ID HAKAI_HUMAN Reviewed; 491 AA.
AC Q75N03; B7ZM03; Q8TAJ4; Q9H5S6;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 18-JAN-2017, entry version 117.
DE RecName: Full=E3 ubiquitin-protein ligase Hakai;
DE EC=2.3.2.27;
DE AltName: Full=Casitas B-lineage lymphoma-transforming sequence-like protein 1;
DE AltName: Full=RING finger protein 188;
DE AltName: Full=RING-type E3 ubiquitin transferase Hakai {ECO:0000305};
DE AltName: Full=c-Cbl-like protein 1;
GN Name=CBLL1; Synonyms=HAKAI, RNF188;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-201, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-290, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
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 [6]
RP IDENTIFICATION IN THE WTAP COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=24100041; DOI=10.1074/jbc.M113.500397;
RA Horiuchi K., Kawamura T., Iwanari H., Ohashi R., Naito M., Kodama T.,
RA Hamakubo T.;
RT "Identification of Wilms' tumor 1-associating protein complex and its
RT role in alternative splicing and the cell cycle.";
RL J. Biol. Chem. 288:33292-33302(2013).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-285, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
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).
CC -!- FUNCTION: Promotes ubiquitination of several tyrosine-
CC phosphorylated Src substrates, including CDH1, CTTN and DOK1.
CC Targets CDH1 for endocytosis and degradation. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY: S-ubiquitinyl-[E2 ubiquitin-conjugating
CC enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-
CC conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor
CC protein]-L-lysine.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Interacts with tyrosine-phosphorylated SRC
CC substrates. Component of the WTAP complex composed of WTAP,
CC ZC3H13, CBLL1, KIAA1429, RBM15, BCLAF1 and THRAP3
CC (PubMed:24100041). {ECO:0000269|PubMed:24100041}.
CC -!- SUBCELLULAR LOCATION: Nucleus speckle
CC {ECO:0000269|PubMed:24100041}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:24100041}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q75N03-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q75N03-2; Sequence=VSP_054879;
CC Note=No experimental confirmation available.;
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}.
CC -!- SIMILARITY: Contains 1 C2H2-type zinc finger. {ECO:0000305}.
CC -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC {ECO:0000255|PROSITE-ProRule:PRU00175}.
DR EMBL; AK026762; BAB15544.1; -; mRNA.
DR EMBL; AC002467; AAS07390.1; -; Genomic_DNA.
DR EMBL; BC027460; AAH27460.2; -; mRNA.
DR EMBL; BC130529; AAI30530.1; -; mRNA.
DR EMBL; BC130531; AAI30532.1; -; mRNA.
DR EMBL; BC144176; AAI44177.1; -; mRNA.
DR CCDS; CCDS5747.1; -. [Q75N03-1]
DR CCDS; CCDS64754.1; -. [Q75N03-2]
DR RefSeq; NP_001271220.1; NM_001284291.1. [Q75N03-2]
DR RefSeq; NP_079090.2; NM_024814.3. [Q75N03-1]
DR UniGene; Hs.592271; -.
DR ProteinModelPortal; Q75N03; -.
DR SMR; Q75N03; -.
DR BioGrid; 122960; 14.
DR IntAct; Q75N03; 5.
DR MINT; MINT-3298121; -.
DR STRING; 9606.ENSP00000401277; -.
DR iPTMnet; Q75N03; -.
DR PhosphoSitePlus; Q75N03; -.
DR DMDM; 74762414; -.
DR EPD; Q75N03; -.
DR MaxQB; Q75N03; -.
DR PaxDb; Q75N03; -.
DR PeptideAtlas; Q75N03; -.
DR PRIDE; Q75N03; -.
DR DNASU; 79872; -.
DR Ensembl; ENST00000222597; ENSP00000222597; ENSG00000105879. [Q75N03-2]
DR Ensembl; ENST00000440859; ENSP00000401277; ENSG00000105879. [Q75N03-1]
DR GeneID; 79872; -.
DR KEGG; hsa:79872; -.
DR UCSC; uc003veq.4; human. [Q75N03-1]
DR CTD; 79872; -.
DR DisGeNET; 79872; -.
DR GeneCards; CBLL1; -.
DR HGNC; HGNC:21225; CBLL1.
DR HPA; HPA021773; -.
DR HPA; HPA026699; -.
DR MIM; 606872; gene.
DR neXtProt; NX_Q75N03; -.
DR OpenTargets; ENSG00000105879; -.
DR PharmGKB; PA134960329; -.
DR eggNOG; KOG2932; Eukaryota.
DR eggNOG; ENOG410XQ6S; LUCA.
DR GeneTree; ENSGT00510000047522; -.
DR HOGENOM; HOG000082498; -.
DR HOVERGEN; HBG057723; -.
DR InParanoid; Q75N03; -.
DR KO; K15685; -.
DR OMA; SEASMYV; -.
DR OrthoDB; EOG091G0AJH; -.
DR PhylomeDB; Q75N03; -.
DR TreeFam; TF332910; -.
DR UniPathway; UPA00143; -.
DR GeneWiki; CBLL1; -.
DR GenomeRNAi; 79872; -.
DR PRO; PR:Q75N03; -.
DR Proteomes; UP000005640; Chromosome 7.
DR Bgee; ENSG00000105879; -.
DR CleanEx; HS_CBLL1; -.
DR ExpressionAtlas; Q75N03; baseline and differential.
DR Genevisible; Q75N03; HS.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; IC:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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 GO; GO:0016567; P:protein ubiquitination; TAS:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IBA:GO_Central.
DR GO; GO:0016337; P:single organismal cell-cell adhesion; IDA:UniProtKB.
DR Gene3D; 3.30.160.60; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 491 E3 ubiquitin-protein ligase Hakai.
FT /FTId=PRO_0000284048.
FT ZN_FING 109 149 RING-type. {ECO:0000255|PROSITE-
FT ProRule:PRU00175}.
FT ZN_FING 164 190 C2H2-type.
FT REGION 148 206 HYB domain. {ECO:0000250}.
FT COMPBIAS 207 481 Pro-rich.
FT MOD_RES 201 201 Phosphoserine.
FT {ECO:0000244|PubMed:18669648}.
FT MOD_RES 285 285 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 290 290 Phosphoserine.
FT {ECO:0000244|PubMed:19690332}.
FT VAR_SEQ 60 60 Missing (in isoform 2).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_054879.
FT CONFLICT 439 439 L -> P (in Ref. 1; BAB15544).
FT {ECO:0000305}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 125 134 ipat:ZF_RING_1 [T]
FT MYHIT 109 149 iprf:ZF_RING_2 [T]
SQ SEQUENCE 491 AA; 54519 MW; 1A733A8CC28F3AA0 CRC64;
MDHTDNELQG TNSSGSLGGL DVRRRIPIKL ISKQANKAKP APRTQRTINR MPAKAPPGDE
EGFDYNEEER YDCKGGELFA NQRRFPGHLF WDFQINILGE KDDTPVHFCD KCGLPIKIYG
RMIPCKHVFC YDCAILHEKK GDKMCPGCSD PVQRIEQCTR GSLFMCSIVQ GCKRTYLSQR
DLQAHINHRH MRAGKPVTRA SLENVHPPIA PPPTEIPERF IMPPDKHHMS HIPPKQHIMM
PPPPLQHVPH EHYNQPHEDI RAPPAELSMA PPPPRSVSQE TFRISTRKHS NLITVPIQDD
SNSGAREPPP PAPAPAHHHP EYQGQPVVSH PHHIMPPQQH YAPPPPPPPP ISHPMPHPPQ
AAGTPHLVYS QAPPPPMTSA PPPITPPPGH IIAQMPPYMN HPPPGPPPPQ HGGPPVTAPP
PHHYNPNSLP QFTEDQGTLS PPFTQPGGMS PGIWPAPRGP PPPPRLQGPP SQTPLPGPHH
PDQTRYRPYY Q
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