B.R., Wu F., Liu Y., Anderson D.M., McAnally J., Lin W.,
RA Cannon S.C., Bassel-Duby R., Olson E.N.;
RT "Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced
RT Ca2+ release and contractility.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:11881-11886(2013).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25548159; DOI=10.1073/pnas.1423113112;
RA Polster A., Perni S., Bichraoui H., Beam K.G.;
RT "Stac adaptor proteins regulate trafficking and function of muscle and
RT neuronal L-type Ca2+ channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:602-606(2015).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF TRP-280.
RX PubMed=27621462; DOI=10.1073/pnas.1612441113;
RA Polster A., Nelson B.R., Olson E.N., Beam K.G.;
RT "Stac3 has a direct role in skeletal muscle-type excitation-contraction
RT coupling that is disrupted by a myopathy-causing mutation.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:10986-10991(2016).
RN [7]
RP SUBCELLULAR LOCATION, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH CACNA1S AND
RP CACNA1C, AND MUTAGENESIS OF VAL-104 AND TYR-133.
RX PubMed=28112192; DOI=10.1038/srep41003;
RA Campiglio M., Flucher B.E.;
RT "STAC3 stably interacts through its C1 domain with CaV1.1 in skeletal
RT muscle triads.";
RL Sci. Rep. 7:41003-41003(2017).
RN [8]
RP FUNCTION, INTERACTION WITH CACNA1S, AND SUBCELLULAR LOCATION.
RX PubMed=29467163; DOI=10.1085/jgp.201711917;
RA Polster A., Nelson B.R., Papadopoulos S., Olson E.N., Beam K.G.;
RT "STAC proteins associate with the critical domain for excitation-
RT contraction coupling in the II-III loop of CaV1.1.";
RL J. Gen. Physiol. 150:613-624(2018).
RN [9]
RP FUNCTION, INTERACTION WITH CACNA1C, AND SUBCELLULAR LOCATION.
RX PubMed=29363593; DOI=10.1073/pnas.1715997115;
RA Campiglio M., Coste de Bagneaux P., Ortner N.J., Tuluc P., Van Petegem F.,
RA Flucher B.E.;
RT "STAC proteins associate to the IQ domain of CaV1.2 and inhibit calcium-
RT dependent inactivation.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:1376-1381(2018).
CC -!- FUNCTION: Required for normal excitation-contraction coupling in
CC skeletal muscle and for normal muscle contraction in response to
CC membrane depolarization (PubMed:23818578, PubMed:27621462,
CC PubMed:29467163). Required for normal Ca(2+) release from the
CC sarcplasmic reticulum, which ultimately leads to muscle contraction
CC (PubMed:23818578). Probably functions via its effects on muscle calcium
CC channels. Increases CACNA1S channel activity, in addition to its role
CC in enhancing the expression of CACNA1S at the cell membrane
CC (PubMed:27621462). Has a redundant role in promoting the expression of
CC the calcium channel CACNA1S at the cell membrane (PubMed:25548159,
CC PubMed:27621462, PubMed:29467163). Slows down the inactivation rate of
CC the calcium channel CACNA1C (PubMed:25548159, PubMed:29363593).
CC {ECO:0000269|PubMed:23818578, ECO:0000269|PubMed:25548159,
CC ECO:0000269|PubMed:27621462, ECO:0000269|PubMed:29363593,
CC ECO:0000269|PubMed:29467163}.
CC -!- SUBUNIT: Interacts (via SH3 domains) with the calcium channels CACNA1S
CC and CACNA1C (PubMed:28112192, PubMed:29467163, PubMed:29363593).
CC Component of a calcium channel complex with CACNA1S and CACNB1
CC (PubMed:28112192). Component of a calcium channel complex with CACNA1C
CC and CACNB1 (PubMed:28112192). {ECO:0000269|PubMed:28112192,
CC ECO:0000269|PubMed:29363593, ECO:0000269|PubMed:29467163}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28112192,
CC ECO:0000269|PubMed:29467163}. Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:23818578, ECO:0000269|PubMed:28112192,
CC ECO:0000269|PubMed:29363593, ECO:0000269|PubMed:29467163,
CC ECO:0000305|PubMed:25548159}; Peripheral membrane protein
CC {ECO:0000269|PubMed:29363593, ECO:0000269|PubMed:29467163,
CC ECO:0000305|PubMed:25548159}; Cytoplasmic side
CC {ECO:0000269|PubMed:29363593, ECO:0000269|PubMed:29467163,
CC ECO:0000305|PubMed:25548159}. Cell membrane, sarcolemma, T-tubule
CC {ECO:0000269|PubMed:23818578, ECO:0000269|PubMed:28112192,
CC ECO:0000269|PubMed:29363593}. Note=Co-localizes with CACNA1S and
CC CACNA1C on T-tubules. {ECO:0000269|PubMed:23818578,
CC ECO:0000269|PubMed:28112192, ECO:0000269|PubMed:29363593}.
CC -!- TISSUE SPECIFICITY: Dected in skeletal muscle, including soleus,
CC extensor digitorum longus, tibialis anterior, quadriceps and
CC gastrocnemius. Detected in tongue. {ECO:0000269|PubMed:23626854,
CC ECO:0000269|PubMed:23818578}.
CC -!- DEVELOPMENTAL STAGE: Detected in somites and limb buds at 9.5 and 13
CC dpc, in embryonic limb muscle and tongue (PubMed:23626854,
CC PubMed:23818578). Detected in tongue and diaphragm at 14.5 dpc
CC (PubMed:23818578). {ECO:0000269|PubMed:23626854,
CC ECO:0000269|PubMed:23818578}.
CC -!- DISRUPTION PHENOTYPE: Complete perinatal lethality, due to paralysis
CC and inability to breathe (PubMed:23626854, PubMed:23818578). Embryos
CC have a curved body with abnormal curvature of the vertebral spine and
CC drooping forelimbs (PubMed:23626854, PubMed:23818578). They display
CC multiple skeletal abnormalities involving ribs, sternum and costal
CC cartilage, and strongly reduced formation of bone ridges at major
CC muscle attachment sites (PubMed:23818578). They weigh about 15% less
CC than wild-type at 18.5 dpc (PubMed:23626854). They do not move or
CC respond to touch, but have a beating heart when dissected out of the
CC uterus (PubMed:23626854). Their myofibers have altered morphology with
CC centrally located nuclei, unlike wild-type, where the nuclei are
CC located in the periphery of the myofibers (PubMed:23626854,
CC PubMed:23818578). Sarcomeres have streaming Z-lines (PubMed:23626854).
CC The diaphragm does not contract in response to membrane depolarization
CC or electric stimulation (PubMed:23818578). Myotubes from mutant mice
CC lack voltage-induced calcium release from the sarcoplasmic reticulum
CC (PubMed:23818578). {ECO:0000269|PubMed:23626854,
CC ECO:0000269|PubMed:23818578}.
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DR EMBL; AK036516; BAC29460.1; -; mRNA.
DR EMBL; BC067208; AAH67208.1; -; mRNA.
DR CCDS; CCDS24242.1; -.
DR RefSeq; NP_808375.1; NM_177707.3.
DR RefSeq; XP_006513703.1; XM_006513640.2.
DR RefSeq; XP_006513705.1; XM_006513642.2.
DR AlphaFoldDB; Q8BZ71; -.
DR SMR; Q8BZ71; -.
DR STRING; 10090.ENSMUSP00000048148; -.
DR iPTMnet; Q8BZ71; -.
DR PhosphoSitePlus; Q8BZ71; -.
DR MaxQB; Q8BZ71; -.
DR PaxDb; Q8BZ71; -.
DR PRIDE; Q8BZ71; -.
DR ProteomicsDB; 258634; -.
DR Antibodypedia; 28547; 91 antibodies from 24 providers.
DR DNASU; 237611; -.
DR Ensembl; ENSMUST00000035839; ENSMUSP00000048148; ENSMUSG00000040287.
DR Ensembl; ENSMUST00000160019; ENSMUSP00000125124; ENSMUSG00000040287.
DR GeneID; 237611; -.
DR KEGG; mmu:237611; -.
DR UCSC; uc007hjr.1; mouse.
DR CTD; 246329; -.
DR MGI; MGI:3606571; Stac3.
DR VEuPathDB; HostDB:ENSMUSG00000040287; -.
DR eggNOG; ENOG502QT6I; Eukaryota.
DR GeneTree; ENSGT00950000183092; -.
DR HOGENOM; CLU_048120_1_1_1; -.
DR InParanoid; Q8BZ71; -.
DR OMA; DQQYACV; -.
DR OrthoDB; 902304at2759; -.
DR PhylomeDB; Q8BZ71; -.
DR TreeFam; TF332878; -.
DR BioGRID-ORCS; 237611; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q8BZ71; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8BZ71; protein.
DR Bgee; ENSMUSG00000040287; Expressed in hindlimb stylopod muscle and 75 other tissues.
DR ExpressionAtlas; Q8BZ71; baseline and differential.
DR Genevisible; Q8BZ71; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0030315; C:T-tubule; IEA:UniProtKB-SubCell.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007274; P:neuromuscular synaptic transmission; ISS:UniProtKB.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IMP:UniProtKB.
DR GO; GO:0003009; P:skeletal muscle contraction; ISS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:MGI.
DR CDD; cd00029; C1; 1.
DR CDD; cd11986; SH3_Stac3_1; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR039688; STAC1/2/3.
DR InterPro; IPR035736; Stac3_SH3_1.
DR PANTHER; PTHR15135; PTHR15135; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50002; SH3; 2.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Membrane; Metal-binding; Reference proteome;
KW Repeat; SH3 domain; Zinc; Zinc-finger.
FT CHAIN 1..360
FT /note="SH3 and cysteine-rich domain-containing protein 3"
FT /id="PRO_0000232583"
FT DOMAIN 243..302
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 303..360
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT ZN_FING 88..139
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 187..241
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 63..77
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 187..237
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 104
FT /note="V->L: Loss of co-localization with CACNA1S and
FT strongly decreased co-localization with CACNA1C; when
FT associated with E-133."
FT /evidence="ECO:0000269|PubMed:28112192"
FT MUTAGEN 133
FT /note="Y->E: Loss of co-localization with CACNA1S and
FT strongly decreased co-localization with CACNA1C; when
FT associated with L-104."
FT /evidence="ECO:0000269|PubMed:28112192"
FT MUTAGEN 280
FT /note="W->S: Loss of normal excitation-contraction
FT coupling. Loss of function in enhancing calcium channel
FT activity."
FT /evidence="ECO:0000269|PubMed:27621462"
SQ SEQUENCE 360 AA; 41000 MW; ADA948B421F5B0F8 CRC64;
MTEKEVVESP QPPFPGETPQ SGLQRLKQLF KKGSPETAEM EPPPEPQANG EAVGAGGGPI
YYIYEEEEEE EEEEEPPPEP PKLVNDKPHK FKDHFFKKPK FCDVCARMIV LNNKFGLRCK
NCKTNIHEHC QSYVEMQRCF GKIPPGFRRA YSSPLYSDQQ YAVSAANRND PVFETLRVGV
IMANKERKKG QADKKNPLAA MMEEEPESAR PEEGKSQDGN NAEKDKKAEK KTPDDKNKQP
GFQQSHYFVA LYRFKALEKD DLDFPPGEKI TVIDDSNEEW WRGKIGEKVG FFPPNFIIRV
RAGERVHRVT RSFVGNREIG QITLKKDQIV VQKGDEAGGY VKVYTGRKVG LFPTDFLEEI
