BICC1_HUMAN
ID BICC1_HUMAN Reviewed; 974 AA.
AC Q9H694;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Protein bicaudal C homolog 1;
DE Short=Bic-C;
GN Name=BICC1;
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] (ISOFORM 1).
RA Ferreira E.N., Pires L.C., Parmigiani R.B., Bettoni F., Puga R.D.,
RA Pinheiro D.G., Andrade L.E.C., Cruz L.O., Degaki T.L., Faria M. Jr.,
RA Festa F., Giannella-Neto D., Giorgi R.R., Goldman G.H., Granja F.,
RA Gruber A., Hackel C., Henrique-Silva F., Malnic B., Manzini C.V.B.,
RA Marie S.K.N., Martinez-Rossi N.M., Oba-Shinjo S.M., Pardini M.I.M.C.,
RA Rahal P., Rainho C.A., Rogatto S.R., Romano C.M., Rodrigues V., Sales M.M.,
RA Savoldi M., da Silva I.D.C.G., da Silva N.P., de Souza S.J., Tajara E.H.,
RA Silva W.A. Jr., Simpson A.J.G., Sogayar M.C., Camargo A.A., Carraro D.M.;
RT "Identification and complete sequencing of novel human transcripts through
RT the use of mouse orthologs and testis cDNA sequences.";
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 367-974 (ISOFORM 2).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-398, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [6]
RP FUNCTION AS NEGATIVE REGULATOR OF WNT SIGNALING, VARIANT CYSRD GLY-932,
RP VARIANT THR-711, AND CHARACTERIZATION OF VARIANT CYSRD GLY-932.
RX PubMed=21922595; DOI=10.1002/humu.21610;
RA Kraus M.R., Clauin S., Pfister Y., Di Maio M., Ulinski T., Constam D.,
RA Bellanne-Chantelot C., Grapin-Botton A.;
RT "Two mutations in human BICC1 resulting in Wnt pathway hyperactivity
RT associated with cystic renal dysplasia.";
RL Hum. Mutat. 33:86-90(2012).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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).
RN [8]
RP VARIANT VAL-270.
RX PubMed=24501278; DOI=10.1093/hmg/ddu056;
RA Lee H., Lin M.C., Kornblum H.I., Papazian D.M., Nelson S.F.;
RT "Exome sequencing identifies de novo gain of function missense mutation in
RT KCND2 in identical twins with autism and seizures that slows potassium
RT channel inactivation.";
RL Hum. Mol. Genet. 23:3481-3489(2014).
CC -!- FUNCTION: Putative RNA-binding protein. Acts as a negative regulator of
CC Wnt signaling. May be involved in regulating gene expression during
CC embryonic development. {ECO:0000269|PubMed:21922595}.
CC -!- SUBUNIT: Interacts (via KH domains) with ANKS6 (via SAM domain) in an
CC RNA-dependent manner (By similarity). Interacts with ANKS3 (By
CC similarity). {ECO:0000250|UniProtKB:Q99MQ1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H694-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H694-2; Sequence=VSP_021949;
CC -!- DISEASE: Renal dysplasia, cystic (CYSRD) [MIM:601331]: An anomaly of
CC the kidney characterized by numerous renal cysts and apparent disorder
CC of differentiation of the renal parenchyma. Kidney of affected
CC individuals lack the normal renal bean shape, and the collection
CC drainage system. The cystic, dysplastic kidney contains
CC undifferentiated mesenchyme, cartilaginous tissue, and immature
CC collecting ducts. {ECO:0000269|PubMed:21922595}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the BicC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15369.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY726586; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK026129; BAB15369.1; ALT_INIT; mRNA.
DR CCDS; CCDS31206.1; -. [Q9H694-1]
DR RefSeq; NP_001073981.1; NM_001080512.2. [Q9H694-1]
DR PDB; 4RQM; X-ray; 1.75 A; A/B/C=870-939.
DR PDB; 4RQN; X-ray; 2.00 A; A/B/C=870-939.
DR PDB; 6GY4; X-ray; 1.99 A; A/B/C/D=47-130.
DR PDBsum; 4RQM; -.
DR PDBsum; 4RQN; -.
DR PDBsum; 6GY4; -.
DR AlphaFoldDB; Q9H694; -.
DR SMR; Q9H694; -.
DR BioGRID; 123119; 20.
DR IntAct; Q9H694; 5.
DR MINT; Q9H694; -.
DR STRING; 9606.ENSP00000362993; -.
DR iPTMnet; Q9H694; -.
DR PhosphoSitePlus; Q9H694; -.
DR BioMuta; BICC1; -.
DR DMDM; 119367815; -.
DR EPD; Q9H694; -.
DR jPOST; Q9H694; -.
DR MassIVE; Q9H694; -.
DR MaxQB; Q9H694; -.
DR PaxDb; Q9H694; -.
DR PeptideAtlas; Q9H694; -.
DR PRIDE; Q9H694; -.
DR ProteomicsDB; 80965; -. [Q9H694-1]
DR ProteomicsDB; 80966; -. [Q9H694-2]
DR Antibodypedia; 51885; 166 antibodies from 26 providers.
DR DNASU; 80114; -.
DR Ensembl; ENST00000373886.8; ENSP00000362993.3; ENSG00000122870.12. [Q9H694-1]
DR GeneID; 80114; -.
DR KEGG; hsa:80114; -.
DR MANE-Select; ENST00000373886.8; ENSP00000362993.3; NM_001080512.3; NP_001073981.1.
DR UCSC; uc001jki.2; human. [Q9H694-1]
DR CTD; 80114; -.
DR DisGeNET; 80114; -.
DR GeneCards; BICC1; -.
DR HGNC; HGNC:19351; BICC1.
DR HPA; ENSG00000122870; Tissue enhanced (kidney).
DR MalaCards; BICC1; -.
DR MIM; 601331; phenotype.
DR MIM; 614295; gene.
DR neXtProt; NX_Q9H694; -.
DR OpenTargets; ENSG00000122870; -.
DR Orphanet; 730; Autosomal dominant polycystic kidney disease.
DR PharmGKB; PA134878124; -.
DR VEuPathDB; HostDB:ENSG00000122870; -.
DR eggNOG; KOG2208; Eukaryota.
DR eggNOG; KOG4374; Eukaryota.
DR GeneTree; ENSGT00940000156276; -.
DR HOGENOM; CLU_008040_0_0_1; -.
DR InParanoid; Q9H694; -.
DR OMA; ATHIHFP; -.
DR OrthoDB; 201055at2759; -.
DR PhylomeDB; Q9H694; -.
DR TreeFam; TF323767; -.
DR PathwayCommons; Q9H694; -.
DR SignaLink; Q9H694; -.
DR BioGRID-ORCS; 80114; 6 hits in 1072 CRISPR screens.
DR ChiTaRS; BICC1; human.
DR GenomeRNAi; 80114; -.
DR Pharos; Q9H694; Tbio.
DR PRO; PR:Q9H694; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9H694; protein.
DR Bgee; ENSG00000122870; Expressed in germinal epithelium of ovary and 156 other tissues.
DR ExpressionAtlas; Q9H694; baseline and differential.
DR Genevisible; Q9H694; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR CDD; cd09520; SAM_BICC1; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 3.30.1370.10; -; 1.
DR InterPro; IPR037974; BICC1_SAM_dom.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR Pfam; PF00013; KH_1; 2.
DR Pfam; PF00536; SAM_1; 1.
DR SMART; SM00322; KH; 3.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF54791; SSF54791; 3.
DR PROSITE; PS50084; KH_TYPE_1; 2.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Developmental protein; Disease variant; Phosphoprotein; Reference proteome;
KW Repeat; RNA-binding.
FT CHAIN 1..974
FT /note="Protein bicaudal C homolog 1"
FT /id="PRO_0000267714"
FT DOMAIN 132..199
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 284..348
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 873..936
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 593..644
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 665..719
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 783..846
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 593..619
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 783..809
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MQ1"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MQ1"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MQ1"
FT MOD_RES 398
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 576
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 612
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MQ1"
FT MOD_RES 679
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MQ1"
FT VAR_SEQ 845..974
FT /note="TEHYLSSSNYMDCISSLTGSNGCNLNSSFKGSDLPELFSKLGLGKYTDVFQQ
FT QEIDLQTFLTLTDQDLKELGITTFGARRKMLLAISELNKNRRKLFESPNARTSFLEGGA
FT SGRLPRQYHSDIASVSGRW -> SELCVLCTLLGIPRLECVYLGWSITDCGLSDFKCLV
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021949"
FT VARIANT 8
FT /note="G -> D (in dbSNP:rs7905025)"
FT /id="VAR_029658"
FT VARIANT 270
FT /note="M -> V (found in a family with atypical autism and
FT severe epilepsy; unknown pathological significance;
FT dbSNP:rs753582128)"
FT /evidence="ECO:0000269|PubMed:24501278"
FT /id="VAR_072077"
FT VARIANT 711
FT /note="N -> T (in dbSNP:rs138916713)"
FT /evidence="ECO:0000269|PubMed:21922595"
FT /id="VAR_066759"
FT VARIANT 932
FT /note="E -> G (in CYSRD; may impair splicing; hypomorphic
FT mutation; dbSNP:rs387907124)"
FT /evidence="ECO:0000269|PubMed:21922595"
FT /id="VAR_066760"
FT VARIANT 943
FT /note="S -> P (in dbSNP:rs4948550)"
FT /id="VAR_033542"
FT VARIANT 945
FT /note="N -> S (in dbSNP:rs7895817)"
FT /id="VAR_060133"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:6GY4"
FT HELIX 55..67
FT /evidence="ECO:0007829|PDB:6GY4"
FT HELIX 76..84
FT /evidence="ECO:0007829|PDB:6GY4"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:6GY4"
FT HELIX 93..97
FT /evidence="ECO:0007829|PDB:6GY4"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:6GY4"
FT HELIX 112..125
FT /evidence="ECO:0007829|PDB:6GY4"
FT HELIX 875..877
FT /evidence="ECO:0007829|PDB:4RQM"
FT HELIX 878..884
FT /evidence="ECO:0007829|PDB:4RQM"
FT HELIX 888..890
FT /evidence="ECO:0007829|PDB:4RQM"
FT HELIX 891..896
FT /evidence="ECO:0007829|PDB:4RQM"
FT HELIX 901..904
FT /evidence="ECO:0007829|PDB:4RQM"
FT HELIX 909..915
FT /evidence="ECO:0007829|PDB:4RQM"
FT HELIX 920..935
FT /evidence="ECO:0007829|PDB:4RQM"
SQ SEQUENCE 974 AA; 104844 MW; D2DB194BD3C8266D CRC64;
MAAQGEPGYL AAQSDPGSNS ERSTDSPVPG SEDDLVAGAT LHSPEWSEER FRVDRKKLEA
MLQAAAEGKG RSGEDFFQKI MEETNTQIAW PSKLKIGAKS KKDPHIKVSG KKEDVKEAKE
MIMSVLDTKS NRVTLKMDVS HTEHSHVIGK GGNNIKKVME ETGCHIHFPD SNRNNQAEKS
NQVSIAGQPA GVESARVRIR ELLPLVLMFE LPIAGILQPV PDPNSPSIQH ISQTYNISVS
FKQRSRMYGA TVIVRGSQNN TSAVKEGTAM LLEHLAGSLA SAIPVSTQLD IAAQHHLFMM
GRNGSNIKHI MQRTGAQIHF PDPSNPQKKS TVYLQGTIES VCLARQYLMG CLPLVLMFDM
KEEIEVDPQF IAQLMEQLDV FISIKPKPKQ PSKSVIVKSV ERNALNMYEA RKCLLGLESS
GVTIATSPSP ASCPAGLACP SLDILASAGL GLTGLGLLGP TTLSLNTSTT PNSLLNALNS
SVSPLQSPSS GTPSPTLWAP PLANTSSATG FSAIPHLMIP STAQATLTNI LLSGVPTYGH
TAPSPPPGLT PVDVHINSMQ TEGKKISAAL NGHAQSPDIK YGAISTSSLG EKVLSANHGD
PSIQTSGSEQ TSPKSSPTEG CNDAFVEVGM PRSPSHSGNA GDLKQMMCPS KVSCAKRQTV
ELLQGTKNSH LHSTDRLLSD PELSATESPL ADKKAPGSER AAERAAAAQQ NSERAHLAPR
SSYVNMQAFD YEQKKLLATK AMLKKPVVTE VRTPTNTWSG LGFSKSMPAE TIKELRRANH
VSYKPTMTTT YEGSSMSLSR SNSREHLGGG SESDNWRDRN GIGPGSHSEF AASIGSPKRK
QNKSTEHYLS SSNYMDCISS LTGSNGCNLN SSFKGSDLPE LFSKLGLGKY TDVFQQQEID
LQTFLTLTDQ DLKELGITTF GARRKMLLAI SELNKNRRKL FESPNARTSF LEGGASGRLP
RQYHSDIASV SGRW