CUL7_HUMAN
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 03-AUG-2022, entry version 204.
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=6; 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};
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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 PDBsum; 2JNG; -.
DR AlphaFoldDB; Q14999; -.
DR BMRB; Q14999; -.
DR SMR; Q14999; -.
DR BioGRID; 115159; 844.
DR CORUM; Q14999; -.
DR DIP; DIP-31618N; -.
DR DIP; DIP-60187N; -.
DR IntAct; Q14999; 39.
DR MINT; Q14999; -.
DR STRING; 9606.ENSP00000438788; -.
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; Q14999; -.
DR PeptideAtlas; Q14999; -.
DR PRIDE; Q14999; -.
DR ProteomicsDB; 25372; -.
DR ProteomicsDB; 60290; -. [Q14999-1]
DR Antibodypedia; 4223; 207 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 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; NCLVVRI; -.
DR OrthoDB; 469819at2759; -.
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; 79 hits in 1124 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 193 other tissues.
DR ExpressionAtlas; Q14999; baseline and differential.
DR Genevisible; Q14999; HS.
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:0031461; C:cullin-RING ubiquitin ligase complex; IBA:GO_Central.
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 Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.30.30.30; -; 1.
DR InterPro; IPR004939; APC_su10/DOC_dom.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR021097; CPH_domain.
DR InterPro; IPR031223; CUL7.
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_L2_dom2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR22771:SF3; PTHR22771:SF3; 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; SSF48371; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF75632; SSF75632; 1.
DR PROSITE; PS50069; CULLIN_2; 1.
DR PROSITE; PS51284; DOC; 1.
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; unknown pathological 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 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"
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
