COTL1_HUMAN
ID COTL1_HUMAN Reviewed; 142 AA.
AC Q14019; B2RDU3; D3DUL9; Q86XM5;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Coactosin-like protein;
GN Name=COTL1; Synonyms=CLP;
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].
RC TISSUE=Placenta;
RX PubMed=9326934; DOI=10.1038/ng1097-154;
RA Chen K.-S., Manian P., Koeuth T., Potocki L., Zhao Q., Chinault A.C.,
RA Lee C.-C., Lupski J.R.;
RT "Homologous recombination of a flanking repeat gene cluster is a mechanism
RT for a common contiguous gene deletion syndrome.";
RL Nat. Genet. 17:154-163(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Cervix, Kidney, Lung, and Uterus;
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 PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP PROTEIN SEQUENCE OF 76-91, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP LYS-75.
RX PubMed=11583571; DOI=10.1042/0264-6021:3590255;
RA Provost P., Doucet J., Stock A., Gerisch G., Samuelsson B., Radmark O.;
RT "Coactosin-like protein, a human F-actin-binding protein: critical role of
RT lysine-75.";
RL Biochem. J. 359:255-263(2001).
RN [9]
RP INTERACTION WITH 5-LIPOXYGENASE, AND MUTAGENESIS OF LYS-130 AND LYS-131.
RX PubMed=11297527; DOI=10.1074/jbc.m011205200;
RA Provost P., Doucet J., Hammarberg T., Gerisch G., Samuelsson B.,
RA Radmark O.;
RT "5-lipoxygenase interacts with coactosin-like protein.";
RL J. Biol. Chem. 276:16520-16527(2001).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-102 AND LYS-126, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=19807693; DOI=10.1042/bj20090856;
RA Esser J., Rakonjac M., Hofmann B., Fischer L., Provost P., Schneider G.,
RA Steinhilber D., Samuelsson B., Radmark O.;
RT "Coactosin-like protein functions as a stabilizing chaperone for 5-
RT lipoxygenase: role of tryptophan 102.";
RL Biochem. J. 425:265-274(2010).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [14]
RP STRUCTURE BY NMR.
RX PubMed=15754059; DOI=10.1007/s10858-004-3449-y;
RA Liepinsh E., Rakonjac M., Boissonneault V., Provost P., Samuelsson B.,
RA Radmark O., Otting G.;
RT "NMR structure of human coactosin-like protein.";
RL J. Biomol. NMR 30:353-356(2004).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND SUBUNIT.
RX PubMed=15459340; DOI=10.1110/ps.04937304;
RA Li X., Liu X., Lou Z., Duan X., Wu H., Liu Y., Rao Z.;
RT "Crystal structure of human coactosin-like protein at 1.9 A resolution.";
RL Protein Sci. 13:2845-2851(2004).
RN [16]
RP STRUCTURE BY NMR, SUBUNIT, AND F-ACTIN BINDING REGION.
RX PubMed=17070122; DOI=10.1016/j.bbapap.2006.06.017;
RA Dai H., Huang W., Xu J., Yao B., Xiong S., Ding H., Tang Y., Liu H., Wu J.,
RA Shi Y.;
RT "Binding model of human coactosin-like protein with filament actin revealed
RT by mutagenesis.";
RL Biochim. Biophys. Acta 1764:1688-1700(2006).
CC -!- FUNCTION: Binds to F-actin in a calcium-independent manner. Has no
CC direct effect on actin depolymerization. Acts as a chaperone for ALOX5
CC (5LO), influencing both its stability and activity in leukotrienes
CC synthesis. {ECO:0000269|PubMed:11583571, ECO:0000269|PubMed:19807693}.
CC -!- SUBUNIT: Interacts with 5-lipoxygenase (ALOX5/5LO) in a calcium-
CC independent manner. Binds to F-actin with a stoichiometry of 1:2.
CC {ECO:0000269|PubMed:11297527, ECO:0000269|PubMed:15459340,
CC ECO:0000269|PubMed:17070122, ECO:0000269|PubMed:19807693}.
CC -!- INTERACTION:
CC Q14019; P09917: ALOX5; NbExp=5; IntAct=EBI-79926, EBI-79934;
CC Q14019; Q13956: PDE6H; NbExp=3; IntAct=EBI-79926, EBI-10231995;
CC Q14019; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-79926, EBI-750109;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11583571}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:11583571}. Nucleus
CC {ECO:0000269|PubMed:19807693}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in placenta,
CC lung, kidney and peripheral blood leukocytes and lower levels in brain,
CC liver and pancreas. {ECO:0000269|PubMed:11583571}.
CC -!- SIMILARITY: Belongs to the actin-binding proteins ADF family. Coactosin
CC subfamily. {ECO:0000305}.
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DR EMBL; L54057; AAA88022.1; -; mRNA.
DR EMBL; BT006968; AAP35614.1; -; mRNA.
DR EMBL; AK315675; BAG38040.1; -; mRNA.
DR EMBL; CH471114; EAW95476.1; -; Genomic_DNA.
DR EMBL; CH471114; EAW95477.1; -; Genomic_DNA.
DR EMBL; BC010039; AAH10039.1; -; mRNA.
DR EMBL; BC010884; AAH10884.1; -; mRNA.
DR EMBL; BC016702; AAH16702.1; -; mRNA.
DR EMBL; BC042970; AAH42970.1; -; mRNA.
DR EMBL; BC053682; AAH53682.1; -; mRNA.
DR CCDS; CCDS10947.1; -.
DR RefSeq; NP_066972.1; NM_021149.3.
DR PDB; 1T2L; X-ray; 2.80 A; A/B=2-142.
DR PDB; 1T3X; X-ray; 2.00 A; A=2-142.
DR PDB; 1T3Y; X-ray; 1.15 A; A=2-142.
DR PDB; 1TMW; NMR; -; A=2-142.
DR PDB; 1VFQ; X-ray; 1.90 A; A=1-142.
DR PDB; 1WNJ; NMR; -; A=1-142.
DR PDBsum; 1T2L; -.
DR PDBsum; 1T3X; -.
DR PDBsum; 1T3Y; -.
DR PDBsum; 1TMW; -.
DR PDBsum; 1VFQ; -.
DR PDBsum; 1WNJ; -.
DR AlphaFoldDB; Q14019; -.
DR BMRB; Q14019; -.
DR SMR; Q14019; -.
DR BioGRID; 116979; 40.
DR DIP; DIP-30951N; -.
DR IntAct; Q14019; 8.
DR STRING; 9606.ENSP00000262428; -.
DR iPTMnet; Q14019; -.
DR MetOSite; Q14019; -.
DR PhosphoSitePlus; Q14019; -.
DR SwissPalm; Q14019; -.
DR BioMuta; COTL1; -.
DR DMDM; 21759076; -.
DR OGP; Q14019; -.
DR REPRODUCTION-2DPAGE; IPI00017704; -.
DR EPD; Q14019; -.
DR jPOST; Q14019; -.
DR MassIVE; Q14019; -.
DR MaxQB; Q14019; -.
DR PaxDb; Q14019; -.
DR PeptideAtlas; Q14019; -.
DR PRIDE; Q14019; -.
DR ProteomicsDB; 59796; -.
DR TopDownProteomics; Q14019; -.
DR Antibodypedia; 30596; 351 antibodies from 30 providers.
DR DNASU; 23406; -.
DR Ensembl; ENST00000262428.5; ENSP00000262428.4; ENSG00000103187.8.
DR GeneID; 23406; -.
DR KEGG; hsa:23406; -.
DR MANE-Select; ENST00000262428.5; ENSP00000262428.4; NM_021149.5; NP_066972.1.
DR UCSC; uc002fid.5; human.
DR CTD; 23406; -.
DR DisGeNET; 23406; -.
DR GeneCards; COTL1; -.
DR HGNC; HGNC:18304; COTL1.
DR HPA; ENSG00000103187; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 606748; gene.
DR neXtProt; NX_Q14019; -.
DR OpenTargets; ENSG00000103187; -.
DR PharmGKB; PA38522; -.
DR VEuPathDB; HostDB:ENSG00000103187; -.
DR eggNOG; KOG3655; Eukaryota.
DR GeneTree; ENSGT00390000012498; -.
DR HOGENOM; CLU_129657_1_0_1; -.
DR InParanoid; Q14019; -.
DR OMA; KSETTWL; -.
DR OrthoDB; 1424839at2759; -.
DR PhylomeDB; Q14019; -.
DR TreeFam; TF324318; -.
DR PathwayCommons; Q14019; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q14019; -.
DR BioGRID-ORCS; 23406; 12 hits in 1077 CRISPR screens.
DR ChiTaRS; COTL1; human.
DR EvolutionaryTrace; Q14019; -.
DR GeneWiki; COTL1; -.
DR GenomeRNAi; 23406; -.
DR Pharos; Q14019; Tbio.
DR PRO; PR:Q14019; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q14019; protein.
DR Bgee; ENSG00000103187; Expressed in monocyte and 195 other tissues.
DR ExpressionAtlas; Q14019; baseline and differential.
DR Genevisible; Q14019; HS.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; IEA:Ensembl.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IBA:GO_Central.
DR DisProt; DP02824; -.
DR Gene3D; 3.40.20.10; -; 1.
DR InterPro; IPR002108; ADF-H.
DR InterPro; IPR029006; ADF-H/Gelsolin-like_dom_sf.
DR InterPro; IPR030502; CLP.
DR PANTHER; PTHR10829:SF29; PTHR10829:SF29; 1.
DR Pfam; PF00241; Cofilin_ADF; 1.
DR SMART; SM00102; ADF; 1.
DR PROSITE; PS51263; ADF_H; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Chaperone; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Nucleus; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..142
FT /note="Coactosin-like protein"
FT /id="PRO_0000214954"
FT DOMAIN 2..130
FT /note="ADF-H"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00599"
FT REGION 66..75
FT /note="Flexible and important for F-actin binding"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 102
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 126
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MUTAGEN 75
FT /note="K->A: Abolishes actin-binding activity."
FT /evidence="ECO:0000269|PubMed:11583571"
FT MUTAGEN 130
FT /note="K->A: No effect on 5LO-binding activity."
FT /evidence="ECO:0000269|PubMed:11297527"
FT MUTAGEN 131
FT /note="K->A: Abolishes 5LO-binding activity."
FT /evidence="ECO:0000269|PubMed:11297527"
FT MUTAGEN 131
FT /note="K->E: Abolishes 5LO-binding activity."
FT /evidence="ECO:0000269|PubMed:11297527"
FT MUTAGEN 131
FT /note="K->R: No effect on 5LO-binding activity."
FT /evidence="ECO:0000269|PubMed:11297527"
FT CONFLICT 38
FT /note="P -> H (in Ref. 5; AAH42970)"
FT /evidence="ECO:0000305"
FT HELIX 7..18
FT /evidence="ECO:0007829|PDB:1T3Y"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:1TMW"
FT STRAND 26..32
FT /evidence="ECO:0007829|PDB:1T3Y"
FT STRAND 35..44
FT /evidence="ECO:0007829|PDB:1T3Y"
FT HELIX 45..51
FT /evidence="ECO:0007829|PDB:1T3Y"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:1WNJ"
FT STRAND 57..66
FT /evidence="ECO:0007829|PDB:1T3Y"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:1T3Y"
FT STRAND 73..82
FT /evidence="ECO:0007829|PDB:1T3Y"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1WNJ"
FT HELIX 88..101
FT /evidence="ECO:0007829|PDB:1T3Y"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:1T3Y"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:1T3Y"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:1T3Y"
FT HELIX 122..131
FT /evidence="ECO:0007829|PDB:1T3Y"
SQ SEQUENCE 142 AA; 15945 MW; A4B881DD8E89A35D CRC64;
MATKIDKEAC RAAYNLVRDD GSAVIWVTFK YDGSTIVPGE QGAEYQHFIQ QCTDDVRLFA
FVRFTTGDAM SKRSKFALIT WIGENVSGLQ RAKTGTDKTL VKEVVQNFAK EFVISDRKEL
EEDFIKSELK KAGGANYDAQ TE
