ID FANCJ_HUMAN Reviewed; 1249 AA. AC Q9BX63; A0A024QZ45; Q3MJE2; Q8NCI5; DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot. DT 10-OCT-2018, sequence version 2. DT 27-MAR-2024, entry version 195. DE RecName: Full=Fanconi anemia group J protein {ECO:0000305}; DE EC=3.6.4.12 {ECO:0000269|PubMed:20639400, ECO:0000269|PubMed:36608669}; DE AltName: Full=BRCA1-associated C-terminal helicase 1; DE AltName: Full=BRCA1-interacting protein C-terminal helicase 1 {ECO:0000303|PubMed:11301010}; DE Short=BRCA1-interacting protein 1 {ECO:0000303|PubMed:11301010}; GN Name=BRIP1 {ECO:0000312|HGNC:HGNC:20473}; GN Synonyms=BACH1 {ECO:0000303|PubMed:11301010}, FANCJ; 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), PROTEIN SEQUENCE OF 708-747; RP 765-790; 815-831; 1079-1085; 1169-1174 AND 1215-1225, FUNCTION, TISSUE RP SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH BRCA1, MUTAGENESIS OF RP LYS-52, VARIANTS BC ALA-47 AND ILE-299, VARIANTS ILE-193 AND PRO-919, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11301010; DOI=10.1016/s0092-8674(01)00304-x; RA Cantor S.B., Bell D.W., Ganesan S., Kass E.M., Drapkin R., Grossman S., RA Wahrer D.C.R., Sgroi D.C., Lane W.S., Haber D.A., Livingston D.M.; RT "BACH1, a novel helicase-like protein, interacts directly with BRCA1 and RT contributes to its DNA repair function."; RL Cell 105:149-160(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-919. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 558-1249 (ISOFORM 2). 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 PHOSPHORYLATION AT SER-990, AND MUTAGENESIS OF SER-986; SER-988; THR-989; RP SER-990; PRO-991; THR-992; PHE-993; THR-997; SER-1001; SER-1003; SER-1004; RP SER-1007; TYR-1011 AND THR-1013. RX PubMed=14576433; DOI=10.1126/science.1088753; RA Yu X., Chini C.C.S., He M., Mer G., Chen J.; RT "The BRCT domain is a phospho-protein binding domain."; RL Science 302:639-642(2003). RN [7] RP FUNCTION, MUTAGENESIS OF LYS-52, AND CHARACTERIZATION OF VARIANTS BC ALA-47 RP AND ILE-299. RX PubMed=14983014; DOI=10.1073/pnas.0308717101; RA Cantor S.B., Drapkin R., Zhang F., Lin Y., Han J., Pamidi S., RA Livingston D.M.; RT "The BRCA1-associated protein BACH1 is a DNA helicase targeted by RT clinically relevant inactivating mutations."; RL Proc. Natl. Acad. Sci. U.S.A. 101:2357-2362(2004). RN [8] RP FUNCTION, VARIANT PRO-919, AND DISEASE. RX PubMed=16153896; DOI=10.1016/j.ccr.2005.08.004; RA Litman R., Peng M., Jin Z., Zhang F., Zhang J., Powell S., Andreassen P.R., RA Cantor S.B.; RT "BACH1 is critical for homologous recombination and appears to be the RT Fanconi anemia gene product FANCJ."; RL Cancer Cell 8:255-265(2005). RN [9] RP FUNCTION, MUTAGENESIS OF LYS-52, AND DISEASE. RX PubMed=16116421; DOI=10.1038/ng1627; RA Bridge W.L., Vandenberg C.J., Franklin R.J., Hiom K.; RT "The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia RT pathway for DNA crosslink repair."; RL Nat. Genet. 37:953-957(2005). RN [10] RP COFACTOR. RX PubMed=16973432; DOI=10.1016/j.molcel.2006.07.019; RA Rudolf J., Makrantoni V., Ingledew W.J., Stark M.J., White M.F.; RT "The DNA repair helicases XPD and FancJ have essential iron-sulfur RT domains."; RL Mol. Cell 23:801-808(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-927; SER-930 AND SER-990, AND 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-930 AND SER-1032, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1237, 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 [14] RP ACETYLATION AT LYS-1249. RX PubMed=22792074; DOI=10.1371/journal.pgen.1002786; RA Xie J., Peng M., Guillemette S., Quan S., Maniatis S., Wu Y., Venkatesh A., RA Shaffer S.A., Brosh R.M. Jr., Cantor S.B.; RT "FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage RT response."; RL PLoS Genet. 8:E1002786-E1002786(2012). RN [15] RP SUBCELLULAR LOCATION, AND INTERACTION WITH CIAO1; CIAO2B AND MMS19. RX PubMed=23585563; DOI=10.1074/jbc.m112.416602; RA Seki M., Takeda Y., Iwai K., Tanaka K.; RT "IOP1 protein is an external component of the human cytosolic iron-sulfur RT cluster assembly (CIA) machinery and functions in the MMS19 protein- RT dependent CIA pathway."; RL J. Biol. Chem. 288:16680-16689(2013). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505; SER-956; SER-1004 AND RP SER-1032, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [17] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-52. RX PubMed=36608669; DOI=10.1016/j.molcel.2022.12.005; RA Yaneva D., Sparks J.L., Donsbach M., Zhao S., Weickert P., Bezalel-Buch R., RA Stingele J., Walter J.C.; RT "The FANCJ helicase unfolds DNA-protein crosslinks to promote their RT repair."; RL Mol. Cell 83:43-56(2023). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 985-998 IN COMPLEX WITH BRCA1, AND RP SUBUNIT. RX PubMed=15125843; DOI=10.1016/s1097-2765(04)00238-2; RA Shiozaki E.N., Gu L., Yan N., Shi Y.; RT "Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: RT implications for signaling."; RL Mol. Cell 14:405-412(2004). RN [19] RP VARIANTS CYS-173 AND PRO-919. RX PubMed=11920628; DOI=10.1002/ijc.10214; RA Luo L., Lei H., Du Q., von Wachenfeldt A., Kockum I., Luthman H., RA Vorechovsky I., Lindblom A.; RT "No mutations in the BACH1 gene in BRCA1 and BRCA2 negative breast-cancer RT families linked to 17q22."; RL Int. J. Cancer 98:638-639(2002). RN [20] RP VARIANTS PRO-919 AND LEU-1034. RX PubMed=12565990; DOI=10.1016/s0959-8049(02)00498-7; RA Karppinen S.-M., Vuosku J., Heikkinen K., Allinen M., Winqvist R.; RT "No evidence of involvement of germline BACH1 mutations in Finnish breast RT and ovarian cancer families."; RL Eur. J. Cancer 39:366-371(2003). RN [21] RP VARIANTS CYS-173; ILE-193; PRO-195; TRP-419; VAL-531; LEU-540; TYR-832; RP PRO-919 AND GLY-935. RX PubMed=12872252; DOI=10.1002/humu.10238; RA Rutter J.L., Smith A.M., Davila M.R., Sigurdson A.J., Giusti R.M., RA Pineda M.A., Doody M.M., Tucker M.A., Greene M.H., Zhang J., RA Struewing J.P.; RT "Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and RT BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian RT cancer families and among early-onset breast cancer cases and reference RT individuals."; RL Hum. Mutat. 22:121-128(2003). RN [22] RP VARIANT FANCJ PRO-349. RX PubMed=16116424; DOI=10.1038/ng1624; RA Levran O., Attwooll C., Henry R.T., Milton K.L., Neveling K., Rio P., RA Batish S.D., Kalb R., Velleuer E., Barral S., Ott J., Petrini J., RA Schindler D., Hanenberg H., Auerbach A.D.; RT "The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia."; RL Nat. Genet. 37:931-933(2005). RN [23] RP VARIANTS FANCJ HIS-255; CYS-647 AND CYS-707, AND VARIANT TRP-264. RX PubMed=16116423; DOI=10.1038/ng1625; RA Levitus M., Waisfisz Q., Godthelp B.C., Vries Y., Hussain S., Wiegant W.W., RA Elghalbzouri-Maghrani E., Steltenpool J., Rooimans M.A., Pals G., RA Arwert F., Mathew C.G., Zdzienicka M.Z., Hiom K., De Winter J.P., RA Joenje H.; RT "The DNA helicase BRIP1 is defective in Fanconi anemia complementation RT group J."; RL Nat. Genet. 37:934-935(2005). RN [24] RP VARIANT [LARGE SCALE ANALYSIS] PRO-919. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). RN [25] RP VARIANT FANCJ PRO-349, COFACTOR, CHARACTERIZATION OF VARIANT FANCJ PRO-349, RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20639400; DOI=10.1182/blood-2009-11-256016; RA Wu Y., Sommers J.A., Suhasini A.N., Leonard T., Deakyne J.S., Mazin A.V., RA Shin-Ya K., Kitao H., Brosh R.M. Jr.; RT "Fanconi anemia group J mutation abolishes its DNA repair function by RT uncoupling DNA translocation from helicase activity or disruption of RT protein-DNA complexes."; RL Blood 116:3780-3791(2010). CC -!- FUNCTION: DNA-dependent helicase and 5' to 3' DNA helicase required for CC the maintenance of chromosomal stability (PubMed:11301010, CC PubMed:14983014, PubMed:16116421, PubMed:16153896, PubMed:36608669). CC Acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination CC (PubMed:14983014, PubMed:16153896). Involved in the repair of DNA CC double-strand breaks by homologous recombination in a manner that CC depends on its association with BRCA1 (PubMed:14983014, CC PubMed:16153896). Involved in the repair of abasic sites at replication CC forks by promoting the degradation of DNA-protein cross-links: acts by CC catalyzing unfolding of HMCES DNA-protein cross-link via its helicase CC activity, exposing the underlying DNA and enabling cleavage of the DNA- CC protein adduct by the SPRTN metalloprotease (PubMed:16116421, CC PubMed:36608669). {ECO:0000269|PubMed:11301010, CC ECO:0000269|PubMed:14983014, ECO:0000269|PubMed:16116421, CC ECO:0000269|PubMed:16153896, ECO:0000269|PubMed:36608669}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; CC Evidence={ECO:0000269|PubMed:20639400, ECO:0000269|PubMed:36608669}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:20639400, ECO:0000269|PubMed:36608669}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000269|PubMed:16973432, ECO:0000269|PubMed:20639400}; CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000269|PubMed:20639400}; CC -!- SUBUNIT: Binds directly to the BRCT domains of BRCA1 (PubMed:15125843). CC Interacts with the CIA complex components CIAO1, CIAO2B and MMS19 CC (PubMed:23585563). {ECO:0000269|PubMed:15125843, CC ECO:0000269|PubMed:23585563}. CC -!- INTERACTION: CC Q9BX63; P54132: BLM; NbExp=16; IntAct=EBI-3509650, EBI-621372; CC Q9BX63; P38398: BRCA1; NbExp=29; IntAct=EBI-3509650, EBI-349905; CC Q9BX63; Q9BPX1: HSD17B14; NbExp=3; IntAct=EBI-3509650, EBI-742664; CC Q9BX63; P40692: MLH1; NbExp=18; IntAct=EBI-3509650, EBI-744248; CC Q9BX63; Q96T76: MMS19; NbExp=4; IntAct=EBI-3509650, EBI-1044169; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11301010, CC ECO:0000269|PubMed:23585563}. Cytoplasm {ECO:0000269|PubMed:23585563}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BX63-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BX63-2; Sequence=VSP_012540, VSP_012541; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in CC testis. {ECO:0000269|PubMed:11301010}. CC -!- DOMAIN: 4Fe-4S iron-sulfur-binding is required for helicase activity. CC {ECO:0000269|PubMed:20639400}. CC -!- PTM: Phosphorylated. Phosphorylation is necessary for interaction with CC BRCA1, and is cell-cycle regulated. {ECO:0000269|PubMed:14576433}. CC -!- PTM: Acetylation at Lys-1249 facilitates DNA end processing required CC for repair and checkpoint signaling. {ECO:0000269|PubMed:22792074}. CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy CC originating from breast epithelial tissue. Breast neoplasms can be CC distinguished by their histologic pattern. Invasive ductal carcinoma is CC by far the most common type. Breast cancer is etiologically and CC genetically heterogeneous. Important genetic factors have been CC indicated by familial occurrence and bilateral involvement. Mutations CC at more than one locus can be involved in different families or even in CC the same case. {ECO:0000269|PubMed:11301010, CC ECO:0000269|PubMed:14983014}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Fanconi anemia complementation group J (FANCJ) [MIM:609054]: A CC disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:16116423, ECO:0000269|PubMed:16116424, CC ECO:0000269|PubMed:20639400}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC11156.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database; CC URL="https://www2.rockefeller.edu/fanconi/genes/jumpj"; 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; AF360549; AAK38111.1; -; mRNA. DR EMBL; AC002994; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005969; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC060798; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471179; EAW51430.1; -; Genomic_DNA. DR EMBL; CH471179; EAW51432.1; -; Genomic_DNA. DR EMBL; CH471179; EAW51431.1; -; Genomic_DNA. DR EMBL; CH471179; EAW51433.1; -; Genomic_DNA. DR EMBL; BC101472; AAI01473.1; -; mRNA. DR EMBL; BC101474; AAI01475.1; -; mRNA. DR EMBL; AK074713; BAC11156.1; ALT_INIT; mRNA. DR CCDS; CCDS11631.1; -. [Q9BX63-1] DR RefSeq; NP_114432.2; NM_032043.2. [Q9BX63-1] DR PDB; 1T15; X-ray; 1.85 A; B=988-995. DR PDB; 1T29; X-ray; 2.30 A; B=985-998. DR PDB; 3AL3; X-ray; 2.15 A; B=1129-1138. DR PDBsum; 1T15; -. DR PDBsum; 1T29; -. DR PDBsum; 3AL3; -. DR AlphaFoldDB; Q9BX63; -. DR EMDB; EMD-27996; -. DR EMDB; EMD-27998; -. DR EMDB; EMD-27999; -. DR EMDB; EMD-28000; -. DR EMDB; EMD-28001; -. DR EMDB; EMD-28002; -. DR EMDB; EMD-29673; -. DR EMDB; EMD-29674; -. DR SMR; Q9BX63; -. DR BioGRID; 123841; 90. DR ComplexPortal; CPX-4426; BRCA1-B complex. DR CORUM; Q9BX63; -. DR DIP; DIP-41787N; -. DR ELM; Q9BX63; -. DR IntAct; Q9BX63; 31. DR MINT; Q9BX63; -. DR STRING; 9606.ENSP00000259008; -. DR BindingDB; Q9BX63; -. DR GlyGen; Q9BX63; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9BX63; -. DR PhosphoSitePlus; Q9BX63; -. DR BioMuta; BRIP1; -. DR DMDM; 57012613; -. DR CPTAC; CPTAC-3220; -. DR CPTAC; CPTAC-3221; -. DR CPTAC; CPTAC-3222; -. DR CPTAC; CPTAC-3281; -. DR CPTAC; CPTAC-918; -. DR EPD; Q9BX63; -. DR jPOST; Q9BX63; -. DR MassIVE; Q9BX63; -. DR MaxQB; Q9BX63; -. DR PaxDb; 9606-ENSP00000259008; -. DR PeptideAtlas; Q9BX63; -. DR ProteomicsDB; 79352; -. [Q9BX63-1] DR ProteomicsDB; 79353; -. [Q9BX63-2] DR Pumba; Q9BX63; -. DR Antibodypedia; 18594; 346 antibodies from 36 providers. DR CPTC; Q9BX63; 5 antibodies. DR DNASU; 83990; -. DR Ensembl; ENST00000259008.7; ENSP00000259008.2; ENSG00000136492.10. [Q9BX63-1] DR Ensembl; ENST00000577598.5; ENSP00000464654.1; ENSG00000136492.10. [Q9BX63-2] DR Ensembl; ENST00000682453.1; ENSP00000506943.1; ENSG00000136492.10. [Q9BX63-1] DR Ensembl; ENST00000683039.1; ENSP00000508303.1; ENSG00000136492.10. [Q9BX63-1] DR GeneID; 83990; -. DR KEGG; hsa:83990; -. DR MANE-Select; ENST00000259008.7; ENSP00000259008.2; NM_032043.3; NP_114432.2. DR UCSC; uc002izk.3; human. [Q9BX63-1] DR AGR; HGNC:20473; -. DR CTD; 83990; -. DR DisGeNET; 83990; -. DR GeneCards; BRIP1; -. DR GeneReviews; BRIP1; -. DR HGNC; HGNC:20473; BRIP1. DR HPA; ENSG00000136492; Group enriched (bone marrow, esophagus, lymphoid tissue, testis). DR MalaCards; BRIP1; -. DR MIM; 114480; phenotype. DR MIM; 605882; gene. DR MIM; 609054; phenotype. DR neXtProt; NX_Q9BX63; -. DR OpenTargets; ENSG00000136492; -. DR Orphanet; 84; Fanconi anemia. DR Orphanet; 145; Hereditary breast and/or ovarian cancer syndrome. DR PharmGKB; PA134906421; -. DR VEuPathDB; HostDB:ENSG00000136492; -. DR eggNOG; KOG1132; Eukaryota. DR GeneTree; ENSGT00950000182970; -. DR InParanoid; Q9BX63; -. DR OMA; FSNDNAR; -. DR OrthoDB; 124793at2759; -. DR PhylomeDB; Q9BX63; -. DR TreeFam; TF329449; -. DR BRENDA; 3.6.4.12; 2681. DR PathwayCommons; Q9BX63; -. DR Reactome; R-HSA-2564830; Cytosolic iron-sulfur cluster assembly. DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint. DR Reactome; R-HSA-9701192; Defective homologous recombination repair (HRR) due to BRCA1 loss of function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. DR SignaLink; Q9BX63; -. DR SIGNOR; Q9BX63; -. DR BioGRID-ORCS; 83990; 108 hits in 1165 CRISPR screens. DR ChiTaRS; BRIP1; human. DR EvolutionaryTrace; Q9BX63; -. DR GeneWiki; BRIP1; -. DR GenomeRNAi; 83990; -. DR Pharos; Q9BX63; Tbio. DR PRO; PR:Q9BX63; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9BX63; Protein. DR Bgee; ENSG00000136492; Expressed in ventricular zone and 126 other cell types or tissues. DR ExpressionAtlas; Q9BX63; baseline and differential. DR GO; GO:0070532; C:BRCA1-B complex; IPI:ComplexPortal. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0043139; F:5'-3' DNA helicase activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB. DR GO; GO:0003678; F:DNA helicase activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC. DR GO; GO:1904385; P:cellular response to angiotensin; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0071295; P:cellular response to vitamin; IEA:Ensembl. DR GO; GO:0051026; P:chiasma assembly; IEA:Ensembl. DR GO; GO:0000077; P:DNA damage checkpoint signaling; NAS:UniProtKB. DR GO; GO:0006281; P:DNA repair; NAS:ComplexPortal. DR GO; GO:0006302; P:double-strand break repair; NAS:UniProtKB. DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; IBA:GO_Central. DR GO; GO:0035825; P:homologous recombination; NAS:ComplexPortal. DR GO; GO:0010705; P:meiotic DNA double-strand break processing involved in reciprocal meiotic recombination; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0006289; P:nucleotide-excision repair; IBA:GO_Central. DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0072520; P:seminiferous tubule development; IEA:Ensembl. DR GO; GO:0007286; P:spermatid development; IEA:Ensembl. DR GO; GO:0007284; P:spermatogonial cell division; IEA:Ensembl. DR CDD; cd17970; DEAHc_FancJ; 1. DR CDD; cd18788; SF2_C_XPD; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 3. DR IDEAL; IID00181; -. DR InterPro; IPR006555; ATP-dep_Helicase_C. DR InterPro; IPR045028; DinG/Rad3-like. DR InterPro; IPR014013; Helic_SF1/SF2_ATP-bd_DinG/Rad3. DR InterPro; IPR006554; Helicase-like_DEXD_c2. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR010614; RAD3-like_helicase_DEAD. DR InterPro; IPR013020; Rad3/Chl1-like. DR NCBIfam; TIGR00604; rad3; 1. DR PANTHER; PTHR11472; DNA REPAIR DEAD HELICASE RAD3/XP-D SUBFAMILY MEMBER; 1. DR PANTHER; PTHR11472:SF47; FANCONI ANEMIA GROUP J PROTEIN; 1. DR Pfam; PF06733; DEAD_2; 1. DR Pfam; PF13307; Helicase_C_2; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00488; DEXDc2; 1. DR SMART; SM00491; HELICc2; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2. DR PROSITE; PS51193; HELICASE_ATP_BIND_2; 1. DR Genevisible; Q9BX63; HS. PE 1: Evidence at protein level; KW 3D-structure; 4Fe-4S; Acetylation; Alternative splicing; ATP-binding; KW Cytoplasm; Direct protein sequencing; Disease variant; DNA damage; KW DNA repair; Fanconi anemia; Helicase; Hydrolase; Iron; Iron-sulfur; KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome. FT CHAIN 1..1249 FT /note="Fanconi anemia group J protein" FT /id="PRO_0000055173" FT DOMAIN 11..442 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT REGION 102..131 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 888..1063 FT /note="Interaction with BRCA1" FT /evidence="ECO:0000269|PubMed:11301010" FT REGION 1018..1042 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1108..1127 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 158..175 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOTIF 393..396 FT /note="DEAH box" FT COMPBIAS 1022..1036 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1108..1126 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 185..192 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT BINDING 283 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250|UniProtKB:Q4JC68" FT BINDING 298 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250|UniProtKB:Q4JC68" FT BINDING 310 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250|UniProtKB:Q4JC68" FT BINDING 350 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250|UniProtKB:Q4JC68" FT MOD_RES 505 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 927 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 930 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 956 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 990 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:14576433, FT ECO:0007744|PubMed:18669648" FT MOD_RES 1004 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1032 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1237 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1249 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:22792074" FT VAR_SEQ 969..994 FT /note="NDPVFLEEAGKAEKIVISRSTSPTFN -> SMKSSSHLPLIEKSFIIFSEMI FT FIWV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_012540" FT VAR_SEQ 995..1249 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_012541" FT VARIANT 47 FT /note="P -> A (in BC; early onset; loss of ATPase and FT helicase activities; dbSNP:rs28903098)" FT /evidence="ECO:0000269|PubMed:11301010, FT ECO:0000269|PubMed:14983014" FT /id="VAR_020896" FT VARIANT 173 FT /note="R -> C (in dbSNP:rs4988345)" FT /evidence="ECO:0000269|PubMed:11920628, FT ECO:0000269|PubMed:12872252" FT /id="VAR_020897" FT VARIANT 193 FT /note="V -> I (in dbSNP:rs4988346)" FT /evidence="ECO:0000269|PubMed:11301010, FT ECO:0000269|PubMed:12872252" FT /id="VAR_020898" FT VARIANT 195 FT /note="L -> P (in dbSNP:rs4988347)" FT /evidence="ECO:0000269|PubMed:12872252" FT /id="VAR_020899" FT VARIANT 255 FT /note="Q -> H (in FANCJ)" FT /evidence="ECO:0000269|PubMed:16116423" FT /id="VAR_023700" FT VARIANT 264 FT /note="R -> W (in dbSNP:rs28997569)" FT /evidence="ECO:0000269|PubMed:16116423" FT /id="VAR_023701" FT VARIANT 299 FT /note="M -> I (in BC; early onset; reduces helicase FT efficiency on longer substrates; dbSNP:rs137852985)" FT /evidence="ECO:0000269|PubMed:11301010, FT ECO:0000269|PubMed:14983014" FT /id="VAR_020900" FT VARIANT 349 FT /note="A -> P (in FANCJ; destabilizes iron-sulfur-binding FT and abolishes helicase activity; dbSNP:rs149364097)" FT /evidence="ECO:0000269|PubMed:16116424, FT ECO:0000269|PubMed:20639400" FT /id="VAR_023702" FT VARIANT 419 FT /note="R -> W (in dbSNP:rs150624408)" FT /evidence="ECO:0000269|PubMed:12872252" FT /id="VAR_020901" FT VARIANT 531 FT /note="F -> V (in dbSNP:rs4988350)" FT /evidence="ECO:0000269|PubMed:12872252" FT /id="VAR_020902" FT VARIANT 540 FT /note="Q -> L (in dbSNP:rs4988349)" FT /evidence="ECO:0000269|PubMed:12872252" FT /id="VAR_020903" FT VARIANT 633 FT /note="I -> M (in dbSNP:rs28997572)" FT /id="VAR_052192" FT VARIANT 647 FT /note="W -> C (in FANCJ; associated with C-707; FT dbSNP:rs786202760)" FT /evidence="ECO:0000269|PubMed:16116423" FT /id="VAR_023703" FT VARIANT 707 FT /note="R -> C (in FANCJ; associated with C-647; FT dbSNP:rs764803896)" FT /evidence="ECO:0000269|PubMed:16116423" FT /id="VAR_023704" FT VARIANT 832 FT /note="C -> Y (in dbSNP:rs4988355)" FT /evidence="ECO:0000269|PubMed:12872252" FT /id="VAR_020904" FT VARIANT 919 FT /note="S -> P (in dbSNP:rs4986764)" FT /evidence="ECO:0000269|PubMed:11301010, FT ECO:0000269|PubMed:11920628, ECO:0000269|PubMed:12565990, FT ECO:0000269|PubMed:12872252, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:16153896, ECO:0000269|PubMed:18987736" FT /id="VAR_020905" FT VARIANT 935 FT /note="V -> G (in dbSNP:rs4988356)" FT /evidence="ECO:0000269|PubMed:12872252" FT /id="VAR_020906" FT VARIANT 1034 FT /note="P -> L (in a patient with ovarian cancer; uncertain FT significance; dbSNP:rs1199923024)" FT /evidence="ECO:0000269|PubMed:12565990" FT /id="VAR_020907" FT VARIANT 1148 FT /note="D -> E (in dbSNP:rs28997573)" FT /id="VAR_052193" FT MUTAGEN 52 FT /note="K->R: Abolished ATPase and DNA helicase activities, FT preventing ability to unfold DNA-protein cross-links. FT Disrupts BRCA1-mediated double-strand break repair." FT /evidence="ECO:0000269|PubMed:11301010, FT ECO:0000269|PubMed:14983014, ECO:0000269|PubMed:16116421, FT ECO:0000269|PubMed:36608669" FT MUTAGEN 986 FT /note="S->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 988 FT /note="S->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 989 FT /note="T->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 990 FT /note="S->A: Disrupts the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 991 FT /note="P->A: Abolishes phosphorylation of S-990. Impairs FT the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 992 FT /note="T->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 993 FT /note="F->A: Abolishes phosphorylation of S-990. Impairs FT the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 997 FT /note="T->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 1001 FT /note="S->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 1003 FT /note="S->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 1004 FT /note="S->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 1007 FT /note="S->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 1011 FT /note="Y->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT MUTAGEN 1013 FT /note="T->A: Does not affect the interaction with BRCA1." FT /evidence="ECO:0000269|PubMed:14576433" FT CONFLICT 641 FT /note="I -> V (in Ref. 5; BAC11156)" FT /evidence="ECO:0000305" FT CONFLICT 767 FT /note="E -> I (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 1249 AA; 140867 MW; 8ED691F03A442BE1 CRC64; MSSMWSEYTI GGVKIYFPYK AYPSQLAMMN SILRGLNSKQ HCLLESPTGS GKSLALLCSA LAWQQSLSGK PADEGVSEKA EVQLSCCCAC HSKDFTNNDM NQGTSRHFNY PSTPPSERNG TSSTCQDSPE KTTLAAKLSA KKQASIYRDE NDDFQVEKKR IRPLETTQQI RKRHCFGTEV HNLDAKVDSG KTVKLNSPLE KINSFSPQKP PGHCSRCCCS TKQGNSQESS NTIKKDHTGK SKIPKIYFGT RTHKQIAQIT RELRRTAYSG VPMTILSSRD HTCVHPEVVG NFNRNEKCME LLDGKNGKSC YFYHGVHKIS DQHTLQTFQG MCKAWDIEEL VSLGKKLKAC PYYTARELIQ DADIIFCPYN YLLDAQIRES MDLNLKEQVV ILDEAHNIED CARESASYSV TEVQLRFARD ELDSMVNNNI RKKDHEPLRA VCCSLINWLE ANAEYLVERD YESACKIWSG NEMLLTLHKM GITTATFPIL QGHFSAVLQK EEKISPIYGK EEAREVPVIS ASTQIMLKGL FMVLDYLFRQ NSRFADDYKI AIQQTYSWTN QIDISDKNGL LVLPKNKKRS RQKTAVHVLN FWCLNPAVAF SDINGKVQTI VLTSGTLSPM KSFSSELGVT FTIQLEANHI IKNSQVWVGT IGSGPKGRNL CATFQNTETF EFQDEVGALL LSVCQTVSQG ILCFLPSYKL LEKLKERWLS TGLWHNLELV KTVIVEPQGG EKTNFDELLQ VYYDAIKYKG EKDGALLVAV CRGKVSEGLD FSDDNARAVI TIGIPFPNVK DLQVELKRQY NDHHSKLRGL LPGRQWYEIQ AYRALNQALG RCIRHRNDWG ALILVDDRFR NNPSRYISGL SKWVRQQIQH HSTFESALES LAEFSKKHQK VLNVSIKDRT NIQDNESTLE VTSLKYSTSP YLLEAASHLS PENFVEDEAK ICVQELQCPK IITKNSPLPS SIISRKEKND PVFLEEAGKA EKIVISRSTS PTFNKQTKRV SWSSFNSLGQ YFTGKIPKAT PELGSSENSA SSPPRFKTEK MESKTVLPFT DKCESSNLTV NTSFGSCPQS ETIISSLKID ATLTRKNHSE HPLCSEEALD PDIELSLVSE EDKQSTSNRD FETEAEDESI YFTPELYDPE DTDEEKNDLA ETDRGNRLAN NSDCILAKDL FEIRTIKEVD SAREVKAEDC IDTKLNGILH IEESKIDDID GNVKTTWINE LELGKTHEIE IKNFKPSPSK NKGMFPGFK //