HAKAI_MACFA
ID HAKAI_MACFA Reviewed; 490 AA.
AC Q4R7I8; Q4R6U4;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=E3 ubiquitin-protein ligase Hakai {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9JIY2};
DE AltName: Full=Casitas B-lineage lymphoma-transforming sequence-like protein 1 {ECO:0000250|UniProtKB:Q9JIY2};
DE Short=c-Cbl-like protein 1 {ECO:0000250|UniProtKB:Q9JIY2};
DE AltName: Full=RING-type E3 ubiquitin transferase Hakai {ECO:0000305};
GN Name=CBLL1 {ECO:0000250|UniProtKB:Q9JIY2};
GN Synonyms=HAKAI {ECO:0000250|UniProtKB:Q9JIY2};
GN ORFNames=QtsA-15158 {ECO:0000303|Ref.1}, QtsA-17111 {ECO:0000303|Ref.1};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of
CC several tyrosine-phosphorylated Src substrates, including CDH1, CTTN
CC and DOK1. Targets CDH1 for endocytosis and degradation. Associated
CC component of the WMM complex, a complex that mediates N6-
CC methyladenosine (m6A) methylation of RNAs, a modification that plays a
CC role in the efficiency of mRNA splicing and RNA processing. Its
CC function in the WMM complex is unknown. {ECO:0000250|UniProtKB:Q9JIY2}.
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:0000250|UniProtKB:Q9JIY2};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9JIY2}.
CC -!- SUBUNIT: Homodimer. Interacts with tyrosine-phosphorylated SRC
CC substrates. Component of the WMM complex, a N6-methyltransferase
CC complex composed of a catalytic subcomplex, named MAC, and of an
CC associated subcomplex, named MACOM. The MAC subcomplex is composed of
CC METTL3 and METTL14. The MACOM subcomplex is composed of WTAP, ZC3H13,
CC CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (By
CC similarity). Also a component of a MACOM-like complex, named WTAP
CC complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and
CC THRAP3 (By similarity). {ECO:0000250|UniProtKB:Q75N03,
CC ECO:0000250|UniProtKB:Q9JIY2}.
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000250|UniProtKB:Q75N03}.
CC Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q9JIY2}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9JIY2}. Note=Mainly nuclear with some fraction
CC located in the cytoplasm. ZC3H13 is required to anchor component of the
CC MACOM subcomplex, such as VIRMA, in the nucleus.
CC {ECO:0000250|UniProtKB:Q9JIY2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q4R7I8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4R7I8-2; Sequence=VSP_024412, VSP_024413, VSP_024414;
CC -!- DOMAIN: The HYB domain forms a phosphotyrosine-binding pocket upon
CC dimerization, and mediates as well the recognition of its flanking
CC acidic amino acids. {ECO:0000250|UniProtKB:Q9JIY2}.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000250|UniProtKB:Q9JIY2}.
CC -!- SIMILARITY: Belongs to the Hakai family. {ECO:0000305}.
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DR EMBL; AB168830; BAE00934.1; -; mRNA.
DR EMBL; AB169086; BAE01180.1; -; mRNA.
DR RefSeq; XP_005550561.1; XM_005550504.2. [Q4R7I8-1]
DR AlphaFoldDB; Q4R7I8; -.
DR BMRB; Q4R7I8; -.
DR SMR; Q4R7I8; -.
DR STRING; 9541.XP_005550558.1; -.
DR Ensembl; ENSMFAT00000013828; ENSMFAP00000039565; ENSMFAG00000045966. [Q4R7I8-2]
DR GeneID; 101866734; -.
DR KEGG; mcf:101866734; -.
DR CTD; 79872; -.
DR eggNOG; KOG2932; Eukaryota.
DR GeneTree; ENSGT00510000047522; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000233100; Chromosome 3.
DR Bgee; ENSMFAG00000045966; Expressed in lymph node and 13 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0036396; C:RNA N6-methyladenosine methyltransferase complex; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0080009; P:mRNA methylation; ISS:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISS:UniProtKB.
DR CDD; cd16508; RING-HC_HAKAI_like; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR040380; HAKAI-like_RING-HC.
DR InterPro; IPR040383; HAKAI/CBLL2.
DR InterPro; IPR041042; Znf_Hakai.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR13480; PTHR13480; 1.
DR Pfam; PF18408; zf_Hakai; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Developmental protein; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..490
FT /note="E3 ubiquitin-protein ligase Hakai"
FT /id="PRO_0000284049"
FT ZN_FING 108..148
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 163..189
FT /note="C2H2-type"
FT REGION 34..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..205
FT /note="HYB domain"
FT /evidence="ECO:0000250|UniProtKB:Q9JIY2"
FT REGION 254..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..360
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..425
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..476
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q75N03"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q75N03"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q75N03"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_024412"
FT VAR_SEQ 60
FT /note="E -> EE (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_024413"
FT VAR_SEQ 375..406
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_024414"
FT CONFLICT 265
FT /note="E -> G (in Ref. 1; BAE01180)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 490 AA; 54376 MW; 26AB6DE9A0AA2066 CRC64;
MDHTDNELQG TNSSGSLGGL DVRRRIPIKL ISKQANKAKP APRTQRTINR MPAKAPPGDE
GFDYNEEERY DCKGGELFGN QRRFPGHLFW DFQINILGEK DDTPVHFCDK CGLPIKIYGR
MIPCKHVFCY DCAILHEKKG DKMCPGCSDP VQRIEQCTRG SLFMCSIVQG CKRTYLSQRD
LQAHINHRHM RAGKPVTRAS LENVHPPIAP PPTEIPERFI MPPDKHHMSH IPPKQHIMMP
PPPLQHVPHE HYNQPHEDIR APPAELSMAP PPPRSVSQET FRISTRKHSN LITVPIQDDS
NSGAREPPPP APAPAHHHPE YQGQPVVSHP HHIMPPQQHY APPPPPPPPI SHPMPHPPQA
AGTPHLVYSQ APPPPMTSAP PPITPPPGHI IAQMPPYMNH PPPGPPPPQH GGPPVTAPPP
HHYNPNSLPQ FTEDQGTLSP PFTQPGGMSP GIWPAPRGPP PPPRLQGPPS QTPLPGPHHP
DQTRYRPYYQ
