ID A0A1B0GW38_HUMAN Unreviewed; 869 AA.
AC A0A1B0GW38;
DT 05-OCT-2016, integrated into UniProtKB/TrEMBL.
DT 05-OCT-2016, sequence version 1.
DT 27-MAR-2024, entry version 45.
DE RecName: Full=E3 ubiquitin-protein ligase CBL {ECO:0000256|RuleBase:RU367001};
DE EC=2.3.2.27 {ECO:0000256|RuleBase:RU367001};
DE Flags: Fragment;
GN Name=CBL {ECO:0000313|Ensembl:ENSP00000490763.1};
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 {ECO:0000313|Ensembl:ENSP00000490763.1, ECO:0000313|Proteomes:UP000005640};
RN [1] {ECO:0007829|PubMed:12522270}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=12522270; DOI=10.1073/pnas.2436191100;
RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C.,
RA Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
RT "Profiling of tyrosine phosphorylation pathways in human cells using mass
RT spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
RN [2] {ECO:0007829|PubMed:15144186}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [3] {ECO:0007829|PubMed:15592455}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [4] {ECO:0000313|Ensembl:ENSP00000490763.1, ECO:0000313|Proteomes:UP000005640}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5] {ECO:0007829|PubMed:18669648}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [6] {ECO:0007829|PubMed:19690332}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7] {ECO:0007829|PubMed:21269460}
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., Burckstummer 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 [8] {ECO:0007829|PubMed:23186163}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=23186163;
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 [9] {ECO:0000313|Ensembl:ENSP00000490763.1}
RP IDENTIFICATION.
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|RuleBase:RU367001}.
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 EMBL; AP002956; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A0A1B0GW38; -.
DR SMR; A0A1B0GW38; -.
DR MassIVE; A0A1B0GW38; -.
DR PeptideAtlas; A0A1B0GW38; -.
DR Antibodypedia; 3815; 1337 antibodies from 49 providers.
DR Ensembl; ENST00000637974.1; ENSP00000490763.1; ENSG00000110395.8.
DR HGNC; HGNC:1541; CBL.
DR VEuPathDB; HostDB:ENSG00000110395; -.
DR GeneTree; ENSGT00940000155772; -.
DR UniPathway; UPA00143; -.
DR ChiTaRS; CBL; human.
DR Proteomes; UP000005640; Chromosome 11.
DR Bgee; ENSG00000110395; Expressed in primordial germ cell in gonad and 187 other cell types or tissues.
DR ExpressionAtlas; A0A1B0GW38; baseline and differential.
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:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0023051; P:regulation of signaling; IEA:InterPro.
DR CDD; cd16708; RING-HC_Cbl; 1.
DR CDD; cd09920; SH2_Cbl-b_TKB; 1.
DR Gene3D; 1.20.930.20; Adaptor protein Cbl, N-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; IPR024159; Cbl_PTB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR036860; SH2_dom_sf.
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:SF5; E3 UBIQUITIN-PROTEIN LIGASE CBL; 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 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; 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 Proteomics identification {ECO:0007829|EPD:A0A1B0GW38,
KW ECO:0007829|MaxQB:A0A1B0GW38};
KW Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Transferase {ECO:0000256|RuleBase:RU367001};
KW Ubl conjugation pathway {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 45..349
FT /note="Cbl-PTB"
FT /evidence="ECO:0000259|PROSITE:PS51506"
FT DOMAIN 379..418
FT /note="RING-type"
FT /evidence="ECO:0000259|PROSITE:PS50089"
FT REGION 430..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 475..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 517..665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 678..717
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 741..779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 797..840
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 534..551
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 601..621
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 637..651
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 797..816
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT NON_TER 1
FT /evidence="ECO:0000313|Ensembl:ENSP00000490763.1"
SQ SEQUENCE 869 AA; 95951 MW; 514BDB3AC57505B1 CRC64;
GNVKKSSGAG GGSGSGGSGS GGLIGLMKDA FQPHHHHHHH LSPHPPGTVD KKMVEKCWKL
MDKVVRLCQN PKLALKNSPP YILDLLPDTY QHLRTILSRY EGKMETLGEN EYFRVFMENL
MKKTKQTISL FKEGKERMYE ENSQPRRNLT KLSLIFSHML AELKGIFPSG LFQGDTFRIT
KADAAEFWRK AFGEKTIVPW KSFRQALHEV HPISSGLEAM ALKSTIDLTC NDYISVFEFD
IFTRLFQPWS SLLRNWNSLA VTHPGYMAFL TYDEVKARLQ KFIHKPGSYI FRLSCTRLGQ
WAIGYVTADG NILQTIPHNK PLFQALIDGF REGFYLFPDG RNQNPDLTGL CEPTPQDHIK
VTQEQYELYC EMGSTFQLCK ICAENDKDVK IEPCGHLMCT SCLTSWQESE GQGCPFCRCE
IKGTEPIVVD PFDPRGSGSL LRQGAEGAPS PNYDDDDDER ADDTLFMMKE LAGAKVERPP
SPFSMAPQAS LPPVPPRLDL LPQRVCVPSS ASALGTASKA ASGSLHKDKP LPVPPTLRDL
PPPPPPDRPY SVGAESRPQR RPLPCTPGDC PSRDKLPPVP SSRLGDSWLP RPIPKVPVSA
PSSSDPWTGR ELTNRHSLPF SLPSQMEPRP DVPRLGSTFS LDTSMSMNSS PLVGPECDHP
KIKPSSSANA IYSLAARPLP VPKLPPGEQC EGEEDTEYMT PSSRPLRPLD TSQSSRACDC
DQQIDSCTYE AMYNIQSQAP SITESSTFGE GNLAAAHANT GPEESENEDD GYDVPKPPVP
AVLARRTLSD ISNASSSFGW LSLDGDPTTN VTEGSQVPER PPKPFPRRIN SERKAGSCQQ
DRVSLLLPRL ECSGTISAHR NLHLPPGFK
//
