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   24-JAN-2024, entry version 159.
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;
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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; 238.
DR   ComplexPortal; CPX-2750; Poly(A) tail exosome targeting complex, RBM26 variant.
DR   ComplexPortal; CPX-2752; Poly(A) tail exosome targeting complex, RBM27 variant.
DR   IntAct; Q8IXZ2; 78.
DR   STRING; 9606.ENSP00000262577; -.
DR   GlyGen; Q8IXZ2; 1 site, 1 O-linked glycan (1 site).
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; 9606-ENSP00000262577; -.
DR   PeptideAtlas; Q8IXZ2; -.
DR   ProteomicsDB; 71078; -. [Q8IXZ2-1]
DR   ProteomicsDB; 71079; -. [Q8IXZ2-2]
DR   Pumba; Q8IXZ2; -.
DR   Antibodypedia; 14596; 119 antibodies from 21 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   AGR; HGNC:28972; -.
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; VSCRTNK; -.
DR   OrthoDB; 827813at2759; -.
DR   PhylomeDB; Q8IXZ2; -.
DR   TreeFam; TF324375; -.
DR   PathwayCommons; Q8IXZ2; -.
DR   SignaLink; Q8IXZ2; -.
DR   BioGRID-ORCS; 23144; 108 hits in 1151 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 111 other cell types or tissues.
DR   ExpressionAtlas; Q8IXZ2; baseline and differential.
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   Gene3D; 3.30.1370.210; -; 1.
DR   Gene3D; 4.10.1000.10; Zinc finger, CCCH-type; 2.
DR   InterPro; IPR000571; Znf_CCCH.
DR   InterPro; IPR036855; Znf_CCCH_sf.
DR   PANTHER; PTHR46156; CCCH ZINGC FINGER; 1.
DR   PANTHER; PTHR46156:SF1; ZINC FINGER CCCH DOMAIN-CONTAINING PROTEIN 3; 1.
DR   Pfam; PF00642; zf-CCCH; 2.
DR   SMART; SM00356; ZnF_C3H1; 5.
DR   SUPFAM; SSF90229; CCCH zinc finger; 2.
DR   PROSITE; PS50103; ZF_C3H1; 5.
DR   Genevisible; Q8IXZ2; HS.
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
//