CENPE_HUMAN
ID CENPE_HUMAN Reviewed; 2701 AA.
AC Q02224; A6NKY9; A8K2U7; Q4LE75;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Centromere-associated protein E;
DE AltName: Full=Centromere protein E;
DE Short=CENP-E;
DE AltName: Full=Kinesin-7 {ECO:0000303|PubMed:25908662};
DE AltName: Full=Kinesin-related protein CENPE;
DE Flags: Precursor;
GN Name=CENPE;
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), AND VARIANTS LEU-1535 AND MET-2090.
RX PubMed=1406971; DOI=10.1038/359536a0;
RA Yen T.J., Li G., Schaar B.T., Szilak I., Cleveland D.W.;
RT "CENP-E is a putative kinetochore motor that accumulates just before
RT mitosis.";
RL Nature 359:536-539(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R.,
RA Okazaki N., Koga H., Nagase T., Ohara O.;
RT "Preparation of a set of expression-ready clones of mammalian long cDNAs
RT encoding large proteins by the ORF trap cloning method.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1126 (ISOFORM 1).
RC TISSUE=Tongue;
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 [6]
RP FUNCTION.
RX PubMed=7889940; DOI=10.1002/j.1460-2075.1995.tb07073.x;
RA Thrower D.A., Jordan M.A., Schaar B.T., Yen T.J., Wilson L.;
RT "Mitotic HeLa cells contain a CENP-E-associated minus end-directed
RT microtubule motor.";
RL EMBO J. 14:918-926(1995).
RN [7]
RP INTERACTION WITH CENPF AND BUB1B, AND SUBCELLULAR LOCATION.
RX PubMed=9763420; DOI=10.1083/jcb.143.1.49;
RA Chan G.K.T., Schaar B.T., Yen T.J.;
RT "Characterization of the kinetochore binding domain of CENP-E reveals
RT interactions with the kinetochore proteins CENP-F and hBUBR1.";
RL J. Cell Biol. 143:49-63(1998).
RN [8]
RP ISOPRENYLATION AT CYS-2698.
RX PubMed=10852915; DOI=10.1074/jbc.m003469200;
RA Ashar H.R., James L., Gray K., Carr D., Black S., Armstrong L.,
RA Bishop W.R., Kirschmeier P.;
RT "Farnesyl transferase inhibitors block the farnesylation of CENP-E and
RT CENP-F and alter the association of CENP-E with the microtubules.";
RL J. Biol. Chem. 275:30451-30457(2000).
RN [9]
RP INTERACTION WITH PRC1.
RX PubMed=15297875; DOI=10.1038/sj.emboj.7600347;
RA Kurasawa Y., Earnshaw W.C., Mochizuki Y., Dohmae N., Todokoro K.;
RT "Essential roles of KIF4 and its binding partner PRC1 in organized central
RT spindle midzone formation.";
RL EMBO J. 23:3237-3248(2004).
RN [10]
RP FUNCTION, INTERACTION WITH NUF2, AND SUBCELLULAR LOCATION.
RX PubMed=17535814; DOI=10.1074/jbc.m609026200;
RA Liu D., Ding X., Du J., Cai X., Huang Y., Ward T., Shaw A., Yang Y., Hu R.,
RA Jin C., Yao X.;
RT "Human NUF2 interacts with centromere-associated protein E and is essential
RT for a stable spindle microtubule-kinetochore attachment.";
RL J. Biol. Chem. 282:21415-21424(2007).
RN [11]
RP INTERACTION WITH SEPT7, AND SUBCELLULAR LOCATION.
RX PubMed=18460473; DOI=10.1074/jbc.m710591200;
RA Zhu M., Wang F., Yan F., Yao P.Y., Du J., Gao X., Wang X., Wu Q., Ward T.,
RA Li J., Kioko S., Hu R., Xie W., Ding X., Yao X.;
RT "Septin 7 interacts with centromere-associated protein E and is required
RT for its kinetochore localization.";
RL J. Biol. Chem. 283:18916-18925(2008).
RN [12]
RP SUMOYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=18374647; DOI=10.1016/j.molcel.2008.01.013;
RA Zhang X.-D., Goeres J., Zhang H., Yen T.J., Porter A.C.G., Matunis M.J.;
RT "SUMO-2/3 modification and binding regulate the association of CENP-E with
RT kinetochores and progression through mitosis.";
RL Mol. Cell 29:729-741(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2647, AND IDENTIFICATION BY
RP 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 [14]
RP INTERACTION WITH KIF18A AND BUB1B.
RX PubMed=19625775; DOI=10.4161/cc.8.16.9366;
RA Huang Y., Yao Y., Xu H.-Z., Wang Z.-G., Lu L., Dai W.;
RT "Defects in chromosome congression and mitotic progression in KIF18A-
RT deficient cells are partly mediated through impaired functions of CENP-E.";
RL Cell Cycle 8:2643-2649(2009).
RN [15]
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 [16]
RP INTERACTION WITH SKAP.
RX PubMed=22110139; DOI=10.1074/jbc.m111.277194;
RA Huang Y., Wang W., Yao P., Wang X., Liu X., Zhuang X., Yan F., Zhou J.,
RA Du J., Ward T., Zou H., Zhang J., Fang G., Ding X., Dou Z., Yao X.;
RT "CENP-E kinesin interacts with SKAP protein to orchestrate accurate
RT chromosome segregation in mitosis.";
RL J. Biol. Chem. 287:1500-1509(2012).
RN [17]
RP FUNCTION.
RX PubMed=23891108; DOI=10.1016/j.cub.2013.06.040;
RA Shrestha R.L., Draviam V.M.;
RT "Lateral to end-on conversion of chromosome-microtubule attachment requires
RT kinesins CENP-E and MCAK.";
RL Curr. Biol. 23:1514-1526(2013).
RN [18]
RP ERRATUM OF PUBMED:23891108.
RA Shrestha R.L., Draviam V.M.;
RL Curr. Biol. 23:2440-2441(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-611; SER-2083; SER-2389;
RP SER-2639 AND SER-2651, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [20]
RP FUNCTION.
RX PubMed=23955301; DOI=10.1038/ncb2831;
RA Gudimchuk N., Vitre B., Kim Y., Kiyatkin A., Cleveland D.W.,
RA Ataullakhanov F.I., Grishchuk E.L.;
RT "Kinetochore kinesin CENP-E is a processive bi-directional tracker of
RT dynamic microtubule tips.";
RL Nat. Cell Biol. 15:1079-1088(2013).
RN [21]
RP INVOLVEMENT IN MCPH13, VARIANTS MCPH13 ASN-933 AND GLU-1355,
RP CHARACTERIZATION OF VARIANTS MCPH13 ASN-933 AND GLU-1355, AND VARIANTS
RP LEU-1535 AND MET-2090.
RX PubMed=24748105; DOI=10.1007/s00439-014-1443-3;
RA Mirzaa G.M., Vitre B., Carpenter G., Abramowicz I., Gleeson J.G.,
RA Paciorkowski A.R., Cleveland D.W., Dobyns W.B., O'Driscoll M.;
RT "Mutations in CENPE define a novel kinetochore-centromeric mechanism for
RT microcephalic primordial dwarfism.";
RL Hum. Genet. 133:1023-1039(2014).
RN [22]
RP INTERACTION WITH CTCF, AND SUBCELLULAR LOCATION.
RX PubMed=26321640; DOI=10.1016/j.celrep.2015.08.005;
RA Xiao T., Wongtrakoongate P., Trainor C., Felsenfeld G.;
RT "CTCF recruits centromeric protein CENP-E to the
RT pericentromeric/centromeric regions of chromosomes through unusual CTCF-
RT binding sites.";
RL Cell Rep. 12:1704-1714(2015).
RN [23]
RP INTERACTION WITH TRAPPC12, AND SUBCELLULAR LOCATION.
RX PubMed=25918224; DOI=10.1083/jcb.201501090;
RA Milev M.P., Hasaj B., Saint-Dic D., Snounou S., Zhao Q., Sacher M.;
RT "TRAMM/TrappC12 plays a role in chromosome congression, kinetochore
RT stability, and CENP-E recruitment.";
RL J. Cell Biol. 209:221-234(2015).
RN [24]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25395579; DOI=10.1242/jcs.163659;
RA Bancroft J., Auckland P., Samora C.P., McAinsh A.D.;
RT "Chromosome congression is promoted by CENP-Q- and CENP-E-dependent
RT pathways.";
RL J. Cell Sci. 128:171-184(2015).
RN [25]
RP FUNCTION.
RX PubMed=25743205; DOI=10.1038/ncomms7447;
RA Iemura K., Tanaka K.;
RT "Chromokinesin Kid and kinetochore kinesin CENP-E differentially support
RT chromosome congression without end-on attachment to microtubules.";
RL Nat. Commun. 6:6447-6447(2015).
RN [26]
RP FUNCTION.
RX PubMed=25908662; DOI=10.1126/science.aaa5175;
RA Barisic M., Silva e Sousa R., Tripathy S.K., Magiera M.M., Zaytsev A.V.,
RA Pereira A.L., Janke C., Grishchuk E.L., Maiato H.;
RT "Mitosis. Microtubule detyrosination guides chromosomes during mitosis.";
RL Science 348:799-803(2015).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2-342 IN COMPLEX WITH ADP, PROTEIN
RP SEQUENCE OF 2-7, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBUNIT.
RX PubMed=15236970; DOI=10.1016/j.jmb.2004.05.053;
RA Garcia-Saez I., Yen T., Wade R.H., Kozielski F.;
RT "Crystal structure of the motor domain of the human kinetochore protein
RT CENP-E.";
RL J. Mol. Biol. 340:1107-1116(2004).
CC -!- FUNCTION: Microtubule plus-end-directed kinetochore motor which plays
CC an important role in chromosome congression, microtubule-kinetochore
CC conjugation and spindle assembly checkpoint activation. Drives
CC chromosome congression (alignment of chromosomes at the spindle equator
CC resulting in the formation of the metaphase plate) by mediating the
CC lateral sliding of polar chromosomes along spindle microtubules towards
CC the spindle equator and by aiding the establishment and maintenance of
CC connections between kinetochores and spindle microtubules
CC (PubMed:7889940, PubMed:23891108, PubMed:25395579). The transport of
CC pole-proximal chromosomes towards the spindle equator is favored by
CC microtubule tracks that are detyrosinated (PubMed:25908662). Acts as a
CC processive bi-directional tracker of dynamic microtubule tips; after
CC chromosomes have congressed, continues to play an active role at
CC kinetochores, enhancing their links with dynamic microtubule ends
CC (PubMed:23955301). Suppresses chromosome congression in NDC80-depleted
CC cells and contributes positively to congression only when microtubules
CC are stabilized (PubMed:25743205). Plays an important role in the
CC formation of stable attachments between kinetochores and spindle
CC microtubules (PubMed:17535814) The stabilization of kinetochore-
CC microtubule attachment also requires CENPE-dependent localization of
CC other proteins to the kinetochore including BUB1B, MAD1 and MAD2. Plays
CC a role in spindle assembly checkpoint activation (SAC) via its
CC interaction with BUB1B resulting in the activation of its kinase
CC activity, which is important for activating SAC. Necessary for the
CC mitotic checkpoint signal at individual kinetochores to prevent
CC aneuploidy due to single chromosome loss (By similarity).
CC {ECO:0000250|UniProtKB:Q6RT24, ECO:0000269|PubMed:17535814,
CC ECO:0000269|PubMed:23891108, ECO:0000269|PubMed:23955301,
CC ECO:0000269|PubMed:25395579, ECO:0000269|PubMed:25743205,
CC ECO:0000269|PubMed:25908662, ECO:0000269|PubMed:7889940}.
CC -!- SUBUNIT: Monomer (PubMed:15236970). Interacts with CENPF
CC (PubMed:9763420). Interacts with BUB1B (PubMed:9763420,
CC PubMed:19625775). Interacts with SEPT7 (PubMed:18460473). Interacts
CC with KIF18A (PubMed:19625775). Interacts with PRC1 (PubMed:15297875).
CC Interacts with NUF2; this interaction determines kinetochore
CC localization (PubMed:17535814). Interacts with SKAP; this interaction
CC greatly favors SKAP binding to microtubules (PubMed:22110139).
CC Interacts with TRAPPC12 (PubMed:25918224). Interacts with CTCF
CC (PubMed:25395579). {ECO:0000269|PubMed:15236970,
CC ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:17535814,
CC ECO:0000269|PubMed:18460473, ECO:0000269|PubMed:19625775,
CC ECO:0000269|PubMed:22110139, ECO:0000269|PubMed:25395579,
CC ECO:0000269|PubMed:25918224, ECO:0000269|PubMed:9763420}.
CC -!- INTERACTION:
CC Q02224; O60566: BUB1B; NbExp=4; IntAct=EBI-1375040, EBI-1001438;
CC Q02224; Q9Y6D9: MAD1L1; NbExp=3; IntAct=EBI-1375040, EBI-742610;
CC Q02224; Q9BZD4: NUF2; NbExp=9; IntAct=EBI-1375040, EBI-724102;
CC -!- SUBCELLULAR LOCATION: Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:17535814, ECO:0000269|PubMed:18374647,
CC ECO:0000269|PubMed:18460473, ECO:0000269|PubMed:25395579,
CC ECO:0000269|PubMed:25918224, ECO:0000269|PubMed:9763420}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:9763420}. Chromosome,
CC centromere {ECO:0000269|PubMed:26321640}. Note=Associates with
CC kinetochores during congression (as early as prometaphase), relocates
CC to the spindle midzone at anaphase, and is quantitatively discarded at
CC the end of the cell division (By similarity). Recruited to the
CC kinetochore in a SEPT7, CENPQ and TRAPPC12-dependent manner
CC (PubMed:18460473, PubMed:25918224, PubMed:25395579). Recruited to the
CC pericentromeric/centromeric regions of the chromosome in a CTCF-
CC dependent manner (PubMed:26321640). {ECO:0000250|UniProtKB:Q6RT24,
CC ECO:0000269|PubMed:18460473, ECO:0000269|PubMed:25395579,
CC ECO:0000269|PubMed:25918224, ECO:0000269|PubMed:26321640}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q02224-1; Sequence=Displayed;
CC Name=3;
CC IsoId=Q02224-3; Sequence=VSP_028820, VSP_028821;
CC -!- DOMAIN: The protein is composed of a N-terminal kinesin-motor domain
CC involved in the chromosome movements, a long coil-coiled region
CC involved in the homodimerization and an inhibitory C-tail involved in
CC autoinhibition of the N-terminal catalytic part. {ECO:0000250}.
CC -!- PTM: The C-terminal inhibitory domain is phosphorylated.
CC Phosphorylation relieves autoinhibition of the kinetochore motor (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the
CC association to the kinetochore. {ECO:0000269|PubMed:18374647}.
CC -!- DISEASE: Microcephaly 13, primary, autosomal recessive (MCPH13)
CC [MIM:616051]: A form of microcephaly, a disease defined as a head
CC circumference more than 3 standard deviations below the age-related
CC mean. Brain weight is markedly reduced and the cerebral cortex is
CC disproportionately small. {ECO:0000269|PubMed:24748105}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase
CC superfamily. Kinesin family. {ECO:0000255|PROSITE-ProRule:PRU00283}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE06078.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA78727.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; Z15005; CAA78727.1; ALT_SEQ; mRNA.
DR EMBL; AB209996; BAE06078.1; ALT_INIT; mRNA.
DR EMBL; AC079919; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX06171.1; -; Genomic_DNA.
DR EMBL; AK290362; BAF83051.1; -; mRNA.
DR CCDS; CCDS34042.1; -. [Q02224-1]
DR CCDS; CCDS68768.1; -. [Q02224-3]
DR PIR; S28261; S28261.
DR RefSeq; NP_001273663.1; NM_001286734.1. [Q02224-3]
DR RefSeq; NP_001804.2; NM_001813.2. [Q02224-1]
DR PDB; 1T5C; X-ray; 2.50 A; A/B=2-342.
DR PDB; 5JVP; X-ray; 2.10 A; A/B/C/D/E/F=336-371.
DR PDB; 6M4I; X-ray; 1.90 A; A/B=1-339.
DR PDBsum; 1T5C; -.
DR PDBsum; 5JVP; -.
DR PDBsum; 6M4I; -.
DR SMR; Q02224; -.
DR BioGRID; 107491; 66.
DR DIP; DIP-38902N; -.
DR IntAct; Q02224; 32.
DR MINT; Q02224; -.
DR STRING; 9606.ENSP00000265148; -.
DR BindingDB; Q02224; -.
DR ChEMBL; CHEMBL5870; -.
DR DrugBank; DB06097; GSK-923295.
DR iPTMnet; Q02224; -.
DR PhosphoSitePlus; Q02224; -.
DR BioMuta; CENPE; -.
DR DMDM; 160358869; -.
DR EPD; Q02224; -.
DR jPOST; Q02224; -.
DR MassIVE; Q02224; -.
DR MaxQB; Q02224; -.
DR PaxDb; Q02224; -.
DR PeptideAtlas; Q02224; -.
DR PRIDE; Q02224; -.
DR ProteomicsDB; 58063; -. [Q02224-1]
DR ProteomicsDB; 58065; -. [Q02224-3]
DR Antibodypedia; 26097; 239 antibodies from 30 providers.
DR DNASU; 1062; -.
DR Ensembl; ENST00000265148.9; ENSP00000265148.3; ENSG00000138778.14. [Q02224-1]
DR Ensembl; ENST00000380026.8; ENSP00000369365.3; ENSG00000138778.14. [Q02224-3]
DR GeneID; 1062; -.
DR KEGG; hsa:1062; -.
DR MANE-Select; ENST00000265148.9; ENSP00000265148.3; NM_001813.3; NP_001804.2.
DR UCSC; uc003hxb.1; human. [Q02224-1]
DR CTD; 1062; -.
DR DisGeNET; 1062; -.
DR GeneCards; CENPE; -.
DR HGNC; HGNC:1856; CENPE.
DR HPA; ENSG00000138778; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; CENPE; -.
DR MIM; 117143; gene.
DR MIM; 616051; phenotype.
DR neXtProt; NX_Q02224; -.
DR OpenTargets; ENSG00000138778; -.
DR Orphanet; 808; Seckel syndrome.
DR PharmGKB; PA26400; -.
DR VEuPathDB; HostDB:ENSG00000138778; -.
DR eggNOG; KOG0242; Eukaryota.
DR GeneTree; ENSGT00940000160597; -.
DR HOGENOM; CLU_000713_1_0_1; -.
DR InParanoid; Q02224; -.
DR OMA; RRCAASW; -.
DR OrthoDB; 21522at2759; -.
DR PhylomeDB; Q02224; -.
DR TreeFam; TF330343; -.
DR PathwayCommons; Q02224; -.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR Reactome; R-HSA-983189; Kinesins.
DR SignaLink; Q02224; -.
DR SIGNOR; Q02224; -.
DR BioGRID-ORCS; 1062; 663 hits in 1056 CRISPR screens.
DR ChiTaRS; CENPE; human.
DR EvolutionaryTrace; Q02224; -.
DR GeneWiki; Centromere_protein_E; -.
DR GenomeRNAi; 1062; -.
DR Pharos; Q02224; Tchem.
DR PRO; PR:Q02224; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q02224; protein.
DR Bgee; ENSG00000138778; Expressed in oocyte and 117 other tissues.
DR ExpressionAtlas; Q02224; baseline and differential.
DR Genevisible; Q02224; HS.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0000775; C:chromosome, centromeric region; IDA:UniProtKB.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005828; C:kinetochore microtubule; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:HPA.
DR GO; GO:1990023; C:mitotic spindle midzone; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0051233; C:spindle midzone; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043515; F:kinetochore binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0003777; F:microtubule motor activity; IDA:UniProtKB.
DR GO; GO:0008574; F:plus-end-directed microtubule motor activity; IBA:GO_Central.
DR GO; GO:0051315; P:attachment of mitotic spindle microtubules to kinetochore; IMP:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0051382; P:kinetochore assembly; IDA:UniProtKB.
DR GO; GO:0099607; P:lateral attachment of mitotic spindle microtubules to kinetochore; IMP:UniProtKB.
DR GO; GO:0051310; P:metaphase plate congression; IMP:UniProtKB.
DR GO; GO:0099606; P:microtubule plus-end directed mitotic chromosome migration; IDA:UniProtKB.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0007079; P:mitotic chromosome movement towards spindle pole; IDA:UniProtKB.
DR GO; GO:0007080; P:mitotic metaphase plate congression; IMP:UniProtKB.
DR GO; GO:0007052; P:mitotic spindle organization; IMP:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:UniProtKB.
DR GO; GO:0030071; P:regulation of mitotic metaphase/anaphase transition; IMP:UniProtKB.
DR Gene3D; 3.40.850.10; -; 1.
DR InterPro; IPR019821; Kinesin_motor_CS.
DR InterPro; IPR001752; Kinesin_motor_dom.
DR InterPro; IPR036961; Kinesin_motor_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00225; Kinesin; 1.
DR PRINTS; PR00380; KINESINHEAVY.
DR SMART; SM00129; KISc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00411; KINESIN_MOTOR_1; 1.
DR PROSITE; PS50067; KINESIN_MOTOR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Centromere; Chromosome; Coiled coil; Cytoplasm; Cytoskeleton;
KW Developmental protein; Direct protein sequencing; Disease variant;
KW Kinetochore; Lipoprotein; Methylation; Microtubule; Mitosis; Motor protein;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Primary microcephaly;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..2698
FT /note="Centromere-associated protein E"
FT /id="PRO_0000125436"
FT PROPEP 2699..2701
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000396742"
FT DOMAIN 6..329
FT /note="Kinesin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT REGION 2126..2476
FT /note="Kinetochore-binding domain"
FT REGION 2355..2376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2508..2533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2510..2698
FT /note="Globular autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 2588..2701
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 336..2590
FT /evidence="ECO:0000255"
FT COMPBIAS 2602..2629
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 86..93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 611
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2083
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2389
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2639
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2647
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2698
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000305"
FT LIPID 2698
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:10852915"
FT VAR_SEQ 549..573
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_028820"
FT VAR_SEQ 1972..2068
FT /note="IQELQKKELQLLRVKEDVNMSHKKINEMEQLKKQFEAQNLSMQSVRMDNFQL
FT TKKLHESLEEIRIVAKERDELRRIKESLKMERDQFIATLREMIAR -> Q (in
FT isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_028821"
FT VARIANT 933
FT /note="D -> N (in MCPH13; results in defective mitotic
FT spindle formation and chromosome segregation; results in
FT delayed mitotic progression; dbSNP:rs144716013)"
FT /evidence="ECO:0000269|PubMed:24748105"
FT /id="VAR_072429"
FT VARIANT 1355
FT /note="K -> E (in MCPH13; results in defective mitotic
FT spindle formation and chromosome segregation; results in
FT delayed mitotic progression; dbSNP:rs141488085)"
FT /evidence="ECO:0000269|PubMed:24748105"
FT /id="VAR_072430"
FT VARIANT 1535
FT /note="F -> L (in dbSNP:rs2615542)"
FT /evidence="ECO:0000269|PubMed:1406971,
FT ECO:0000269|PubMed:24748105"
FT /id="VAR_049689"
FT VARIANT 1581
FT /note="S -> R (in dbSNP:rs35100664)"
FT /id="VAR_049690"
FT VARIANT 1911
FT /note="S -> T (in dbSNP:rs1381657)"
FT /id="VAR_059370"
FT VARIANT 1925
FT /note="E -> D (in dbSNP:rs2306106)"
FT /id="VAR_049691"
FT VARIANT 2090
FT /note="T -> M (in dbSNP:rs2243682)"
FT /evidence="ECO:0000269|PubMed:1406971,
FT ECO:0000269|PubMed:24748105"
FT /id="VAR_049692"
FT CONFLICT 51
FT /note="R -> H (in Ref. 5; BAF83051)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="A -> P (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="F -> S (in Ref. 2; BAE06078)"
FT /evidence="ECO:0000305"
FT CONFLICT 566
FT /note="A -> R (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT CONFLICT 902
FT /note="T -> P (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT CONFLICT 1297
FT /note="E -> K (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT CONFLICT 1546
FT /note="K -> N (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT CONFLICT 1876
FT /note="K -> E (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT CONFLICT 2008..2017
FT /note="AQNLSMQSVR -> PNYLCKCE (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT CONFLICT 2131..2166
FT /note="Missing (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT CONFLICT 2190
FT /note="S -> C (in Ref. 1; CAA78727)"
FT /evidence="ECO:0000305"
FT STRAND 7..13
FT /evidence="ECO:0007829|PDB:6M4I"
FT TURN 22..25
FT /evidence="ECO:0007829|PDB:1T5C"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 59..66
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 68..75
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 92..96
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:1T5C"
FT HELIX 105..116
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 123..135
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:6M4I"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:6M4I"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:1T5C"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 170..174
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 175..190
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 204..215
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 226..235
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:1T5C"
FT HELIX 260..273
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 287..291
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:6M4I"
FT STRAND 298..308
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 314..326
FT /evidence="ECO:0007829|PDB:6M4I"
FT HELIX 341..376
FT /evidence="ECO:0007829|PDB:5JVP"
SQ SEQUENCE 2701 AA; 316415 MW; 4BC59C2EF0B02D88 CRC64;
MAEEGAVAVC VRVRPLNSRE ESLGETAQVY WKTDNNVIYQ VDGSKSFNFD RVFHGNETTK
NVYEEIAAPI IDSAIQGYNG TIFAYGQTAS GKTYTMMGSE DHLGVIPRAI HDIFQKIKKF
PDREFLLRVS YMEIYNETIT DLLCGTQKMK PLIIREDVNR NVYVADLTEE VVYTSEMALK
WITKGEKSRH YGETKMNQRS SRSHTIFRMI LESREKGEPS NCEGSVKVSH LNLVDLAGSE
RAAQTGAAGV RLKEGCNINR SLFILGQVIK KLSDGQVGGF INYRDSKLTR ILQNSLGGNA
KTRIICTITP VSFDETLTAL QFASTAKYMK NTPYVNEVST DEALLKRYRK EIMDLKKQLE
EVSLETRAQA MEKDQLAQLL EEKDLLQKVQ NEKIENLTRM LVTSSSLTLQ QELKAKRKRR
VTWCLGKINK MKNSNYADQF NIPTNITTKT HKLSINLLRE IDESVCSESD VFSNTLDTLS
EIEWNPATKL LNQENIESEL NSLRADYDNL VLDYEQLRTE KEEMELKLKE KNDLDEFEAL
ERKTKKDQEM QLIHEISNLK NLVKHAEVYN QDLENELSSK VELLREKEDQ IKKLQEYIDS
QKLENIKMDL SYSLESIEDP KQMKQTLFDA ETVALDAKRE SAFLRSENLE LKEKMKELAT
TYKQMENDIQ LYQSQLEAKK KMQVDLEKEL QSAFNEITKL TSLIDGKVPK DLLCNLELEG
KITDLQKELN KEVEENEALR EEVILLSELK SLPSEVERLR KEIQDKSEEL HIITSEKDKL
FSEVVHKESR VQGLLEEIGK TKDDLATTQS NYKSTDQEFQ NFKTLHMDFE QKYKMVLEEN
ERMNQEIVNL SKEAQKFDSS LGALKTELSY KTQELQEKTR EVQERLNEME QLKEQLENRD
STLQTVEREK TLITEKLQQT LEEVKTLTQE KDDLKQLQES LQIERDQLKS DIHDTVNMNI
DTQEQLRNAL ESLKQHQETI NTLKSKISEE VSRNLHMEEN TGETKDEFQQ KMVGIDKKQD
LEAKNTQTLT ADVKDNEIIE QQRKIFSLIQ EKNELQQMLE SVIAEKEQLK TDLKENIEMT
IENQEELRLL GDELKKQQEI VAQEKNHAIK KEGELSRTCD RLAEVEEKLK EKSQQLQEKQ
QQLLNVQEEM SEMQKKINEI ENLKNELKNK ELTLEHMETE RLELAQKLNE NYEEVKSITK
ERKVLKELQK SFETERDHLR GYIREIEATG LQTKEELKIA HIHLKEHQET IDELRRSVSE
KTAQIINTQD LEKSHTKLQE EIPVLHEEQE LLPNVKEVSE TQETMNELEL LTEQSTTKDS
TTLARIEMER LRLNEKFQES QEEIKSLTKE RDNLKTIKEA LEVKHDQLKE HIRETLAKIQ
ESQSKQEQSL NMKEKDNETT KIVSEMEQFK PKDSALLRIE IEMLGLSKRL QESHDEMKSV
AKEKDDLQRL QEVLQSESDQ LKENIKEIVA KHLETEEELK VAHCCLKEQE ETINELRVNL
SEKETEISTI QKQLEAINDK LQNKIQEIYE KEEQFNIKQI SEVQEKVNEL KQFKEHRKAK
DSALQSIESK MLELTNRLQE SQEEIQIMIK EKEEMKRVQE ALQIERDQLK ENTKEIVAKM
KESQEKEYQF LKMTAVNETQ EKMCEIEHLK EQFETQKLNL ENIETENIRL TQILHENLEE
MRSVTKERDD LRSVEETLKV ERDQLKENLR ETITRDLEKQ EELKIVHMHL KEHQETIDKL
RGIVSEKTNE ISNMQKDLEH SNDALKAQDL KIQEELRIAH MHLKEQQETI DKLRGIVSEK
TDKLSNMQKD LENSNAKLQE KIQELKANEH QLITLKKDVN ETQKKVSEME QLKKQIKDQS
LTLSKLEIEN LNLAQKLHEN LEEMKSVMKE RDNLRRVEET LKLERDQLKE SLQETKARDL
EIQQELKTAR MLSKEHKETV DKLREKISEK TIQISDIQKD LDKSKDELQK KIQELQKKEL
QLLRVKEDVN MSHKKINEME QLKKQFEAQN LSMQSVRMDN FQLTKKLHES LEEIRIVAKE
RDELRRIKES LKMERDQFIA TLREMIARDR QNHQVKPEKR LLSDGQQHLT ESLREKCSRI
KELLKRYSEM DDHYECLNRL SLDLEKEIEF QKELSMRVKA NLSLPYLQTK HIEKLFTANQ
RCSMEFHRIM KKLKYVLSYV TKIKEEQHES INKFEMDFID EVEKQKELLI KIQHLQQDCD
VPSRELRDLK LNQNMDLHIE EILKDFSESE FPSIKTEFQQ VLSNRKEMTQ FLEEWLNTRF
DIEKLKNGIQ KENDRICQVN NFFNNRIIAI MNESTEFEER SATISKEWEQ DLKSLKEKNE
KLFKNYQTLK TSLASGAQVN PTTQDNKNPH VTSRATQLTT EKIRELENSL HEAKESAMHK
ESKIIKMQKE LEVTNDIIAK LQAKVHESNK CLEKTKETIQ VLQDKVALGA KPYKEEIEDL
KMKLVKIDLE KMKNAKEFEK EISATKATVE YQKEVIRLLR ENLRRSQQAQ DTSVISEHTD
PQPSNKPLTC GGGSGIVQNT KALILKSEHI RLEKEISKLK QQNEQLIKQK NELLSNNQHL
SNEVKTWKER TLKREAHKQV TCENSPKSPK VTGTASKKKQ ITPSQCKERN LQDPVPKESP
KSCFFDSRSK SLPSPHPVRY FDNSSLGLCP EVQNAGAESV DSQPGPWHAS SGKDVPECKT
Q
