CARL2_HUMAN
ID CARL2_HUMAN Reviewed; 1435 AA.
AC Q6F5E8; B8X2Z3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Capping protein, Arp2/3 and myosin-I linker protein 2 {ECO:0000303|PubMed:19846667};
DE AltName: Full=Capping protein regulator and myosin 1 linker 2 {ECO:0000312|HGNC:HGNC:27089};
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:0000303|PubMed:15588584};
GN Name=CARMIL2 {ECO:0000312|HGNC:HGNC:27089};
GN Synonyms=LRRC16C, RLTPR {ECO:0000303|PubMed:15588584};
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 1), ALTERNATIVE SPLICING, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Keratinocyte;
RX PubMed=15588584; DOI=10.1016/j.gene.2004.09.004;
RA Matsuzaka Y., Okamoto K., Mabuchi T., Iizuka M., Ozawa A., Oka A.,
RA Tamiya G., Kulski J.K., Inoko H.;
RT "Identification, expression analysis and polymorphism of a novel RLTPR gene
RT encoding a RGD motif, tropomodulin domain and proline/leucine-rich
RT regions.";
RL Gene 343:291-304(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND SUBCELLULAR LOCATION
RP (ISOFORM 2).
RX PubMed=19846667; DOI=10.1091/mbc.e08-10-1071;
RA Liang Y., Niederstrasser H., Edwards M., Jackson C.E., Cooper J.A.;
RT "Distinct roles for CARMIL isoforms in cell migration.";
RL Mol. Biol. Cell 20:5290-5305(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-993 AND SER-1246, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-991, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-991, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP FUNCTION, INTERACTION WITH F-ACTIN-CAPPING PROTEIN (ISOFORM 2), SUBCELLULAR
RP LOCATION (ISOFORM 2), DOMAIN (ISOFORM 2), AND MUTAGENESIS OF ARG-1021 AND
RP ARG-1023.
RX PubMed=26466680; DOI=10.1091/mbc.e15-08-0552;
RA Lanier M.H., Kim T., Cooper J.A.;
RT "CARMIL2 is a novel molecular connection between vimentin and actin
RT essential for cell migration and invadopodia formation.";
RL Mol. Biol. Cell 26:4577-4588(2015).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION (ISOFORM 2), DOMAIN (ISOFORM 2), AND
RP MUTAGENESIS OF 1096-LYS--LYS-1106.
RX PubMed=26578515; DOI=10.1074/jbc.m115.676882;
RA Lanier M.H., McConnell P., Cooper J.A.;
RT "Cell migration and invadopodia formation require a membrane-binding domain
RT of CARMIL2.";
RL J. Biol. Chem. 291:1076-1091(2016).
RN [12]
RP FUNCTION, SUBUNIT, TISSUE SPECIFICITY, INVOLVEMENT IN IMD58, VARIANTS IMD58
RP ARG-372; GLN-525 AND 853-GLN--PRO-1435 DEL, AND CHARACTERIZATION OF
RP VARIANTS IMD58 ARG-372; GLN-525 AND 853-GLN--PRO-1435 DEL.
RX PubMed=27647349; DOI=10.1084/jem.20160576;
RA Wang Y., Ma C.S., Ling Y., Bousfiha A., Camcioglu Y., Jacquot S., Payne K.,
RA Crestani E., Roncagalli R., Belkadi A., Kerner G., Lorenzo L., Deswarte C.,
RA Chrabieh M., Patin E., Vincent Q.B., Mueller-Fleckenstein I.,
RA Fleckenstein B., Ailal F., Quintana-Murci L., Fraitag S., Alyanakian M.A.,
RA Leruez-Ville M., Picard C., Puel A., Bustamante J., Boisson-Dupuis S.,
RA Malissen M., Malissen B., Abel L., Hovnanian A., Notarangelo L.D.,
RA Jouanguy E., Tangye S.G., Beziat V., Casanova J.L.;
RT "Dual T cell- and B cell-intrinsic deficiency in humans with biallelic
RT RLTPR mutations.";
RL J. Exp. Med. 213:2413-2435(2016).
RN [13]
RP FUNCTION, AND SUBUNIT.
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).
RN [14]
RP INVOLVEMENT IN IMD58, AND VARIANT IMD58 HIS-639.
RX PubMed=27896283; DOI=10.1002/mgg3.237;
RA Sorte H.S., Osnes L.T., Fevang B., Aukrust P., Erichsen H.C., Backe P.H.,
RA Abrahamsen T.G., Kittang O.B., Oeverland T., Jhangiani S.N., Muzny D.M.,
RA Vigeland M.D., Samarakoon P., Gambin T., Akdemir Z.H., Gibbs R.A.,
RA Roedningen O.K., Lyle R., Lupski J.R., Stray-Pedersen A.;
RT "A potential founder variant in CARMIL2/RLTPR in three Norwegian families
RT with warts, molluscum contagiosum, and T-cell dysfunction.";
RL Mol. Genet. Genomic Med. 4:604-616(2016).
RN [15]
RP FUNCTION, AND INVOLVEMENT IN IMD58.
RX PubMed=28112205; DOI=10.1038/ncomms14209;
RA Schober T., Magg T., Laschinger M., Rohlfs M., Linhares N.D., Puchalka J.,
RA Weisser T., Fehlner K., Mautner J., Walz C., Hussein K., Jaeger G.,
RA Kammer B., Schmid I., Bahia M., Pena S.D., Behrends U., Belohradsky B.H.,
RA Klein C., Hauck F.;
RT "A human immunodeficiency syndrome caused by mutations in CARMIL2.";
RL Nat. Commun. 8:14209-14209(2017).
RN [16]
RP VARIANT IMD58 THR-50, AND CHARACTERIZATION OF VARIANT IMD58 THR-50.
RX PubMed=29479355; DOI=10.3389/fimmu.2018.00203;
RA Alazami A.M., Al-Helale M., Alhissi S., Al-Saud B., Alajlan H., Monies D.,
RA Shah Z., Abouelhoda M., Arnaout R., Al-Dhekri H., Al-Numair N.S.,
RA Ghebeh H., Sheikh F., Al-Mousa H.;
RT "Novel CARMIL2 mutations in patients with variable clinical dermatitis,
RT infections, and combined immunodeficiency.";
RL Front. Immunol. 9:203-203(2018).
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
CC (PubMed:26466680). Plays a role in cell protrusion formations; involved
CC in cell polarity, lamellipodial assembly, membrane ruffling and
CC macropinosome formations (PubMed:19846667, PubMed:26578515,
CC PubMed:26466680). Involved as well in cell migration and invadopodia
CC formation during wound healing (PubMed:19846667, PubMed:26578515,
CC PubMed:26466680). 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 and T regulatory cells
CC (PubMed:27647349, PubMed:27647348, PubMed:28112205).
CC {ECO:0000269|PubMed:19846667, ECO:0000269|PubMed:26466680,
CC ECO:0000269|PubMed:26578515, ECO:0000269|PubMed:27647348,
CC ECO:0000269|PubMed:27647349, ECO:0000269|PubMed:28112205}.
CC -!- SUBUNIT: Forms homodimers (PubMed:27647349, PubMed:27647348). Interacts
CC (via C-terminus) with heterodimeric capping protein (CP); the
CC interaction inhibits CP activity and hence promotes actin
CC polymerization at the barbed end of actin filaments (PubMed:26466680).
CC {ECO:0000269|PubMed:26466680, ECO:0000269|PubMed:27647348,
CC ECO:0000269|PubMed:27647349}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:19846667, ECO:0000269|PubMed:26466680}. Cytoplasm,
CC cytoskeleton {ECO:0000269|PubMed:19846667, ECO:0000269|PubMed:26466680,
CC ECO:0000269|PubMed:26578515}. Cell membrane
CC {ECO:0000269|PubMed:26466680, ECO:0000269|PubMed:26578515}; Peripheral
CC membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cell
CC projection, lamellipodium {ECO:0000269|PubMed:26578515}. Cell
CC projection, ruffle {ECO:0000269|PubMed:26466680,
CC ECO:0000269|PubMed:26578515}. Note=Colocalizes to dynamic vimentin
CC filaments both in the central cytoplasm and at leading edges of
CC migrating cells (PubMed:26578515, PubMed:26466680, PubMed:19846667).
CC Colocalizes with F-actin, Arp2/3 complex and cortactin to leading edge
CC lamellipodia, ruffles and macropinosomes of migrating cells
CC (PubMed:26578515). {ECO:0000269|PubMed:19846667,
CC ECO:0000269|PubMed:26466680, ECO:0000269|PubMed:26578515}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=CARMIL2a {ECO:0000303|PubMed:19846667};
CC IsoId=Q6F5E8-1; Sequence=Displayed;
CC Name=2; Synonyms=CARMIL2b {ECO:0000303|PubMed:19846667};
CC IsoId=Q6F5E8-2; Sequence=VSP_047857, VSP_047858;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested, including thymus,
CC spleen, colon, leukocytes, peripheral blood, skin, skin keratinocytes
CC and skin fibroblasts. Strong expression is detected in naive and memory
CC CD4+ and CD8+ T cells, naive and memory B cells, regulatory T cells and
CC NK cells, whereas it is poorly expressed in monocytes
CC (PubMed:27647349). {ECO:0000269|PubMed:15588584,
CC ECO:0000269|PubMed:27647349}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal skin.
CC {ECO:0000269|PubMed:15588584}.
CC -!- DOMAIN: The N-terminal leucine-rich repeat (LRR) domain is necessary
CC for localization to vimentin filaments (PubMed:26466680). The C-
CC terminus is necessary for localization to the cell membrane
CC (PubMed:26578515). {ECO:0000269|PubMed:26466680,
CC ECO:0000269|PubMed:26578515}.
CC -!- DISEASE: Immunodeficiency 58 (IMD58) [MIM:618131]: An autosomal
CC recessive primary immunodeficiency characterized by a variety of
CC infectious diseases, including mycobacterial diseases, mucocutaneous
CC candidiasis, silent but detectable EBV viremia, and staphylococcal
CC diseases. Patients suffer from dermatitis, esophagitis, recurrent skin
CC abscesses and chest infections. Immunologic analysis shows defective T-
CC cell function and deficient CD3/CD28 stimulation responses in both CD4+
CC and CD8+ T cells. B-cell function may also be impaired.
CC {ECO:0000269|PubMed:27647349, ECO:0000269|PubMed:27896283,
CC ECO:0000269|PubMed:28112205, ECO:0000269|PubMed:29479355}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the CARMIL family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD26751.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB113647; BAD26751.1; ALT_INIT; mRNA.
DR EMBL; FJ026014; ACI49710.1; -; mRNA.
DR EMBL; AC009095; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS45513.1; -. [Q6F5E8-1]
DR CCDS; CCDS81998.1; -. [Q6F5E8-2]
DR RefSeq; NP_001013860.1; NM_001013838.1. [Q6F5E8-1]
DR RefSeq; NP_001303955.1; NM_001317026.1. [Q6F5E8-2]
DR AlphaFoldDB; Q6F5E8; -.
DR SMR; Q6F5E8; -.
DR BioGRID; 126970; 17.
DR IntAct; Q6F5E8; 5.
DR MINT; Q6F5E8; -.
DR STRING; 9606.ENSP00000334958; -.
DR GlyGen; Q6F5E8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6F5E8; -.
DR MetOSite; Q6F5E8; -.
DR PhosphoSitePlus; Q6F5E8; -.
DR BioMuta; CARMIL2; -.
DR DMDM; 172045901; -.
DR EPD; Q6F5E8; -.
DR jPOST; Q6F5E8; -.
DR MassIVE; Q6F5E8; -.
DR MaxQB; Q6F5E8; -.
DR PaxDb; Q6F5E8; -.
DR PeptideAtlas; Q6F5E8; -.
DR PRIDE; Q6F5E8; -.
DR ProteomicsDB; 66290; -. [Q6F5E8-1]
DR ProteomicsDB; 7286; -.
DR Antibodypedia; 49241; 57 antibodies from 12 providers.
DR DNASU; 146206; -.
DR Ensembl; ENST00000334583.11; ENSP00000334958.5; ENSG00000159753.14. [Q6F5E8-1]
DR Ensembl; ENST00000545661.5; ENSP00000441481.1; ENSG00000159753.14. [Q6F5E8-2]
DR GeneID; 146206; -.
DR KEGG; hsa:146206; -.
DR MANE-Select; ENST00000334583.11; ENSP00000334958.5; NM_001013838.3; NP_001013860.1.
DR UCSC; uc002etn.4; human. [Q6F5E8-1]
DR CTD; 146206; -.
DR DisGeNET; 146206; -.
DR GeneCards; CARMIL2; -.
DR HGNC; HGNC:27089; CARMIL2.
DR HPA; ENSG00000159753; Tissue enhanced (brain, intestine, lymphoid tissue).
DR MalaCards; CARMIL2; -.
DR MIM; 610859; gene.
DR MIM; 618131; phenotype.
DR neXtProt; NX_Q6F5E8; -.
DR OpenTargets; ENSG00000159753; -.
DR Orphanet; 542301; Combined immunodeficiency due to CARMIL2 deficiency.
DR PharmGKB; PA162401371; -.
DR VEuPathDB; HostDB:ENSG00000159753; -.
DR eggNOG; KOG4242; Eukaryota.
DR GeneTree; ENSGT00940000161003; -.
DR HOGENOM; CLU_003119_3_1_1; -.
DR InParanoid; Q6F5E8; -.
DR OMA; YIHNWRQ; -.
DR OrthoDB; 208951at2759; -.
DR PhylomeDB; Q6F5E8; -.
DR TreeFam; TF316381; -.
DR PathwayCommons; Q6F5E8; -.
DR SignaLink; Q6F5E8; -.
DR BioGRID-ORCS; 146206; 9 hits in 1012 CRISPR screens.
DR ChiTaRS; CARMIL2; human.
DR GenomeRNAi; 146206; -.
DR Pharos; Q6F5E8; Tbio.
DR PRO; PR:Q6F5E8; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q6F5E8; protein.
DR Bgee; ENSG00000159753; Expressed in right frontal lobe and 135 other tissues.
DR ExpressionAtlas; Q6F5E8; baseline and differential.
DR Genevisible; Q6F5E8; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0031252; C:cell leading edge; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; NAS:UniProtKB.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0044354; C:macropinosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0051639; P:actin filament network formation; IDA:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IDA:UniProtKB.
DR GO; GO:0061339; P:establishment or maintenance of monopolar cell polarity; IDA:UniProtKB.
DR GO; GO:0030011; P:maintenance of cell polarity; IEA:InterPro.
DR GO; GO:2000813; P:negative regulation of barbed-end actin filament capping; IDA:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0090091; P:positive regulation of extracellular matrix disassembly; IDA:UniProtKB.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IDA:UniProtKB.
DR GO; GO:1902745; P:positive regulation of lamellipodium organization; IDA:UniProtKB.
DR GO; GO:1900029; P:positive regulation of ruffle assembly; IDA:UniProtKB.
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:0044319; P:wound healing, spreading of cells; IDA: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; 1.
DR Pfam; PF13516; LRR_6; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Disease variant; Leucine-rich repeat; Membrane; Methylation;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..1435
FT /note="Capping protein, Arp2/3 and myosin-I linker protein
FT 2"
FT /id="PRO_0000325817"
FT REPEAT 64..88
FT /note="LRR 1"
FT REPEAT 89..111
FT /note="LRR 2"
FT REPEAT 249..272
FT /note="LRR 3"
FT REPEAT 274..297
FT /note="LRR 4"
FT REPEAT 303..326
FT /note="LRR 5"
FT REPEAT 335..362
FT /note="LRR 6"
FT REPEAT 393..423
FT /note="LRR 7"
FT REPEAT 429..452
FT /note="LRR 8"
FT REPEAT 461..481
FT /note="LRR 9"
FT REPEAT 492..514
FT /note="LRR 10"
FT REPEAT 519..543
FT /note="LRR 11"
FT REPEAT 546..572
FT /note="LRR 12"
FT REPEAT 581..604
FT /note="LRR 13"
FT REPEAT 608..631
FT /note="LRR 14"
FT REPEAT 636..660
FT /note="LRR 15"
FT REPEAT 664..687
FT /note="LRR 16"
FT REGION 573..667
FT /note="Tropomodulin-like"
FT REGION 965..1435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1087..1114
FT /note="Necessary for localization at the cell membrane"
FT /evidence="ECO:0000269|PubMed:26578515"
FT COMPBIAS 992..1006
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1020..1034
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1059..1079
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1187..1206
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1230..1249
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1257..1271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1284..1302
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1407..1421
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 993
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1120
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3V9"
FT MOD_RES 1246
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1303
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3V9"
FT MOD_RES 1315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3V9"
FT MOD_RES 1420
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3V9"
FT VAR_SEQ 384..419
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19846667"
FT /id="VSP_047857"
FT VAR_SEQ 1346..1372
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19846667"
FT /id="VSP_047858"
FT VARIANT 50
FT /note="R -> T (in IMD58; decreased protein expression in
FT patient's cells; dbSNP:rs1567626023)"
FT /evidence="ECO:0000269|PubMed:29479355"
FT /id="VAR_081149"
FT VARIANT 372
FT /note="L -> R (in IMD58; decreased protein expression in
FT patient's leukocytes; no effect on homodimerization;
FT dbSNP:rs1567628757)"
FT /evidence="ECO:0000269|PubMed:27647349"
FT /id="VAR_081150"
FT VARIANT 525
FT /note="L -> Q (in IMD58; decreased protein expression in
FT patient's leukocytes; no effect on homodimerization;
FT dbSNP:rs1567629943)"
FT /evidence="ECO:0000269|PubMed:27647349"
FT /id="VAR_081151"
FT VARIANT 639
FT /note="L -> H (in IMD58; dbSNP:rs775061512)"
FT /evidence="ECO:0000269|PubMed:27896283"
FT /id="VAR_081152"
FT VARIANT 853..1435
FT /note="Missing (in IMD58; no detectable protein expression
FT in patient's leukocytes; no effect on homodimerization)"
FT /evidence="ECO:0000269|PubMed:27647349"
FT /id="VAR_081153"
FT MUTAGEN 1021
FT /note="R->A: Loss of ability to bind heterodimeric capping
FT protein (CP), unable to inhibit the actin-capping activity
FT of CP and to rescue the loss of lamellipodial ruffling,
FT macropinocytosis, cell polarity, and invadopodia-mediated
FT matrix degradation; when associated with A-1023."
FT /evidence="ECO:0000269|PubMed:26466680"
FT MUTAGEN 1023
FT /note="R->A: Loss of ability to bind heterodimeric capping
FT protein (CP), unable to inhibit the actin-capping activity
FT of CP and to rescue the loss of lamellipodial ruffling,
FT macropinocytosis, cell polarity, and invadopodia-mediated
FT matrix degradation; when associated with A-1021."
FT /evidence="ECO:0000269|PubMed:26466680"
FT MUTAGEN 1096..1106
FT /note="KKLGTLFAFKK->EEEEEEEEEEE: Loss of accumulation at
FT the cell membrane. Does not alter colocalization at
FT vimentin filaments. Alters monopolar cell polarity,
FT increasing the number of leading edges lacking lamellipodia
FT and ruffles. Inhibits cell migration during wound healing."
FT /evidence="ECO:0000269|PubMed:26578515"
FT MUTAGEN 1096..1106
FT /note="KKLGTLFAFKK->GGGGGGGGGGG: Loss of accumulation at
FT the cell membrane. Does not alter colocalization at
FT vimentin filaments. Alters monopolar cell polarity,
FT increasing the number of leading edges lacking lamellipodia
FT and ruffles. Inhibits cell migration during wound healing."
FT /evidence="ECO:0000269|PubMed:26578515"
FT MUTAGEN 1096..1106
FT /note="Missing: Loss of accumulation at the cell membrane.
FT Does not alter colocalization at vimentin filaments. Alters
FT monopolar cell polarity, increasing the number of leading
FT edges lacking lamellipodia and ruffles. Inhibits cell
FT migration during wound healing."
FT /evidence="ECO:0000269|PubMed:26578515"
SQ SEQUENCE 1435 AA; 154689 MW; B0D452CE375436A5 CRC64;
MAQTPDGISC ELRGEITRFL WPKEVELLLK TWLPGEGAVQ NHVLALLRWR AYLLHTTCLP
LRVDCTFSYL EVQAMALQET PPQVTFELES LRELVLEFPG VAALEQLAQH VAAAIKKVFP
RSTLGKLFRR PTPASMLARL ERSSPSESTD PCSPCGGFLE TYEALCDYNG FPFREEIQWD
VDTIYHRQGC RHFSLGDFSH LGSRDLALSV AALSYNLWFR CLSCVDMKLS LEVSEQILHM
MSQSSHLEEL VLETCSLRGD FVRRLAQALA GHSSSGLREL SLAGNLLDDR GMTALSRHLE
RCPGALRRLS LAQTGLTPRG MRALGRALAT NAAFDSTLTH LDLSGNPGAL GASEDSGGLY
SFLSRPNVLS FLNLAGTDTA LDTVRGCSVG GWMTGRADWR AGRGGLGPPA GVANSLPPQL
FAAVSRGCCT SLTHLDASRN VFSRTKSRAA PAALQLFLSR ARTLRHLGLA GCKLPPDALR
ALLDGLALNT HLRDLHLDLS ACELRSAGAQ VIQDLVCDAG AVSSLDLADN GFGSDMVTLV
LAIGRSRSLR HVALGRNFNV RCKETLDDVL HRIVQLMQDD DCPLQSLSVA ESRLKLGASV
LLRALATNPN LTALDISGNA MGDAGAKLLA KALRVNSRLR SVVWDRNHTS ALGLLDVAQA
LEQNHSLKAM PLPLNDVAQA QRSRPELTAR AVHQIQACLL RNNRADPASS DHTTRLQPLG
LVSDPSEQEV NELCQSVQEH VELLGCGAGP QGEAAVRQAE DAIQNANFSL SILPILYEAG
SSPSHHWQLG QKLEGLLRQV GEVCRQDIQD FTQATLDTAR SLCPQMLQGS SWREQLEGVL
AGSRGLPELL PEQLLQDAFT RLRDMRLSIT GTLAESIVAQ ALAGLSAARD QLVESLAQQA
TVTMPPALPA PDGGEPSLLE PGELEGLFFP EEKEEEKEKD DSPPQKWPEL SHGLHLVPFI
HSAAEEAEPE PELAAPGEDA EPQAGPSARG SPSPAAPGPP AGPLPRMDLP LAGQPLRHPT
RARPRPRRQH HHRPPPGGPQ VPPALPQEGN GLSARVDEGV EEFFSKRLIQ QDRLWAPEED
PATEGGATPV PRTLRKKLGT LFAFKKPRST RGPRTDLETS PGAAPRTRKT TFGDLLRPPT
RPSRGEELGG AEGDTSSPDP AGRSRPRYTR DSKAYSMILL PAEEEATLGA RPDKRRPLER
GETELAPSFE QRVQVMLQRI GVSRGSGGAE GKRKQSKDGE IKKAGSDGDI MDSSTEAPPI
SIKSRTHSVS ADPSCRPGPG SQGPESATWK TLGQQLNAEL RSRGWGQQDG PGPPSPGQSP
SPCRTSPSPD SLGLPEDPCL GPRNEDGQLR PRPLSAGRRA VSVHEDQLQA PAERPLRLQR
SPVLKRRPKL EAPPSPSLGS GLGTEPLPPQ PTEPSSPERS PPSPATDQRG GGPNP
