ID A0A0G2K8K2_RAT Unreviewed; 982 AA.
AC A0A0G2K8K2;
DT 22-JUL-2015, integrated into UniProtKB/TrEMBL.
DT 22-JUL-2015, sequence version 1.
DT 27-MAR-2024, entry version 56.
DE RecName: Full=E3 ubiquitin-protein ligase CBL {ECO:0000256|RuleBase:RU367001};
DE EC=2.3.2.27 {ECO:0000256|RuleBase:RU367001};
GN Name=Cblb {ECO:0000313|Ensembl:ENSRNOP00000074638.1,
GN ECO:0000313|RGD:620535};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000074638.1, ECO:0000313|Proteomes:UP000002494};
RN [1] {ECO:0000313|Ensembl:ENSRNOP00000074638.1, ECO:0000313|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000074638.1,
RC ECO:0000313|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RG Rat Genome Sequencing Project Consortium;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0007829|PubMed:16641100}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [3] {ECO:0007829|PubMed:22673903}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4] {ECO:0000313|Ensembl:ENSRNOP00000074638.1}
RP IDENTIFICATION.
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000074638.1};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from
CC specific E2 ubiquitin-conjugating enzymes, and transfers it to
CC substrates, generally promoting their degradation by the proteasome.
CC {ECO:0000256|RuleBase:RU367001}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000256|ARBA:ARBA00000900,
CC ECO:0000256|RuleBase:RU367001};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000256|ARBA:ARBA00004906, ECO:0000256|RuleBase:RU367001}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}.
CC -!- DOMAIN: The N-terminus is composed of the phosphotyrosine binding (PTB)
CC domain, a short linker region and the RING-type zinc finger. The PTB
CC domain, which is also called TKB (tyrosine kinase binding) domain, is
CC composed of three different subdomains: a four-helix bundle (4H), a
CC calcium-binding EF hand and a divergent SH2 domain.
CC {ECO:0000256|RuleBase:RU367001}.
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DR RefSeq; XP_006248320.1; XM_006248258.3.
DR RefSeq; XP_006248321.1; XM_006248259.3.
DR RefSeq; XP_008766848.1; XM_008768626.2.
DR AlphaFoldDB; A0A0G2K8K2; -.
DR SMR; A0A0G2K8K2; -.
DR jPOST; A0A0G2K8K2; -.
DR Ensembl; ENSRNOT00000077220.2; ENSRNOP00000074638.1; ENSRNOG00000001982.8.
DR GeneID; 171136; -.
DR CTD; 868; -.
DR RGD; 620535; Cblb.
DR GeneTree; ENSGT00940000156631; -.
DR OMA; FACFPPP; -.
DR OrthoDB; 1123734at2759; -.
DR PhylomeDB; A0A0G2K8K2; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000001982; Expressed in spleen and 20 other cell types or tissues.
DR ExpressionAtlas; A0A0G2K8K2; baseline and differential.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:InterPro.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0002669; P:positive regulation of T cell anergy; IEA:Ensembl.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:2000583; P:regulation of platelet-derived growth factor receptor-alpha signaling pathway; IEA:Ensembl.
DR GO; GO:0002870; P:T cell anergy; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl.
DR CDD; cd16709; RING-HC_Cbl-b; 1.
DR CDD; cd09920; SH2_Cbl-b_TKB; 1.
DR CDD; cd14392; UBA_Cbl-b; 1.
DR Gene3D; 1.20.930.20; Adaptor protein Cbl, N-terminal domain; 1.
DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1.
DR Gene3D; 1.10.238.10; EF-hand; 1.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR024162; Adaptor_Cbl.
DR InterPro; IPR014741; Adaptor_Cbl_EF_hand-like.
DR InterPro; IPR036537; Adaptor_Cbl_N_dom_sf.
DR InterPro; IPR003153; Adaptor_Cbl_N_hlx.
DR InterPro; IPR014742; Adaptor_Cbl_SH2-like.
DR InterPro; IPR039520; CBL-B_RING-HC.
DR InterPro; IPR024159; Cbl_PTB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR23007; CBL; 1.
DR PANTHER; PTHR23007:SF3; E3 UBIQUITIN-PROTEIN LIGASE CBL-B; 1.
DR Pfam; PF02262; Cbl_N; 1.
DR Pfam; PF02761; Cbl_N2; 1.
DR Pfam; PF02762; Cbl_N3; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF47473; EF-hand; 1.
DR SUPFAM; SSF47668; N-terminal domain of cbl (N-cbl); 1.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR PROSITE; PS51506; CBL_PTB; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Calcium {ECO:0000256|ARBA:ARBA00022837, ECO:0000256|RuleBase:RU367001};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|RuleBase:RU367001};
KW Reference proteome {ECO:0000313|Proteomes:UP000002494};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|RuleBase:RU367001};
KW Ubl conjugation pathway {ECO:0000256|ARBA:ARBA00022786,
KW ECO:0000256|RuleBase:RU367001};
KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|RuleBase:RU367001};
KW Zinc-finger {ECO:0000256|ARBA:ARBA00022771, ECO:0000256|PROSITE-
KW ProRule:PRU00175}.
FT DOMAIN 35..343
FT /note="Cbl-PTB"
FT /evidence="ECO:0000259|PROSITE:PS51506"
FT DOMAIN 373..412
FT /note="RING-type"
FT /evidence="ECO:0000259|PROSITE:PS50089"
FT DOMAIN 931..970
FT /note="UBA"
FT /evidence="ECO:0000259|PROSITE:PS50030"
FT REGION 465..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 765..929
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 468..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 541..568
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 817..832
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 836..850
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 884..901
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 982 AA; 109265 MW; BB34CEA08062F439 CRC64;
MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC
QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR
AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDN FRITKADAAE
FWRKFFGDKT IVPWKVFRQC LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF
QPWGSILRNW NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV
TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH DHIKVTQEQY
ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW QESDGQGCPF CRCEIKGTEP
IIVDPFDPRD EGSRCCSIID PFSIPMLDLD DDDDREESLM MNRLASVRKC TDRQNSPVTS
PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ
DKPLPAPPPP LRDPPPPPER PPPIPPDSRL SRHFHHGEGV PSRDQPMPLE AWCPRDAFGT
NQVMGCRILG DGSPKPGVTA NSNLNGRHSR MGSDQVLMRK HRRHDLPSEG AKVFSNGHLA
PEEYDVPPRL SPPPPVTALL PSIKCTGPIA NCLSEKTRDT VEEDDDEYKI PSSHPVSLNS
QPSHCHNVKP PVRSCDNGHC ILNGTHGTPS EMKKSNIPDL GIYLKGDVSD SASDPVPLPP
ARPPPRDNLK HGSSVNRTPS DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG
SSSRPSSGQD LFLLPSDPFF DPASGQVPLP PARRAPGDGV KSNRASQDYD QLPSSSDGSQ
APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK RALEIAQNNL
EVARSILREF AFPPPVSPRL NL
//