ID A0A9L0R2T8_HORSE Unreviewed; 939 AA.
AC A0A9L0R2T8;
DT 13-SEP-2023, integrated into UniProtKB/TrEMBL.
DT 13-SEP-2023, sequence version 1.
DT 18-JUN-2025, entry version 11.
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:ENSECAP00000057175.1,
GN ECO:0000313|VGNC:VGNC:16092};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796 {ECO:0000313|Ensembl:ENSECAP00000057175.1, ECO:0000313|Proteomes:UP000002281};
RN [1] {ECO:0000313|Ensembl:ENSECAP00000057175.1, ECO:0000313|Proteomes:UP000002281}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000057175.1,
RC ECO:0000313|Proteomes:UP000002281};
RX PubMed=19892987; DOI=10.1126/science.1178158;
RG Broad Institute Genome Sequencing Platform;
RG Broad Institute Whole Genome Assembly Team;
RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT "Genome sequence, comparative analysis, and population genetics of the
RT domestic horse.";
RL Science 326:865-867(2009).
RN [2] {ECO:0000313|Ensembl:ENSECAP00000057175.1}
RP IDENTIFICATION.
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000057175.1};
RG Ensembl;
RL Submitted (MAR-2025) 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 -!- SUBUNIT: Interacts with SH3 domain-containing proteins LCK, CRK and
CC SORBS1. Interacts with LCP2 and ZAP70. Interacts with CBL. Interacts
CC with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL,
CC PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with
CC SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two
CC copies of the other protein. Interacts with poly-ubiquitinated
CC proteins. Dimerization is required for the binding of poly-ubiquitin,
CC but not for the binding of mono-ubiquitin. Interacts with EGFR
CC (phosphorylated). Interacts with IFT20.
CC {ECO:0000256|ARBA:ARBA00065060}.
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_005602081.1; XM_005602024.2.
DR RefSeq; XP_070098988.1; XM_070242887.1.
DR RefSeq; XP_070098989.1; XM_070242888.1.
DR Ensembl; ENSECAT00000086381.1; ENSECAP00000057175.1; ENSECAG00000014300.4.
DR GeneID; 100061819; -.
DR VGNC; VGNC:16092; CBLB.
DR GeneTree; ENSGT00940000156631; -.
DR Proteomes; UP000002281; Chromosome 19.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0008270; F:zinc ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0023051; P:regulation of signaling; IEA:InterPro.
DR CDD; cd16709; RING-HC_Cbl-b; 1.
DR CDD; cd09920; SH2_Cbl-b_TKB; 1.
DR CDD; cd14392; UBA_Cbl-b; 1.
DR FunFam; 1.10.238.10:FF:000022; E3 ubiquitin-protein ligase CBL; 1.
DR FunFam; 1.20.930.20:FF:000001; E3 ubiquitin-protein ligase CBL; 1.
DR FunFam; 3.30.40.10:FF:000015; E3 ubiquitin-protein ligase CBL; 1.
DR FunFam; 3.30.505.10:FF:000154; E3 ubiquitin-protein ligase CBL; 1.
DR FunFam; 1.10.8.10:FF:000037; E3 ubiquitin-protein ligase CBL-B isoform 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 4: Predicted;
KW Calcium {ECO:0000256|ARBA:ARBA00022837, ECO:0000256|RuleBase:RU367001};
KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|RuleBase:RU367001};
KW Reference proteome {ECO:0000313|Proteomes:UP000002281};
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 888..927
FT /note="UBA"
FT /evidence="ECO:0000259|PROSITE:PS50030"
FT REGION 466..572
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 666..726
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 772..883
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..486
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 544..567
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..785
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 795..805
FT /note="Low complexity"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 837..855
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 863..879
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 939 AA; 104865 MW; 34FC4069556CE523 CRC64;
MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC
QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR
AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDT 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 PFGMPMLDLD DDDDREESLM MNRLANVRKC TDRQNSPVTS
PGSSPLAQRR KPHPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ
DKPLPAPPPP LRDPPPPPPE RPPPVPPDNR LSRHFHHMES VPSRDQPMPL EAWCPRDVFG
TNQSVGCRLL GDGSPKPGIT ASSNVNGRHS RMGTDPVLIR KHRRHDLPAE GAKVFSNGHL
GSEEYDVPPR LSPPPPATTL LPSIKCTGPL ANSLSEKTRD PAEEEDEEYK VPSSHPVPLN
SQPSHCHNLK PSLRSCDNGH CILNGTHGTS SEMKKSNIPE LGIYLKGEDA FDALPPSLPP
PPPPARHSLV EHSKPSGSSS RPSSGQELFL LPSDPFFDSA SNQVPLPPAR RLPGENVKSN
RTSQDYDQLP SSADGSQAPA RPPKPRPRRT APEVHHRKPH GPEAALENVD AKIAKLMGEG
YAFEEVKRAL EIAQNNVEVA RSILREFAFP PPVSPRLNL
//
