CAND1_HUMAN
ID CAND1_HUMAN Reviewed; 1230 AA.
AC Q86VP6; B2RAU3; O94918; Q6PIY4; Q8NDJ4; Q96JZ9; Q96T19; Q9BTC4; Q9H0G2;
AC Q9P0H7; Q9UF85;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Cullin-associated NEDD8-dissociated protein 1;
DE AltName: Full=Cullin-associated and neddylation-dissociated protein 1;
DE AltName: Full=TBP-interacting protein of 120 kDa A;
DE Short=TBP-interacting protein 120A;
DE AltName: Full=p120 CAND1;
GN Name=CAND1; Synonyms=KIAA0829, TIP120, TIP120A;
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).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [2]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R., Ishikawa K., Suyama M.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-952.
RC TISSUE=Cervix, Testis, and Uterus;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta;
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 [8]
RP PROTEIN SEQUENCE OF 2-14 AND 374-382, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Ramsay A., Leung H.Y.;
RL Submitted (MAR-2009) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 2-14; 535-548; 668-679; 730-743; 859-873; 958-969 AND
RP 983-990, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [10]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH
RP CUL1 AND RBX1.
RX PubMed=12504026; DOI=10.1016/s1097-2765(02)00784-0;
RA Zheng J., Yang X., Harrell J.M., Ryzhikov S., Shim E.-H.,
RA Lykke-Andersen K., Wei N., Sun H., Kobayashi R., Zhang H.;
RT "CAND1 binds to unneddylated CUL1 and regulates the formation of SCF
RT ubiquitin E3 ligase complex.";
RL Mol. Cell 10:1519-1526(2002).
RN [11]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH CUL1 AND RBX1, AND INTERACTION
RP WITH UNNEDDYLATED CUL1; CUL4A AND CUL5.
RX PubMed=12504025; DOI=10.1016/s1097-2765(02)00783-9;
RA Liu J., Furukawa M., Matsumoto T., Xiong Y.;
RT "NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-
RT SKP1 binding and SCF ligases.";
RL Mol. Cell 10:1511-1518(2002).
RN [12]
RP FUNCTION, INTERACTION WITH CUL1; CUL2; CUL3; CUL4A; CUL4B AND RBX1, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12609982; DOI=10.1074/jbc.m213070200;
RA Min K.-W., Hwang J.-W., Lee J.-S., Park Y., Tamura T.-A., Yoon J.-B.;
RT "TIP120A associates with cullins and modulates ubiquitin ligase activity.";
RL J. Biol. Chem. 278:15905-15910(2003).
RN [13]
RP FUNCTION, AND INTERACTION WITH CUL3.
RX PubMed=16449638; DOI=10.1128/mcb.26.4.1235-1244.2006;
RA Lo S.C., Hannink M.;
RT "CAND1-mediated substrate adaptor recycling is required for efficient
RT repression of Nrf2 by Keap1.";
RL Mol. Cell. Biol. 26:1235-1244(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-55 AND LYS-971, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [18]
RP INDUCTION.
RX PubMed=20820187; DOI=10.1038/pcan.2010.32;
RA Murata T., Takayama K., Katayama S., Urano T., Horie-Inoue K., Ikeda K.,
RA Takahashi S., Kawazu C., Hasegawa A., Ouchi Y., Homma Y., Hayashizaki Y.,
RA Inoue S.;
RT "miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate
RT cell growth by repressing its target CAND1 expression.";
RL Prostate Cancer Prostatic Dis. 13:356-361(2010).
RN [19]
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 [20]
RP INTERACTION WITH CUL2.
RX PubMed=21778237; DOI=10.1074/jbc.m111.278408;
RA Mao X., Gluck N., Chen B., Starokadomskyy P., Li H., Maine G.N.,
RA Burstein E.;
RT "COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates
RT Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-
RT dissociated protein 1) binding.";
RL J. Biol. Chem. 286:32355-32365(2011).
RN [21]
RP FUNCTION, INTERACTION WITH CUL2; CUL3; CUL4A AND CUL5, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21249194; DOI=10.1371/journal.pone.0016071;
RA Chua Y.S., Boh B.K., Ponyeam W., Hagen T.;
RT "Regulation of cullin RING E3 ubiquitin ligases by CAND1 in vivo.";
RL PLoS ONE 6:E16071-E16071(2011).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [24]
RP FUNCTION, AND REACTION MECHANISM.
RX PubMed=23453757; DOI=10.1016/j.cell.2013.02.024;
RA Pierce N.W., Lee J.E., Liu X., Sweredoski M.J., Graham R.L., Larimore E.A.,
RA Rome M., Zheng N., Clurman B.E., Hess S., Shan S.O., Deshaies R.J.;
RT "Cand1 promotes assembly of new SCF complexes through dynamic exchange of F
RT box proteins.";
RL Cell 153:206-215(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-558, AND IDENTIFICATION BY
RP 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 [26]
RP INTERACTION WITH DCUN1D5.
RX PubMed=24192928; DOI=10.1158/1078-0432.ccr-13-1252;
RA Bommelje C.C., Weeda V.B., Huang G., Shah K., Bains S., Buss E., Shaha M.,
RA Goenen M., Ghossein R., Ramanathan S.Y., Singh B.;
RT "Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylation E3 activity
RT and nuclear localization.";
RL Clin. Cancer Res. 20:372-381(2014).
RN [27]
RP INTERACTION WITH DCUN1D3.
RX PubMed=25349211; DOI=10.1074/jbc.m114.585505;
RA Huang G., Stock C., Bommelje C.C., Weeda V.B., Shah K., Bains S., Buss E.,
RA Shaha M., Rechler W., Ramanathan S.Y., Singh B.;
RT "SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of
RT SCCRO (DCUN1D1).";
RL J. Biol. Chem. 289:34728-34742(2014).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [29]
RP INTERACTION WITH ERCC6.
RX PubMed=26030138; DOI=10.1371/journal.pone.0128558;
RA Nicolai S., Filippi S., Caputo M., Cipak L., Gregan J., Ammerer G.,
RA Frontini M., Willems D., Prantera G., Balajee A.S., Proietti-De-Santis L.;
RT "Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group
RT B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin
RT Dynamics.";
RL PLoS ONE 10:E0128558-E0128558(2015).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [31]
RP INTERACTION WITH DCUN1D1; DCUN1D2; DCUN1D3; DCUN1D4 AND DCUN1D5.
RX PubMed=26906416; DOI=10.1242/jcs.181784;
RA Keuss M.J., Thomas Y., Mcarthur R., Wood N.T., Knebel A., Kurz T.;
RT "Characterization of the mammalian family of DCN-type NEDD8 E3 ligases.";
RL J. Cell Sci. 129:1441-1454(2016).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH CUL1 AND RBX1.
RX PubMed=15537541; DOI=10.1016/j.cell.2004.10.019;
RA Goldenberg S.J., Cascio T.C., Shumway S.D., Garbutt K.C., Liu J., Xiong Y.,
RA Zheng N.;
RT "Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for
RT the assembly of the multisubunit cullin-dependent ubiquitin ligases.";
RL Cell 119:517-528(2004).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) IN COMPLEX WITH CUL4B AND RBX1.
RX PubMed=22118460; DOI=10.1016/j.cell.2011.10.035;
RA Fischer E.S., Scrima A., Bohm K., Matsumoto S., Lingaraju G.M., Faty M.,
RA Yasuda T., Cavadini S., Wakasugi M., Hanaoka F., Iwai S., Gut H.,
RA Sugasawa K., Thoma N.H.;
RT "The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture,
RT targeting, and activation.";
RL Cell 147:1024-1039(2011).
CC -!- FUNCTION: Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3
CC ubiquitin ligase complexes that promotes the exchange of the substrate-
CC recognition F-box subunit in SCF complexes, thereby playing a key role
CC in the cellular repertoire of SCF complexes. Acts as a F-box protein
CC exchange factor. The exchange activity of CAND1 is coupled with cycles
CC of neddylation conjugation: in the deneddylated state, cullin-binding
CC CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and
CC promoting exchange of the F-box protein. Probably plays a similar role
CC in other cullin-RING E3 ubiquitin ligase complexes.
CC {ECO:0000269|PubMed:12504025, ECO:0000269|PubMed:12504026,
CC ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:16449638,
CC ECO:0000269|PubMed:21249194, ECO:0000269|PubMed:23453757}.
CC -!- SUBUNIT: Interacts with TBP (By similarity). Part of a complex that
CC contains CUL1 and RBX1. Interacts with unneddylated cullins: interacts
CC with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5. Does not bind neddylated
CC CUL1. Interaction with cullins is abolished in presence of COMMD1,
CC which antagonizes with CAND1 for interacting with cullins. Interacts
CC with ERCC6 (PubMed:26030138). Interacts with DCUN1D1, DCUN1D2, DCUN1D3,
CC DCUN1D4 AND DCUN1D5; these interactions are bridged by cullins and
CC strongly inhibits the neddylation of cullins (PubMed:24192928,
CC PubMed:26906416, PubMed:25349211). {ECO:0000250|UniProtKB:P97536,
CC ECO:0000269|PubMed:12504025, ECO:0000269|PubMed:12504026,
CC ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:15537541,
CC ECO:0000269|PubMed:16449638, ECO:0000269|PubMed:21249194,
CC ECO:0000269|PubMed:21778237, ECO:0000269|PubMed:22118460,
CC ECO:0000269|PubMed:24192928, ECO:0000269|PubMed:25349211,
CC ECO:0000269|PubMed:26030138, ECO:0000269|PubMed:26906416}.
CC -!- INTERACTION:
CC Q86VP6; Q13616: CUL1; NbExp=33; IntAct=EBI-456077, EBI-359390;
CC Q86VP6; Q13617: CUL2; NbExp=3; IntAct=EBI-456077, EBI-456179;
CC Q86VP6; Q13618: CUL3; NbExp=6; IntAct=EBI-456077, EBI-456129;
CC Q86VP6; Q13619: CUL4A; NbExp=6; IntAct=EBI-456077, EBI-456106;
CC Q86VP6; Q13620: CUL4B; NbExp=13; IntAct=EBI-456077, EBI-456067;
CC Q86VP6; P46776: RPL27A; NbExp=2; IntAct=EBI-456077, EBI-350581;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21249194}. Nucleus
CC {ECO:0000269|PubMed:21249194}. Note=Predominantly cytoplasmic.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q86VP6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86VP6-2; Sequence=VSP_013948;
CC Name=3;
CC IsoId=Q86VP6-3; Sequence=VSP_013947, VSP_013949, VSP_013950;
CC -!- INDUCTION: Repressed by miR-148a. {ECO:0000269|PubMed:20820187}.
CC -!- MISCELLANEOUS: A model has been proposed to explain the mechanisms of
CC cullin-RING E3 ubiquitin ligase complexes assembly. According to this
CC hypothesis, cullin-RING E3 ubiquitin ligase complexes exist in a
CC 'stable' active state when saturated with substrate, occluding access
CC to deneddylation by the COP9 signalosome (CSN) complex. The
CC neddylation-conjugated cullin-RING E3 ubiquitin ligase complexes
CC mediate ubiquitination of substrates and can recruit downstream factors
CC involved in substrate degradation. Depletion of the substrate promotes
CC the ability of CSN to bind the cullin-RING E3 ubiquitin ligase complex
CC and mediate deneddylation. In this 'intermediate' deneddylated state,
CC the complex can bind CAND1 and enter the 'exchange' state, resulting in
CC high increase in dissociation rate of the substrate-recognition
CC subunit. The resulting CAND1-cullin-RING complex rapidly assembles with
CC another available substrate-recognition subunit to form an unstable
CC ternary intermediate and yield a new cullin-RING E3 ubiquitin ligase
CC complex. Subsequent neddylation of the cullin, which is stabilized by
CC substrate, completes the cycle (PubMed:23453757).
CC {ECO:0000305|PubMed:23453757}.
CC -!- SIMILARITY: Belongs to the CAND family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74852.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55090.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB020636; BAA74852.2; ALT_INIT; mRNA.
DR EMBL; AF157326; AAF67492.1; -; mRNA.
DR EMBL; AL133560; CAB63714.1; -; mRNA.
DR EMBL; AL136810; CAB66744.1; -; mRNA.
DR EMBL; AL833880; CAD38737.1; -; mRNA.
DR EMBL; CH471054; EAW97172.1; -; Genomic_DNA.
DR EMBL; BC004232; AAH04232.1; -; mRNA.
DR EMBL; BC026220; AAH26220.1; -; mRNA.
DR EMBL; BC050341; AAH50341.1; -; mRNA.
DR EMBL; AK027404; BAB55090.1; ALT_INIT; mRNA.
DR EMBL; AK027783; BAB55365.1; -; mRNA.
DR EMBL; AK314358; BAG36990.1; -; mRNA.
DR CCDS; CCDS8977.1; -. [Q86VP6-1]
DR PIR; T43441; T43441.
DR RefSeq; NP_060918.2; NM_018448.4. [Q86VP6-1]
DR PDB; 1U6G; X-ray; 3.10 A; C=1-1230.
DR PDB; 4A0C; X-ray; 3.80 A; A/B=1-1230.
DR PDBsum; 1U6G; -.
DR PDBsum; 4A0C; -.
DR AlphaFoldDB; Q86VP6; -.
DR SMR; Q86VP6; -.
DR BioGRID; 120937; 862.
DR CORUM; Q86VP6; -.
DR DIP; DIP-31608N; -.
DR IntAct; Q86VP6; 612.
DR MINT; Q86VP6; -.
DR STRING; 9606.ENSP00000442318; -.
DR GlyGen; Q86VP6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86VP6; -.
DR MetOSite; Q86VP6; -.
DR PhosphoSitePlus; Q86VP6; -.
DR SwissPalm; Q86VP6; -.
DR BioMuta; CAND1; -.
DR DMDM; 67460541; -.
DR EPD; Q86VP6; -.
DR jPOST; Q86VP6; -.
DR MassIVE; Q86VP6; -.
DR MaxQB; Q86VP6; -.
DR PaxDb; Q86VP6; -.
DR PeptideAtlas; Q86VP6; -.
DR PRIDE; Q86VP6; -.
DR ProteomicsDB; 70051; -. [Q86VP6-1]
DR ProteomicsDB; 70052; -. [Q86VP6-2]
DR ProteomicsDB; 70053; -. [Q86VP6-3]
DR Antibodypedia; 16667; 222 antibodies from 27 providers.
DR DNASU; 55832; -.
DR Ensembl; ENST00000545606.6; ENSP00000442318.1; ENSG00000111530.13. [Q86VP6-1]
DR GeneID; 55832; -.
DR KEGG; hsa:55832; -.
DR MANE-Select; ENST00000545606.6; ENSP00000442318.1; NM_018448.5; NP_060918.2.
DR UCSC; uc001stn.3; human. [Q86VP6-1]
DR CTD; 55832; -.
DR DisGeNET; 55832; -.
DR GeneCards; CAND1; -.
DR HGNC; HGNC:30688; CAND1.
DR HPA; ENSG00000111530; Low tissue specificity.
DR MIM; 607727; gene.
DR neXtProt; NX_Q86VP6; -.
DR OpenTargets; ENSG00000111530; -.
DR PharmGKB; PA142672207; -.
DR VEuPathDB; HostDB:ENSG00000111530; -.
DR eggNOG; KOG1824; Eukaryota.
DR GeneTree; ENSGT00390000017740; -.
DR HOGENOM; CLU_007157_0_0_1; -.
DR InParanoid; Q86VP6; -.
DR OMA; MGGTQDD; -.
DR OrthoDB; 194023at2759; -.
DR PhylomeDB; Q86VP6; -.
DR TreeFam; TF300355; -.
DR PathwayCommons; Q86VP6; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-917937; Iron uptake and transport.
DR SignaLink; Q86VP6; -.
DR BioGRID-ORCS; 55832; 262 hits in 1093 CRISPR screens.
DR ChiTaRS; CAND1; human.
DR EvolutionaryTrace; Q86VP6; -.
DR GeneWiki; CAND1; -.
DR GenomeRNAi; 55832; -.
DR Pharos; Q86VP6; Tbio.
DR PRO; PR:Q86VP6; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q86VP6; protein.
DR Bgee; ENSG00000111530; Expressed in adrenal tissue and 208 other tissues.
DR ExpressionAtlas; Q86VP6; baseline and differential.
DR Genevisible; Q86VP6; HS.
DR GO; GO:0031461; C:cullin-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0017025; F:TBP-class protein binding; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IDA:UniProtKB.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0045899; P:positive regulation of RNA polymerase II transcription preinitiation complex assembly; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0010265; P:SCF complex assembly; IDA:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR IDEAL; IID00089; -.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR039852; CAND1/CAND2.
DR InterPro; IPR013932; TATA-bd_TIP120.
DR PANTHER; PTHR12696; PTHR12696; 1.
DR Pfam; PF08623; TIP120; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0000269|Ref.9,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895"
FT CHAIN 2..1230
FT /note="Cullin-associated NEDD8-dissociated protein 1"
FT /id="PRO_0000089293"
FT REPEAT 2..39
FT /note="HEAT 1"
FT REPEAT 44..81
FT /note="HEAT 2"
FT REPEAT 83..119
FT /note="HEAT 3"
FT REPEAT 131..165
FT /note="HEAT 4"
FT REPEAT 171..208
FT /note="HEAT 5"
FT REPEAT 210..247
FT /note="HEAT 6"
FT REPEAT 248..282
FT /note="HEAT 7"
FT REPEAT 289..366
FT /note="HEAT 8"
FT REPEAT 370..407
FT /note="HEAT 9"
FT REPEAT 424..467
FT /note="HEAT 10"
FT REPEAT 471..510
FT /note="HEAT 11"
FT REPEAT 515..552
FT /note="HEAT 12"
FT REPEAT 563..602
FT /note="HEAT 13"
FT REPEAT 606..643
FT /note="HEAT 14"
FT REPEAT 646..683
FT /note="HEAT 15"
FT REPEAT 688..725
FT /note="HEAT 16"
FT REPEAT 729..768
FT /note="HEAT 17"
FT REPEAT 770..808
FT /note="HEAT 18"
FT REPEAT 809..845
FT /note="HEAT 19"
FT REPEAT 852..889
FT /note="HEAT 20"
FT REPEAT 890..927
FT /note="HEAT 21"
FT REPEAT 928..960
FT /note="HEAT 22"
FT REPEAT 961..998
FT /note="HEAT 23"
FT REPEAT 1002..1039
FT /note="HEAT 24"
FT REPEAT 1043..1097
FT /note="HEAT 25"
FT REPEAT 1099..1133
FT /note="HEAT 26"
FT REPEAT 1140..1189
FT /note="HEAT 27"
FT REGION 315..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 315..342
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.8, ECO:0000269|Ref.9,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895"
FT MOD_RES 55
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 558
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 971
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..157
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013947"
FT VAR_SEQ 458..625
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166"
FT /id="VSP_013948"
FT VAR_SEQ 549..560
FT /note="VIRPLDQPSSFD -> AHHMPEAQWLRL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013949"
FT VAR_SEQ 561..1230
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013950"
FT VARIANT 803
FT /note="V -> A (in dbSNP:rs12580996)"
FT /id="VAR_054041"
FT VARIANT 952
FT /note="A -> V (in dbSNP:rs17854618)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_025327"
FT CONFLICT 272
FT /note="R -> K (in Ref. 7; BAB55365)"
FT /evidence="ECO:0000305"
FT CONFLICT 457
FT /note="M -> I (in Ref. 7; BAB55090)"
FT /evidence="ECO:0000305"
FT CONFLICT 606
FT /note="S -> P (in Ref. 3; AAF67492)"
FT /evidence="ECO:0000305"
FT CONFLICT 609
FT /note="P -> S (in Ref. 3; AAF67492)"
FT /evidence="ECO:0000305"
FT CONFLICT 1047
FT /note="T -> S (in Ref. 3; AAF67492)"
FT /evidence="ECO:0000305"
FT CONFLICT 1177
FT /note="M -> T (in Ref. 7; BAB55090)"
FT /evidence="ECO:0000305"
FT HELIX 6..14
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 20..33
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 45..56
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 62..76
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 81..94
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 101..116
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 127..142
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 148..164
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 173..180
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 181..185
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 189..202
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 203..205
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 214..224
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 234..244
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 256..264
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 272..284
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 291..301
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 348..361
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 368..372
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 376..380
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 389..405
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 424..431
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 434..442
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 448..464
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 466..469
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 473..483
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 491..506
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 510..513
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 514..517
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 518..520
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 521..528
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 533..550
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 562..576
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 579..581
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 583..599
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 601..603
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 607..618
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 621..623
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 624..635
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 645..658
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 664..680
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 687..694
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 698..700
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 706..719
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 724..729
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 730..734
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 735..742
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 749..763
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 772..779
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 781..785
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 793..809
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 815..818
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 819..824
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 826..829
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 832..848
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 856..863
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 864..866
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 870..886
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 888..900
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 903..905
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 906..918
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 923..925
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 926..936
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 947..960
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 963..965
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 967..970
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 971..973
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 974..977
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 979..988
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 990..992
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1001..1007
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 1009..1014
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 1015..1019
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1021..1036
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1038..1040
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1042..1044
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1045..1054
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1060..1062
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 1063..1068
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 1071..1076
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1079..1094
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 1098..1100
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1102..1111
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1117..1132
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1136..1139
FT /evidence="ECO:0007829|PDB:1U6G"
FT TURN 1140..1145
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1146..1154
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1163..1182
FT /evidence="ECO:0007829|PDB:1U6G"
FT STRAND 1190..1194
FT /evidence="ECO:0007829|PDB:1U6G"
FT HELIX 1200..1208
FT /evidence="ECO:0007829|PDB:1U6G"
SQ SEQUENCE 1230 AA; 136376 MW; FE344558F72D79D8 CRC64;
MASASYHISN LLEKMTSSDK DFRFMATNDL MTELQKDSIK LDDDSERKVV KMILKLLEDK
NGEVQNLAVK CLGPLVSKVK EYQVETIVDT LCTNMLSDKE QLRDISSIGL KTVIGELPPA
SSGSALAANV CKKITGRLTS AIAKQEDVSV QLEALDIMAD MLSRQGGLLV NFHPSILTCL
LPQLTSPRLA VRKRTIIALG HLVMSCGNIV FVDLIEHLLS ELSKNDSMST TRTYIQCIAA
ISRQAGHRIG EYLEKIIPLV VKFCNVDDDE LREYCIQAFE SFVRRCPKEV YPHVSTIINI
CLKYLTYDPN YNYDDEDEDE NAMDADGGDD DDQGSDDEYS DDDDMSWKVR RAAAKCLDAV
VSTRHEMLPE FYKTVSPALI SRFKEREENV KADVFHAYLS LLKQTRPVQS WLCDPDAMEQ
GETPLTMLQS QVPNIVKALH KQMKEKSVKT RQCCFNMLTE LVNVLPGALT QHIPVLVPGI
IFSLNDKSSS SNLKIDALSC LYVILCNHSP QVFHPHVQAL VPPVVACVGD PFYKITSEAL
LVTQQLVKVI RPLDQPSSFD ATPYIKDLFT CTIKRLKAAD IDQEVKERAI SCMGQIICNL
GDNLGSDLPN TLQIFLERLK NEITRLTTVK ALTLIAGSPL KIDLRPVLGE GVPILASFLR
KNQRALKLGT LSALDILIKN YSDSLTAAMI DAVLDELPPL ISESDMHVSQ MAISFLTTLA
KVYPSSLSKI SGSILNELIG LVRSPLLQGG ALSAMLDFFQ ALVVTGTNNL GYMDLLRMLT
GPVYSQSTAL THKQSYYSIA KCVAALTRAC PKEGPAVVGQ FIQDVKNSRS TDSIRLLALL
SLGEVGHHID LSGQLELKSV ILEAFSSPSE EVKSAASYAL GSISVGNLPE YLPFVLQEIT
SQPKRQYLLL HSLKEIISSA SVVGLKPYVE NIWALLLKHC ECAEEGTRNV VAECLGKLTL
IDPETLLPRL KGYLISGSSY ARSSVVTAVK FTISDHPQPI DPLLKNCIGD FLKTLEDPDL
NVRRVALVTF NSAAHNKPSL IRDLLDTVLP HLYNETKVRK ELIREVEMGP FKHTVDDGLD
IRKAAFECMY TLLDSCLDRL DIFEFLNHVE DGLKDHYDIK MLTFLMLVRL STLCPSAVLQ
RLDRLVEPLR ATCTTKVKAN SVKQEFEKQD ELKRSAMRAV AALLTIPEAE KSPLMSEFQS
QISSNPELAA IFESIQKDSS STNLESMDTS
