ID BMP15_HUMAN Reviewed; 392 AA. AC O95972; Q17RM6; Q5JST1; Q9UMS1; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 16-AUG-2004, sequence version 2. DT 13-FEB-2019, entry version 157. DE RecName: Full=Bone morphogenetic protein 15; DE Short=BMP-15; DE AltName: Full=Growth/differentiation factor 9B; DE Short=GDF-9B; DE Flags: Precursor; GN Name=BMP15; Synonyms=GDF9B; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-103. RX PubMed=9849956; DOI=10.1210/mend.12.12.0206; RA Dube J.L., Wang P., Elvin J., Lyons K.M., Celeste A.J., Matzuk M.M.; RT "The bone morphogenetic protein 15 gene is X-linked and expressed in RT oocytes."; RL Mol. Endocrinol. 12:1809-1817(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10443672; DOI=10.1210/jcem.84.8.5921; RA Aaltonen J., Laitinen M.P., Vuojolainen K., Jaatinen R., RA Horelli-Kuitunen N., Seppae L., Louhio H., Tuuri T., Sjoeberg J., RA Buetzow R., Hovatta O., Dale L., Ritvos O.; RT "Human growth differentiation factor 9 (GDF-9) and its novel homolog RT GDF-9B are expressed in oocytes during early folliculogenesis."; RL J. Clin. Endocrinol. Metab. 84:2744-2750(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, PYROGLUTAMATE FORMATION AT GLN-268, PHOSPHORYLATION AT RP SER-273, GLYCOSYLATION AT THR-277, AND HOMODIMERIZATION. RX PubMed=18227435; DOI=10.1110/ps.073232608; RA Saito S., Yano K., Sharma S., McMahon H.E., Shimasaki S.; RT "Characterization of the post-translational modification of RT recombinant human BMP-15 mature protein."; RL Protein Sci. 17:362-370(2008). RN [6] RP SPECIES-SPECIFIC OVULATION RATE DETERMINATION. RX PubMed=21970812; DOI=10.1016/j.mce.2011.09.033; RA Crawford J.L., McNatty K.P.; RT "The ratio of growth differentiation factor 9: bone morphogenetic RT protein 15 mRNA expression is tightly co-regulated and differs between RT species over a wide range of ovulation rates."; RL Mol. Cell. Endocrinol. 348:339-343(2012). RN [7] RP VARIANT ODG2 CYS-235, AND CHARACTERIZATION OF VARIANT ODG2 CYS-235. RX PubMed=15136966; DOI=10.1086/422103; RA Di Pasquale E., Beck-Peccoz P., Persani L.; RT "Hypergonadotropic ovarian failure associated with an inherited RT mutation of human bone morphogenetic protein-15 (BMP15) gene."; RL Am. J. Hum. Genet. 75:106-111(2004). RN [8] RP VARIANTS POF4 PRO-148 AND THR-180, AND VARIANT LEU-263 INS. RX PubMed=16645022; DOI=10.1530/eje.1.02135; RA Laissue P., Christin-Maitre S., Touraine P., Kuttenn F., Ritvos O., RA Aittomaki K., Bourcigaux N., Jacquesson L., Bouchard P., Frydman R., RA Dewailly D., Reyss A.-C., Jeffery L., Bachelot A., Massin N., RA Fellous M., Veitia R.A.; RT "Mutations and sequence variants in GDF9 and BMP15 in patients with RT premature ovarian failure."; RL Eur. J. Endocrinol. 154:739-744(2006). RN [9] RP VARIANTS POF4 TRP-61; GLN-61; CYS-76; HIS-76; THR-180; LYS-196; RP HIS-206; ARG-221 AND VAL-243, AND VARIANTS SER-103; PHE-180 AND RP LEU-263 INS. RX PubMed=16508750; DOI=10.1007/s00439-006-0150-0; RA Dixit H., Rao L.K., Padmalatha V.V., Kanakavalli M., Deenadayal M., RA Gupta N., Chakrabarty B., Singh L.; RT "Missense mutations in the BMP15 gene are associated with ovarian RT failure."; RL Hum. Genet. 119:408-415(2006). RN [10] RP VARIANTS POF4 TRP-68; THR-180 AND CYS-235, AND VARIANT LEU-263 INS. RX PubMed=16464940; DOI=10.1210/jc.2005-2650; RA Di Pasquale E., Rossetti R., Marozzi A., Bodega B., Borgato S., RA Cavallo L., Einaudi S., Radetti G., Russo G., Sacco M., Wasniewska M., RA Cole T., Beck-Peccoz P., Nelson L.M., Persani L.; RT "Identification of new variants of human BMP15 gene in a large cohort RT of women with premature ovarian failure."; RL J. Clin. Endocrinol. Metab. 91:1976-1979(2006). RN [11] RP VARIANTS POF4 TRP-68; HIS-138; PRO-148 AND THR-180, VARIANTS ARG-5 AND RP LEU-263 INS, CHARACTERIZATION OF VARIANTS POF4 TRP-68; HIS-138; RP PRO-148 AND THR-180, AND CHARACTERIZATION OF VARIANTS ARG-5 AND RP LEU-263 INS. RX PubMed=19263482; DOI=10.1002/humu.20961; RA Rossetti R., Di Pasquale E., Marozzi A., Bione S., Toniolo D., RA Grammatico P., Nelson L.M., Beck-Peccoz P., Persani L.; RT "BMP15 mutations associated with primary ovarian insufficiency cause a RT defective production of bioactive protein."; RL Hum. Mutat. 30:804-810(2009). RN [12] RP VARIANT TYR-200, AND VARIANT POF4 CYS-329. RX PubMed=19438907; DOI=10.1111/j.1365-2265.2009.03613.x; RA Wang B., Wen Q., Ni F., Zhou S., Wang J., Cao Y., Ma X.; RT "Analyses of growth differentiation factor 9 (GDF9) and bone RT morphogenetic protein 15 (BMP15) mutation in Chinese women with RT premature ovarian failure."; RL Clin. Endocrinol. (Oxf.) 72:135-136(2010). CC -!- FUNCTION: May be involved in follicular development. Oocyte- CC specific growth/differentiation factor that stimulates CC folliculogenesis and granulosa cell (GC) growth. CC {ECO:0000269|PubMed:18227435}. CC -!- SUBUNIT: Homodimer. But, in contrast to other members of this CC family, cannot be disulfide-linked. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- DISEASE: Ovarian dysgenesis 2 (ODG2) [MIM:300510]: A disorder CC characterized by lack of spontaneous pubertal development, primary CC amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism CC as a result of streak gonads. {ECO:0000269|PubMed:15136966}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Premature ovarian failure 4 (POF4) [MIM:300510]: An CC ovarian disorder defined as the cessation of ovarian function CC under the age of 40 years. It is characterized by oligomenorrhea CC or amenorrhea, in the presence of elevated levels of serum CC gonadotropins and low estradiol. {ECO:0000269|PubMed:16464940, CC ECO:0000269|PubMed:16508750, ECO:0000269|PubMed:16645022, CC ECO:0000269|PubMed:19263482, ECO:0000269|PubMed:19438907}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- MISCELLANEOUS: The mature protein migrates in two distinct mature CC proteins, P16 (16KDa) and P17 (17KDa). CC -!- MISCELLANEOUS: Ovarian physiology and fertility are controlled by CC endocrine and paracrine signals. These act in a species-dependent CC manner and determine the ovulation quota in different mammalian CC species. While humans, and mammals such as the cow or red deer, CC normally ovulate only one egg per cycle, other mammals such as CC mouse and pig can ovulate in excess of ten per cycle. The CC mechanisms that regulate the species-specific differences in the CC number of follicles that go onto ovulate during each reproductive CC cycle are poorly understood. According to PubMed:21970812, mRNA CC expression levels of GDF9 and BMP15 are tightly coregulated within CC each species and influence species-specific ovulation-rates. CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}. 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; AF082350; AAC99768.1; -; Genomic_DNA. DR EMBL; AF082349; AAC99768.1; JOINED; Genomic_DNA. DR EMBL; AJ132405; CAB43531.1; -; Genomic_DNA. DR EMBL; AL359914; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC069155; AAH69155.1; -; mRNA. DR EMBL; BC117264; AAI17265.1; -; mRNA. DR EMBL; BC117266; AAI17267.1; -; mRNA. DR CCDS; CCDS14334.1; -. DR RefSeq; NP_005439.2; NM_005448.2. DR UniGene; Hs.532692; -. DR ProteinModelPortal; O95972; -. DR BioGrid; 114644; 4. DR IntAct; O95972; 2. DR MINT; O95972; -. DR STRING; 9606.ENSP00000252677; -. DR iPTMnet; O95972; -. DR PhosphoSitePlus; O95972; -. DR BioMuta; BMP15; -. DR PaxDb; O95972; -. DR PeptideAtlas; O95972; -. DR PRIDE; O95972; -. DR ProteomicsDB; 51155; -. DR DNASU; 9210; -. DR Ensembl; ENST00000252677; ENSP00000252677; ENSG00000130385. DR GeneID; 9210; -. DR KEGG; hsa:9210; -. DR UCSC; uc011mnw.3; human. DR CTD; 9210; -. DR DisGeNET; 9210; -. DR EuPathDB; HostDB:ENSG00000130385.5; -. DR GeneCards; BMP15; -. DR HGNC; HGNC:1068; BMP15. DR MalaCards; BMP15; -. DR MIM; 300247; gene. DR MIM; 300510; phenotype. DR neXtProt; NX_O95972; -. DR OpenTargets; ENSG00000130385; -. DR Orphanet; 243; 46,XX gonadal dysgenesis. DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure. DR PharmGKB; PA25378; -. DR eggNOG; KOG3900; Eukaryota. DR eggNOG; ENOG410XT8Z; LUCA. DR GeneTree; ENSGT00940000160940; -. DR HOGENOM; HOG000095242; -. DR HOVERGEN; HBG004660; -. DR InParanoid; O95972; -. DR KO; K05498; -. DR OMA; LYTPNYC; -. DR OrthoDB; 724783at2759; -. DR PhylomeDB; O95972; -. DR TreeFam; TF316134; -. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SignaLink; O95972; -. DR SIGNOR; O95972; -. DR GeneWiki; Bone_morphogenetic_protein_15; -. DR GenomeRNAi; 9210; -. DR PRO; PR:O95972; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; ENSG00000130385; Expressed in 9 organ(s), highest expression level in secondary oocyte. DR Genevisible; O95972; HS. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central. DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central. DR GO; GO:0048468; P:cell development; IBA:GO_Central. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc. DR GO; GO:0060016; P:granulosa cell development; IEA:InterPro. DR GO; GO:0001541; P:ovarian follicle development; IEA:InterPro. DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central. DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central. DR Gene3D; 2.10.90.10; -; 1. DR InterPro; IPR015923; BMP-15. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR001839; TGF-b_C. DR InterPro; IPR015615; TGF-beta-rel. DR InterPro; IPR017948; TGFb_CS. DR PANTHER; PTHR11848; PTHR11848; 1. DR PANTHER; PTHR11848:SF22; PTHR11848:SF22; 1. DR Pfam; PF00019; TGF_beta; 1. DR SMART; SM00204; TGFB; 1. DR SUPFAM; SSF57501; SSF57501; 1. DR PROSITE; PS00250; TGF_BETA_1; 1. DR PROSITE; PS51362; TGF_BETA_2; 1. PE 1: Evidence at protein level; KW Complete proteome; Cytokine; Disease mutation; Disulfide bond; KW Glycoprotein; Growth factor; Phosphoprotein; KW Premature ovarian failure; Pyrrolidone carboxylic acid; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 18 {ECO:0000255}. FT PROPEP 19 267 FT /FTId=PRO_0000033892. FT CHAIN 268 392 Bone morphogenetic protein 15. FT /FTId=PRO_0000033893. FT MOD_RES 268 268 Pyrrolidone carboxylic acid; in P16 and FT P17. {ECO:0000269|PubMed:18227435}. FT MOD_RES 273 273 Phosphoserine; in P16. FT {ECO:0000269|PubMed:18227435}. FT CARBOHYD 87 87 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 147 147 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 237 237 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 277 277 O-linked (HexNAc...) threonine; in P17. FT {ECO:0000269|PubMed:18227435}. FT CARBOHYD 373 373 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 291 357 {ECO:0000250}. FT DISULFID 320 389 {ECO:0000250}. FT DISULFID 324 391 {ECO:0000250}. FT VARIANT 5 5 S -> R (polymorphism; no or minor FT deleterious effect observed; FT dbSNP:rs113099187). FT {ECO:0000269|PubMed:19263482}. FT /FTId=VAR_058974. FT VARIANT 61 61 R -> Q (in POF4). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058975. FT VARIANT 61 61 R -> W (in POF4; dbSNP:rs144392417). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058976. FT VARIANT 68 68 R -> W (in POF4; leads to marked FT reduction of mature protein production; FT does not generate a complete recovery of FT wild-type activity in granulosa cell line FT transfected with defective mutant and FT with equal amount of wild-type protein; FT dbSNP:rs104894763). FT {ECO:0000269|PubMed:16464940, FT ECO:0000269|PubMed:19263482}. FT /FTId=VAR_058977. FT VARIANT 76 76 R -> C (in POF4; dbSNP:rs104894766). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058978. FT VARIANT 76 76 R -> H (in POF4). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058979. FT VARIANT 103 103 N -> S (in dbSNP:rs41308602). FT {ECO:0000269|PubMed:16508750, FT ECO:0000269|PubMed:9849956}. FT /FTId=VAR_058980. FT VARIANT 138 138 R -> H (in POF4; leads to marked FT reduction of mature protein production; FT does not generate a complete recovery of FT wild-type activity in granulosa cell line FT transfected with defective mutant and FT with equal amount of wild-type protein; FT dbSNP:rs371418883). FT {ECO:0000269|PubMed:19263482}. FT /FTId=VAR_058981. FT VARIANT 148 148 L -> P (in POF4; leads to marked FT reduction of mature protein production; FT does not generate a complete recovery of FT wild-type activity in granulosa cell line FT transfected with defective mutant and FT with equal amount of wild-type protein; FT dbSNP:rs114823607). FT {ECO:0000269|PubMed:16645022, FT ECO:0000269|PubMed:19263482}. FT /FTId=VAR_058982. FT VARIANT 180 180 A -> F (requires 2 nucleotide FT substitutions). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058983. FT VARIANT 180 180 A -> T (in POF4; unknown pathological FT significance; no or minor deleterious FT effect detected; dbSNP:rs104894767). FT {ECO:0000269|PubMed:16464940, FT ECO:0000269|PubMed:16508750, FT ECO:0000269|PubMed:16645022, FT ECO:0000269|PubMed:19263482}. FT /FTId=VAR_058984. FT VARIANT 196 196 N -> K (in POF4). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058985. FT VARIANT 200 200 H -> Y (in dbSNP:rs202165852). FT {ECO:0000269|PubMed:19438907}. FT /FTId=VAR_066932. FT VARIANT 206 206 R -> H (in POF4; dbSNP:rs782516193). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058986. FT VARIANT 221 221 W -> R (in POF4; dbSNP:rs375284458). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058987. FT VARIANT 235 235 Y -> C (in ODG2; dominant-negative FT effect; may cause relevant modifications FT in the conformation of the precursor FT protein possibly leading to altered FT processing and impaired activation of FT latent forms or to abnormal dimerization; FT dbSNP:rs104894765). FT {ECO:0000269|PubMed:15136966, FT ECO:0000269|PubMed:16464940}. FT /FTId=VAR_021195. FT VARIANT 243 243 I -> V (in POF4; dbSNP:rs782379521). FT {ECO:0000269|PubMed:16508750}. FT /FTId=VAR_058988. FT VARIANT 263 263 L -> LL (no or minor deleterious effect FT detected). {ECO:0000269|PubMed:16464940, FT ECO:0000269|PubMed:16508750, FT ECO:0000269|PubMed:16645022, FT ECO:0000269|PubMed:19263482}. FT /FTId=VAR_058989. FT VARIANT 329 329 R -> C (in POF4; dbSNP:rs782375794). FT {ECO:0000269|PubMed:19438907}. FT /FTId=VAR_066933. SQ SEQUENCE 392 AA; 45055 MW; A957275EF275A2E8 CRC64; MVLLSILRIL FLCELVLFME HRAQMAEGGQ SSIALLAEAP TLPLIEELLE ESPGEQPRKP RLLGHSLRYM LELYRRSADS HGHPRENRTI GATMVRLVKP LTNVARPHRG TWHIQILGFP LRPNRGLYQL VRATVVYRHH LQLTRFNLSC HVEPWVQKNP TNHFPSSEGD SSKPSLMSNA WKEMDITQLV QQRFWNNKGH RILRLRFMCQ QQKDSGGLEL WHGTSSLDIA FLLLYFNDTH KSIRKAKFLP RGMEEFMERE SLLRRTRQAD GISAEVTASS SKHSGPENNQ CSLHPFQISF RQLGWDHWII APPFYTPNYC KGTCLRVLRD GLNSPNHAII QNLINQLVDQ SVPRPSCVPY KYVPISVLMI EANGSILYKE YEGMIAESCT CR //