ID MTMRD_HUMAN Reviewed; 1849 AA. AC Q86WG5; Q3MJF0; Q68DQ3; Q6P459; Q6PJD1; Q7Z325; Q7Z621; Q86VE2; Q96FE2; AC Q9C097; DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 24-JAN-2024, entry version 168. DE RecName: Full=Myotubularin-related protein 13 {ECO:0000305}; DE AltName: Full=Inactive phosphatidylinositol 3-phosphatase 13 {ECO:0000305}; DE AltName: Full=SET-binding factor 2 {ECO:0000303|PubMed:12554688}; GN Name=SBF2; Synonyms=CMT4B2, KIAA1766, MTMR13; 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), INVOLVEMENT IN CMT4B2, AND TISSUE RP SPECIFICITY. RC TISSUE=Sciatic nerve; RX PubMed=12554688; DOI=10.1093/hmg/ddg030; RA Senderek J., Bergmann C., Weber S., Ketelsen U.-P., Schorle H., RA Rudnik-Schoeneborn S., Buettner R., Buchheim E., Zerres K.; RT "Mutation of the SBF2 gene, encoding a novel member of the myotubularin RT family, in Charcot-Marie-Tooth neuropathy type 4B2/11p15."; RL Hum. Mol. Genet. 12:349-356(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-1216. RC TISSUE=Brain, Cervix, Duodenum, and Placenta; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 30-1152 (ISOFORM 3). RX PubMed=11214970; DOI=10.1093/dnares/7.6.347; RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIX. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:347-355(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1187-1849 (ISOFORM 1). RC TISSUE=Fetal brain, and Liver; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP INVOLVEMENT IN CMT4B2. RX PubMed=12687498; DOI=10.1086/375034; RA Azzedine H., Bolino A., Taieb T., Birouk N., Di Duca M., Bouhouche A., RA Benamou S., Mrabet A., Hammadouche T., Chkili T., Gouider R., Ravazzolo R., RA Brice A., Laporte J., LeGuern E.; RT "Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, RT in two families with an autosomal recessive demyelinating form of Charcot- RT Marie-Tooth disease associated with early-onset glaucoma."; RL Am. J. Hum. Genet. 72:1141-1153(2003). RN [6] RP INVOLVEMENT IN CMT4B2. RX PubMed=15304601; DOI=10.1212/01.wnl.0000133211.40288.9a; RA Hirano R., Takashima H., Umehara F., Arimura H., Michizono K., Okamoto Y., RA Nakagawa M., Boerkoel C.F., Lupski J.R., Osame M., Arimura K.; RT "SET binding factor 2 (SBF2) mutation causes CMT4B with juvenile onset RT glaucoma."; RL Neurology 63:577-580(2004). RN [7] RP INVOLVEMENT IN CMT4B2. RX PubMed=15477569; DOI=10.1212/01.wnl.0000140617.02312.80; RA Conforti F.L., Muglia M., Mazzei R., Patitucci A., Valentino P., RA Magariello A., Sprovieri T., Bono F., Bergmann C., Gabriele A.L., RA Peluso G., Nistico R., Senderek J., Quattrone A.; RT "A new SBF2 mutation in a family with recessive demyelinating Charcot- RT Marie-Tooth (CMT4B2)."; RL Neurology 63:1327-1328(2004). RN [8] RP INTERACTION WITH MTMR2, SUBCELLULAR LOCATION, AND DOMAIN. RX PubMed=15998640; DOI=10.1074/jbc.m505159200; RA Robinson F.L., Dixon J.E.; RT "The phosphoinositide-3-phosphatase MTMR2 associates with MTMR13, a RT membrane-associated pseudophosphatase also mutated in type 4B Charcot- RT Marie-Tooth disease."; RL J. Biol. Chem. 280:31699-31707(2005). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP FUNCTION AS GUANYL-NUCLEOTIDE EXCHANGE FACTOR. RX PubMed=20937701; DOI=10.1083/jcb.201008051; RA Yoshimura S., Gerondopoulos A., Linford A., Rigden D.J., Barr F.A.; RT "Family-wide characterization of the DENN domain Rab GDP-GTP exchange RT factors."; RL J. Cell Biol. 191:367-381(2010). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1127, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1279, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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 [13] RP FUNCTION, AND INTERACTION WITH RAB21 AND VAMP8. RX PubMed=25648148; DOI=10.15252/embr.201439464; RA Jean S., Cox S., Nassari S., Kiger A.A.; RT "Starvation-induced MTMR13 and RAB21 activity regulates VAMP8 to promote RT autophagosome-lysosome fusion."; RL EMBO Rep. 16:297-311(2015). CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) which activates CC RAB21 and possibly RAB28 (PubMed:20937701, PubMed:25648148). Promotes CC the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins CC into their active GTP-bound form (PubMed:20937701, PubMed:25648148). In CC response to starvation-induced autophagy, activates RAB21 which in turn CC binds to and regulates SNARE protein VAMP8 endolysosomal transport CC required for SNARE-mediated autophagosome-lysosome fusion CC (PubMed:25648148). Acts as an adapter for the phosphatase MTMR2 (By CC similarity). Increases MTMR2 catalytic activity towards CC phosphatidylinositol 3,5-bisphosphate and to a lesser extent towards CC phosphatidylinositol 3-phosphate (By similarity). CC {ECO:0000250|UniProtKB:E9PXF8, ECO:0000269|PubMed:20937701, CC ECO:0000269|PubMed:25648148}. CC -!- SUBUNIT: Homodimer (By similarity). Heterotetramer consisting of one CC MTMR2 dimer and one SBF2/MTMR13 dimer (PubMed:15998640). Interacts with CC class II PI3-kinase PIK3C2A (By similarity). Interacts (via DENN CC domain) with RAB21 (in GDP-bound form) in response to starvation; the CC interaction activates RAB21 (PubMed:25648148). Interacts with VAMP8 in CC response to starvation (PubMed:25648148). CC {ECO:0000250|UniProtKB:E9PXF8, ECO:0000269|PubMed:15998640, CC ECO:0000269|PubMed:25648148}. CC -!- INTERACTION: CC Q86WG5; Q13643: FHL3; NbExp=3; IntAct=EBI-2683289, EBI-741101; CC Q86WG5; Q93062: RBPMS; NbExp=3; IntAct=EBI-2683289, EBI-740322; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15998640}. CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:E9PXF8}. Membrane CC {ECO:0000269|PubMed:15998640}; Peripheral membrane protein CC {ECO:0000269|PubMed:15998640}. Endosome membrane CC {ECO:0000250|UniProtKB:E9PXF8}; Peripheral membrane protein CC {ECO:0000305}. Cell projection, axon {ECO:0000250|UniProtKB:E9PXF8}. CC Note=Associated with membranes (PubMed:15998640). Localizes to vacuoles CC in hypo-osmotic conditions (By similarity). Membrane localization is CC likely to be mediated via its interaction with MTMR2 (By similarity). CC {ECO:0000250|UniProtKB:E9PXF8, ECO:0000269|PubMed:15998640}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q86WG5-1; Sequence=Displayed; CC Name=3; CC IsoId=Q86WG5-3; Sequence=VSP_017157, VSP_017158; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in spinal cord. CC {ECO:0000269|PubMed:12554688}. CC -!- DOMAIN: The C-terminal domain mediates homodimerization (By CC similarity). By mediating SBF2/MTMR13 homodimerization, indirectly CC involved in SBF2/MTMR13 and MTMR2 heterotetramerization (By CC similarity). {ECO:0000250|UniProtKB:E9PXF8}. CC -!- DOMAIN: The GRAM domain mediates binding to phosphatidylinositol 4- CC phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5- CC biphosphate and phosphatidylinositol 3,4,5-trisphosphate. CC {ECO:0000250|UniProtKB:E9PXF8}. CC -!- DOMAIN: The PH domain binds preferentially phosphatidylinositol 3,4,5- CC trisphosphate (By similarity). Appears to be dispensable for CC localization to membranes (By similarity). CC {ECO:0000250|UniProtKB:E9PXF8}. CC -!- DISEASE: Charcot-Marie-Tooth disease 4B2 (CMT4B2) [MIM:604563]: A CC recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder CC of the peripheral nervous system, characterized by progressive weakness CC and atrophy, initially of the peroneal muscles and later of the distal CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two CC main groups on the basis of electrophysiologic properties and CC histopathology: primary peripheral demyelinating neuropathies CC (designated CMT1 when they are dominantly inherited) and primary CC peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are CC characterized by severely reduced nerve conduction velocities (less CC than 38 m/sec), segmental demyelination and remyelination with onion CC bulb formations on nerve biopsy, slowly progressive distal muscle CC atrophy and weakness, absent deep tendon reflexes, and hollow feet. By CC convention autosomal recessive forms of demyelinating Charcot-Marie- CC Tooth disease are designated CMT4. {ECO:0000269|PubMed:12554688, CC ECO:0000269|PubMed:12687498, ECO:0000269|PubMed:15304601, CC ECO:0000269|PubMed:15477569}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non- CC receptor class myotubularin subfamily. {ECO:0000305}. CC -!- CAUTION: Although it belongs to the non-receptor class myotubularin CC subfamily, lacks the conserved active site cysteine residue at position CC 1410 in the dsPTPase catalytic loop, suggesting that it has no CC phosphatase activity. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="https://uantwerpen.vib.be/CMTMutations"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY234241; AAO62733.1; -; mRNA. DR EMBL; BC011143; AAH11143.1; -; mRNA. DR EMBL; BC043389; AAH43389.1; -; mRNA. DR EMBL; BC053867; AAH53867.1; -; mRNA. DR EMBL; BC063656; AAH63656.1; -; mRNA. DR EMBL; BC101466; AAI01467.1; -; mRNA. DR EMBL; AB051553; BAB21857.1; -; mRNA. DR EMBL; BX538184; CAD98056.1; -; mRNA. DR EMBL; CR749312; CAH18167.1; -; mRNA. DR CCDS; CCDS31427.1; -. [Q86WG5-1] DR RefSeq; NP_112224.1; NM_030962.3. [Q86WG5-1] DR AlphaFoldDB; Q86WG5; -. DR SMR; Q86WG5; -. DR BioGRID; 123597; 51. DR IntAct; Q86WG5; 23. DR MINT; Q86WG5; -. DR STRING; 9606.ENSP00000256190; -. DR DEPOD; SBF2; -. DR iPTMnet; Q86WG5; -. DR PhosphoSitePlus; Q86WG5; -. DR BioMuta; SBF2; -. DR DMDM; 74750502; -. DR EPD; Q86WG5; -. DR jPOST; Q86WG5; -. DR MassIVE; Q86WG5; -. DR MaxQB; Q86WG5; -. DR PaxDb; 9606-ENSP00000256190; -. DR PeptideAtlas; Q86WG5; -. DR ProteomicsDB; 70158; -. [Q86WG5-1] DR ProteomicsDB; 70159; -. [Q86WG5-3] DR Pumba; Q86WG5; -. DR Antibodypedia; 24321; 52 antibodies from 11 providers. DR DNASU; 81846; -. DR Ensembl; ENST00000256190.13; ENSP00000256190.8; ENSG00000133812.18. [Q86WG5-1] DR Ensembl; ENST00000533770.6; ENSP00000509247.1; ENSG00000133812.18. [Q86WG5-3] DR GeneID; 81846; -. DR KEGG; hsa:81846; -. DR MANE-Select; ENST00000256190.13; ENSP00000256190.8; NM_030962.4; NP_112224.1. DR UCSC; uc001mib.2; human. [Q86WG5-1] DR AGR; HGNC:2135; -. DR CTD; 81846; -. DR DisGeNET; 81846; -. DR GeneCards; SBF2; -. DR GeneReviews; SBF2; -. DR HGNC; HGNC:2135; SBF2. DR HPA; ENSG00000133812; Low tissue specificity. DR MalaCards; SBF2; -. DR MIM; 604563; phenotype. DR MIM; 607697; gene. DR neXtProt; NX_Q86WG5; -. DR OpenTargets; ENSG00000133812; -. DR Orphanet; 99956; Charcot-Marie-Tooth disease type 4B2. DR PharmGKB; PA26649; -. DR VEuPathDB; HostDB:ENSG00000133812; -. DR eggNOG; KOG1090; Eukaryota. DR eggNOG; KOG4471; Eukaryota. DR GeneTree; ENSGT00940000155385; -. DR HOGENOM; CLU_002298_1_1_1; -. DR InParanoid; Q86WG5; -. DR OrthoDB; 3195274at2759; -. DR PhylomeDB; Q86WG5; -. DR TreeFam; TF318583; -. DR PathwayCommons; Q86WG5; -. DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane. DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs. DR SignaLink; Q86WG5; -. DR BioGRID-ORCS; 81846; 12 hits in 1169 CRISPR screens. DR ChiTaRS; SBF2; human. DR GeneWiki; SBF2; -. DR GenomeRNAi; 81846; -. DR Pharos; Q86WG5; Tbio. DR PRO; PR:Q86WG5; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q86WG5; Protein. DR Bgee; ENSG00000133812; Expressed in epithelial cell of pancreas and 188 other cell types or tissues. DR ExpressionAtlas; Q86WG5; baseline and differential. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005774; C:vacuolar membrane; IEA:Ensembl. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0019902; F:phosphatase binding; IEA:Ensembl. DR GO; GO:0019208; F:phosphatase regulator activity; IEA:Ensembl. DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:Ensembl. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0042552; P:myelination; NAS:UniProtKB. DR CDD; cd13339; PH-GRAM_MTMR13; 1. DR CDD; cd01235; PH_Sbf1_hMTMR5; 1. DR CDD; cd14589; PTP-MTMR13; 1. DR Gene3D; 3.30.450.200; -; 1. DR Gene3D; 3.40.50.11500; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 2. DR InterPro; IPR001194; cDENN_dom. DR InterPro; IPR005112; dDENN_dom. DR InterPro; IPR043153; DENN_C. DR InterPro; IPR004182; GRAM. DR InterPro; IPR037823; MTMR13_PH-GRAM. DR InterPro; IPR010569; Myotubularin-like_Pase_dom. DR InterPro; IPR030564; Myotubularin_fam. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR022096; SBF1/SBF2. DR InterPro; IPR037516; Tripartite_DENN. DR InterPro; IPR005113; uDENN_dom. DR PANTHER; PTHR10807; MYOTUBULARIN-RELATED; 1. DR PANTHER; PTHR10807:SF4; MYOTUBULARIN-RELATED PROTEIN 13; 1. DR Pfam; PF02141; DENN; 1. DR Pfam; PF02893; GRAM; 1. DR Pfam; PF06602; Myotub-related; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF12335; SBF2; 1. DR Pfam; PF03456; uDENN; 1. DR SMART; SM00801; dDENN; 1. DR SMART; SM00799; DENN; 1. DR SMART; SM00568; GRAM; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00800; uDENN; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF50729; PH domain-like; 2. DR PROSITE; PS50211; DENN; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS51339; PPASE_MYOTUBULARIN; 1. DR Genevisible; Q86WG5; HS. PE 1: Evidence at protein level; KW Alternative splicing; Autophagy; Cell projection; KW Charcot-Marie-Tooth disease; Cytoplasm; Endosome; KW Guanine-nucleotide releasing factor; Membrane; Neurodegeneration; KW Neuropathy; Phosphoprotein; Reference proteome. FT CHAIN 1..1849 FT /note="Myotubularin-related protein 13" FT /id="PRO_0000094945" FT DOMAIN 7..172 FT /note="uDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT DOMAIN 191..324 FT /note="cDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT DOMAIN 326..427 FT /note="dDENN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00304" FT DOMAIN 871..957 FT /note="GRAM" FT /evidence="ECO:0000255" FT DOMAIN 1108..1584 FT /note="Myotubularin phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00669" FT DOMAIN 1743..1847 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT REGION 1629..1682 FT /note="Required for homodimerization and interaction with FT MTMR2" FT /evidence="ECO:0000250|UniProtKB:E9PXF8, FT ECO:0000269|PubMed:15998640" FT REGION 1674..1694 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1127 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1279 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1152 FT /note="S -> R (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11214970" FT /id="VSP_017157" FT VAR_SEQ 1153..1849 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11214970" FT /id="VSP_017158" FT VARIANT 303 FT /note="P -> L (in dbSNP:rs16907355)" FT /id="VAR_051766" FT VARIANT 679 FT /note="E -> K (in dbSNP:rs7102464)" FT /id="VAR_051767" FT VARIANT 1216 FT /note="Q -> E (in dbSNP:rs12574508)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_051768" FT CONFLICT 1586 FT /note="E -> G (in Ref. 4; CAH18167)" FT /evidence="ECO:0000305" FT CONFLICT 1665 FT /note="E -> V (in Ref. 4; CAH18167)" FT /evidence="ECO:0000305" SQ SEQUENCE 1849 AA; 208464 MW; 9EDBA3E3AC05DD3E CRC64; MARLADYFIV VGYDHEKPGS GEGLGKIIQR FPQKDWDDTP FPQGIELFCQ PGGWQLSRER KQPTFFVVVL TDIDSDRHYC SCLTFYEAEI NLQGTKKEEI EGEAKVSGLI QPAEVFAPKS LVLVSRLYYP EIFRACLGLI YTVYVDSLNV SLESLIANLC ACLVPAAGGS QKLFSLGAGD RQLIQTPLHD SLPITGTSVA LLFQQLGIQN VLSLFCAVLT ENKVLFHSAS FQRLSDACRA LESLMFPLKY SYPYIPILPA QLLEVLSSPT PFIIGVHSVF KTDVHELLDV IIADLDGGTI KIPECIHLSS LPEPLLHQTQ SALSLILHPD LEVADHAFPP PRTALSHSKM LDKEVRAVFL RLFAQLFQGY RSCLQLIRIH AEPVIHFHKT AFLGQRGLVE NDFLTKVLSG MAFAGFVSER GPPYRSCDLF DELVAFEVER IKVEENNPVK MIKHVRELAE QLFKNENPNP HMAFQKVPRP TEGSHLRVHI LPFPEINEAR VQELIQENVA KNQNAPPATR IEKKCVVPAG PPVVSIMDKV TTVFNSAQRL EVVRNCISFI FENKILETEK TLPAALRALK GKAARQCLTD ELGLHVQQNR AILDHQQFDY IIRMMNCTLQ DCSSLEEYNI AAALLPLTSA FYRKLAPGVS QFAYTCVQDH PIWTNQQFWE TTFYNAVQEQ VRSLYLSAKE DNHAPHLKQK DKLPDDHYQE KTAMDLAAEQ LRLWPTLSKS TQQELVQHEE STVFSQAIHF ANLMVNLLVP LDTSKNKLLR TSAPGDWESG SNSIVTNSIA GSVAESYDTE SGFEDSENTD IANSVVRFIT RFIDKVCTES GVTQDHIKSL HCMIPGIVAM HIETLEAVHR ESRRLPPIQK PKILRPALLP GEEIVCEGLR VLLDPDGREE ATGGLLGGPQ LLPAEGALFL TTYRILFRGT PHDQLVGEQT VVRSFPIASI TKEKKITMQN QLQQNMQEGL QITSASFQLI KVAFDEEVSP EVVEIFKKQL MKFRYPQSIF STFAFAAGQT TPQIILPKQK EKNTSFRTFS KTIVKGAKRA GKMTIGRQYL LKKKTGTIVE ERVNRPGWNE DDDVSVSDES ELPTSTTLKA SEKSTMEQLV EKACFRDYQR LGLGTISGSS SRSRPEYFRI TASNRMYSLC RSYPGLLVVP QAVQDSSLPR VARCYRHNRL PVVCWKNSRS GTLLLRSGGF HGKGVVGLFK SQNSPQAAPT SSLESSSSIE QEKYLQALLN AVSVHQKLRG NSTLTVRPAF ALSPGVWASL RSSTRLISSP TSFIDVGARL AGKDHSASFS NSSYLQNQLL KRQAALYIFG EKSQLRNFKV EFALNCEFVP VEFHEIRQVK ASFKKLMRAC IPSTIPTDSE VTFLKALGDS EWFPQLHRIM QLAVVVSEVL ENGSSVLVCL EEGWDITAQV TSLVQLLSDP FYRTLEGFQM LVEKEWLSFG HKFSQRSSLT LNCQGSGFAP VFLQFLDCVH QVHNQYPTEF EFNLYYLKFL AFHYVSNRFK TFLLDSDYER LEHGTLFDDK GEKHAKKGVC IWECIDRMHK RSPIFFNYLY SPLEIEALKP NVNVSSLKKW DYYIEETLST GPSYDWMMLT PKHFPSEDSD LAGEAGPRSQ RRTVWPCYDD VSCTQPDALT SLFSEIEKLE HKLNQAPEKW QQLWERVTVD LKEEPRTDRS QRHLSRSPGI VSTNLPSYQK RSLLHLPDSS MGEEQNSSIS PSNGVERRAA TLYSQYTSKN DENRSFEGTL YKRGALLKGW KPRWFVLDVT KHQLRYYDSG EDTSCKGHID LAEVEMVIPA GPSMGAPKHT SDKAFFDLKT SKRVYNFCAQ DGQSAQQWMD KIQSCISDA //