SEP1_CAEEL
ID SEP1_CAEEL Reviewed; 1262 AA.
AC G5ED39;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Separin homolog sep-1 {ECO:0000305};
DE EC=3.4.22.49 {ECO:0000305|PubMed:25919583};
DE AltName: Full=Separase {ECO:0000312|WormBase:Y47G6A.12};
GN Name=sep-1 {ECO:0000312|WormBase:Y47G6A.12};
GN ORFNames=Y47G6A.12 {ECO:0000312|WormBase:Y47G6A.12};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAK77200.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS
RP OF CYS-450.
RX PubMed=11728305; DOI=10.1016/s0960-9822(01)00588-7;
RA Siomos M.F., Badrinath A., Pasierbek P., Livingstone D., White J.,
RA Glotzer M., Nasmyth K.;
RT "Separase is required for chromosome segregation during meiosis I in
RT Caenorhabditis elegans.";
RL Curr. Biol. 11:1825-1835(2001).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH IFY-1, AND DISRUPTION PHENOTYPE.
RX PubMed=12498686; DOI=10.1016/s0960-9822(02)01392-1;
RA Kitagawa R., Law E., Tang L., Rose A.M.;
RT "The Cdc20 homolog, FZY-1, and its interacting protein, IFY-1, are required
RT for proper chromosome segregation in Caenorhabditis elegans.";
RL Curr. Biol. 12:2118-2123(2002).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11832245; DOI=10.1016/s1534-5807(02)00114-4;
RA Rappleye C.A., Tagawa A., Lyczak R., Bowerman B., Aroian R.V.;
RT "The anaphase-promoting complex and separin are required for embryonic
RT anterior-posterior axis formation.";
RL Dev. Cell 2:195-206(2002).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-450.
RX PubMed=17913784; DOI=10.1242/dev.011361;
RA Bembenek J.N., Richie C.T., Squirrell J.M., Campbell J.M., Eliceiri K.W.,
RA Poteryaev D., Spang A., Golden A., White J.G.;
RT "Cortical granule exocytosis in C. elegans is regulated by cell cycle
RT components including separase.";
RL Development 134:3837-3848(2007).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF CYS-450 AND CYS-1040.
RX PubMed=20116245; DOI=10.1016/j.cub.2009.12.045;
RA Bembenek J.N., White J.G., Zheng Y.;
RT "A role for separase in the regulation of RAB-11-positive vesicles at the
RT cleavage furrow and midbody.";
RL Curr. Biol. 20:259-264(2010).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP CYS-232 AND LEU-556.
RX PubMed=21878498; DOI=10.1242/jcs.073379;
RA Richie C.T., Bembenek J.N., Chestnut B., Furuta T., Schumacher J.M.,
RA Wallenfang M., Golden A.;
RT "Protein phosphatase 5 is a negative regulator of separase function during
RT cortical granule exocytosis in C. elegans.";
RL J. Cell Sci. 124:2903-2913(2011).
RN [8] {ECO:0000305}
RP ACTIVITY REGULATION, INTERACTION WITH IFY-1, AND DISRUPTION PHENOTYPE.
RX PubMed=23578927; DOI=10.1242/dev.090688;
RA Wang R., Kaul Z., Ambardekar C., Yamamoto T.G., Kavdia K., Kodali K.,
RA High A.A., Kitagawa R.;
RT "HECT-E3 ligase ETC-1 regulates securin and cyclin B1 cytoplasmic abundance
RT to promote timely anaphase during meiosis in C. elegans.";
RL Development 140:2149-2159(2013).
RN [9] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP CYS-450.
RX PubMed=23401519; DOI=10.1073/pnas.1213888110;
RA Schvarzstein M., Pattabiraman D., Bembenek J.N., Villeneuve A.M.;
RT "Meiotic HORMA domain proteins prevent untimely centriole disengagement
RT during Caenorhabditis elegans spermatocyte meiosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E898-E907(2013).
RN [10] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=25919583; DOI=10.1371/journal.pone.0125382;
RA Monen J., Hattersley N., Muroyama A., Stevens D., Oegema K., Desai A.;
RT "Separase Cleaves the N-Tail of the CENP-A Related Protein CPAR-1 at the
RT Meiosis I Metaphase-Anaphase Transition in C. elegans.";
RL PLoS ONE 10:E0125382-E0125382(2015).
RN [11] {ECO:0000305}
RP STRUCTURE BY ELECTRON MICROSCOPY (24 ANGSTROMS) IN COMPLEX WITH IFY-1, AND
RP ACTIVITY REGULATION.
RX PubMed=27249343; DOI=10.1098/rsob.160032;
RA Bachmann G., Richards M.W., Winter A., Beuron F., Morris E., Bayliss R.;
RT "A closed conformation of the Caenorhabditis elegans separase-securin
RT complex.";
RL Open Biol. 6:160032-160032(2016).
RN [12] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) IN COMPLEX WITH IFY-1, AND ACTIVITY
RP REGULATION.
RX PubMed=28263324; DOI=10.1038/nsmb.3386;
RA Boland A., Martin T.G., Zhang Z., Yang J., Bai X.C., Chang L.,
RA Scheres S.H., Barford D.;
RT "Cryo-EM structure of a metazoan separase-securin complex at near-atomic
RT resolution.";
RL Nat. Struct. Mol. Biol. 24:414-418(2017).
CC -!- FUNCTION: Cysteine protease, which plays a central role in homologous
CC chromosome separation during meiosis I and in sister chromatid
CC separation during embryonic mitosis (PubMed:11728305, PubMed:12498686,
CC PubMed:20116245, PubMed:21878498). Promotes chromosome/sister chromatid
CC segregation by cleaving the scc-1 (mitosis) and rec-8 (meiosis)
CC subunits of the cohesin complex at the onset of anaphase (Probable).
CC May cleave histone H3-like protein cpar-1 during meiosis I metaphase-
CC anaphase transition (PubMed:25919583). Promotes cortical granule
CC exocytosis after oocyte fertilization during the first meiotic anaphase
CC (PubMed:17913784, PubMed:21878498). Essential for embryonic cytokinesis
CC by regulating rab-11-positive vesicle trafficking at the plasma
CC membrane at the cleavage furrow and midbody (PubMed:20116245).
CC Regulates centriole segregation during spermatocyte meiosis
CC (PubMed:23401519). Required for embryonic anterior-posterior axis
CC formation (PubMed:11832245). {ECO:0000269|PubMed:11728305,
CC ECO:0000269|PubMed:11832245, ECO:0000269|PubMed:12498686,
CC ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245,
CC ECO:0000269|PubMed:21878498, ECO:0000269|PubMed:23401519,
CC ECO:0000269|PubMed:25919583, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=All bonds known to be hydrolyzed by this endopeptidase have
CC arginine in P1 and an acidic residue in P4. P6 is often occupied by
CC an acidic residue or by a hydroxy-amino-acid residue, the
CC phosphorylation of which enhances cleavage.; EC=3.4.22.49;
CC Evidence={ECO:0000305|PubMed:25919583};
CC -!- ACTIVITY REGULATION: Probably maintained in an inactive state via its
CC interaction with securin ify-1 which acts as a pseudosubstrate thereby
CC blocking access to the catalytic site. Upon ify-1 degradation at the
CC onset of anaphase, sep-1 is likely to become active. In addition,
CC interaction with ify-1 stabilizes sep-1. {ECO:0000305|PubMed:23578927,
CC ECO:0000305|PubMed:27249343, ECO:0000305|PubMed:28263324}.
CC -!- SUBUNIT: Forms a complex with securin-like protein ify-1 (via C-
CC terminus) (PubMed:12498686, PubMed:23578927, PubMed:27249343,
CC PubMed:28263324). Interaction with ify-1 stabilizes sep-1
CC (PubMed:27249343, PubMed:28263324). Also maintains the complex in the
CC cytoplasm during interphase and recruits it to chromosomes during the
CC first meiotic division (PubMed:23578927). {ECO:0000269|PubMed:12498686,
CC ECO:0000269|PubMed:23578927, ECO:0000269|PubMed:27249343,
CC ECO:0000269|PubMed:28263324}.
CC -!- INTERACTION:
CC G5ED39; Q18235: ify-1; NbExp=4; IntAct=EBI-326265, EBI-331643;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17913784,
CC ECO:0000269|PubMed:23401519}. Chromosome {ECO:0000269|PubMed:17913784,
CC ECO:0000269|PubMed:20116245, ECO:0000269|PubMed:23401519}. Cytoplasmic
CC granule {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:21878498}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:17913784}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245,
CC ECO:0000269|PubMed:23401519}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245,
CC ECO:0000269|PubMed:21878498}. Cleavage furrow
CC {ECO:0000269|PubMed:20116245}. Midbody {ECO:0000269|PubMed:20116245}.
CC Note=Before ovulation, accumulates on chromosomes and cortical
CC filaments in oocytes (PubMed:17913784). By metaphase I, dissociates
CC from filaments and transiently localizes to cortical granules until
CC their exocytosis during anaphase I followed by an accumulation at the
CC cortex near the polar body (PubMed:17913784). Localizes to meiotic
CC spindle matrix (PubMed:21878498). During mitotic metaphase and
CC anaphase, localizes to chromosomes, centrosomes and the spindle matrix
CC (PubMed:17913784, PubMed:20116245, PubMed:21878498). During
CC spermatogenesis, localizes to the spermatocyte cytoplasm throughout
CC meiotic prophase I (PubMed:23401519). At the diplotene stage of
CC prophase I accumulates at low levels in puncta around the nuclear
CC envelope (PubMed:23401519). At diakinesis, transiently localizes to
CC centrosomes until nuclear envelope breakdown (PubMed:23401519). At
CC metaphase I and II becomes highly enriched around chromosomes
CC (PubMed:23401519). At anaphase I and II, chromosomal localization is
CC reduced and centrosome localization is highly increased
CC (PubMed:23401519). Localizes to residual body during the budding
CC division leading to spermatid formation (PubMed:23401519).
CC {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245,
CC ECO:0000269|PubMed:21878498, ECO:0000269|PubMed:23401519}.
CC -!- TISSUE SPECIFICITY: Expressed in oocytes (PubMed:17913784). Expressed
CC in male germline (PubMed:23401519). Expressed in spermatocytes but
CC undetectable in spermatids (at protein level) (PubMed:23401519).
CC {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:23401519}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos (at protein level).
CC {ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes embryonic
CC lethality where embryos are arrested at the onset of meiotic anaphase I
CC (PubMed:11728305, PubMed:12498686, PubMed:23578927). During the first
CC meiotic cell division, homologous chromosome segregation and formation
CC of polar bodies are impaired, and multiple centrosomes accumulate
CC resulting from a failure to undergo cytokinesis (PubMed:11728305,
CC PubMed:12498686, PubMed:17913784, PubMed:20116245, PubMed:21878498).
CC During meiotic anaphase I, impaired cortical granules exocytosis
CC resulting in the formation of a one-layered eggshell instead of the
CC normal three-layered eggshell (PubMed:11728305, PubMed:17913784,
CC PubMed:21878498). In oocytes, ify-1 prematurely enters the nucleus
CC prior to the nuclear envelope breakdown and fails to associate with
CC chromosomes during meiosis I without affecting its spindle association
CC (PubMed:23578927). Prevents histone H3-like cpar-1 cleavage at the
CC onset of meiotic anaphase I and during embryonic mitosis
CC (PubMed:25919583). In addition, in the one-cell embryo, causes defects
CC in embryonic anterior-posterior polarization characterized by a failure
CC of cortical association and posterior positioning of the paternal
CC pronucleus and the mislocalization of par-2 and pie-1
CC (PubMed:11832245). During the first embryonic mitosis, abnormal
CC accumulation of rab-11 at the cleavage furrow and midbody and furrow
CC regression resulting in a failure to complete cytokinesis
CC (PubMed:20116245). {ECO:0000269|PubMed:11728305,
CC ECO:0000269|PubMed:11832245, ECO:0000269|PubMed:12498686,
CC ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245,
CC ECO:0000269|PubMed:21878498, ECO:0000269|PubMed:23578927,
CC ECO:0000269|PubMed:25919583}.
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DR EMBL; AF399825; AAK77200.1; -; mRNA.
DR EMBL; BX284601; CCD72557.1; -; Genomic_DNA.
DR RefSeq; NP_491160.1; NM_058759.3.
DR PDB; 5MZ6; EM; 3.80 A; 1=1-1262.
DR PDBsum; 5MZ6; -.
DR AlphaFoldDB; G5ED39; -.
DR SMR; G5ED39; -.
DR ComplexPortal; CPX-1411; Separase-Securin complex.
DR IntAct; G5ED39; 3.
DR STRING; 6239.Y47G6A.12; -.
DR MEROPS; C50.004; -.
DR EPD; G5ED39; -.
DR PaxDb; G5ED39; -.
DR PeptideAtlas; G5ED39; -.
DR EnsemblMetazoa; Y47G6A.12.1; Y47G6A.12.1; WBGene00004775.
DR GeneID; 171912; -.
DR KEGG; cel:CELE_Y47G6A.12; -.
DR CTD; 171912; -.
DR WormBase; Y47G6A.12; CE22098; WBGene00004775; sep-1.
DR eggNOG; KOG1849; Eukaryota.
DR GeneTree; ENSGT00390000004990; -.
DR HOGENOM; CLU_278759_0_0_1; -.
DR InParanoid; G5ED39; -.
DR OMA; YARTACK; -.
DR OrthoDB; 142006at2759; -.
DR BRENDA; 3.4.22.49; 1045.
DR Reactome; R-CEL-2467813; Separation of Sister Chromatids.
DR SignaLink; G5ED39; -.
DR PRO; PR:G5ED39; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00004775; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005938; C:cell cortex; IDA:WormBase.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0032154; C:cleavage furrow; IDA:WormBase.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:WormBase.
DR GO; GO:0060473; C:cortical granule; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0072687; C:meiotic spindle; IDA:WormBase.
DR GO; GO:0070090; C:metaphase plate; IDA:WormBase.
DR GO; GO:0030496; C:midbody; IDA:WormBase.
DR GO; GO:0072686; C:mitotic spindle; IDA:WormBase.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1990520; C:separase-securin complex; IDA:ComplexPortal.
DR GO; GO:0005819; C:spindle; IDA:WormBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:WormBase.
DR GO; GO:0060471; P:cortical granule exocytosis; IMP:WormBase.
DR GO; GO:0030703; P:eggshell formation; IMP:UniProtKB.
DR GO; GO:0034090; P:maintenance of meiotic sister chromatid cohesion; IMP:ComplexPortal.
DR GO; GO:0034088; P:maintenance of mitotic sister chromatid cohesion; IMP:ComplexPortal.
DR GO; GO:0051307; P:meiotic chromosome separation; IMP:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB.
DR GO; GO:0051306; P:mitotic sister chromatid separation; IMP:UniProtKB.
DR GO; GO:0048609; P:multicellular organismal reproductive process; IMP:WormBase.
DR GO; GO:0040038; P:polar body extrusion after meiotic divisions; IMP:UniProtKB.
DR GO; GO:0009949; P:polarity specification of anterior/posterior axis; IMP:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IMP:UniProtKB.
DR GO; GO:0030997; P:regulation of centriole-centriole cohesion; IMP:UniProtKB.
DR GO; GO:0017157; P:regulation of exocytosis; IMP:UniProtKB.
DR GO; GO:0040012; P:regulation of locomotion; IMP:WormBase.
DR GO; GO:0061062; P:regulation of nematode larval development; IMP:WormBase.
DR DisProt; DP03050; -.
DR InterPro; IPR005314; Peptidase_C50.
DR InterPro; IPR030397; SEPARIN_core_dom.
DR PANTHER; PTHR12792; PTHR12792; 2.
DR PROSITE; PS51700; SEPARIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Chromosome; Chromosome partition;
KW Cytoplasm; Cytoskeleton; Hydrolase; Meiosis; Mitosis; Protease;
KW Reference proteome; Thiol protease.
FT CHAIN 1..1262
FT /note="Separin homolog sep-1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000440177"
FT DOMAIN 957..1051
FT /note="Peptidase C50"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01037"
FT REGION 1147..1262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1147..1199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1212..1228
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1242..1262
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1040
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01037"
FT MUTAGEN 232
FT /note="C->Y: In ax521; embryos are arrested at the one-cell
FT stage. No extrusion of polar bodies. Multiple rounds of DNA
FT replication occur without cytokinesis. Slower chromosome
FT segregation during the first embryonic mitosis but no
FT chromosome separation defects during meiosis. Reduced
FT cortical granules exocytosis during anaphase I resulting in
FT eggshell defects. Loss of cortical granule localization."
FT /evidence="ECO:0000269|PubMed:21878498"
FT MUTAGEN 450
FT /note="C->Y: In e2406; temperature sensitive mutant which
FT at the restrictive temperature of 25 degrees Celsius
FT displays slow chromosome segregation and lacks cytokinesis
FT in the one-cell stage embryo and during meiosis I. Reduced
FT cortical granules exocytosis during anaphase I. Loss of
FT cortical granule localization. Loss of cytokinesis
FT resulting from furrow regression. At the end of second
FT meiotic division, causes a premature dissociation of the
FT two centrioles in spermatocytes. Permanent localization to
FT centrosome throughout meiosis. Abnormal localization to
FT sperm DNA in to a foci near the sperm chromatin in
FT fertilized embryos."
FT /evidence="ECO:0000269|PubMed:11728305,
FT ECO:0000269|PubMed:17913784, ECO:0000269|PubMed:20116245,
FT ECO:0000269|PubMed:23401519"
FT MUTAGEN 556
FT /note="L->F: In ax110; embryos are arrested at the one-cell
FT stage. No extrusion of polar bodies. Multiple rounds of DNA
FT replication occur without cytokinesis. Slower chromosome
FT segregation during the first embryonic mitosis but no
FT chromosome separation defects during meiosis. Reduced
FT cortical granules exocytosis during anaphase I resulting in
FT eggshell defects. Loss of meiotic spindle and cortical
FT granule localization. In a php-5 (av101) mutant background,
FT cortical granule exocytosis and chromosome segregation are
FT normal."
FT /evidence="ECO:0000269|PubMed:21878498"
FT MUTAGEN 1040
FT /note="C->S: Probable loss of catalytic activity. Stronger
FT accumulation at chromosomes, centrosomes, spindle, cleavage
FT furrow and midbody during the first embryonic mitosis."
FT /evidence="ECO:0000269|PubMed:20116245"
SQ SEQUENCE 1262 AA; 144121 MW; 4CBAAB9E0330CEB3 CRC64;
MKITNKSVDK QHIEKLDELR KNVSCTVIGF AEQTAELQQE ISELFIAEFG VNGPIDMNSL
SKLARITSYY ASSEYFQGLA KYQRTACKMF ITWQTLRKEA MECRSKDREI FASIPAKLCF
FYFYNGELCR AVVCLLDYID LSDDTLAKEA ALRWLMFLGE TELIEKKLKT WKMDKSSKDM
FSATEFAMNY LKKSEYRVEM LEKLMKLRDK VKSDPTRSFS RYELASYVSW LCSTLSNVPV
GSALRECEFP DRVSHIQEAA LKSDSLVRNR IPGLASSQFD NSVNASIWPF LDGHQEDSNY
YVHIGSTIAW HFEMRRECAL VNVTTAQTRD SMSAMILNLR VALKSASFFR VLQTTNTLAY
YSSIIEEAGS EKNAKLMRVS CVNLLSSNPI IVRCSTPKET GATSRAHTPM AGSSVSEKQN
TMRPDLADLL GDLELLDEQS FHPITRSCVC NVCTIYPLHS SFAAEYMMSY AIHSDFSQLS
IKHFNDEFAR IRERGMSSQV LMHRDSSVRP RPNIIQNEIF GMCVIRWLTK KLDSKESADE
DTMEIFNNAL KIVRYLQQRT TDMILAVTQL GRQLEFPMEC NYSWMRPTIR KPRVKATIDC
AVDILRAVSP FGRRPKVEKL EKNLQPFDKE RFEKVRLAMR NEMNHYGHIL YREWRCRLFA
YVGRTSRDPW EAAYAWAEST QIGARNAVQS RLEKCKRGLV TMSGHDRFKT CVQSMPDEMT
LVQIAMADDK TIYLVKLHAD RDPIIMPLAH YSQAVELMDK FTFLLDEDEM IAKYPGDITP
EEFWKRRKIV DGRMMTFVDE VQKHFLGVAA SLLMPSGQLG PKAAELAIKI HKLSKGGLLL
GEAKEMVYQS KLMDAKSWEA LILRFCEMRT TDEKFKSFLP LMHRNSVEVM NQDDSIVTEK
KYTYLVICPH LSQFCWERLP IFDEYPYVGR QVSIHSTFSQ LEAMKSQEKQ IPLQIDVQNA
YYILDPDNNL GETQKRMVEY INKFNWEGTV GSAPKSNEIS AALSQRDAFF FIGHGSGSSV
MPRSVLKQST CNAISLLMGC GSVRTIPQAL GFDGKTAILD YAMAKCPLIV GCLWTVTDGE
IDRFLIRMID DCFEDSKSLT GIDKLRQLSE AMHEARSKAR LKYLTGAAVV MYGLPVVAKQ
TTPFVEKDQR NLPQTPKTSA RTSMRMETVP KTPKQEFVTS KSVPMTPIFS NNENKSPSRA
RMPSRVLKTP RQVKTFQEED DEAPKRSTTR QLKPLVAPPI PATPTTRTTR SSARTPSRSR
NL
