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Protein

E3 ubiquitin-protein ligase Hakai

Gene

CBLL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1 (By similarity). Targets CDH1 for endocytosis and degradation (By similarity). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Its function in the WMM complex is unknown (PubMed:29507755).By similarity1 Publication

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarity
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri109 – 149RING-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri164 – 190C2H2-typeAdd BLAST27

GO - Molecular functioni

GO - Biological processi

  • cell-cell adhesion Source: UniProtKB
  • entry of bacterium into host cell Source: Reactome
  • mRNA methylation Source: UniProtKB
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of cell adhesion Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of endocytosis Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of cell adhesion Source: GO_Central

Keywordsi

Molecular functionDevelopmental protein, Transferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-8876493 InlA-mediated entry of Listeria monocytogenes into host cells
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase HakaiCurated (EC:2.3.2.27By similarity)
Alternative name(s):
Casitas B-lineage lymphoma-transforming sequence-like protein 1By similarity
Short name:
c-Cbl-like protein 1By similarity
RING finger protein 188
RING-type E3 ubiquitin transferase HakaiCurated
Gene namesi
Name:CBLL1Imported
Synonyms:HAKAI1 Publication, RNF188
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000105879.11
HGNCiHGNC:21225 CBLL1
MIMi606872 gene
neXtProtiNX_Q75N03

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi79872
OpenTargetsiENSG00000105879
PharmGKBiPA134960329

Polymorphism and mutation databases

DMDMi74762414

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002840481 – 491E3 ubiquitin-protein ligase HakaiAdd BLAST491

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei201PhosphoserineCombined sources1
Modified residuei285PhosphoserineCombined sources1
Modified residuei290PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ75N03
MaxQBiQ75N03
PaxDbiQ75N03
PeptideAtlasiQ75N03
PRIDEiQ75N03
ProteomicsDBi68642

PTM databases

iPTMnetiQ75N03
PhosphoSitePlusiQ75N03

Expressioni

Gene expression databases

BgeeiENSG00000105879
CleanExiHS_CBLL1
ExpressionAtlasiQ75N03 baseline and differential
GenevisibleiQ75N03 HS

Organism-specific databases

HPAiHPA021773
HPA026699

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with tyrosine-phosphorylated SRC substrates (By similarity). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29507755). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29507755). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29507755). Also component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3 (PubMed:24100041).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RBM10P981753EBI-2832762,EBI-721525

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122960, 14 interactors
IntActiQ75N03, 6 interactors
MINTiQ75N03
STRINGi9606.ENSP00000401277

Structurei

3D structure databases

ProteinModelPortaliQ75N03
SMRiQ75N03
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni148 – 206HYB domainBy similarityAdd BLAST59

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi207 – 481Pro-richAdd BLAST275

Domaini

The HYB domain forms a phosphotyrosine-binding pocket upon dimerization, and mediates as well the recognition of its flanking acidic amino acids.By similarity

Sequence similaritiesi

Belongs to the Hakai family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri109 – 149RING-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri164 – 190C2H2-typeAdd BLAST27

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2932 Eukaryota
ENOG410XQ6S LUCA
GeneTreeiENSGT00510000047522
HOGENOMiHOG000082498
HOVERGENiHBG057723
InParanoidiQ75N03
KOiK15685
OMAiISHPMQH
OrthoDBiEOG091G0AJH
PhylomeDBiQ75N03
TreeFamiTF332910

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q75N03-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDHTDNELQG TNSSGSLGGL DVRRRIPIKL ISKQANKAKP APRTQRTINR
60 70 80 90 100
MPAKAPPGDE EGFDYNEEER YDCKGGELFA NQRRFPGHLF WDFQINILGE
110 120 130 140 150
KDDTPVHFCD KCGLPIKIYG RMIPCKHVFC YDCAILHEKK GDKMCPGCSD
160 170 180 190 200
PVQRIEQCTR GSLFMCSIVQ GCKRTYLSQR DLQAHINHRH MRAGKPVTRA
210 220 230 240 250
SLENVHPPIA PPPTEIPERF IMPPDKHHMS HIPPKQHIMM PPPPLQHVPH
260 270 280 290 300
EHYNQPHEDI RAPPAELSMA PPPPRSVSQE TFRISTRKHS NLITVPIQDD
310 320 330 340 350
SNSGAREPPP PAPAPAHHHP EYQGQPVVSH PHHIMPPQQH YAPPPPPPPP
360 370 380 390 400
ISHPMPHPPQ AAGTPHLVYS QAPPPPMTSA PPPITPPPGH IIAQMPPYMN
410 420 430 440 450
HPPPGPPPPQ HGGPPVTAPP PHHYNPNSLP QFTEDQGTLS PPFTQPGGMS
460 470 480 490
PGIWPAPRGP PPPPRLQGPP SQTPLPGPHH PDQTRYRPYY Q
Length:491
Mass (Da):54,519
Last modified:July 5, 2004 - v1
Checksum:i1A733A8CC28F3AA0
GO
Isoform 2 (identifier: Q75N03-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     60-60: Missing.

Note: No experimental confirmation available.
Show »
Length:490
Mass (Da):54,390
Checksum:i142CD58C5CF50D7E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti439L → P in BAB15544 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05487960Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK026762 mRNA Translation: BAB15544.1
AC002467 Genomic DNA Translation: AAS07390.1
BC027460 mRNA Translation: AAH27460.2
BC130529 mRNA Translation: AAI30530.1
BC130531 mRNA Translation: AAI30532.1
BC144176 mRNA Translation: AAI44177.1
CCDSiCCDS5747.1 [Q75N03-1]
CCDS64754.1 [Q75N03-2]
RefSeqiNP_001271220.1, NM_001284291.1 [Q75N03-2]
NP_079090.2, NM_024814.3 [Q75N03-1]
UniGeneiHs.592271

Genome annotation databases

EnsembliENST00000222597; ENSP00000222597; ENSG00000105879 [Q75N03-2]
ENST00000440859; ENSP00000401277; ENSG00000105879 [Q75N03-1]
GeneIDi79872
KEGGihsa:79872
UCSCiuc003veq.4 human [Q75N03-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHAKAI_HUMAN
AccessioniPrimary (citable) accession number: Q75N03
Secondary accession number(s): B7ZM03, Q8TAJ4, Q9H5S6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 17, 2007
Last sequence update: July 5, 2004
Last modified: July 18, 2018
This is version 130 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. SIMILARITY comments
    Index of protein domains and families

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