CBLL2_HUMAN
ID CBLL2_HUMAN Reviewed; 425 AA.
AC Q8N7E2; A0AV29; A0AV31; E3SBK4; Q6DJY9;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=E3 ubiquitin-protein ligase CBLL2 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:20657603};
DE AltName: Full=Cbl proto-oncogene-like protein 2;
DE AltName: Full=RING-type E3 ubiquitin transferase ZNF645;
DE AltName: Full=Zinc finger protein 645;
DE AltName: Full=c-Cbl-like protein 2;
GN Name=CBLL2 {ECO:0000312|HGNC:HGNC:26371}; Synonyms=ZNF645;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP VARIANT GLU-166, AND CATALYTIC ACTIVITY.
RC TISSUE=Testis;
RX PubMed=20657603; DOI=10.1038/aja.2010.54;
RA Liu Y.Q., Bai G., Zhang H., Su D., Tao D.C., Yang Y., Ma Y.X., Zhang S.Z.;
RT "Human RING finger protein ZNF645 is a novel testis-specific E3 ubiquitin
RT ligase.";
RL Asian J. Androl. 12:658-666(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-166.
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND DOMAIN HYB.
RX PubMed=22252131; DOI=10.1038/emboj.2011.496;
RA Mukherjee M., Chow S.Y., Yusoff P., Seetharaman J., Ng C., Sinniah S.,
RA Koh X.W., Asgar N.F., Li D., Yim D., Jackson R.A., Yew J., Qian J., Iyu A.,
RA Lim Y.P., Zhou X., Sze S.K., Guy G.R., Sivaraman J.;
RT "Structure of a novel phosphotyrosine-binding domain in Hakai that targets
RT E-cadherin.";
RL EMBO J. 31:1308-1319(2012).
CC -!- FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of
CC ubiquitin moieties onto substrate proteins (PubMed:20657603). May
CC operate on tyrosine-phosphorylated SRC substrates (PubMed:22252131).
CC {ECO:0000269|PubMed:20657603, ECO:0000269|PubMed:22252131}.
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:0000269|PubMed:20657603};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:20657603}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9JIY2}.
CC -!- INTERACTION:
CC Q8N7E2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12196065, EBI-3867333;
CC Q8N7E2; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-12196065, EBI-10176379;
CC Q8N7E2; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-12196065, EBI-2341787;
CC Q8N7E2; P45984: MAPK9; NbExp=3; IntAct=EBI-12196065, EBI-713568;
CC Q8N7E2; Q99750: MDFI; NbExp=3; IntAct=EBI-12196065, EBI-724076;
CC Q8N7E2; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-12196065, EBI-10232538;
CC Q8N7E2; Q9NZ81: PRR13; NbExp=3; IntAct=EBI-12196065, EBI-740924;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20657603}.
CC Note=Localized over the postacrosomal perinuclear theca region and the
CC entire length of sperm tail. {ECO:0000269|PubMed:20657603}.
CC -!- TISSUE SPECIFICITY: Exclusively expressed in testis and sperm,
CC including spermatocytes, round and elongated spermatids, and Leydig
CC cells. {ECO:0000269|PubMed:20657603}.
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}.
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DR EMBL; GQ355336; ADI56589.1; -; mRNA.
DR EMBL; AK098601; BAC05348.1; -; mRNA.
DR EMBL; BX293560; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074910; AAH74910.1; -; mRNA.
DR EMBL; BC126190; AAI26191.1; -; mRNA.
DR EMBL; BC126192; AAI26193.1; -; mRNA.
DR CCDS; CCDS14205.1; -.
DR RefSeq; NP_689790.1; NM_152577.3.
DR AlphaFoldDB; Q8N7E2; -.
DR SMR; Q8N7E2; -.
DR BioGRID; 127688; 21.
DR IntAct; Q8N7E2; 13.
DR STRING; 9606.ENSP00000323348; -.
DR iPTMnet; Q8N7E2; -.
DR PhosphoSitePlus; Q8N7E2; -.
DR BioMuta; ZNF645; -.
DR DMDM; 74759980; -.
DR PaxDb; Q8N7E2; -.
DR PeptideAtlas; Q8N7E2; -.
DR PRIDE; Q8N7E2; -.
DR Antibodypedia; 399; 86 antibodies from 22 providers.
DR DNASU; 158506; -.
DR Ensembl; ENST00000323684.4; ENSP00000323348.2; ENSG00000175809.6.
DR GeneID; 158506; -.
DR KEGG; hsa:158506; -.
DR MANE-Select; ENST00000323684.4; ENSP00000323348.2; NM_152577.4; NP_689790.1.
DR UCSC; uc004dai.3; human.
DR CTD; 158506; -.
DR DisGeNET; 158506; -.
DR GeneCards; CBLL2; -.
DR HGNC; HGNC:26371; CBLL2.
DR HPA; ENSG00000175809; Tissue enriched (testis).
DR neXtProt; NX_Q8N7E2; -.
DR OpenTargets; ENSG00000175809; -.
DR PharmGKB; PA134934025; -.
DR VEuPathDB; HostDB:ENSG00000175809; -.
DR eggNOG; KOG2932; Eukaryota.
DR GeneTree; ENSGT00510000047522; -.
DR HOGENOM; CLU_031291_1_0_1; -.
DR InParanoid; Q8N7E2; -.
DR OMA; PIQWETV; -.
DR OrthoDB; 765364at2759; -.
DR PhylomeDB; Q8N7E2; -.
DR TreeFam; TF332910; -.
DR PathwayCommons; Q8N7E2; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8N7E2; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 158506; 8 hits in 736 CRISPR screens.
DR GenomeRNAi; 158506; -.
DR Pharos; Q8N7E2; Tdark.
DR PRO; PR:Q8N7E2; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q8N7E2; protein.
DR Bgee; ENSG00000175809; Expressed in sperm and 14 other tissues.
DR Genevisible; Q8N7E2; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0030155; P:regulation of cell adhesion; IBA:GO_Central.
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; IPR013087; Znf_C2H2_type.
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.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..425
FT /note="E3 ubiquitin-protein ligase CBLL2"
FT /id="PRO_0000056316"
FT ZN_FING 57..97
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 112..138
FT /note="C2H2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 96..154
FT /note="HYB domain"
FT REGION 241..297
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 382..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..295
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 166
FT /note="D -> E (in dbSNP:rs5951426)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:20657603"
FT /id="VAR_030340"
FT VARIANT 287
FT /note="S -> F (in dbSNP:rs12860105)"
FT /id="VAR_030341"
FT CONFLICT 267
FT /note="P -> L (in Ref. 1; ADI56589)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="H -> Q (in Ref. 1; ADI56589)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 425 AA; 48785 MW; 873C2802514CD9E5 CRC64;
MNKMPAGEQE CEYNKEGKYY SKGVKLVRKK KKIPGYRWGD IKINIIGEKD DLPIHFCDKC
DLPIKIYGRI IPCKHAFCYH CANLYDKVGY KVCPRCRYPV LRIEAHKRGS VFMCSIVQQC
KRTYLSQKSL QAHIKRRHKR ARKQVTSASL EKVRPHIAPP QTEISDIPKR LQDRDHLSYI
PPEQHTMVSL PSVQHMLQEQ HNQPHKDIQA PPPELSLSLP FPIQWETVSI FTRKHGNLTV
DHIQNNSDSG AKKPTPPDYY PECQSQPAVS SPHHIIPQKQ HYAPPPSPSS PVNHQMPYPP
QDVVTPNSVR SQVPALTTTY DPSSGYIIVK VPPDMNSPPL RAPQSQNGNP SASEFASHHY
NLNILPQFTE NQETLSPQFT QTDAMDHRRW PAWKRLSPCP PTRSPPPSTL HGRSHHSHQR
RHRRY
