ZC3H3_HUMAN
ID ZC3H3_HUMAN Reviewed; 948 AA.
AC Q8IXZ2; Q14163; Q8N4E2; Q9BUS4;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Zinc finger CCCH domain-containing protein 3;
DE AltName: Full=Smad-interacting CPSF-like factor {ECO:0000250|UniProtKB:Q8CHP0};
GN Name=ZC3H3;
GN Synonyms=KIAA0150, SMICL {ECO:0000250|UniProtKB:Q8CHP0}, ZC3HDC3;
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 GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP MET-6; ARG-102; LYS-165; ALA-231; GLY-452; HIS-578; TRP-636 AND ARG-727.
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-948 (ISOFORM 1), AND VARIANTS
RP ASP-151; GLY-399 AND GLY-452.
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV. The
RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [4]
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-918 AND SER-920, AND
RP IDENTIFICATION 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 [6]
RP FUNCTION.
RX PubMed=19364924; DOI=10.1083/jcb.200811072;
RA Hurt J.A., Obar R.A., Zhai B., Farny N.G., Gygi S.P., Silver P.A.;
RT "A conserved CCCH-type zinc finger protein regulates mRNA nuclear
RT adenylation and export.";
RL J. Cell Biol. 185:265-277(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408, AND IDENTIFICATION BY
RP 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: Required for the export of polyadenylated mRNAs from the
CC nucleus (PubMed:19364924). Enhances ACVR1B-induced SMAD-dependent
CC transcription. Binds to single-stranded DNA but not to double-stranded
CC DNA in vitro. Involved in RNA cleavage (By similarity).
CC {ECO:0000250|UniProtKB:Q8CHP0, ECO:0000269|PubMed:19364924}.
CC -!- SUBUNIT: Interacts with SMAD1, SMAD3, SMAD4, CPSF2 and CPSF3 (By
CC similarity). {ECO:0000250|UniProtKB:Q8CHP0}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8CHP0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IXZ2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IXZ2-2; Sequence=VSP_010272, VSP_010273;
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AC067930; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC105118; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034435; AAH34435.1; -; mRNA.
DR EMBL; BC038670; AAH38670.1; -; mRNA.
DR EMBL; D63484; BAA09771.1; -; mRNA.
DR CCDS; CCDS6402.1; -. [Q8IXZ2-1]
DR RefSeq; NP_055932.2; NM_015117.2. [Q8IXZ2-1]
DR AlphaFoldDB; Q8IXZ2; -.
DR SMR; Q8IXZ2; -.
DR BioGRID; 116761; 237.
DR IntAct; Q8IXZ2; 78.
DR STRING; 9606.ENSP00000262577; -.
DR iPTMnet; Q8IXZ2; -.
DR PhosphoSitePlus; Q8IXZ2; -.
DR BioMuta; ZC3H3; -.
DR DMDM; 308153538; -.
DR EPD; Q8IXZ2; -.
DR jPOST; Q8IXZ2; -.
DR MassIVE; Q8IXZ2; -.
DR MaxQB; Q8IXZ2; -.
DR PaxDb; Q8IXZ2; -.
DR PeptideAtlas; Q8IXZ2; -.
DR PRIDE; Q8IXZ2; -.
DR ProteomicsDB; 71078; -. [Q8IXZ2-1]
DR ProteomicsDB; 71079; -. [Q8IXZ2-2]
DR Antibodypedia; 14596; 102 antibodies from 20 providers.
DR DNASU; 23144; -.
DR Ensembl; ENST00000262577.6; ENSP00000262577.5; ENSG00000014164.7. [Q8IXZ2-1]
DR GeneID; 23144; -.
DR KEGG; hsa:23144; -.
DR MANE-Select; ENST00000262577.6; ENSP00000262577.5; NM_015117.3; NP_055932.2.
DR UCSC; uc003yyd.3; human. [Q8IXZ2-1]
DR CTD; 23144; -.
DR DisGeNET; 23144; -.
DR GeneCards; ZC3H3; -.
DR HGNC; HGNC:28972; ZC3H3.
DR HPA; ENSG00000014164; Low tissue specificity.
DR MIM; 618640; gene.
DR neXtProt; NX_Q8IXZ2; -.
DR OpenTargets; ENSG00000014164; -.
DR PharmGKB; PA134933089; -.
DR VEuPathDB; HostDB:ENSG00000014164; -.
DR eggNOG; KOG1492; Eukaryota.
DR GeneTree; ENSGT00940000161068; -.
DR HOGENOM; CLU_014207_0_0_1; -.
DR InParanoid; Q8IXZ2; -.
DR OMA; TPNKGLM; -.
DR OrthoDB; 400525at2759; -.
DR PhylomeDB; Q8IXZ2; -.
DR TreeFam; TF324375; -.
DR PathwayCommons; Q8IXZ2; -.
DR SignaLink; Q8IXZ2; -.
DR BioGRID-ORCS; 23144; 94 hits in 1073 CRISPR screens.
DR ChiTaRS; ZC3H3; human.
DR GenomeRNAi; 23144; -.
DR Pharos; Q8IXZ2; Tbio.
DR PRO; PR:Q8IXZ2; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q8IXZ2; protein.
DR Bgee; ENSG00000014164; Expressed in right lobe of liver and 109 other tissues.
DR ExpressionAtlas; Q8IXZ2; baseline and differential.
DR Genevisible; Q8IXZ2; HS.
DR GO; GO:0005847; C:mRNA cleavage and polyadenylation specificity factor complex; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070412; F:R-SMAD binding; IEA:Ensembl.
DR GO; GO:0031124; P:mRNA 3'-end processing; IEA:Ensembl.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:1900363; P:regulation of mRNA polyadenylation; IMP:UniProtKB.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR Pfam; PF00642; zf-CCCH; 2.
DR SMART; SM00356; ZnF_C3H1; 5.
DR SUPFAM; SSF90229; SSF90229; 2.
DR PROSITE; PS50103; ZF_C3H1; 5.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Metal-binding; mRNA transport; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transport; Zinc; Zinc-finger.
FT CHAIN 1..948
FT /note="Zinc finger CCCH domain-containing protein 3"
FT /id="PRO_0000213896"
FT ZN_FING 667..695
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 699..722
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 723..749
FT /note="C3H1-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 750..777
FT /note="C3H1-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 778..800
FT /note="C3H1-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 25..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 121..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 265..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 798..891
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 913..948
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..165
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..413
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 457..471
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 829..849
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 863..887
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 918
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..613
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010272"
FT VAR_SEQ 614..634
FT /note="NKLSKTSGQPSDAGSRPLLRT -> MEPGGEPTGAKESSTLMESLA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010273"
FT VARIANT 6
FT /note="I -> M (in dbSNP:rs2242093)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_018457"
FT VARIANT 102
FT /note="Q -> R (in dbSNP:rs17857167)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060402"
FT VARIANT 149
FT /note="F -> Y (in dbSNP:rs3750206)"
FT /id="VAR_018458"
FT VARIANT 151
FT /note="E -> D (in dbSNP:rs3750207)"
FT /evidence="ECO:0000269|PubMed:8590280"
FT /id="VAR_018459"
FT VARIANT 165
FT /note="E -> K (in dbSNP:rs17853852)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060403"
FT VARIANT 168
FT /note="R -> W (in dbSNP:rs3750208)"
FT /id="VAR_057484"
FT VARIANT 228
FT /note="A -> S (in dbSNP:rs4873802)"
FT /id="VAR_057485"
FT VARIANT 231
FT /note="P -> A (in dbSNP:rs17853853)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060404"
FT VARIANT 351
FT /note="P -> L (in dbSNP:rs34674128)"
FT /id="VAR_057486"
FT VARIANT 399
FT /note="S -> G (in dbSNP:rs1318196)"
FT /evidence="ECO:0000269|PubMed:8590280"
FT /id="VAR_018460"
FT VARIANT 415
FT /note="P -> L (in dbSNP:rs36008851)"
FT /id="VAR_057487"
FT VARIANT 452
FT /note="S -> G (in dbSNP:rs4874147)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8590280"
FT /id="VAR_018461"
FT VARIANT 503
FT /note="T -> K (in dbSNP:rs11548254)"
FT /id="VAR_057488"
FT VARIANT 578
FT /note="R -> H (in dbSNP:rs17855618)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060405"
FT VARIANT 636
FT /note="R -> W (in dbSNP:rs17857164)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060406"
FT VARIANT 727
FT /note="P -> R (in dbSNP:rs17857168)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060407"
FT CONFLICT 572
FT /note="R -> G (in Ref. 2; AAH38670)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 948 AA; 101941 MW; 9CDD4F29EE40946B CRC64;
MEEKEILRRQ IRLLQGLIDD YKTLHGNAPA PGTPAASGWQ PPTYHSGRAF SARYPRPSRR
GYSSHHGPSW RKKYSLVNRP PGPSDPPADH AVRPLHGARG GQPPVPQQHV LERQVQLSQG
QNVVIKVKPP SKSGSASASG AQRGSLEEFE ETPWSDQRPR EGEGEPPRGQ LQPSRPTRAR
GTCSVEDPLL VCQKEPGKPR MVKSVGSVGD SPREPRRTVS ESVIAVKASF PSSALPPRTG
VALGRKLGSH SVASCAPQLL GDRRVDAGHT DQPVPSGSVG GPARPASGPR QAREASLVVT
CRTNKFRKNN YKWVAASSKS PRVARRALSP RVAAENVCKA SAGMANKVEK PQLIADPEPK
PRKPATSSKP GSAPSKYKWK ASSPSASSSS SFRWQSEASS KDHASQLSPV LSRSPSGDRP
AVGHSGLKPL SGETPLSAYK VKSRTKIIRR RSSTSLPGDK KSGTSPAATA KSHLSLRRRQ
ALRGKSSPVL KKTPNKGLVQ VTTHRLCRLP PSRAHLPTKE ASSLHAVRTA PTSKVIKTRY
RIVKKTPASP LSAPPFPLSL PSWRARRLSL SRSLVLNRLR PVASGGGKAQ PGSPWWRSKG
YRCIGGVLYK VSANKLSKTS GQPSDAGSRP LLRTGRLDPA GSCSRSLASR AVQRSLAIIR
QARQRREKRK EYCMYYNRFG RCNRGERCPY IHDPEKVAVC TRFVRGTCKK TDGTCPFSHH
VSKEKMPVCS YFLKGICSNS NCPYSHVYVS RKAEVCSDFL KGYCPLGAKC KKKHTLLCPD
FARRGACPRG AQCQLLHRTQ KRHSRRAATS PAPGPSDATA RSRVSASHGP RKPSASQRPT
RQTPSSAALT AAAVAAPPHC PGGSASPSSS KASSSSSSSS SPPASLDHEA PSLQEAALAA
ACSNRLCKLP SFISLQSSPS PGAQPRVRAP RAPLTKDSGK PLHIKPRL
