KLD8B_HUMAN
ID KLD8B_HUMAN Reviewed; 354 AA.
AC Q8IXV7;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Kelch domain-containing protein 8B {ECO:0000303|PubMed:19706467};
GN Name=KLHDC8B {ECO:0000303|PubMed:19706467}; ORFNames=FP17659;
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 [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, CHROMOSOMAL TRANSLOCATION, AND
RP INVOLVEMENT IN CHL.
RX PubMed=19706467; DOI=10.1073/pnas.0904231106;
RA Salipante S.J., Mealiffe M.E., Wechsler J., Krem M.M., Liu Y., Namkoong S.,
RA Bhagat G., Kirchhoff T., Offit K., Lynch H., Wiernik P.H., Roshal M.,
RA McMaster M.L., Tucker M., Fromm J.R., Goldin L.R., Horwitz M.S.;
RT "Mutations in a gene encoding a midbody kelch protein in familial and
RT sporadic classical Hodgkin lymphoma lead to binucleated cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14920-14925(2009).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND 3D-STRUCTURE MODELING.
RX PubMed=20107318; DOI=10.4161/cc.9.4.10780;
RA Krem M.M., Salipante S.J., Horwitz M.S.;
RT "Mutations in a gene encoding a midbody protein in binucleated Reed-
RT Sternberg cells of Hodgkin lymphoma.";
RL Cell Cycle 9:670-675(2010).
RN [5]
RP FUNCTION.
RX PubMed=22988245; DOI=10.1074/jbc.m112.390088;
RA Krem M.M., Luo P., Ing B.I., Horwitz M.S.;
RT "The kelch protein KLHDC8B guards against mitotic errors, centrosomal
RT amplification, and chromosomal instability.";
RL J. Biol. Chem. 287:39083-39093(2012).
RN [6]
RP FUNCTION.
RX PubMed=23713010; DOI=10.4161/cib.23544;
RA Krem M.M., Horwitz M.S.;
RT "Mitotic errors, aneuploidy and micronuclei in Hodgkin lymphoma
RT pathogenesis.";
RL Commun. Integr. Biol. 6:E23544-E23544(2013).
CC -!- FUNCTION: Involved in pinching off the separated nuclei at the cleavage
CC furrow and in cytokinesis (PubMed:20107318). Required for mitotic
CC integrity and maintenance of chromosomal stability. Protects cells
CC against mitotic errors, centrosomal amplification, micronucleus
CC formation and aneuploidy. Plays a key role of midbody function
CC involving abscission of the daughter cells during cytokinesis and
CC appropriate chromosomal and nuclear segregation into the daughter cells
CC (PubMed:22988245, PubMed:23713010). {ECO:0000269|PubMed:20107318,
CC ECO:0000269|PubMed:22988245, ECO:0000269|PubMed:23713010}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19706467,
CC ECO:0000269|PubMed:20107318}. Midbody {ECO:0000269|PubMed:19706467,
CC ECO:0000269|PubMed:20107318}. Note=In mitotic cells, concentrates in
CC the midbody of the cytoplasmic bridge linking daughter cells as they
CC are about to separate during cytokinesis. {ECO:0000269|PubMed:19706467,
CC ECO:0000269|PubMed:20107318}.
CC -!- DEVELOPMENTAL STAGE: Transcribed predominantly during S phase,
CC translated exclusively during mitosis and cytokinesis and rapidly
CC degraded after cell division. {ECO:0000269|PubMed:19706467}.
CC -!- DISEASE: Lymphoma, Hodgkin, classic (CHL) [MIM:236000]: A malignant
CC disease characterized by progressive enlargement of the lymph nodes,
CC spleen and general lymphoid tissue, and the presence of large, usually
CC multinucleate, cells (Reed-Sternberg cells). Reed-Sternberg cells
CC compose only 1-2% of the total tumor cell mass. The remainder is
CC composed of a variety of reactive, mixed inflammatory cells consisting
CC of lymphocytes, plasma cells, neutrophils, eosinophils and histiocytes.
CC {ECO:0000269|PubMed:19706467}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC A variant in the 5'-UTR of KLHDC8B, responsible for decreasing its
CC expression, is associated with classic Hodgkin lymphoma and segregates
CC with the disease in some families (PubMed:19706467).
CC {ECO:0000269|PubMed:19706467}.
CC -!- DISEASE: Note=A chromosomal aberration disrupting KLHDC8B has been
CC found in a family with the nodular sclerosis type of Hodgkin lymphoma.
CC Translocation t(2,3)(q11.2;p21.31).
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DR EMBL; AY129011; AAM98754.1; -; mRNA.
DR EMBL; BC039083; AAH39083.1; -; mRNA.
DR CCDS; CCDS2791.1; -.
DR RefSeq; NP_775817.1; NM_173546.2.
DR AlphaFoldDB; Q8IXV7; -.
DR SMR; Q8IXV7; -.
DR BioGRID; 128359; 8.
DR IntAct; Q8IXV7; 4.
DR MINT; Q8IXV7; -.
DR STRING; 9606.ENSP00000327468; -.
DR GlyGen; Q8IXV7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IXV7; -.
DR PhosphoSitePlus; Q8IXV7; -.
DR BioMuta; KLHDC8B; -.
DR DMDM; 74728248; -.
DR EPD; Q8IXV7; -.
DR jPOST; Q8IXV7; -.
DR MassIVE; Q8IXV7; -.
DR MaxQB; Q8IXV7; -.
DR PaxDb; Q8IXV7; -.
DR PeptideAtlas; Q8IXV7; -.
DR PRIDE; Q8IXV7; -.
DR ProteomicsDB; 71068; -.
DR Antibodypedia; 2038; 149 antibodies from 24 providers.
DR DNASU; 200942; -.
DR Ensembl; ENST00000332780.4; ENSP00000327468.2; ENSG00000185909.15.
DR GeneID; 200942; -.
DR KEGG; hsa:200942; -.
DR MANE-Select; ENST00000332780.4; ENSP00000327468.2; NM_173546.3; NP_775817.1.
DR UCSC; uc003cwh.4; human.
DR CTD; 200942; -.
DR DisGeNET; 200942; -.
DR GeneCards; KLHDC8B; -.
DR HGNC; HGNC:28557; KLHDC8B.
DR HPA; ENSG00000185909; Tissue enhanced (adrenal).
DR MalaCards; KLHDC8B; -.
DR MIM; 236000; phenotype.
DR MIM; 613169; gene.
DR neXtProt; NX_Q8IXV7; -.
DR OpenTargets; ENSG00000185909; -.
DR Orphanet; 98843; Classic Hodgkin lymphoma, nodular sclerosis type.
DR PharmGKB; PA142671584; -.
DR VEuPathDB; HostDB:ENSG00000185909; -.
DR eggNOG; KOG1072; Eukaryota.
DR GeneTree; ENSGT00940000160815; -.
DR HOGENOM; CLU_046864_0_0_1; -.
DR InParanoid; Q8IXV7; -.
DR OMA; TRFPCIP; -.
DR OrthoDB; 933937at2759; -.
DR PhylomeDB; Q8IXV7; -.
DR PathwayCommons; Q8IXV7; -.
DR SignaLink; Q8IXV7; -.
DR BioGRID-ORCS; 200942; 10 hits in 1076 CRISPR screens.
DR GenomeRNAi; 200942; -.
DR Pharos; Q8IXV7; Tbio.
DR PRO; PR:Q8IXV7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8IXV7; protein.
DR Bgee; ENSG00000185909; Expressed in right adrenal gland cortex and 176 other tissues.
DR Genevisible; Q8IXV7; HS.
DR GO; GO:0110070; C:cellularization cleavage furrow; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0045171; C:intercellular bridge; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:1902410; P:mitotic cytokinetic process; IMP:UniProtKB.
DR GO; GO:0140014; P:mitotic nuclear division; IMP:UniProtKB.
DR GO; GO:0098813; P:nuclear chromosome segregation; IMP:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR Pfam; PF01344; Kelch_1; 4.
DR SMART; SM00612; Kelch; 6.
DR SUPFAM; SSF117281; SSF117281; 2.
PE 2: Evidence at transcript level;
KW Cell cycle; Cell division; Chromosomal rearrangement; Cytoplasm;
KW Kelch repeat; Reference proteome; Repeat.
FT CHAIN 1..354
FT /note="Kelch domain-containing protein 8B"
FT /id="PRO_0000119131"
FT REPEAT 1..31
FT /note="Kelch 1"
FT REPEAT 32..79
FT /note="Kelch 2"
FT REPEAT 81..127
FT /note="Kelch 3"
FT REPEAT 128..175
FT /note="Kelch 4"
FT REPEAT 176..222
FT /note="Kelch 5"
FT REPEAT 224..281
FT /note="Kelch 6"
FT REPEAT 282..329
FT /note="Kelch 7"
FT REPEAT 331..354
FT /note="Kelch 8"
SQ SEQUENCE 354 AA; 37676 MW; 91305FE1EE0783FC CRC64;
MSAGGGRAFA WQVFPPMPTC RVYGTVAHQD GHLLVLGGCG RAGLPLDTAE TLDMASHTWL
ALAPLPTARA GAAAVVLGKQ VLVVGGVDEV QSPVAAVEAF LMDEGRWERR ATLPQAAMGV
ATVERDGMVY ALGGMGPDTA PQAQVRVYEP RRDCWLSLPS MPTPCYGAST FLHGNKIYVL
GGRQGKLPVT AFEAFDLEAR TWTRHPSLPS RRAFAGCAMA EGSVFSLGGL QQPGPHNFYS
RPHFVNTVEM FDLEHGSWTK LPRSLRMRDK RADFVVGSLG GHIVAIGGLG NQPCPLGSVE
SFSLARRRWE ALPAMPTARC SCSSLQAGPR LFVIGGVAQG PSQAVEALCL RDGV
