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US 2004/0146980 A1 Merkulov Et Al US 2004O146980A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0146980 A1 Merkulov et al. (43) Pub. Date: Jul. 29, 2004 (54) ISOLATED HUMAN LIPASE PROTEINS, (22) Filed: Mar 18, 2004 NUCLEC ACID MOLECULES ENCODING HUMAN LIPASE PROTEINS, AND USES Related U.S. Application Data THEREOF (62) Division of application No. 10/003,302, filed on Dec. (75) Inventors: Gennady V. Merkulov, Baltimore, MD 6, 2001, which is a division of application No. (US); Karen A. Ketchum, 09/820,001, filed on Mar. 29, 2001, now Pat. No. Germantown, MD (US), Valentina Di 6,387,680. Francesco, Rockville, MD (US); Ellen M. Beasley, Darnestown, MD (US) Publication Classification Correspondence Address: (51) - - - - - - - - C12N 9/20; CO7H 21/04 CELERA GENOMICS CORP. (52) U.S. Cl. ..................... 435/69.1; 435/198; 435/320.1; ATTN: WAYNE MONTGOMERY, VICE PRES, 435/325; 536/23.2 INTEL PROPERTY ABSTRACT 45 WEST GUDE DRIVE (57) C2-4iii.20 The present invention provides amino acid Sequences of ROCKVILLE, MD 20850 (US) peptides that are encoded by genes within the human genome, the lipase peptides of the present invention. The (73) Assignee: APPLERACORPORATION, Norwalk, present invention specifically provides isolated peptide and CT nucleic acid molecules, methods of identifying orthologs and paralogs of the lipase peptides, and methods of identi (21) Appl. No.: 10/802,805 fying modulators of the lipase peptides. 1. CTOTTACTOT TO AGCCTGA GTCAAAAGCA AAAGTTCAGA AGT TOOTCAT 51 CAATAAGGAG TCCGGAG CAGGGAAGCTCATCTAACT AGGCATC 101 ATGATGTGGC TGCTTT TAAC AACAACT GT TTGATC-TGTG GAACT TAAA 1S1 TGCTGGTGGA TCCTGATT TIGGAAAATGA AGTGAATCOT GAGGGGGA 201 TGAAFACTAG TGAAATCATC ATCTACAATG GCTACCCCAG TGAAGAGTAT 251 GAAGTCACGACTGAAGATGG GTATATACTC CTTGTCAACA GAATTCOTTA 301 TGGGCGAACA CATGCTAGGA GCACAGGTCC CCGGCCAGTT GTGTATATGC 351 AGCAIGCCCT GITTTGCAGAC AATGCCTACT GGCTTGAGAA TATGCCAAT 401 GGAAGCOTTG GATTCOT TOT AGCAGATGCA GGTTATGATG TAGGATGGG 451 AAACAGTCGG GGAAACACTT GGTCAAGAAG ACACAAAACA CTOTCAGAGA 501 CAGATGAGAA Al TCTGGGCC TTAGTTTTG ATGAAATGGC CAAATATGAT 551. OTCCCAGGAG TAATAGACTT CATTGTAAAT AAAACTGGTCAGGAGAAATT 601 GATCATT GGACATCAC TTGGCACTAC AATAGGGTTT GTAGCCTTTT 651 CCACCATGCC TGAACTGGCA CAAAGAATCA AAATGAATTT TGCGTTGGGT 701 COTACGAO CATTCAAATA TOCCACGGGC ATTACCA GGTTTTTOT 751 ACT TCCAAAT CCAAATCA AGGCTGT T T T GG TACCAAA GGT I TOT T T T 801. TAGAAGATAA GAAAACGAAG ATAGCTTCTA CCAAAATCTG CAACAATAAG 851 AACTCTGG GATAGAG. CGAATTATG CCTTATGGG CGGATCCAA 901 CAAGAAAAA ATGAATCAGA GCGAAT GGA GTGTATA TG TOACA TGCC 951 CCAGTGG TO ATCAGTACAC AACATTCTGC ATATAAAACA GOTTACCAC 1001. TCTGATGAAT TCAGAGCTA TGACTGGGGA AATGACGCTGATAATATGAA 1051 ACATACAATCAGAGTCACCCCCTATATA TGACCTGACT GCCATGAAAG 1101 TGCGTAGTGC TATT TGGGC GGTGGACATG ATGTCCTGGG AACACCCCAG 1151 GATGTGGCCA GGA ACTCCC TCAAA TCAAG AG TOTT TCAT TAGTGCAAG 1201. ???? ?CCCA GAA TOGAAC CCACCI I I GA T IT TO ???CG GCCCT TO???. 1251 CCCCI CAACG GATGT TCAG GGAAATCATA ACCT I TAAG AAGGCATAT T 1301 TCCTAAATGC CAATGCAT, TACCTTTCAATAAAGG TGGTCCA 1351 AAGCOOTAC (SEQ ID NO: 1) FEATURES 5 "?TR: 1 - 100 Start Codon: 101 Stop Codon: 1286 3 UTR: 1289 Homologous proteins: Top 10 BLAST Hits: CRA||18000004922653 /alltid=gi | 7434997 /def=pir||G01416 lysosoma . 431 e-120 CRA||18000004903706 /alltid=gi || 542751 /def=pir||S41408 lysosomal . 430 e-119 CRA|18000004924799 /altid-gi 4557721 /def=ref|NP 000226.1| lipa... 428 e-119 CRAI98000043616611 /altid=gi 12844223 /def=dbjIBAB26283.1 (AKO. 415 e-115 CRAI98000043617058 /altid-gi 12845127 /def=dbjIBAB26629.1 CAKO. 415 e-115 CRA||98000043616593 /alltid=gi 12844194 /def=dbj || BAB26272.1 (AK0. 414 e-115 CRAI98000043617174 /altid=gi 12845372 /def=dbjIBAB26725.1 CAKO. 414 e-115 Patent Application Publication Jul. 29, 2004 Sheet 1 of 36 US 2004/0146980 A1 1 CTOTTACTOT TCAGCOTGAT GTCAAAAGCA AAAGTTCAGA AGITCOTCAT 51 CAATAAGGAG TCCTTGTGAG CAGGTGAAGC TCATCTAACTAGGCATTTCT 101 ATGATGTGGC TGCTTT TAAC AACAACTTGT TTGATCTGTG GAACTT TAAA 151 TGCTGGTGGA TTCCTTGATT TGGAAAATGA AGTGAATCOT GAGGTGTGGA 201 TGAATACTAG TGAAATCATC ATCTACAATG, GCTACCCCAG TGAAGAG TAT 251 GAAGTCACCA CTGAAGATGG GTATATACTC CTTGTCAACA GAATTCCTTA 301 TGGGCGAACA CATGCTAGGA GCACAGGTCC CCGGCCAGTT GTGTATATGC 351 AGCATGCCCT GITTGCAGAC AATGCCTACT GGCTTGAGAWA TATGCCAAT 401 GGAAGCCT TG GATTCCTTCT AGCAGATGCA GGT TATGATG TATGGATGGG 451 AAACAGTCGG GGAAACACTT GGTCAAGAAG ACACAAAACA CTOTCAGAGA 501 CAGATGAGAA ATTCTGGGCC TTTAGTTTTG ATGAAATGGC CAAATATGAT 551. OTCCCAGGAG TAATAGACTT CATTG TAAAT AAAACTGGTC AGGAGAAATT 601 GTATTTCATT GGACATTCAC TTGGCACTAC AATAGGGTTT GTAGCCTTTT 651 CCACCATGCC TGAACTCGCA CAAAGAATCA AAATGAATTT TGCCTTGGGT 701 CCTACGAC CATCAAATA TCCCACGGGC ATTTTTACCA GGTTTTTCT 751 ACTTCCAAAT TOCATAATCA AGGOTG TT GG TACCAAA GGT T TOT T T T 801 TAGAAGATAA GAAAACGAAG ATTAGCTCTA CCAAAATC TG CAACAATAAG 851 ATACTCTGGT TIGATAG TAG CGAAT I TATG CCT TATGGG CTGGATCCAA 901 CAAGAAAAAT ATGAATCAGA GTCGAATGGA TGTGTATATG TCACATGCTC 951 CCACTCG! TC ATCAGTACAC AACATTCTGC ATATAAAACA GCTT TACCAC 1001. TCTGATGAAT TCAGAGCTTA TGACTGGGGA AATGACGCTGATAATATGAA 1051 ACATTACAAT CAGAGTCATC CCCCTATATA TGACCTGACT GCCATGAAAG 1101 TGCCTACTGC TATT TGGGCT GGTGGACATG ATGTCCTCGG AACACCCCAG 1151 GATGTGGCCA GGATACTCCC TCAAACAAG AG TOTT TCAT TAGTGCTTAAG 1201 CCATTGCCA GAATGGGAAC CCACCTTGA TTTTGTCTGG GGCCTTGATG 1251 CCCCTCAACG GATGTTCAGTGGAAATCATA ACCTTTAATG AAGGCATATT 1301 TCCTAAATGC CAATGCATTT TACCTTTTTC AATTTAAAGG TTGGTTTCCA 1351 AAGCCCITTAC (SEQ ID NO: 1) FEATURES S"?TR: 1 - 100 Start Codon: 101 Stop Codon: 1286 3 UTR: 1289 Homologous proteins: Top 10 BLAST Hits: CRA||18000004922653 /alltid=gi | 7434997 /def=pi r || ||G01416 lysosomal . 431 e-120 CRA||18000004903706 /alltid=gi || 542751 /def=pir||S41408 lysosomal . 430 e-119 CRA|18000004924799 /altid=gi 14557721 /def=ref|NP 000226.1| lipa... 428 e-119 CRAI98000043616611 /altid=gi 12844223 /def=dbjIBAB26283.1 (AKO. 415 e-115 CRAI98000043617058 /altid-gi 12845127 /def=dbjIBAB26629.1 (AKO. 415 e-115 CRAI98000043616593 /altid=gi | 12844194 /def-dbjIBAB26272.1 (AKO. 414 e-115 CRAI98000043617174 /altid-gi|12845372 /def=dbjIBAB26725.1 (AKO. 414 e-115 FIG.1A Patent Application Publication Jul. 29, 2004 Sheet 2 of 36 US 2004/0146980 A1 CRAI98000043617140 /altid=gi 12845298 /def=dbjI BAB26697.1 CAKO. 414 e-115 CRA98000043617224 /altid-gi 12845477 /def=dbjIBAB26766.1 (AKO. 414 e-114 CRA 98000043616955 /altid=gi|12844939 /def=dbjIBAB26556.1 (AKO. 414 e-114 EST: gi || 8003062 /dataset=dbest /taxon=960. 62 4-e-07 gi 8000757 /dataset=dbest /taxon=960. .. 54 9e-05 EXPRESSION INFORMATION FOR MODULATORY USE: gi| 8003062 Stomach normal gi|8000757 Stormoach normal Tissue expression: Human leukocyte FIG.1B Patent Application Publication Jul. 29, 2004 Sheet 3 of 36 US 2004/0146980 A1 1 MMWLLLTTC LICGTLNAGG FDLENEVNP EWMNTSEII YNGYPSEEY 51 EVTTEDGYIL LVNRIPYGRT HARSTGPRPV VYMOHALFAD NAYWLENYAN 101 GSLGFLLADA GYDVWMGNSR GNTWSRRHKT LSETDEKFWA FSFDEMAKYD 151 LPGVIDFIVN KTGQEKLYFI GHSLGT TIGF VAFSTIMPELA QRIKMNFALG 201 PTISFKYPTG IFTRFFLLPN SIIKAVFGTK GFFLEDKKTK IASTKIONNK 251 ILWLICSEFM SLWAGSNKKN MNOSRMDVYM SHAPTGSSVH NILHIKOLYH 301 SDEFRAYDWIG NDADNMKHYN QSHPPIYDLT AMKVPTAIWA GGHDVLGTPQ 351 DVARILPQIK SLSLVLSLLP WEPTFDFW GLDAPQRMFS GNHNL CSEQ ID NO: 2) FEATURES: Functional domains and key regions: [1] PDOC00001 PS00001 ASNU GLYCOSYLATION N-glycosylation site Number of matches: 5 1. 35–38 NTSE 2 100-103 NGSL 3 160–163 NKTG 4. 272-275 NQSR 5 320-323 NOQSH [2] PDOC00005 PS00005 PKC_PHOSPHO_SITE Protein kinase C phosphorylation site Number of matches: 4 1. 125-127 SRR 2 204-206 SFK 3 243–245 STK 4. 266-268 SNK [3] PDOC00006 PS00006 CK2_PHOSPHO_SITE Casein kinase II phosphorylation site Number of matches: 8 53-56 TITED 130-133 TLSE 132-135 SETD 142-145 SFDE 162-165 TGOE 185-188 MPE 274-277 SSR?MD 348-351 TPOD [4] PDOC00007 PS00007 TYR_PHOSPHO_SITE FIG.2A Patent Application Publication Jul. 29, 2004 Sheet 4 of 36 US 2004/0146980 A1 Tyrosine kinase phosphorylation site 161-168 KTGQEKLY [5] PDOC00008 PSO0008 MYRISTYL N-myristoylation site Number of matches: 4 1. 14-19 GTLNAG 2 117-122 GNSRGN 3 1211-126 GNTWSR 4. 175-180 GTT GF 6. PDOC00110 PS00120 LIPASE SER Lipases, serine active site 167-176 LYFIGHSLGT Membrane Spanning structure and domains: Helix Begin End Score Certainity 1. 3 23 1.398 Certain 2 167 187 1.637 Certain 3 248 268 0.715 Putative BLAST Alignment to Top Hit: >CRA||18000004903706 /alltid=gi || 542751 /def=pir||S41408 lysosomal acid lipase (EC 3.1.1. -) / Sterol esterase (EC 3.1.1.13) precursor - human /orghuman /taxon=9606 /dataset=nraa /length=399 Length = 399 Score = 430 bits (1094), Expect = e-119 Identities = 211/394 (53%), Positives = 274/394 (68%), Gaps = 2/394 (0%) Query: 2 MWLLLTTTCLICGTLNAGGFLDLENEVNPEWMNTSEIIIYNGYPSEEYEVTTEDGYILL 61 M CL-- TL-H+ G WPE MN SETI Y GPSEEY V EDGYL Sbjct: 3 MRFLGLWCLVLWTLHSEGSGGKLTAVDPETNMNVSEIISYWGFPSEEYLVETEDGYILC 62 Query: 62 VNRIPYGRTHARSTGPRPWYMOHALFADNAYWLENYANGSLGFLLADAGYDWMGNSRG 121 -NRIP--GR -- GP+PWH-QH L AD++ W+ N AN SLGF-LADAGHDWMGNSRG Sbjct: 63 LNRIPHGRKNHSDKGPKPWFLQHGLLADSSNWTNLANSSLGFILADAGFDWMGNSRG 122 FIG.2B Patent Application Publication Jul. 29, 2004 Sheet 6 of 36 US 2004/0146980 A1 1 TTATGGCCTA ACCTTTTTAA CTTTGAGTTA TTTTCAAGAG AAAATTTGAA 51 AAAGCAGCCT TTGAGGAGAA AGAAGCAATC CAACAAACAA AAAGATAACC 101 ACACTGTAAT AGGAAATGTG TTTTGAATAG GACATTGGAA GAAAAATAAT 151 AATCATTTT ACAGGTAGAT CCCAAAGTCA AGGATCTATG TTCAACCATG 201 TGTGTTCCAC CATOTTCACAATTGAATGAGTAACCATCATTAAGCAGTTA 251. GOTTAGGCCG TAA TATGAT CTTGGACTGA GATTTCAAAA ATACCACAGG 301 COTTCTGAAA GGTACCCCT TTCTAGOTCC ACTATCATCT AAT I T TATA 351 AAAAAAAAAA AAAAGGAAAA ATTTGAGCTT CTAGAGAGTA GGGGCTACCA 401 TTTTGTATCC CACAGGGCCA AGGAACAAGT
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