ID CLPB_HUMAN Reviewed; 707 AA.
AC Q9H078; B4DXJ7; B4DXP7; B4DXW4; E7EWN6; F8W7P6; Q8ND11; Q9H8Y0;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 24-JAN-2024, entry version 185.
DE RecName: Full=Mitochondrial disaggregase;
DE EC=3.6.1.- {ECO:0000269|PubMed:25597510, ECO:0000269|PubMed:35247700, ECO:0000269|PubMed:36170828, ECO:0000269|PubMed:36745679};
DE AltName: Full=Suppressor of potassium transport defect 3;
DE Contains:
DE RecName: Full=Mitochondrial disaggregase, cleaved form;
DE Flags: Precursor;
GN Name=CLPB {ECO:0000312|HGNC:HGNC:30664}; Synonyms=SKD3;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-589, AND IDENTIFICATION BY MASS
RP 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 [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].
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=28288130; DOI=10.1038/ncb3488;
RA Saita S., Nolte H., Fiedler K.U., Kashkar H., Venne A.S., Zahedi R.P.,
RA Krueger M., Langer T.;
RT "PARL mediates Smac proteolytic maturation in mitochondria to promote
RT apoptosis.";
RL Nat. Cell Biol. 19:318-328(2017).
RN [10]
RP INTERACTION WITH MAVS; PHB AND PHB2, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31522117; DOI=10.1016/j.isci.2019.08.056;
RA Yoshinaka T., Kosako H., Yoshizumi T., Furukawa R., Hirano Y., Kuge O.,
RA Tamada T., Koshiba T.;
RT "Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes:
RT Insight into a Role of the Coiled-Coil Region.";
RL IScience 19:1065-1078(2019).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=32866687; DOI=10.1016/j.biocel.2020.105841;
RA Thevarajan I., Zolkiewski M., Zolkiewska A.;
RT "Human CLPB forms ATP-dependent complexes in the mitochondrial
RT intermembrane space.";
RL Int. J. Biochem. Cell Biol. 127:105841-105841(2020).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=35247700; DOI=10.1016/j.bbrc.2022.02.101;
RA Spaulding Z., Thevarajan I., Schrag L.G., Zubcevic L., Zolkiewska A.,
RA Zolkiewski M.;
RT "Human mitochondrial AAA+ ATPase SKD3/CLPB assembles into nucleotide-
RT stabilized dodecamers.";
RL Biochem. Biophys. Res. Commun. 602:21-26(2022).
RN [13] {ECO:0007744|PDB:7TTR, ECO:0007744|PDB:7TTS}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 127-707 IN COMPLEX
RP WITH ADP AND PROTEIN SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, DOMAIN, AND MUTAGENESIS
RP OF ARG-417 AND VAL-431.
RX PubMed=36170828; DOI=10.1016/j.celrep.2022.111408;
RA Cupo R.R., Rizo A.N., Braun G.A., Tse E., Chuang E., Gupta K.,
RA Southworth D.R., Shorter J.;
RT "Unique structural features govern the activity of a human mitochondrial
RT AAA+ disaggregase, Skd3.";
RL Cell Rep. 40:111408-111408(2022).
RN [14] {ECO:0007744|PDB:7XBK, ECO:0007744|PDB:7XC5}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.7 ANGSTROMS) OF ISOFORM 2 IN COMPLEX
RP WITH ATP AND PROTEIN SUBSTRATE, X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF
RP 128-327, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, AND MUTAGENESIS OF
RP ARG-178; ARG-257 AND GLU-455.
RX PubMed=36745679; DOI=10.1371/journal.pbio.3001987;
RA Wu D., Liu Y., Dai Y., Wang G., Lu G., Chen Y., Li N., Lin J., Gao N.;
RT "Comprehensive structural characterization of the human AAA+ disaggregase
RT CLPB in the apo- and substrate-bound states reveals a unique mode of action
RT driven by oligomerization.";
RL PLoS Biol. 21:e3001987-e3001987(2023).
RN [15]
RP FUNCTION, DOMAIN, REGION, MUTAGENESIS OF LYS-387; TYR-430; GLU-455; ARG-475
RP AND ARG-650, AND CHARACTERIZATION OF VARIANTS MGCA7B MET-268 AND VAL-591.
RX PubMed=32573439; DOI=10.7554/elife.55279;
RA Cupo R.R., Shorter J.;
RT "Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is
RT inactivated by 3-methylglutaconic aciduria-linked mutations.";
RL Elife 9:0-0(2020).
RN [16]
RP INVOLVEMENT IN MGCA7A, VARIANTS MGCA7A THR-404; LEU-427; ARG-560 AND
RP TRP-561, AND CHARACTERIZATION OF VARIANTS MGCA7A THR-404; LEU-427 AND
RP ARG-560.
RX PubMed=34140661; DOI=10.1038/s41436-021-01194-x;
RA Wortmann S.B., Zietkiewicz S., Guerrero-Castillo S., Feichtinger R.G.,
RA Wagner M., Russell J., Ellaway C., Mroz D., Wyszkowski H., Weis D.,
RA Hannibal I., von Stuelpnagel C., Cabrera-Orefice A., Lichter-Konecki U.,
RA Gaesser J., Windreich R., Myers K.C., Lorsbach R., Dale R.C., Gersting S.,
RA Prada C.E., Christodoulou J., Wolf N.I., Venselaar H., Mayr J.A.,
RA Wevers R.A.;
RT "Neutropenia and intellectual disability are hallmarks of biallelic and de
RT novo CLPB deficiency.";
RL Genet. Med. 23:1705-1714(2021).
RN [17]
RP INVOLVEMENT IN SCN9, VARIANTS SCN9 LYS-388; LYS-496; LYS-557; GLN-561;
RP GLY-561 AND CYS-620, VARIANTS TRP-327 AND HIS-603, CHARACTERIZATION OF
RP VARIANTS SCN9 LYS-496; LYS-557; GLY-561 AND CYS-620, CHARACTERIZATION OF
RP VARIANT HIS-603, CHARACTERIZATION OF VARIANT MGCA7B GLY-408, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=34115842; DOI=10.1182/blood.2021010762;
RA Warren J.T., Cupo R.R., Wattanasirakul P., Spencer D.H., Locke A.E.,
RA Makaryan V., Bolyard A.A., Kelley M.L., Kingston N.L., Shorter J.,
RA Bellanne-Chantelot C., Donadieu J., Dale D.C., Link D.C.;
RT "Heterozygous variants of CLPB are a cause of severe congenital
RT neutropenia.";
RL Blood 139:779-791(2022).
RN [18]
RP VARIANTS MGCA7B CYS-272; GLY-408; ILE-411; 435-ASP-PRO-436 DELINS ASP-PRO;
RP ARG-486; LYS-501; CYS-567; VAL-591; CYS-617; VAL-646 AND ASN-682, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=25597510; DOI=10.1016/j.ajhg.2014.12.013;
RA Wortmann S.B., Zietkiewicz S., Kousi M., Szklarczyk R., Haack T.B.,
RA Gersting S.W., Muntau A.C., Rakovic A., Renkema G.H., Rodenburg R.J.,
RA Strom T.M., Meitinger T., Rubio-Gozalbo M.E., Chrusciel E., Distelmaier F.,
RA Golzio C., Jansen J.H., van Karnebeek C., Lillquist Y., Luecke T.,
RA Ounap K., Zordania R., Yaplito-Lee J., van Bokhoven H., Spelbrink J.N.,
RA Vaz F.M., Pras-Raves M., Ploski R., Pronicka E., Klein C., Willemsen M.A.,
RA de Brouwer A.P., Prokisch H., Katsanis N., Wevers R.A.;
RT "CLPB mutations cause 3-methylglutaconic aciduria, progressive brain
RT atrophy, intellectual disability, congenital neutropenia, cataracts,
RT movement disorder.";
RL Am. J. Hum. Genet. 96:245-257(2015).
RN [19]
RP VARIANT MGCA7B MET-268, AND TISSUE SPECIFICITY.
RX PubMed=25597511; DOI=10.1016/j.ajhg.2014.12.020;
RA Saunders C., Smith L., Wibrand F., Ravn K., Bross P., Thiffault I.,
RA Christensen M., Atherton A., Farrow E., Miller N., Kingsmore S.F.,
RA Ostergaard E.;
RT "CLPB variants associated with autosomal-recessive mitochondrial disorder
RT with cataract, neutropenia, epilepsy, and methylglutaconic aciduria.";
RL Am. J. Hum. Genet. 96:258-265(2015).
RN [20]
RP VARIANTS MGCA7B CYS-628 AND LYS-635.
RX PubMed=35616898; DOI=10.1111/pai.13782;
RA Rivalta B., Torraco A., Martinelli D., Luciani M., Carrozzo R.,
RA Finocchi A.;
RT "Biallelic CLPB mutation associated with isolated neutropenia and 3-MGA-
RT uria.";
RL Pediatr. Allergy Immunol. 33:e13782-e13782(2022).
CC -!- FUNCTION: Functions as a regulatory ATPase and participates in
CC secretion/protein trafficking process. Has ATP-dependent protein
CC disaggregase activity and is required to maintain the solubility of key
CC mitochondrial proteins (PubMed:32573439, PubMed:34115842,
CC PubMed:35247700, PubMed:36170828, PubMed:36745679). Involved in
CC mitochondrial-mediated antiviral innate immunity, activates RIG-I-
CC mediated signal transduction and production of IFNB1 and pro-
CC inflammatory cytokine IL6 (PubMed:31522117). Plays a role in
CC granulocyte differentiation (PubMed:34115842).
CC {ECO:0000269|PubMed:31522117, ECO:0000269|PubMed:32573439,
CC ECO:0000269|PubMed:34115842, ECO:0000269|PubMed:35247700,
CC ECO:0000269|PubMed:36170828, ECO:0000269|PubMed:36745679}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:25597510, ECO:0000269|PubMed:35247700,
CC ECO:0000269|PubMed:36170828, ECO:0000269|PubMed:36745679};
CC -!- ACTIVITY REGULATION: Disaggregase activity is inhibited by ADP.
CC {ECO:0000269|PubMed:36170828}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=64.6 uM for ATP {ECO:0000269|PubMed:36170828};
CC -!- SUBUNIT: Homododecamer when substrate-bound; the homododecamer consists
CC of 2 homohexamers stacked head-to-head via ANK repeat-mediated
CC interactions (PubMed:35247700, PubMed:36170828, PubMed:36745679). The
CC active substrate-bound form is likely to exist in a dynamic equilibrium
CC between homohexamers and homododecamers (PubMed:36170828).
CC Homotetradecamer in the unbound state which is remodeled upon substrate
CC binding into the homododecamer (PubMed:36170828, PubMed:36745679).
CC Interacts with PHB and PHB2 (PubMed:31522117). Interacts with MAVS; the
CC interaction is enhanced by Sendai virus infection (PubMed:31522117).
CC {ECO:0000269|PubMed:31522117, ECO:0000269|PubMed:35247700,
CC ECO:0000269|PubMed:36170828, ECO:0000269|PubMed:36745679}.
CC -!- INTERACTION:
CC Q9H078; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-2107221, EBI-739624;
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:25597510, ECO:0000269|PubMed:31522117,
CC ECO:0000269|PubMed:32866687, ECO:0000269|PubMed:34115842}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9H078-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H078-2; Sequence=VSP_001106;
CC Name=3;
CC IsoId=Q9H078-3; Sequence=VSP_044726, VSP_001106;
CC Name=4;
CC IsoId=Q9H078-4; Sequence=VSP_044725;
CC Name=5;
CC IsoId=Q9H078-5; Sequence=VSP_057397, VSP_001106;
CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level)
CC (PubMed:25597511). Expressed in fetal, as well as in adult tissues,
CC with highest levels in adult brain, including thalamus, hippocampus,
CC occipital cortex and parietal cortex. Low expression in granulocytes
CC (PubMed:25597510). {ECO:0000269|PubMed:25597510,
CC ECO:0000269|PubMed:25597511}.
CC -!- DOMAIN: The ankyrin-repeat region is necessary for ATP-dependent
CC protein disaggregase activity (PubMed:32573439, PubMed:36745679). It
CC plays an important role in stabilizing the substrate-bound
CC homododecamer by mediating contacts between the two homohexamers
CC (PubMed:36170828). {ECO:0000269|PubMed:32573439,
CC ECO:0000269|PubMed:36170828, ECO:0000269|PubMed:36745679}.
CC -!- PTM: Proteolytically cleaved by protease PARL (PubMed:28288130). ATP-
CC dependent protein disaggregase activity is stimulated by PARL-mediated
CC cleavage of the N-terminal autoinhibitory peptide.
CC {ECO:0000269|PubMed:28288130, ECO:0000269|PubMed:32573439}.
CC -!- DISEASE: 3-methylglutaconic aciduria 7B (MGCA7B) [MIM:616271]: An
CC autosomal recessive inborn error of metabolism with a highly variable
CC phenotype. Primary disease symptoms are increased levels of 3-
CC methylglutaconic acid, neurologic deterioration and neutropenia. Other
CC common features include progressive encephalopathy, movement
CC abnormalities, delayed psychomotor development,impaired intellectual
CC development, cataracts, seizures, and recurrent infections.
CC {ECO:0000269|PubMed:25597510, ECO:0000269|PubMed:25597511,
CC ECO:0000269|PubMed:32573439, ECO:0000269|PubMed:34115842,
CC ECO:0000269|PubMed:35616898}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: 3-methylglutaconic aciduria 7A (MGCA7A) [MIM:619835]: An
CC autosomal dominant inborn error of metabolism with a highly variable
CC phenotype. Primary disease symptoms are increased levels of 3-
CC methylglutaconic acid, neurologic deterioration and neutropenia. Other
CC common features include progressive encephalopathy, movement
CC abnormalities, delayed psychomotor development, impaired intellectual
CC development, cataracts, seizures, and recurrent infections.
CC {ECO:0000269|PubMed:34140661}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neutropenia, severe congenital 9, autosomal dominant (SCN9)
CC [MIM:619813]: A form of severe congenital neutropenia, a disorder of
CC hematopoiesis characterized by maturation arrest of granulopoiesis at
CC the level of promyelocytes with peripheral blood absolute neutrophil
CC counts below 0.5 x 10(9)/l and early onset of severe bacterial
CC infections. SCN9 is characterized by onset of neutropenia in the first
CC years of life. Rare patients may exhibit additional features such as
CC seizures, learning difficulties, or cataracts. Patients with SCN9 do
CC not have 3-methylglutaconic aciduria. {ECO:0000269|PubMed:34115842}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Hexamers display robustness and can tolerate some mutant
CC subunits without loss of activity (PubMed:36170828). Subunits
CC containing SCN9-linked variants Lys-496, Gly-561 and Cys-620 inhibit
CC ATPase and disaggregase activities of the hexamer more severely than
CC those containing MGCA7-linked variants Gly-408, Gly-475 and Val-591
CC (PubMed:36170828). {ECO:0000269|PubMed:36170828}.
CC -!- SIMILARITY: Belongs to the ClpA/ClpB family. {ECO:0000305}.
CC -!- CAUTION: Despite its gene name, this protein differs in domain
CC structure from bacterial clpB. Bacterial clpB contains two AAA modules,
CC one in the N-terminal part of the protein and one in the C-terminal
CC part, separated by a coiled coil, while vertebrate CLPB contains a
CC single C-terminal AAA region and an N-terminal ANK repeat region which
CC is absent from bacterial clpB. {ECO:0000305}.
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DR EMBL; AL136909; CAB66843.1; -; mRNA.
DR EMBL; AL834484; CAD39142.1; -; mRNA.
DR EMBL; AK023214; BAB14467.1; -; mRNA.
DR EMBL; AK302006; BAG63409.1; -; mRNA.
DR EMBL; AK302069; BAG63459.1; -; mRNA.
DR EMBL; AK302158; BAG63526.1; -; mRNA.
DR EMBL; AP000593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003785; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006404; AAH06404.1; -; mRNA.
DR CCDS; CCDS58153.1; -. [Q9H078-3]
DR CCDS; CCDS58154.1; -. [Q9H078-2]
DR CCDS; CCDS8215.1; -. [Q9H078-1]
DR RefSeq; NP_001245321.1; NM_001258392.2. [Q9H078-2]
DR RefSeq; NP_001245322.1; NM_001258393.2. [Q9H078-3]
DR RefSeq; NP_001245323.1; NM_001258394.2. [Q9H078-4]
DR RefSeq; NP_110440.1; NM_030813.5. [Q9H078-1]
DR PDB; 7TTR; EM; 2.96 A; A/B/C/D/E/F=127-707.
DR PDB; 7TTS; EM; 2.90 A; A/B/C/D/E/F=127-707.
DR PDB; 7US2; EM; 2.76 A; A/B/C/D/E/F=127-707.
DR PDB; 7XBK; EM; 3.70 A; A/B/C/D/E/F/G/H/I=1-707.
DR PDB; 7XC5; X-ray; 2.10 A; A=128-327.
DR PDB; 8DEH; X-ray; 1.81 A; A=132-351.
DR PDB; 8FDS; X-ray; 1.65 A; A=127-330.
DR PDBsum; 7TTR; -.
DR PDBsum; 7TTS; -.
DR PDBsum; 7US2; -.
DR PDBsum; 7XBK; -.
DR PDBsum; 7XC5; -.
DR PDBsum; 8DEH; -.
DR PDBsum; 8FDS; -.
DR AlphaFoldDB; Q9H078; -.
DR EMDB; EMD-26121; -.
DR EMDB; EMD-26122; -.
DR EMDB; EMD-26722; -.
DR EMDB; EMD-26725; -.
DR EMDB; EMD-26726; -.
DR EMDB; EMD-26728; -.
DR EMDB; EMD-33104; -.
DR EMDB; EMD-33105; -.
DR SMR; Q9H078; -.
DR BioGRID; 123531; 228.
DR IntAct; Q9H078; 91.
DR MINT; Q9H078; -.
DR STRING; 9606.ENSP00000294053; -.
DR GlyGen; Q9H078; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H078; -.
DR MetOSite; Q9H078; -.
DR PhosphoSitePlus; Q9H078; -.
DR SwissPalm; Q9H078; -.
DR BioMuta; CLPB; -.
DR DMDM; 25009267; -.
DR EPD; Q9H078; -.
DR jPOST; Q9H078; -.
DR MassIVE; Q9H078; -.
DR MaxQB; Q9H078; -.
DR PaxDb; 9606-ENSP00000294053; -.
DR PeptideAtlas; Q9H078; -.
DR ProteomicsDB; 18882; -.
DR ProteomicsDB; 29984; -.
DR ProteomicsDB; 5473; -.
DR ProteomicsDB; 80212; -. [Q9H078-1]
DR ProteomicsDB; 80213; -. [Q9H078-2]
DR Pumba; Q9H078; -.
DR Antibodypedia; 30838; 208 antibodies from 27 providers.
DR DNASU; 81570; -.
DR Ensembl; ENST00000294053.9; ENSP00000294053.3; ENSG00000162129.15. [Q9H078-1]
DR Ensembl; ENST00000340729.9; ENSP00000340385.5; ENSG00000162129.15. [Q9H078-3]
DR Ensembl; ENST00000538039.6; ENSP00000441518.1; ENSG00000162129.15. [Q9H078-2]
DR GeneID; 81570; -.
DR KEGG; hsa:81570; -.
DR MANE-Select; ENST00000538039.6; ENSP00000441518.1; NM_001258392.3; NP_001245321.1. [Q9H078-2]
DR UCSC; uc001osj.5; human. [Q9H078-1]
DR UCSC; uc010rqz.3; human.
DR AGR; HGNC:30664; -.
DR CTD; 81570; -.
DR DisGeNET; 81570; -.
DR GeneCards; CLPB; -.
DR GeneReviews; CLPB; -.
DR HGNC; HGNC:30664; CLPB.
DR HPA; ENSG00000162129; Tissue enriched (testis).
DR MalaCards; CLPB; -.
DR MIM; 616254; gene.
DR MIM; 616271; phenotype.
DR MIM; 619813; phenotype.
DR MIM; 619835; phenotype.
DR neXtProt; NX_Q9H078; -.
DR OpenTargets; ENSG00000162129; -.
DR Orphanet; 445038; 3-methylglutaconic aciduria type 7.
DR Orphanet; 486; Autosomal dominant severe congenital neutropenia.
DR PharmGKB; PA142672092; -.
DR VEuPathDB; HostDB:ENSG00000162129; -.
DR eggNOG; KOG1051; Eukaryota.
DR GeneTree; ENSGT00390000012961; -.
DR HOGENOM; CLU_005070_9_3_1; -.
DR InParanoid; Q9H078; -.
DR OMA; AKERHMI; -.
DR OrthoDB; 35211at2759; -.
DR PhylomeDB; Q9H078; -.
DR TreeFam; TF328654; -.
DR PathwayCommons; Q9H078; -.
DR SignaLink; Q9H078; -.
DR BioGRID-ORCS; 81570; 106 hits in 1161 CRISPR screens.
DR ChiTaRS; CLPB; human.
DR GeneWiki; CLPB; -.
DR GenomeRNAi; 81570; -.
DR Pharos; Q9H078; Tbio.
DR PRO; PR:Q9H078; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H078; Protein.
DR Bgee; ENSG00000162129; Expressed in sperm and 123 other cell types or tissues.
DR ExpressionAtlas; Q9H078; baseline and differential.
DR Genevisible; Q9H078; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:UniProtKB.
DR GO; GO:0140545; F:ATP-dependent protein disaggregase activity; IDA:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:0030851; P:granulocyte differentiation; IMP:UniProtKB.
DR GO; GO:0039529; P:RIG-I signaling pathway; IDA:UniProtKB.
DR CDD; cd19499; RecA-like_ClpB_Hsp104-like; 1.
DR Gene3D; 1.10.8.60; -; 1.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 2.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR019489; Clp_ATPase_C.
DR InterPro; IPR001270; ClpA/B.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11638; ATP-DEPENDENT CLP PROTEASE; 1.
DR PANTHER; PTHR11638:SF93; CASEINOLYTIC PEPTIDASE B PROTEIN HOMOLOG; 1.
DR Pfam; PF07724; AAA_2; 1.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF10431; ClpB_D2-small; 1.
DR PRINTS; PR00300; CLPPROTEASEA.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00248; ANK; 3.
DR SMART; SM01086; ClpB_D2-small; 1.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ANK repeat; ATP-binding;
KW Cataract; Disease variant; Epilepsy; Hydrolase; Intellectual disability;
KW Mitochondrion; Nucleotide-binding; Reference proteome; Repeat;
KW Transit peptide.
FT TRANSIT 1..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 37..707
FT /note="Mitochondrial disaggregase"
FT /id="PRO_0000191239"
FT CHAIN 127..707
FT /note="Mitochondrial disaggregase, cleaved form"
FT /evidence="ECO:0000269|PubMed:28288130"
FT /id="PRO_0000458241"
FT REPEAT 133..162
FT /note="ANK 1"
FT REPEAT 166..195
FT /note="ANK 2"
FT REPEAT 265..295
FT /note="ANK 3"
FT REPEAT 298..327
FT /note="ANK 4"
FT REGION 92..126
FT /note="Autoinhibitory"
FT /evidence="ECO:0000269|PubMed:32573439"
FT REGION 507..535
FT /note="Regulatory; slows ATPase and disaggregase
FT activities"
FT /evidence="ECO:0000269|PubMed:36170828"
FT BINDING 346
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36170828,
FT ECO:0007744|PDB:7TTR, ECO:0007744|PDB:7TTS"
FT BINDING 348
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36170828,
FT ECO:0000269|PubMed:36745679, ECO:0007744|PDB:7TTR,
FT ECO:0007744|PDB:7TTS, ECO:0007744|PDB:7XBK"
FT BINDING 383
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36745679,
FT ECO:0007744|PDB:7XBK"
FT BINDING 384
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36170828,
FT ECO:0007744|PDB:7TTR, ECO:0007744|PDB:7TTS"
FT BINDING 385
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36745679,
FT ECO:0007744|PDB:7XBK"
FT BINDING 386
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36170828,
FT ECO:0000269|PubMed:36745679, ECO:0007744|PDB:7TTR,
FT ECO:0007744|PDB:7TTS, ECO:0007744|PDB:7XBK"
FT BINDING 387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36745679,
FT ECO:0007744|PDB:7XBK"
FT BINDING 388
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36170828,
FT ECO:0000269|PubMed:36745679, ECO:0007744|PDB:7TTR,
FT ECO:0007744|PDB:7TTS, ECO:0007744|PDB:7XBK"
FT BINDING 455
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36745679,
FT ECO:0007744|PDB:7XBK"
FT BINDING 496
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36745679,
FT ECO:0007744|PDB:7XBK"
FT BINDING 561
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36745679,
FT ECO:0007744|PDB:7XBK"
FT BINDING 620
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:36170828,
FT ECO:0000269|PubMed:36745679, ECO:0007744|PDB:7TTR,
FT ECO:0007744|PDB:7TTS, ECO:0007744|PDB:7XBK"
FT SITE 126..127
FT /note="Cleavage; by PARL"
FT /evidence="ECO:0000269|PubMed:28288130"
FT MOD_RES 589
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..171
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057397"
FT VAR_SEQ 1..151
FT /note="MLGSLVLRRKALAPRLLLRLLRSPTLRGHGGASGRNVTTGSLGEPQWLRVAT
FT GGRPGTSPALFSGRGAATGGRQGGRFDTKCLAAATWGRLPGPEETLPGQDSWNGVPSRA
FT GLGMCALAAALVVHCYSKSPSNKDAALLEAARANNMQEVS -> MPRGCHLGTPSWSRR
FT NTPRTGQLERGPQQGRTGHVRPGRSAGGSLLQQESVQQGCSPVGSCPCQQYARSQQPQE
FT TAKNDAQSRSWAGLNAGVSLKNTKISSSEWPL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044725"
FT VAR_SEQ 152..180
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044726"
FT VAR_SEQ 216..245
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_001106"
FT VARIANT 268
FT /note="T -> M (in MGCA7B; increased ATP hydrolysis
FT activity; severely decreased ATP-dependent protein
FT disaggregase activity; dbSNP:rs200032855)"
FT /evidence="ECO:0000269|PubMed:25597511,
FT ECO:0000269|PubMed:32573439"
FT /id="VAR_073397"
FT VARIANT 272
FT /note="Y -> C (in MGCA7B; dbSNP:rs777313457)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073398"
FT VARIANT 295
FT /note="R -> T (in dbSNP:rs7938203)"
FT /id="VAR_048740"
FT VARIANT 327
FT /note="R -> W (in dbSNP:rs148534573)"
FT /evidence="ECO:0000269|PubMed:34115842"
FT /id="VAR_087351"
FT VARIANT 388
FT /note="T -> K (in SCN9)"
FT /evidence="ECO:0000269|PubMed:34115842"
FT /id="VAR_087352"
FT VARIANT 404
FT /note="K -> T (in MGCA7A; decreased ATP hydrolysis
FT activity; decreased ATP-dependent protein disaggregase
FT activity)"
FT /evidence="ECO:0000269|PubMed:34140661"
FT /id="VAR_087353"
FT VARIANT 408
FT /note="R -> G (in MGCA7B; decreased ATP hydrolysis
FT activity; decreased ATP-dependent protein disaggregase
FT activity; not changed mitochondrial respiration;
FT dbSNP:rs144078282)"
FT /evidence="ECO:0000269|PubMed:25597510,
FT ECO:0000269|PubMed:34115842"
FT /id="VAR_073399"
FT VARIANT 411
FT /note="M -> I (in MGCA7B; dbSNP:rs786205137)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073400"
FT VARIANT 427
FT /note="P -> L (in MGCA7A; decreased ATP hydrolysis
FT activity; decreased ATP-dependent protein disaggregase
FT activity)"
FT /evidence="ECO:0000269|PubMed:34140661"
FT /id="VAR_087354"
FT VARIANT 435..436
FT /note="EG -> DP (in MGCA7B)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073401"
FT VARIANT 486
FT /note="C -> R (in MGCA7B; dbSNP:rs886041118)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073402"
FT VARIANT 496
FT /note="N -> K (in SCN9; decreased granulocyte
FT differentiation; decreased ATP hydrolysis activity;
FT decreased ATP-dependent protein disaggregase activity; does
FT not render cells more sensitive to ER stress-induced
FT apoptosis)"
FT /evidence="ECO:0000269|PubMed:34115842"
FT /id="VAR_087355"
FT VARIANT 501
FT /note="E -> K (in MGCA7B; dbSNP:rs748915609)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073403"
FT VARIANT 557
FT /note="E -> K (in SCN9; decreased granulocyte
FT differentiation; decreased ATP hydrolysis activity;
FT decreased ATP-dependent protein disaggregase activity;
FT decreased mitochondrial respiration; dbSNP:rs1590753263)"
FT /evidence="ECO:0000269|PubMed:34115842"
FT /id="VAR_087356"
FT VARIANT 560
FT /note="G -> R (in MGCA7A; decreased ATP hydrolysis
FT activity; decreased ATP-dependent protein disaggregase
FT activity)"
FT /evidence="ECO:0000269|PubMed:34140661"
FT /id="VAR_087357"
FT VARIANT 561
FT /note="R -> G (in SCN9; decreased granulocyte
FT differentiation; loss of ATP hydrolysis activity; loss of
FT ATP-dependent protein disaggregase activity; decreased
FT mitochondrial respiration)"
FT /evidence="ECO:0000269|PubMed:34115842"
FT /id="VAR_087358"
FT VARIANT 561
FT /note="R -> Q (in SCN9; decreased mitochondrial
FT respiration; dbSNP:rs1590753221)"
FT /evidence="ECO:0000269|PubMed:34115842"
FT /id="VAR_087359"
FT VARIANT 561
FT /note="R -> W (in MGCA7A; dbSNP:rs1949512456)"
FT /evidence="ECO:0000269|PubMed:34140661"
FT /id="VAR_087360"
FT VARIANT 567
FT /note="Y -> C (in MGCA7B; dbSNP:rs150857620)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073404"
FT VARIANT 591
FT /note="A -> V (in MGCA7B; loss of ATP hydrolysis activity;
FT loss of ATP-dependent protein disaggregase activity;
FT dbSNP:rs748010262)"
FT /evidence="ECO:0000269|PubMed:25597510,
FT ECO:0000269|PubMed:32573439"
FT /id="VAR_073405"
FT VARIANT 603
FT /note="R -> H (normal ATP hydrolysis activity; normal ATP-
FT dependent protein disaggregase activity;
FT dbSNP:rs765245566)"
FT /evidence="ECO:0000269|PubMed:34115842"
FT /id="VAR_087361"
FT VARIANT 617
FT /note="Y -> C (in MGCA7B; dbSNP:rs786205138)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073406"
FT VARIANT 620
FT /note="R -> C (in SCN9; decreased granulocyte
FT differentiation; loss of ATP hydrolysis activity; loss of
FT ATP-dependent protein disaggregase activity; does not
FT render cells more sensitive to ER stress-induced
FT apoptosis)"
FT /evidence="ECO:0000269|PubMed:34115842"
FT /id="VAR_087362"
FT VARIANT 628
FT /note="R -> C (in MGCA7B; uncertain significance;
FT dbSNP:rs150343959)"
FT /evidence="ECO:0000269|PubMed:35616898"
FT /id="VAR_087363"
FT VARIANT 635
FT /note="A -> K (in MGCA7B; uncertain significance; requires
FT 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:35616898"
FT /id="VAR_087364"
FT VARIANT 646
FT /note="G -> V (in MGCA7B; dbSNP:rs759500860)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073407"
FT VARIANT 682
FT /note="I -> N (in MGCA7B; dbSNP:rs886041120)"
FT /evidence="ECO:0000269|PubMed:25597510"
FT /id="VAR_073408"
FT MUTAGEN 178
FT /note="R->E: Shows higher order assembly but disaggregase
FT activity is severely impaired by 70-80%."
FT /evidence="ECO:0000269|PubMed:36745679"
FT MUTAGEN 257
FT /note="R->E: Shows higher order assembly but disaggregase
FT activity is severely impaired by 70-80%."
FT /evidence="ECO:0000269|PubMed:36745679"
FT MUTAGEN 387
FT /note="K->A: Loss of ATP hydrolysis activity. Loss of ATP-
FT dependent protein disaggregase activity."
FT /evidence="ECO:0000269|PubMed:32573439"
FT MUTAGEN 417
FT /note="R->A: No effect on ATPase activity but shows
FT decreased disaggregase activity."
FT /evidence="ECO:0000269|PubMed:36170828"
FT MUTAGEN 430
FT /note="Y->A: Decreased ATP hydrolysis activity. Loss of
FT ATP-dependent protein disaggregase activity."
FT /evidence="ECO:0000269|PubMed:32573439"
FT MUTAGEN 431
FT /note="V->G: Decreased ATP hydrolysis activity. Loss of
FT ATP-dependent protein disaggregase activity."
FT /evidence="ECO:0000269|PubMed:36170828"
FT MUTAGEN 455
FT /note="E->Q: Loss of ATP hydrolysis activity at pH 8.0. No
FT effect on ATP hydrolysis activity at pH 6.8. Loss of ATP-
FT dependent protein disaggregase activity at pH 8.0 and 6.8."
FT /evidence="ECO:0000269|PubMed:32573439,
FT ECO:0000269|PubMed:36745679"
FT MUTAGEN 475
FT /note="R->Q: Severely decreased ATP hydrolysis activity.
FT Loss of ATP-dependent protein disaggregase activity."
FT /evidence="ECO:0000269|PubMed:32573439"
FT MUTAGEN 650
FT /note="R->P: No effect on ATP hydrolysis activity. Loss of
FT ATP-dependent protein disaggregase activity."
FT /evidence="ECO:0000269|PubMed:32573439"
FT CONFLICT 413
FT /note="E -> K (in Ref. 2; BAG63459)"
FT /evidence="ECO:0000305"
FT CONFLICT 563
FT /note="N -> S (in Ref. 2; BAG63409)"
FT /evidence="ECO:0000305"
FT CONFLICT 650
FT /note="R -> C (in Ref. 2; BAG63459)"
FT /evidence="ECO:0000305"
FT HELIX 133..144
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 147..155
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 170..176
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 180..188
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 202..209
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 233..239
FT /evidence="ECO:0007829|PDB:8DEH"
FT HELIX 246..253
FT /evidence="ECO:0007829|PDB:8FDS"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:8FDS"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:8DEH"
FT HELIX 269..275
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 279..287
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 310..327
FT /evidence="ECO:0007829|PDB:8FDS"
FT HELIX 328..335
FT /evidence="ECO:0007829|PDB:7TTR"
FT HELIX 339..343
FT /evidence="ECO:0007829|PDB:8DEH"
FT HELIX 351..365
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 375..381
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 387..399
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 406..410
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 417..419
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 420..424
FT /evidence="ECO:0007829|PDB:7TTS"
FT TURN 431..435
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 438..443
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 450..454
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 456..458
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 461..473
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 474..477
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 490..495
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 499..505
FT /evidence="ECO:0007829|PDB:7TTS"
FT TURN 509..512
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 545..552
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 555..561
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 564..567
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 573..589
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 594..596
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 604..611
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 615..617
FT /evidence="ECO:0007829|PDB:7TTS"
FT HELIX 619..640
FT /evidence="ECO:0007829|PDB:7TTS"
FT STRAND 657..665
FT /evidence="ECO:0007829|PDB:7TTS"
SQ SEQUENCE 707 AA; 78729 MW; 0E0F2A244CA20635 CRC64;
MLGSLVLRRK ALAPRLLLRL LRSPTLRGHG GASGRNVTTG SLGEPQWLRV ATGGRPGTSP
ALFSGRGAAT GGRQGGRFDT KCLAAATWGR LPGPEETLPG QDSWNGVPSR AGLGMCALAA
ALVVHCYSKS PSNKDAALLE AARANNMQEV SRLLSEGADV NAKHRLGWTA LMVAAINRNN
SVVQVLLAAG ADPNLGDDFS SVYKTAKEQG IHSLEDGGQD GASRHITNQW TSALEFRRWL
GLPAGVLITR EDDFNNRLNN RASFKGCTAL HYAVLADDYR TVKELLDGGA NPLQRNEMGH
TPLDYAREGE VMKLLRTSEA KYQEKQRKRE AEERRRFPLE QRLKEHIIGQ ESAIATVGAA
IRRKENGWYD EEHPLVFLFL GSSGIGKTEL AKQTAKYMHK DAKKGFIRLD MSEFQERHEV
AKFIGSPPGY VGHEEGGQLT KKLKQCPNAV VLFDEVDKAH PDVLTIMLQL FDEGRLTDGK
GKTIDCKDAI FIMTSNVASD EIAQHALQLR QEALEMSRNR IAENLGDVQI SDKITISKNF
KENVIRPILK AHFRRDEFLG RINEIVYFLP FCHSELIQLV NKELNFWAKR AKQRHNITLL
WDREVADVLV DGYNVHYGAR SIKHEVERRV VNQLAAAYEQ DLLPGGCTLR ITVEDSDKQL
LKSPELPSPQ AEKRLPKLRL EIIDKDSKTR RLDIRAPLHP EKVCNTI
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