CARL2_MOUSE
ID CARL2_MOUSE Reviewed; 1296 AA.
AC Q3V3V9;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Capping protein, Arp2/3 and myosin-I linker protein 2 {ECO:0000250|UniProtKB:Q6F5E8};
DE AltName: Full=Capping protein regulator and myosin 1 linker 2 {ECO:0000312|MGI:MGI:2685431};
DE AltName: Full=F-actin-uncapping protein RLTPR {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 16C;
DE AltName: Full=RGD, leucine-rich repeat, tropomodulin and proline-rich-containing protein {ECO:0000250|UniProtKB:Q6F5E8, ECO:0000312|MGI:MGI:2685431};
GN Name=Carmil2 {ECO:0000312|MGI:MGI:2685431};
GN Synonyms=Lrrc16c, Rltpr {ECO:0000312|MGI:MGI:2685431};
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] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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 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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1008; SER-1134; THR-1145;
RP SER-1203 AND SER-1281, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Lung, and Spleen;
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 [4]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1191, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [5]
RP FUNCTION.
RX PubMed=27647348; DOI=10.1084/jem.20160579;
RA Roncagalli R., Cucchetti M., Jarmuzynski N., Gregoire C., Bergot E.,
RA Audebert S., Baudelet E., Menoita M.G., Joachim A., Durand S., Suchanek M.,
RA Fiore F., Zhang L., Liang Y., Camoin L., Malissen M., Malissen B.;
RT "The scaffolding function of the RLTPR protein explains its essential role
RT for CD28 co-stimulation in mouse and human T cells.";
RL J. Exp. Med. 213:2437-2457(2016).
CC -!- FUNCTION: Cell membrane-cytoskeleton-associated protein that plays a
CC role in the regulation of actin polymerization at the barbed end of
CC actin filaments. Prevents F-actin heterodimeric capping protein (CP)
CC activity at the leading edges of migrating cells, and hence generates
CC uncapped barbed ends and enhances actin polymerization. Plays a role in
CC cell protrusion formations; involved in cell polarity, lamellipodial
CC assembly, membrane ruffling and macropinosome formations. Involved as
CC well in cell migration and invadopodia formation during wound healing
CC (By similarity). Required for CD28-mediated stimulation of NF-kappa-B
CC signaling, involved in naive T cells activation, maturation into T
CC memory cells, and differentiation into T helper cells
CC (PubMed:27647348). Required for CD28-mediated differentiation of T
CC regulatory cells (By similarity). {ECO:0000250|UniProtKB:Q6F5E8,
CC ECO:0000269|PubMed:27647348}.
CC -!- SUBUNIT: Forms homodimers. Interacts (via C-terminus) with
CC heterodimeric capping protein (CP); the interaction inhibits CP
CC activity and hence promotes actin polymerization at the barbed end of
CC actin filaments. {ECO:0000250|UniProtKB:Q6F5E8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6F5E8}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q6F5E8}. Cell membrane
CC {ECO:0000250|UniProtKB:Q6F5E8}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q6F5E8}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q6F5E8}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q6F5E8}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:Q6F5E8}. Note=Colocalizes to dynamic vimentin
CC filaments both in the central cytoplasm and at leading edges of
CC migrating cells. Colocalizes with F-actin, Arp2/3 complex and cortactin
CC to leading edge lamellipodia, ruffles and macropinosomes of migrating
CC cells. {ECO:0000250|UniProtKB:Q6F5E8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3V3V9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3V3V9-2; Sequence=VSP_032634, VSP_032635;
CC -!- DOMAIN: The N-terminal leucine-rich repeat (LRR) domain is necessary
CC for localization to vimentin filaments. The C-terminus is necessary for
CC localization to the cell membrane. {ECO:0000250|UniProtKB:Q6F5E8}.
CC -!- SIMILARITY: Belongs to the CARMIL family. {ECO:0000305}.
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DR EMBL; AK031012; BAE20471.1; -; mRNA.
DR EMBL; AC152826; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001028492.1; NM_001033320.2.
DR AlphaFoldDB; Q3V3V9; -.
DR SMR; Q3V3V9; -.
DR BioGRID; 231561; 3.
DR IntAct; Q3V3V9; 20.
DR iPTMnet; Q3V3V9; -.
DR PhosphoSitePlus; Q3V3V9; -.
DR EPD; Q3V3V9; -.
DR jPOST; Q3V3V9; -.
DR MaxQB; Q3V3V9; -.
DR PaxDb; Q3V3V9; -.
DR PeptideAtlas; Q3V3V9; -.
DR PRIDE; Q3V3V9; -.
DR ProteomicsDB; 265546; -. [Q3V3V9-1]
DR ProteomicsDB; 265547; -. [Q3V3V9-2]
DR UCSC; uc009ndo.1; mouse. [Q3V3V9-2]
DR MGI; MGI:2685431; Carmil2.
DR HOGENOM; CLU_375944_0_0_1; -.
DR InParanoid; Q3V3V9; -.
DR OrthoDB; 208951at2759; -.
DR PhylomeDB; Q3V3V9; -.
DR TreeFam; TF316381; -.
DR BioGRID-ORCS; 234695; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Rltpr; mouse.
DR PRO; PR:Q3V3V9; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q3V3V9; protein.
DR Genevisible; Q3V3V9; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0008290; C:F-actin capping protein complex; IDA:MGI.
DR GO; GO:0001772; C:immunological synapse; IDA:MGI.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0044354; C:macropinosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:UniProtKB.
DR GO; GO:0051639; P:actin filament network formation; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0045184; P:establishment of protein localization; IMP:MGI.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; ISS:UniProtKB.
DR GO; GO:0061339; P:establishment or maintenance of monopolar cell polarity; ISS:UniProtKB.
DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
DR GO; GO:0030011; P:maintenance of cell polarity; IEA:InterPro.
DR GO; GO:2000813; P:negative regulation of barbed-end actin filament capping; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0090091; P:positive regulation of extracellular matrix disassembly; ISS:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IMP:MGI.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:MGI.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:1902745; P:positive regulation of lamellipodium organization; ISS:UniProtKB.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IMP:MGI.
DR GO; GO:1900029; P:positive regulation of ruffle assembly; ISS:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:MGI.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IBA:GO_Central.
DR GO; GO:0034315; P:regulation of Arp2/3 complex-mediated actin nucleation; IBA:GO_Central.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0048538; P:thymus development; IMP:MGI.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR029763; CARMIL2.
DR InterPro; IPR031943; CARMIL_C.
DR InterPro; IPR041245; CARMIL_PH.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR PANTHER; PTHR24112:SF32; PTHR24112:SF32; 1.
DR Pfam; PF17888; Carm_PH; 1.
DR Pfam; PF16000; CARMIL_C; 2.
DR Pfam; PF13516; LRR_6; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Leucine-rich repeat; Membrane; Methylation; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1296
FT /note="Capping protein, Arp2/3 and myosin-I linker protein
FT 2"
FT /id="PRO_0000326239"
FT REPEAT 63..87
FT /note="LRR 1"
FT REPEAT 88..110
FT /note="LRR 2"
FT REPEAT 248..271
FT /note="LRR 3"
FT REPEAT 273..296
FT /note="LRR 4"
FT REPEAT 305..328
FT /note="LRR 5"
FT REPEAT 363..386
FT /note="LRR 6"
FT REPEAT 395..415
FT /note="LRR 7"
FT REPEAT 426..448
FT /note="LRR 8"
FT REPEAT 453..477
FT /note="LRR 9"
FT REPEAT 480..506
FT /note="LRR 10"
FT REPEAT 515..538
FT /note="LRR 11"
FT REPEAT 542..565
FT /note="LRR 12"
FT REPEAT 570..594
FT /note="LRR 13"
FT REPEAT 598..621
FT /note="LRR 14"
FT REPEAT 836..859
FT /note="LRR 15"
FT REGION 507..601
FT /note="Tropomodulin-like"
FT REGION 975..1002
FT /note="Necessary for localization at the cell membrane"
FT /evidence="ECO:0000250|UniProtKB:Q6F5E8"
FT REGION 988..1296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1075..1094
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1118..1137
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1138..1159
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1199..1213
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1228..1248
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1268..1282
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1008
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1145
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1191
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..603
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_032634"
FT VAR_SEQ 873..928
FT /note="VLLRKRNGTPSWQLRGKMQSRRLGRLHAVAEKHWAAGPRDTPASAVYQRVDV
FT CVGW -> DESSSWKWLEPSNCFHLVSSLHGAAEEAERDPELAAPGEDAEPQAGPSARG
FT SPSPAAPGPPAGPLPRMDLPPAGQPLRHPTRARPRPRRQHHHRPPPGGPQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_032635"
SQ SEQUENCE 1296 AA; 141372 MW; 9FB10DA18A26BCAA CRC64;
MAQTPDDISC ELRGEITRFL WPKEAELLLK TWLPQEGAEQ SHILALLRWR AYLLHTCLPL
RVDCTFSYLE VQAMALQETP PRVTFELESL PELVLEFPCV AALEQLAQHV AAAIKKVFPR
STLGKLFRKP TPSSLLARLE RSHPLESTIP SSPCGGFLET YEALCDYNGF PFREEIQWDV
DTIYHRQGCR HFCLGDFSHF GSRDLALSVA ALSYNLWFRR LSCEDMKLSL EVSEQILHMT
SQSSYLEELV LEACGLRGDF VRRLAQALAG HFNSGLRELS LSGNLLDDRG MRALGRALAT
NATFDSTLTH LDLSGNPGAL GPSQDSGGLY TFLSRPNVLA YLNLAGTDAT LGTLFTALAG
GCCSSLTHLE ASRNIFSRMK SQAAPAALQR FLGGTRMLRH LGLAGCKLPP EALRALLEGL
ALNTQIHDLH LDLSACELRS VGAQVIQDLV CDAGALSSLD LSDNGFGSDM VTLVLAIGRS
RSLKHVALGR NFNVRCKETL DDVLHRIAQL MQDDDCPLQS LSVAESRLKQ GASILIRALG
TNPKLTALDI SGNAIGDAGA KMLAKALRVN TRLRSVIWDR NNTSALGLLD VAQALEQNHS
LKSMPLPLND VTQAHRSRPE LTTRAVHQIQ ACLWRNNQVD STSDLKPCLQ PLGLISDHSE
QEVNELCQSV QEHMELLGCG AGPQGEVAVH QAEDAIQNAN FSLSILPILY EAGRSPSHHW
QLQQKLESLL GQVGEICRQD IQDFTQTTLD TTRSLCPQML QTPGWRKQLE GVLVGSGGLP
ELLPEHLLQD AFSRLRDMRL SITGTLAESI VAQALAGLHA ARDRLVERLT QQAPVTMAPA
VPPLGGNELS PLETGGLEEL FFPTEKEEER EKVLLRKRNG TPSWQLRGKM QSRRLGRLHA
VAEKHWAAGP RDTPASAVYQ RVDVCVGWVP PALLQEGNGL TARVDEGVEE FFSKRLIQQD
HFWAPEEDPA TEGGATPVPR TLRKKLGTLF AFKKPRSTRG PRPDLETSPG AAARARKSTL
GDLLRPPARP GRGEEPGGAE GGTSSPDPAR RNRPRYTRES KAYSMILLPA EEEAAVGTRP
DKRRPLERGD TELAPSFEQR VQVMLQRIGV SRASGGAESK RKQSKDGEIK KAGSDGDIMD
SSTETPPISI KSRTHSVSAD PSCRPGPGGQ GPESATWKTL GQQLNAELRG RGWGQQDGPG
PPSPCPSPSP RRTSPAPDIL SLPEDPCLGP RNEERPLRLQ RSPVLKRRPK LEAPPSPSLG
SGLGSKPLPP YPTEPSSPER SPPSPATDQR GGGPNP
