ID CUL7_HUMAN Reviewed; 1698 AA. AC Q14999; B4DYZ0; F5H0L1; Q5T654; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 23-OCT-2007, sequence version 2. DT 27-MAR-2024, entry version 213. DE RecName: Full=Cullin-7; DE Short=CUL-7; GN Name=CUL7; Synonyms=KIAA0076; 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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-813. RC TISSUE=Bone marrow; RX PubMed=7584044; DOI=10.1093/dnares/1.5.223; RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., RA Kawarabayasi Y., Ishikawa K., Tabata S.; RT "Prediction of the coding sequences of unidentified human genes. II. The RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 1:223-229(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ARG-813. RC TISSUE=Testis; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-813. RC TISSUE=Eye; 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 IDENTIFICATION IN A COMPLEX WITH SKP1; FBXW8 AND RBX1. RX PubMed=12481031; DOI=10.1073/pnas.252646399; RA Dias D.C., Dolios G., Wang R., Pan Z.Q.; RT "CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to form RT an SCF-like complex."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002). RN [6] RP INTERACTION WITH RBX1, AND IDENTIFICATION IN A COMPLEX WITH SKP1; FBXW8; RP RBX1 AND GLMN. RX PubMed=12904573; DOI=10.1073/pnas.1733908100; RA Arai T., Kasper J.S., Skaar J.R., Ali S.H., Takahashi C., DeCaprio J.A.; RT "Targeted disruption of p185/Cul7 gene results in abnormal vascular RT morphogenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 100:9855-9860(2003). RN [7] RP INTERACTION WITH SV40 LARGE ANTIGEN (MICROBIAL INFECTION). RX PubMed=16140746; DOI=10.1128/jvi.79.18.11685-11692.2005; RA Kasper J.S., Kuwabara H., Arai T., Ali S.H., DeCaprio J.A.; RT "Simian virus 40 large T antigen's association with the CUL7 SCF complex RT contributes to cellular transformation."; RL J. Virol. 79:11685-11692(2005). RN [8] RP INTERACTION WITH CUL9. RX PubMed=15964813; DOI=10.1128/mcb.25.13.5579-5589.2005; RA Skaar J.R., Arai T., DeCaprio J.A.; RT "Dimerization of CUL7 and PARC is not required for all CUL7 functions and RT mouse development."; RL Mol. Cell. Biol. 25:5579-5589(2005). RN [9] RP FUNCTION, INTERACTION WITH RBX1 AND TP53, AND SUBCELLULAR LOCATION. RX PubMed=16547496; DOI=10.1038/sj.onc.1209490; RA Andrews P., He Y.J., Xiong Y.; RT "Cytoplasmic localized ubiquitin ligase cullin 7 binds to p53 and promotes RT cell growth by antagonizing p53 function."; RL Oncogene 25:4534-4548(2006). RN [10] RP FUNCTION, INTERACTION WITH CUL9; SKP1; FBXW8; RBX1 AND TP53, AND LACK OF RP NEDDYLATION. RX PubMed=17332328; DOI=10.1158/0008-5472.can-06-3241; RA Skaar J.R., Florens L., Tsutsumi T., Arai T., Tron A., Swanson S.K., RA Washburn M.P., DeCaprio J.A.; RT "PARC and CUL7 form atypical cullin RING ligase complexes."; RL Cancer Res. 67:2006-2014(2007). RN [11] RP INVOLVEMENT IN 3M1. RX PubMed=17675530; DOI=10.1136/jmg.2007.051979; RA Maksimova N., Hara K., Miyashia A., Nikolaeva I., Shiga A., Nogovicina A., RA Sukhomyasova A., Argunov V., Shvedova A., Ikeuchi T., Nishizawa M., RA Kuwano R., Onodera O.; RT "Clinical, molecular and histopathological features of short stature RT syndrome with novel CUL7 mutation in Yakuts: new population isolate in RT Asia."; RL J. Med. Genet. 44:772-778(2007). RN [12] RP FUNCTION. RX PubMed=18498745; DOI=10.1016/j.molcel.2008.03.009; RA Xu X., Sarikas A., Dias-Santagata D.C., Dolios G., Lafontant P.J., RA Tsai S.C., Zhu W., Nakajima H., Nakajima H.O., Field L.J., Wang R., RA Pan Z.Q.; RT "The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for RT ubiquitin-dependent degradation."; RL Mol. Cell 30:403-414(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339, AND IDENTIFICATION BY RP 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 [14] RP IDENTIFICATION BY 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 [15] RP INTERACTION WITH OBSL1. RX PubMed=21737058; DOI=10.1016/j.ajhg.2011.05.028; RA Hanson D., Murray P.G., O'Sullivan J., Urquhart J., Daly S., Bhaskar S.S., RA Biesecker L.G., Skae M., Smith C., Cole T., Kirk J., Chandler K., RA Kingston H., Donnai D., Clayton P.E., Black G.C.; RT "Exome sequencing identifies CCDC8 mutations in 3-M syndrome, Suggesting RT that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human RT Growth."; RL Am. J. Hum. Genet. 89:148-153(2011). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP FUNCTION, INTERACTION WITH FBXW8 AND OBSL1, AND SUBCELLULAR LOCATION. RX PubMed=21572988; DOI=10.1371/journal.pbio.1001060; RA Litterman N., Ikeuchi Y., Gallardo G., O'Connell B.C., Sowa M.E., RA Gygi S.P., Harper J.W., Bonni A.; RT "An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi RT morphology and dendrite patterning."; RL PLoS Biol. 9:E1001060-E1001060(2011). RN [18] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=20139075; DOI=10.1074/jbc.m109.004200; RA Fu J., Lv X., Lin H., Wu L., Wang R., Zhou Z., Zhang B., Wang Y.L., RA Tsang B.K., Zhu C., Wang H.; RT "Ubiquitin ligase cullin 7 induces epithelial-mesenchymal transition in RT human choriocarcinoma cells."; RL J. Biol. Chem. 285:10870-10879(2010). RN [19] RP IDENTIFICATION BY 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 [20] RP FUNCTION, AND INTERACTION WITH FBXW8. RX PubMed=24362026; DOI=10.1074/jbc.m113.520106; RA Wang H., Chen Y., Lin P., Li L., Zhou G., Liu G., Logsdon C., Jin J., RA Abbruzzese J.L., Tan T.H., Wang H.; RT "The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin RT ligase promotes degradation of hematopoietic progenitor kinase 1."; RL J. Biol. Chem. 289:4009-4017(2014). RN [21] RP FUNCTION, IDENTIFICATION IN THE 3M COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=24793695; DOI=10.1016/j.molcel.2014.03.047; RA Yan J., Yan F., Li Z., Sinnott B., Cappell K.M., Yu Y., Mo J., Duncan J.A., RA Chen X., Cormier-Daire V., Whitehurst A.W., Xiong Y.; RT "The 3M complex maintains microtubule and genome integrity."; RL Mol. Cell 54:791-804(2014). RN [22] RP FUNCTION, AND INTERACTION WITH CUL9. RX PubMed=24793696; DOI=10.1016/j.molcel.2014.03.046; RA Li Z., Pei X.H., Yan J., Yan F., Cappell K.M., Whitehurst A.W., Xiong Y.; RT "CUL9 mediates the functions of the 3M complex and ubiquitylates survivin RT to maintain genome integrity."; RL Mol. Cell 54:805-819(2014). RN [23] RP INTERACTION WITH HDAC4 AND HDAC5. RX PubMed=25752541; DOI=10.1016/j.str.2015.02.001; RA Nie J., Xu C., Jin J., Aka J.A., Tempel W., Nguyen V., You L., Weist R., RA Min J., Pawson T., Yang X.J.; RT "Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome RT protein CCDC8."; RL Structure 23:700-712(2015). RN [24] RP STRUCTURE BY NMR OF 360-460, AND INTERACTION WITH TP53. RX PubMed=17298945; DOI=10.1074/jbc.m611297200; RA Kaustov L., Lukin J., Lemak A., Duan S., Ho M., Doherty R., Penn L.Z., RA Arrowsmith C.H.; RT "The conserved CPH domains of Cul7 and PARC are protein-protein interaction RT modules that bind the tetramerization domain of p53."; RL J. Biol. Chem. 282:11300-11307(2007). RN [25] RP VARIANTS 3M1 ARG-1014; GLY-1246 AND PRO-1464, AND TISSUE SPECIFICITY. RX PubMed=16142236; DOI=10.1038/ng1628; RA Huber C., Dias-Santagata D., Glaser A., O'Sullivan J., Brauner R., Wu K., RA Xu X., Pearce K., Wang R., Giovannucci Uzielli M.L., Dagoneau N., RA Chemaitilly W., Superti-Furga A., Dos Santos H., Megarbane A., Morin G., RA Gillessen-Kaesbach G., Hennekam R.C.M., Van der Burgt I., Black G.C.M., RA Clayton P.E., Read A., Le Merrer M., Scambler P.J., Munnich A., Pan Z.-Q., RA Winter R., Cormier-Daire V.; RT "Identification of mutations in CUL7 in 3-M syndrome."; RL Nat. Genet. 37:1119-1124(2005). RN [26] RP VARIANT 3M1 PRO-1588. RX PubMed=23018678; DOI=10.1530/jme-12-0034; RA Hanson D., Murray P.G., Coulson T., Sud A., Omokanye A., Stratta E., RA Sakhinia F., Bonshek C., Wilson L.C., Wakeling E., Temtamy S.A., Aglan M., RA Rosser E.M., Mansour S., Carcavilla A., Nampoothiri S., Khan W.I., RA Banerjee I., Chandler K.E., Black G.C., Clayton P.E.; RT "Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered RT growth factor signalling."; RL J. Mol. Endocrinol. 49:267-275(2012). CC -!- FUNCTION: Core component of the 3M and Cul7-RING(FBXW8) complexes, CC which mediates the ubiquitination of target proteins. Core component of CC the 3M complex, a complex required to regulate microtubule dynamics and CC genome integrity. It is unclear how the 3M complex regulates CC microtubules, it could act by controlling the level of a microtubule CC stabilizer (PubMed:24793695). Interaction with CUL9 is required to CC inhibit CUL9 activity and ubiquitination of BIRC5 (PubMed:24793696). CC Core component of a Cul7-RING ubiquitin-protein ligase with FBXW8, CC which mediates ubiquitination and consequent degradation of target CC proteins such as GORASP1, IRS1 and MAP4K1/HPK1 (PubMed:21572988, CC PubMed:24362026). Ubiquitination of GORASP1 regulates Golgi CC morphogenesis and dendrite patterning in brain (PubMed:21572988). CC Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent CC manner: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 CC previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2) CC (PubMed:18498745). The Cul7-RING(FBXW8) complex also mediates CC ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated CC MAP4K1/HPK1, leading to its degradation, thereby affecting cell CC proliferation and differentiation (PubMed:24362026). Acts as a CC regulator in trophoblast cell epithelial-mesenchymal transition and CC placental development (PubMed:20139075). Does not promote CC polyubiquitination and proteasomal degradation of p53/TP53 CC (PubMed:16547496, PubMed:17332328). While the Cul7-RING(FBXW8) and the CC 3M complexes are associated and involved in common processes, CUL7 and CC the Cul7-RING(FBXW8) complex may be have additional functions. CC {ECO:0000269|PubMed:16547496, ECO:0000269|PubMed:17332328, CC ECO:0000269|PubMed:18498745, ECO:0000269|PubMed:20139075, CC ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, CC ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Component of the 3M complex, composed of core components CUL7, CC CCDC8 and OBSL1. Part of a Cul7-RING complex consisting of CUL7, RBX1, CC SKP1 and FBXW8. Interacts with a complex of SKP1 and FBXW8, but not CC with SKP1 alone. Interacts with CUL9; leading to inhibit CUL9 activity. CC Interacts with FBXW8; interaction is mutually exclusive of binding to CC CUL9 or p53/TP53. Interacts with p53/TP53; the interaction CC preferentially involves tetrameric and dimeric p53/TP53. The CUL7-CUL9 CC heterodimer seems to interact specifically with p53/TP53. Interacts CC with CUL1; the interactions seems to be mediated by FBXW8. Interacts CC with OBSL1. Interacts (as part of the 3M complex) with HDAC4 and HDAC5; CC it is negatively regulated by ANKRA2. {ECO:0000269|PubMed:12481031, CC ECO:0000269|PubMed:12904573, ECO:0000269|PubMed:15964813, CC ECO:0000269|PubMed:16547496, ECO:0000269|PubMed:17298945, CC ECO:0000269|PubMed:17332328, ECO:0000269|PubMed:21572988, CC ECO:0000269|PubMed:21737058, ECO:0000269|PubMed:24362026, CC ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696, CC ECO:0000269|PubMed:25752541}. CC -!- SUBUNIT: (Microbial infection) Interacts with SV40 Large T antigen; CC this interaction seems to inhibit CUL7. {ECO:0000269|PubMed:16140746}. CC -!- INTERACTION: CC Q14999; O75147-2: OBSL1; NbExp=4; IntAct=EBI-308606, EBI-15927144; CC Q14999; P04637: TP53; NbExp=16; IntAct=EBI-308606, EBI-366083; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome. Cytoplasm, perinuclear region. Golgi CC apparatus. Note=Colocalizes with FBXW8 at the Golgi apparatus in CC neurons; localization to Golgi is mediated by OBSL1. During mitosis, CC localizes to the mitotic apparatus (PubMed:24793695). CCDC8 is required CC for centrosomal location (PubMed:24793695). CC {ECO:0000269|PubMed:24793695}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q14999-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14999-2; Sequence=VSP_046105, VSP_046106; CC -!- TISSUE SPECIFICITY: Highly expressed in fetal kidney and adult skeletal CC muscle. Also abundant in fetal brain, as well as in adult pancreas, CC kidney, placenta and heart. Detected in trophoblasts, lymphoblasts, CC osteoblasts, chondrocytes and skin fibroblasts. CC {ECO:0000269|PubMed:16142236}. CC -!- DEVELOPMENTAL STAGE: Highly expressed in invasive placental villi CC during first trimester. {ECO:0000269|PubMed:20139075}. CC -!- PTM: According to a report, may not be neddylated despite the conserved CC consensus site for neddylation at Lys-1576. CC {ECO:0000269|PubMed:17332328}. CC -!- DISEASE: 3M syndrome 1 (3M1) [MIM:273750]: An autosomal recessive CC disorder characterized by severe pre- and postnatal growth retardation, CC facial dysmorphism, large head circumference, and normal intelligence CC and endocrine function. Skeletal changes include long slender tubular CC bones and tall vertebral bodies. {ECO:0000269|PubMed:16142236, CC ECO:0000269|PubMed:17675530, ECO:0000269|PubMed:23018678}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the cullin family. {ECO:0000255|PROSITE- CC ProRule:PRU00330}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA07551.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; D38548; BAA07551.2; ALT_INIT; mRNA. DR EMBL; AK302668; BAG63902.1; -; mRNA. DR EMBL; AL355385; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL136304; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC033647; AAH33647.1; -; mRNA. DR CCDS; CCDS4881.1; -. [Q14999-1] DR RefSeq; NP_001161842.1; NM_001168370.1. DR RefSeq; NP_055595.2; NM_014780.4. [Q14999-1] DR PDB; 2JNG; NMR; -; A=360-460. DR PDB; 7Z8B; EM; 2.80 A; C=1-1698. DR PDBsum; 2JNG; -. DR PDBsum; 7Z8B; -. DR AlphaFoldDB; Q14999; -. DR BMRB; Q14999; -. DR EMDB; EMD-14547; -. DR SMR; Q14999; -. DR BioGRID; 115159; 854. DR ComplexPortal; CPX-2838; 3M complex. DR ComplexPortal; CPX-7784; SCF E3 ubiquitin ligase complex, FBXW8-CUL7 variant. DR CORUM; Q14999; -. DR DIP; DIP-31618N; -. DR DIP; DIP-60187N; -. DR IntAct; Q14999; 40. DR MINT; Q14999; -. DR STRING; 9606.ENSP00000438788; -. DR GlyGen; Q14999; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q14999; -. DR PhosphoSitePlus; Q14999; -. DR BioMuta; CUL7; -. DR DMDM; 160370003; -. DR EPD; Q14999; -. DR jPOST; Q14999; -. DR MassIVE; Q14999; -. DR MaxQB; Q14999; -. DR PaxDb; 9606-ENSP00000438788; -. DR PeptideAtlas; Q14999; -. DR ProteomicsDB; 25372; -. DR ProteomicsDB; 60290; -. [Q14999-1] DR Pumba; Q14999; -. DR Antibodypedia; 4223; 227 antibodies from 37 providers. DR DNASU; 9820; -. DR Ensembl; ENST00000265348.9; ENSP00000265348.4; ENSG00000044090.13. [Q14999-1] DR Ensembl; ENST00000690231.1; ENSP00000508461.1; ENSG00000044090.13. [Q14999-1] DR GeneID; 9820; -. DR KEGG; hsa:9820; -. DR MANE-Select; ENST00000265348.9; ENSP00000265348.4; NM_014780.5; NP_055595.2. DR UCSC; uc003otq.4; human. [Q14999-1] DR AGR; HGNC:21024; -. DR CTD; 9820; -. DR DisGeNET; 9820; -. DR GeneCards; CUL7; -. DR GeneReviews; CUL7; -. DR HGNC; HGNC:21024; CUL7. DR HPA; ENSG00000044090; Low tissue specificity. DR MalaCards; CUL7; -. DR MIM; 273750; phenotype. DR MIM; 609577; gene. DR neXtProt; NX_Q14999; -. DR OpenTargets; ENSG00000044090; -. DR Orphanet; 2616; 3M syndrome. DR PharmGKB; PA134897835; -. DR VEuPathDB; HostDB:ENSG00000044090; -. DR eggNOG; ENOG502RDJD; Eukaryota. DR GeneTree; ENSGT00940000153954; -. DR HOGENOM; CLU_001067_1_0_1; -. DR InParanoid; Q14999; -. DR OMA; RCWPVAS; -. DR OrthoDB; 4161627at2759; -. DR PhylomeDB; Q14999; -. DR TreeFam; TF101154; -. DR PathwayCommons; Q14999; -. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q14999; -. DR SIGNOR; Q14999; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 9820; 83 hits in 1211 CRISPR screens. DR ChiTaRS; CUL7; human. DR EvolutionaryTrace; Q14999; -. DR GeneWiki; CUL7; -. DR GenomeRNAi; 9820; -. DR Pharos; Q14999; Tbio. DR PRO; PR:Q14999; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q14999; Protein. DR Bgee; ENSG00000044090; Expressed in stromal cell of endometrium and 195 other cell types or tissues. DR ExpressionAtlas; Q14999; baseline and differential. DR GO; GO:1990393; C:3M complex; IDA:UniProtKB. DR GO; GO:0005680; C:anaphase-promoting complex; NAS:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0031467; C:Cul7-RING ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:InterPro. DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:UniProtKB. DR GO; GO:0007030; P:Golgi organization; ISS:UniProtKB. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB. DR GO; GO:0001890; P:placenta development; IDA:UniProtKB. DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IGI:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; NAS:UniProtKB. DR GO; GO:0007088; P:regulation of mitotic nuclear division; IMP:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro. DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB. DR CDD; cd08665; APC10-CUL7; 1. DR Gene3D; 2.30.30.30; -; 1. DR Gene3D; 1.20.1310.10; Cullin Repeats; 1. DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR InterPro; IPR004939; APC_su10/DOC_dom. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR021097; CPH_domain. DR InterPro; IPR045093; Cullin. DR InterPro; IPR016158; Cullin_homology. DR InterPro; IPR036317; Cullin_homology_sf. DR InterPro; IPR001373; Cullin_N. DR InterPro; IPR019559; Cullin_neddylation_domain. DR InterPro; IPR008979; Galactose-bd-like_sf. DR InterPro; IPR014722; Rib_uL2_dom2. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR PANTHER; PTHR22771; CULLIN AND GALACTOSE-BINDING DOMAIN-CONTAINING; 1. DR PANTHER; PTHR22771:SF3; CULLIN-7; 1. DR Pfam; PF03256; ANAPC10; 1. DR Pfam; PF11515; Cul7; 1. DR Pfam; PF00888; Cullin; 1. DR SMART; SM01337; APC10; 1. DR SMART; SM00884; Cullin_Nedd8; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF75632; Cullin homology domain; 1. DR SUPFAM; SSF49785; Galactose-binding domain-like; 1. DR SUPFAM; SSF63748; Tudor/PWWP/MBT; 1. DR PROSITE; PS50069; CULLIN_2; 1. DR PROSITE; PS51284; DOC; 1. DR Genevisible; Q14999; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Cytoskeleton; KW Disease variant; Dwarfism; Golgi apparatus; Host-virus interaction; KW Isopeptide bond; Phosphoprotein; Reference proteome; Ubl conjugation; KW Ubl conjugation pathway. FT CHAIN 1..1698 FT /note="Cullin-7" FT /id="PRO_0000119802" FT DOMAIN 814..993 FT /note="DOC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00614" FT REGION 315..357 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 360..460 FT /note="Interaction with TP53" FT REGION 601..623 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1345..1370 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1345..1362 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 339 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT CROSSLNK 1576 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in NEDD8)" FT /evidence="ECO:0000255" FT VAR_SEQ 1 FT /note="M -> MSRGFWLAEPLAGTGPHPAPVAADSRGCSSVPRRHAPSRLSVSTPSR FT GPGARM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046105" FT VAR_SEQ 194 FT /note="G -> GEGQCGEEGKAGEGLGRLRDSQDTVAGASDLIR (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046106" FT VARIANT 616 FT /note="S -> G (in dbSNP:rs7774330)" FT /id="VAR_048841" FT VARIANT 813 FT /note="Q -> R (in dbSNP:rs9381231)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7584044" FT /id="VAR_026121" FT VARIANT 852 FT /note="R -> Q (in dbSNP:rs34574340)" FT /id="VAR_048842" FT VARIANT 1014 FT /note="L -> R (in 3M1; uncertain significance; FT dbSNP:rs61752334)" FT /evidence="ECO:0000269|PubMed:16142236" FT /id="VAR_026122" FT VARIANT 1246 FT /note="Q -> G (in 3M1; requires 2 nucleotide FT substitutions)" FT /evidence="ECO:0000269|PubMed:16142236" FT /id="VAR_026123" FT VARIANT 1246 FT /note="Q -> H (in dbSNP:rs36071170)" FT /id="VAR_048843" FT VARIANT 1464 FT /note="H -> P (in 3M1; impairs the ability to interact with FT RBX1, thus hampers the assembly of polyubiquitin chains; FT dbSNP:rs121918229)" FT /evidence="ECO:0000269|PubMed:16142236" FT /id="VAR_026124" FT VARIANT 1588 FT /note="L -> P (in 3M1; dbSNP:rs759300846)" FT /evidence="ECO:0000269|PubMed:23018678" FT /id="VAR_071120" FT STRAND 12..15 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 18..30 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 34..45 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 63..69 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 71..77 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 82..84 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 116..119 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 142..148 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 150..152 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 153..157 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 158..161 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 162..170 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 176..186 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 198..204 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 207..211 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 216..228 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 247..268 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 288..310 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 360..362 FT /evidence="ECO:0007829|PDB:2JNG" FT STRAND 363..366 FT /evidence="ECO:0007829|PDB:2JNG" FT HELIX 367..376 FT /evidence="ECO:0007829|PDB:2JNG" FT STRAND 382..385 FT /evidence="ECO:0007829|PDB:2JNG" FT STRAND 397..403 FT /evidence="ECO:0007829|PDB:2JNG" FT STRAND 407..414 FT /evidence="ECO:0007829|PDB:2JNG" FT TURN 415..418 FT /evidence="ECO:0007829|PDB:2JNG" FT STRAND 419..424 FT /evidence="ECO:0007829|PDB:2JNG" FT HELIX 425..427 FT /evidence="ECO:0007829|PDB:2JNG" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:2JNG" FT HELIX 467..469 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 491..501 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 506..519 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 526..529 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 537..546 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 553..561 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 563..567 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 620..625 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 633..640 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 652..661 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 664..671 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 680..682 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 683..693 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 696..698 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 699..701 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 704..706 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 711..714 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 723..738 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 741..749 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 751..759 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 760..762 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 766..768 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 769..810 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 820..828 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 841..848 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 850..856 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 857..859 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 874..880 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 887..892 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 897..912 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 913..915 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 918..924 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 930..935 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 943..952 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 953..955 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 963..967 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 977..1002 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1004..1009 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1010..1028 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1029..1031 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1032..1055 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1059..1061 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1064..1074 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1087..1100 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1128..1131 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1139..1161 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1162..1164 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1168..1187 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1191..1205 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1210..1229 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1239..1252 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1253..1255 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1258..1260 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1261..1276 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1284..1292 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1293..1295 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1300..1324 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1388..1394 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1419..1432 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1448..1458 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1464..1466 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1467..1477 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1484..1491 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1498..1502 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1504..1506 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1507..1509 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1524..1526 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1529..1531 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1555..1576 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 1577..1581 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1585..1597 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1600..1602 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1604..1609 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 1618..1631 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1633..1636 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1638..1640 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 1643..1646 FT /evidence="ECO:0007829|PDB:7Z8B" SQ SEQUENCE 1698 AA; 191161 MW; EC9EED17E98FC9A1 CRC64; MVGELRYREF RVPLGPGLHA YPDELIRQRV GHDGHPEYQI RWLILRRGDE GDGGSGQVDC KAEHILLWMS KDEIYANCHK MLGEDGQVIG PSQESAGEVG ALDKSVLEEM ETDVKSLIQR ALRQLEECVG TIPPAPLLHT VHVLSAYASI EPLTGVFKDP RVLDLLMHML SSPDYQIRWS AGRMIQALSS HDAGTRTQIL LSLSQQEAIE KHLDFDSRCA LLALFAQATL SEHPMSFEGI QLPQVPGRVL FSLVKRYLHV TSLLDQLNDS AAEPGAQNTS APEELSGERG QLELEFSMAM GTLISELVQA MRWDQASDRP RSSARSPGSI FQPQLADVSP GLPAAQAQPS FRRSRRFRPR SEFASGNTYA LYVRDTLQPG MRVRMLDDYE EISAGDEGEF RQSNNGVPPV QVFWESTGRT YWVHWHMLEI LGFEEDIEDM VEADEYQGAV ASRVLGRALP AWRWRPMTEL YAVPYVLPED EDTEECEHLT LAEWWELLFF IKKLDGPDHQ EVLQILQENL DGEILDDEIL AELAVPIELA QDLLLTLPQR LNDSALRDLI NCHVYKKYGP EALAGNQAYP SLLEAQEDVL LLDAQAQAKD SEDAAKVEAK EPPSQSPNTP LQRLVEGYGP AGKILLDLEQ ALSSEGTQEN KVKPLLLQLQ RQPQPFLALM QSLDTPETNR TLHLTVLRIL KQLVDFPEAL LLPWHEAVDA CMACLRSPNT DREVLQELIF FLHRLTSVSR DYAVVLNQLG ARDAISKALE KHLGKLELAQ ELRDMVFKCE KHAHLYRKLI TNILGGCIQM VLGQIEDHRR THQPINIPFF DVFLRYLCQG SSVEVKEDKC WEKVEVSSNP HRASKLTDHN PKTYWESNGS AGSHYITLHM RRGILIRQLT LLVASEDSSY MPARVVVCGG DSTSSLHTEL NSVNVMPSAS RVILLENLTR FWPIIQIRIK RCQQGGIDTR IRGLEILGPK PTFWPVFREQ LCRHTRLFYM VRAQAWSQDM AEDRRSLLHL SSRLNGALRQ EQNFADRFLP DDEAAQALGK TCWEALVSPV VQNITSPDED GISPLGWLLD QYLECQEAVF NPQSRGPAFF SRVRRLTHLL VHVEPCEAPP PVVATPRPKG RNRSHDWSSL ATRGLPSSIM RNLTRCWRAV VEKQVNNFLT SSWRDDDFVP RYCEHFNILQ NSSSELFGPR AAFLLALQNG CAGALLKLPF LKAAHVSEQF ARHIDQQIQG SRIGGAQEME RLAQLQQCLQ AVLIFSGLEI ATTFEHYYQH YMADRLLGVV SSWLEGAVLE QIGPCFPNRL PQQMLQSLST SKELQRQFHV YQLQQLDQEL LKLEDTEKKI QVGLGASGKE HKSEKEEEAG AAAVVDVAEG EEEEEENEDL YYEGAMPEVS VLVLSRHSWP VASICHTLNP RTCLPSYLRG TLNRYSNFYN KSQSHPALER GSQRRLQWTW LGWAELQFGN QTLHVSTVQM WLLLYLNDLK AVSVESLLAF SGLSADMLNQ AIGPLTSSRG PLDLHEQKDI PGGVLKIRDG SKEPRSRWDI VRLIPPQTYL QAEGEDGQNL EKRRNLLNCL IVRILKAHGD EGLHIDQLVC LVLEAWQKGP CPPRGLVSSL GKGSACSSTD VLSCILHLLG KGTLRRHDDR PQVLSYAVPV TVMEPHTESL NPGSSGPNPP LTFHTLQIRS RGVPYASCTA TQSFSTFR //