Q13191 (CBLB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase CBL-B
EC=6.3.2.-

Alternative name(s):
Casitas B-lineage lymphoma proto-oncogene b
RING finger protein 56
SH3-binding protein CBL-B
Signal transduction protein CBL-B

Gene names

Name:	CBLB
Synonyms:	RNF56
ORF Names:	Nbla00127

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	982 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. May also be involved in EGFR ubiquitination and internalization. Ref.8 Ref.9 Ref.10 Ref.12
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. May interact with CBL By similarity. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Ref.2 Ref.8 Ref.9 Ref.10 Ref.13 Ref.14 Ref.21 Ref.22
Subcellular location	Cytoplasm. Note: Upon EGF stimulation, associates with endocytic vesicles. Ref.13
Tissue specificity	Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level). Ref.2 Ref.8
Domain	The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain. The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme. The UBA domain interacts with poly-ubiquitinated proteins.
Post-translational modification	Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation. Ref.8 Ref.9 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.23 Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.
Miscellaneous	This protein has one functional calcium-binding site By similarity.
Sequence similarities	Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain. Contains 1 RING-type zinc finger. Contains 1 UBA domain.
Sequence caution	The sequence BAE45748.1 differs from that shown. Reason: Erroneous termination at position 904. Translated as Arg. The sequence CAH56175.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	Calcium Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	NLS-bearing substrate import into nucleus Traceable author statement. Source: ProtInc cell surface receptor linked signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro phosphotyrosine binding Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from electronic annotation. Source: InterPro ubiquitin-protein ligase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	4	EBI-744027,EBI-401755

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q13191-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Truncated 1 (identifier: Q13191-2)

The sequence of this isoform differs from the canonical sequence as follows:
     812-982: Missing.

Isoform Truncated 2 (identifier: Q13191-3)

The sequence of this isoform differs from the canonical sequence as follows:
     767-770: DVFD → TYRI
     771-982: Missing.

Isoform 4 (identifier: Q13191-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-939: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 982

982

E3 ubiquitin-protein ligase CBL-B

PRO_0000055860

Regions

Domain

35 – 343

309

Cbl-PTB

Domain

931 – 970

40

UBA

Calcium binding

219 – 232

14

By similarity

Zinc finger

373 – 412

40

RING-type

Region

35 – 167

133

4H

Region

168 – 240

73

EF-hand-like

Region

241 – 343

103

SH2-like

Region

344 – 372

29

Linker

Region

543 – 568

26

Interaction with VAV1

Region

891 – 927

37

Interaction with SH3KBP1

Compositional bias

477 – 925

449

Pro-rich

Sites

Binding site

286

1

Phosphotyrosine By similarity

Amino acid modifications

Modified residue

282

1

Phosphoserine; by PKC/PRKCQ Ref.20

Modified residue

363

1

Phosphotyrosine Ref.19

Modified residue

480

1

Phosphoserine Ref.15

Modified residue

484

1

Phosphoserine Ref.15

Modified residue

521

1

Phosphoserine Ref.18

Modified residue

525

1

Phosphoserine Ref.18

Modified residue

529

1

Phosphoserine Ref.18

Modified residue

614

1

Phosphoserine Ref.17

Modified residue

665

1

Phosphotyrosine Ref.8 Ref.19

Modified residue

709

1

Phosphotyrosine Ref.8

Modified residue

889

1

Phosphotyrosine Ref.16 Ref.19

Natural variations

Alternative sequence

1 – 939

939

Missing in isoform 4.

VSP_031697

Alternative sequence

767 – 770

4

DVFD → TYRI in isoform Truncated 2.

VSP_005730

Alternative sequence

771 – 982

212

Missing in isoform Truncated 2.

VSP_005731

Alternative sequence

812 – 982

171

Missing in isoform Truncated 1.

VSP_005729

Natural variant

584

1

R → K. Ref.5
Corresponds to variant rs17853100 [ dbSNP | Ensembl ].

VAR_025303

Natural variant

883

1

N → D.
Corresponds to variant rs35835913 [ dbSNP | Ensembl ].

VAR_039241

Experimental info

Mutagenesis

298

1

G → E: Inhibits interaction with SYK. No effect on E3 activity. Ref.8 Ref.10

Mutagenesis

373

1

C → A: Abolishes E3 activity but does not affect binding to substrates. Ref.10 Ref.11

Mutagenesis

665

1

Y → F: Slightly inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-709. Ref.8

Mutagenesis

709

1

Y → F: Inhibits interaction with CRKL. Abolishes interaction with CRKL; when associated with F-665. Ref.8

Mutagenesis

904

1

R → A: No effect on interaction with CD2AP. Reduced interaction with SH3KBP1. Strongly reduced interaction with SH3KBP1; when associated with A-911. Ref.21 Ref.22

Mutagenesis

907

1

K → A: No effect on interaction with SH3KBP1. Reduced interaction with CD2AP. Strongly reduced interaction with CD2AP; when associated with A-911. Ref.22

Mutagenesis

911

1

R → A: Reduced interaction with CD2AP and with SH3KBP1. Strongly reduced interaction with CD2AP; when associated with A-907. Strongly reduced interaction with SH3KBP1; when associated with A-904. Ref.21 Ref.22

Mutagenesis

937

1

A → E: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. Ref.23

Mutagenesis

940

1

M → A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. Ref.23

Mutagenesis

943 – 944

2

GY → AQ: Abolishes interaction with ubiquitinated proteins.

Mutagenesis

946

1

F → A: Loss of ubiquitin binding. Reduced levels of tyrosine phosphorylation. Ref.23

Mutagenesis

966

1

I → E: Interferes with dimerization. Reduced E3 ubiquitin-protein ligase activity. Reduced levels of tyrosine phosphorylation. Ref.23

Mutagenesis

967

1

L → A: No effect on interaction with ubiquitinated proteins. Ref.14

Sequence conflict

210

1

G → S in AAB09291. Ref.1

Sequence conflict

210

1

G → S in AAB09292. Ref.1

Sequence conflict

210

1

G → S in AAB09293. Ref.1

Sequence conflict

911

1

R → C in CAH56175. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

982

Helix Strand Turn

Details...

Helix

933 – 941

9

Helix

946 – 955

10

Turn

956 – 958

3

Helix

960 – 970

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified February 7, 2006. Version 2. Checksum: B4E307D31B9F0779	FASTA	982	109,450
	10 20 30 40 50 60 MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC 70 80 90 100 110 120 QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR 130 140 150 160 170 180 AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDN FRITKADAAE 190 200 210 220 230 240 FWRKFFGDKT IVPWKVFRQC LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF 250 260 270 280 290 300 QPWGSILRNW NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV 310 320 330 340 350 360 TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH DHIKVTQEQY 370 380 390 400 410 420 ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW QESDGQGCPF CRCEIKGTEP 430 440 450 460 470 480 IIVDPFDPRD EGSRCCSIID PFGMPMLDLD DDDDREESLM MNRLANVRKC TDRQNSPVTS 490 500 510 520 530 540 PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ 550 560 570 580 590 600 DKPLPAPPPP LRDPPPPPPE RPPPIPPDNR LSRHIHHVES VPSRDPPMPL EAWCPRDVFG 610 620 630 640 650 660 TNQLVGCRLL GEGSPKPGIT ASSNVNGRHS RVGSDPVLMR KHRRHDLPLE GAKVFSNGHL 670 680 690 700 710 720 GSEEYDVPPR LSPPPPVTTL LPSIKCTGPL ANSLSEKTRD PVEEDDDEYK IPSSHPVSLN 730 740 750 760 770 780 SQPSHCHNVK PPVRSCDNGH CMLNGTHGPS SEKKSNIPDL SIYLKGDVFD SASDPVPLPP 790 800 810 820 830 840 ARPPTRDNPK HGSSLNRTPS DYDLLIPPLG EDAFDALPPS LPPPPPPARH SLIEHSKPPG 850 860 870 880 890 900 SSSRPSSGQD LFLLPSDPFV DLASGQVPLP PARRLPGENV KTNRTSQDYD QLPSCSDGSQ 910 920 930 940 950 960 APARPPKPRP RRTAPEIHHR KPHGPEAALE NVDAKIAKLM GEGYAFEEVK RALEIAQNNV 970 980 EVARSILREF AFPPPVSPRL NL
	Isoform Truncated 1 [UniParc]. Checksum: A63D22F7C9C677DB	FASTA	811	90,883
	10 20 30 40 50 60 MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC 70 80 90 100 110 120 QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR 130 140 150 160 170 180 AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDN FRITKADAAE 190 200 210 220 230 240 FWRKFFGDKT IVPWKVFRQC LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF 250 260 270 280 290 300 QPWGSILRNW NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV 310 320 330 340 350 360 TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH DHIKVTQEQY 370 380 390 400 410 420 ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW QESDGQGCPF CRCEIKGTEP 430 440 450 460 470 480 IIVDPFDPRD EGSRCCSIID PFGMPMLDLD DDDDREESLM MNRLANVRKC TDRQNSPVTS 490 500 510 520 530 540 PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ 550 560 570 580 590 600 DKPLPAPPPP LRDPPPPPPE RPPPIPPDNR LSRHIHHVES VPSRDPPMPL EAWCPRDVFG 610 620 630 640 650 660 TNQLVGCRLL GEGSPKPGIT ASSNVNGRHS RVGSDPVLMR KHRRHDLPLE GAKVFSNGHL 670 680 690 700 710 720 GSEEYDVPPR LSPPPPVTTL LPSIKCTGPL ANSLSEKTRD PVEEDDDEYK IPSSHPVSLN 730 740 750 760 770 780 SQPSHCHNVK PPVRSCDNGH CMLNGTHGPS SEKKSNIPDL SIYLKGDVFD SASDPVPLPP 790 800 810 ARPPTRDNPK HGSSLNRTPS DYDLLIPPLG E
	Isoform Truncated 2 [UniParc]. Checksum: DEE458DFFEE1AF2F	FASTA	770	86,582
	10 20 30 40 50 60 MANSMNGRNP GGRGGNPRKG RILGIIDAIQ DAVGPPKQAA ADRRTVEKTW KLMDKVVRLC 70 80 90 100 110 120 QNPKLQLKNS PPYILDILPD TYQHLRLILS KYDDNQKLAQ LSENEYFKIY IDSLMKKSKR 130 140 150 160 170 180 AIRLFKEGKE RMYEEQSQDR RNLTKLSLIF SHMLAEIKAI FPNGQFQGDN FRITKADAAE 190 200 210 220 230 240 FWRKFFGDKT IVPWKVFRQC LHEVHQISSG LEAMALKSTI DLTCNDYISV FEFDIFTRLF 250 260 270 280 290 300 QPWGSILRNW NFLAVTHPGY MAFLTYDEVK ARLQKYSTKP GSYIFRLSCT RLGQWAIGYV 310 320 330 340 350 360 TGDGNILQTI PHNKPLFQAL IDGSREGFYL YPDGRSYNPD LTGLCEPTPH DHIKVTQEQY 370 380 390 400 410 420 ELYCEMGSTF QLCKICAEND KDVKIEPCGH LMCTSCLTAW QESDGQGCPF CRCEIKGTEP 430 440 450 460 470 480 IIVDPFDPRD EGSRCCSIID PFGMPMLDLD DDDDREESLM MNRLANVRKC TDRQNSPVTS 490 500 510 520 530 540 PGSSPLAQRR KPQPDPLQIP HLSLPPVPPR LDLIQKGIVR SPCGSPTGSP KSSPCMVRKQ 550 560 570 580 590 600 DKPLPAPPPP LRDPPPPPPE RPPPIPPDNR LSRHIHHVES VPSRDPPMPL EAWCPRDVFG 610 620 630 640 650 660 TNQLVGCRLL GEGSPKPGIT ASSNVNGRHS RVGSDPVLMR KHRRHDLPLE GAKVFSNGHL 670 680 690 700 710 720 GSEEYDVPPR LSPPPPVTTL LPSIKCTGPL ANSLSEKTRD PVEEDDDEYK IPSSHPVSLN 730 740 750 760 770 SQPSHCHNVK PPVRSCDNGH CMLNGTHGPS SEKKSNIPDL SIYLKGTYRI
	Isoform 4 [UniParc]. Checksum: 302A356C8DD9D75C	FASTA	43	4,860
	10 20 30 40 MGEGYAFEEV KRALEIAQNN VEVARSILRE FAFPPPVSPR LNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene." Keane M.M., Rivero-Lezcano O.M., Mitchell J.A., Robbins K.C., Lipkowitz S. Oncogene 10:2367-2377(1995) [PubMed: 7784085] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG; TRUNCATED 1 AND TRUNCATED 2).
[2]	"Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation." Bustelo X.R., Crespo P., Lopez-Barahona M., Gutkind J.S., Barbacid M. Oncogene 15:2511-2520(1997) [PubMed: 9399639] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), TISSUE SPECIFICITY, INTERACTION WITH VAV1.
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), VARIANT LYS-584. Tissue: Testis.
[6]	"Neuroblastoma oligo-capping cDNA project: toward the understanding of the genesis and biology of neuroblastoma." Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S., Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S., Hirato J., Nakagawara A. Cancer Lett. 197:63-68(2003) [PubMed: 12880961] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 543-982 (ISOFORM LONG). Tissue: Neuroblastoma.
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Small intestine.
[8]	"Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation." Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C. Oncogene 18:1147-1156(1999) [PubMed: 10022120] [Abstract] Cited for: TISSUE SPECIFICITY, MUTAGENESIS OF GLY-298; TYR-665 AND TYR-709, INTERACTION WITH GRB2 AND CRKL, PHOSPHORYLATION AT TYR-665 AND TYR-709, FUNCTION.
[9]	"cbl-b inhibits epidermal growth factor receptor signaling." Ettenberg S.A., Keane M.M., Nau M.M., Frankel M., Wang L.-M., Pierce J.H., Lipkowitz S. Oncogene 18:1855-1866(1999) [PubMed: 10086340] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH GRB2 AND PIK3R1.
[10]	"Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells." Fang D., Wang H.-Y., Fang N., Altman Y., Elly C., Liu Y.-C. J. Biol. Chem. 276:4872-4878(2001) [PubMed: 11087752] [Abstract] Cited for: FUNCTION, INTERACTION WITH PIK3R1, MUTAGENESIS OF GLY-298 AND CYS-373.
[11]	"Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex." Ettenberg S.A., Magnifico A., Cuello M., Nau M.M., Rubinstein Y.R., Yarden Y., Weissman A.M., Lipkowitz S. J. Biol. Chem. 276:27677-27684(2001) [PubMed: 11375397] [Abstract] Cited for: UBIQUITINATION, MUTAGENESIS OF CYS-373.
[12]	"Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells." Fang D., Liu Y.-C. Nat. Immunol. 2:870-875(2001) [PubMed: 11526404] [Abstract] Cited for: FUNCTION.
[13]	"CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases." Szymkiewicz I., Kowanetz K., Soubeyran P., Dinarina A., Lipkowitz S., Dikic I. J. Biol. Chem. 277:39666-39672(2002) [PubMed: 12177062] [Abstract] Cited for: INTERACTION WITH SH3KBP1, SUBCELLULAR LOCATION.
[14]	"Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b." Davies G.C., Ettenberg S.A., Coats A.O., Mussante M., Ravichandran S., Collins J., Nau M.M., Lipkowitz S. Oncogene 23:7104-7115(2004) [PubMed: 15273720] [Abstract] Cited for: INTERACTION WITH UBIQUITINATED PROTEINS, MUTAGENESIS OF 943-GLY-TYR-944 AND LEU-967.
[15]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480 AND SER-484, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-889, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[17]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521; SER-525 AND SER-529, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-363; TYR-665 AND TYR-889, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[20]	"PKC-theta modulates the strength of T cell responses by targeting Cbl-b for ubiquitination and degradation." Gruber T., Hermann-Kleiter N., Hinterleitner R., Fresser F., Schneider R., Gastl G., Penninger J.M., Baier G. Sci. Signal. 2:RA30-RA30(2009) [PubMed: 19549985] [Abstract] Cited for: PHOSPHORYLATION AT SER-282.
[21]	"Cbl promotes clustering of endocytic adaptor proteins." Jozic D., Cardenes N., Deribe Y.L., Moncalian G., Hoeller D., Groemping Y., Dikic I., Rittinger K., Bravo J. Nat. Struct. Mol. Biol. 12:972-979(2005) [PubMed: 16228008] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 899-914 IN COMPLEXES WITH SH3KBP1 AND ARHGEF7, MUTAGENESIS OF ARG-904 AND ARG-911, SUBUNIT.
[22]	"Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain." Moncalian G., Cardenes N., Deribe Y.L., Spinola-Amilibia M., Dikic I., Bravo J. J. Biol. Chem. 281:38845-38853(2006) [PubMed: 17020880] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 902-912 IN COMPLEX WITH CD2AP, MUTAGENESIS OF ARG-904; LYS-907 AND ARG-911, SUBUNIT.
[23]	"Structural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b." Peschard P., Kozlov G., Lin T., Mirza I.A., Berghuis A.M., Lipkowitz S., Park M., Gehring K. Mol. Cell 27:474-485(2007) [PubMed: 17679095] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 924-973 IN COMPLEX WITH UBIQUITIN, STRUCTURE BY NMR OF 924-973, TYROSINE PHOSPHORYLATION, MUTAGENESIS OF ALA-937; MET-940; PHE-946 AND ILE-966.
[24]	"Solution structure of RSGI RUH-065, a UBA domain from human cDNA." RIKEN structural genomics initiative (RSGI) Submitted (MAY-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 931-970.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U26710 mRNA. Translation: AAB09291.1.
U26711 mRNA. Translation: AAB09292.1.
U26712 mRNA. Translation: AAB09293.1.
AC016138 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79752.1.
BC032851 mRNA. Translation: AAH32851.1.
AB075490 mRNA. Translation: BAE45748.1. Sequence problems.
BX537484 mRNA. Translation: CAH56175.1. Different initiation.

IPI

IPI00292856.
IPI00382825.
IPI00793846.
IPI00914020.

RefSeq

NP_733762.2. NM_170662.3.

UniGene

Hs.430589.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AK5	X-ray	1.85	D	904-911	[»]
2BZ8	X-ray	2.00	C	902-912	[»]
2DO6	NMR	-	A/B	931-970	[»]
2J6F	X-ray	1.70	C	902-912	[»]
2JNH	NMR	-	A	926-971	[»]
2OOA	X-ray	1.56	A/B	924-973	[»]
2OOB	X-ray	1.90	A	924-973	[»]
3PFV	X-ray	2.27	A/B	38-344	[»]

ProteinModelPortal

Q13191.

SMR

Q13191. Positions 35-429, 929-972.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33091N.

IntAct

Q13191. 8 interactions.

MINT

MINT-256380.

STRING

Q13191.

PTM databases

PhosphoSite

Q13191.

Polymorphism databases

DMDM

88911265.

Proteomic databases

PRIDE

Q13191.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264122; ENSP00000264122; ENSG00000114423.

GeneID

868.

KEGG

hsa:868.

NMPDR

fig|9606.3.peg.22921.

UCSC

uc003dwc.1. human.
uc003dwd.1. human.
uc003dwe.1. human.

Organism-specific databases

CTD

868.

GeneCards

GC03M105374.

H-InvDB

HIX0003518.

HGNC

HGNC:1542. CBLB.

HPA

HPA016864.
HPA018327.
HPA019880.

MIM

604491. gene.

neXtProt

NX_Q13191.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17632.

GeneTree

ENSGT00390000011617.

HOGENOM

HBG715842.

HOVERGEN

HBG005255.

InParanoid

Q13191.

OMA

PMLDLDD.

OrthoDB

EOG4PG60J.

PhylomeDB

Q13191.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q13191.

Bgee

Q13191.

CleanEx

HS_CBLB.

Genevestigator

Q13191.

GermOnline

ENSG00000114423. Homo sapiens.

Family and domain databases

InterPro

IPR024162. Adaptor_Cbl.
IPR014741. Adaptor_Cbl_EF_hand-like.
IPR003153. Adaptor_Cbl_N_hlx.
IPR014742. Adaptor_Cbl_SH2-like.
IPR024159. Cbl_PTB.
IPR011992. EF-hand-like_dom.
IPR000980. SH2.
IPR000449. UBA/transl_elong_EF1B_N.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Gene3D

G3DSA:1.20.930.20. Adaptor_Cbl_N. 1 hit.
G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
G3DSA:3.30.505.10. SH2. 2 hits.
G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K04707.

PANTHER

PTHR23007. PTHR23007. 1 hit.

Pfam

PF02262. Cbl_N. 1 hit.
PF02761. Cbl_N2. 1 hit.
PF02762. Cbl_N3. 1 hit.
PF00627. UBA. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
SM00252. SH2. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]

SUPFAM

SSF47668. Adaptor_Cbl_N. 1 hit.

PROSITE

PS51506. CBL_PTB. 1 hit.
PS50030. UBA. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

3622.

SOURCE

Search...

Entry information

Entry name

CBLB_HUMAN

Accession

Primary (citable) accession number: Q13191
Secondary accession number(s): B7WNM4 , Q13192, Q13193, Q3LIC0, Q63Z43, Q8IVC5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	February 7, 2006
Last modified:	January 25, 2012
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.