ID   ZFP91_HUMAN             Reviewed;         570 AA.
AC   Q96JP5; A6NHC4; A8MSG7; Q86V47; Q96JP4; Q96QA3;
DT   01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=E3 ubiquitin-protein ligase ZFP91;
DE            EC=2.3.2.27;
DE   AltName: Full=RING-type E3 ubiquitin transferase ZFP91;
DE   AltName: Full=Zinc finger protein 757;
DE   AltName: Full=Zinc finger protein 91 homolog;
DE            Short=Zfp-91;
GN   Name=ZFP91; Synonyms=ZNF757; ORFNames=FKSG11;
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] (ISOFORMS 1 AND 2), FUNCTION, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Leukocyte;
RX   PubMed=12738986;
RA   Unoki M., Okutsu J., Nakamura Y.;
RT   "Identification of a novel human gene, ZFP91, involved in acute myelogenous
RT   leukemia.";
RL   Int. J. Oncol. 22:1217-1223(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-37.
RC   TISSUE=Testis;
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   PROTEIN SEQUENCE OF 2-23, CLEAVAGE OF INITIATOR METHIONINE, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RA   Bienvenut W.V., Waridel P., Quadroni M.;
RL   Submitted (MAR-2009) to UniProtKB.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 67-570 (ISOFORM 1), AND VARIANT GLY-207.
RA   Wang Y.-G.;
RT   "Identification of FKSG11, a novel gene related to breast cancer.";
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   FUNCTION, INTERACTION WITH MAP3K14, AND MUTAGENESIS OF CYS-344 AND CYS-349.
RX   PubMed=20682767; DOI=10.1074/jbc.m110.129551;
RA   Jin X., Jin H.R., Jung H.S., Lee S.J., Lee J.H., Lee J.J.;
RT   "An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-
RT   kappaB-inducing kinase via Lys63-linked ubiquitination.";
RL   J. Biol. Chem. 285:30539-30547(2010).
RN   [8]
RP   STRUCTURE BY NMR OF 370-456 IN COMPLEX WITH ZINC IONS.
RG   Northeast structural genomics consortium (NESG);
RT   "Solution structure of HR7784A.";
RL   Submitted (JUL-2013) to the PDB data bank.
CC   -!- FUNCTION: Atypical E3 ubiquitin-protein ligase that mediates 'Lys-63'-
CC       linked ubiquitination of MAP3K14/NIK, leading to stabilize and activate
CC       MAP3K14/NIK. It thereby acts as an activator of the non-canonical NF-
CC       kappa-B2/NFKB2 pathway. May also play an important role in cell
CC       proliferation and/or anti-apoptosis. {ECO:0000269|PubMed:12738986,
CC       ECO:0000269|PubMed:20682767}.
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;
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with MAP3K14/NIK. {ECO:0000269|PubMed:20682767,
CC       ECO:0000269|Ref.8}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12738986}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q96JP5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96JP5-2; Sequence=VSP_012686, VSP_012687;
CC   -!- TISSUE SPECIFICITY: Expressed ubiquitously, particularly at high level
CC       in testis. Isoform 2 is testis specific.
CC   -!- MISCELLANEOUS: In contrast to other E3 ubiquitin-protein ligase, does
CC       not contain any domain (RING-type zinc finger or HECT domain) known to
CC       mediate E3 ligase activity.
CC   -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAL09963.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AB056107; BAB63373.1; -; mRNA.
DR   EMBL; AB057443; BAB63374.1; -; mRNA.
DR   EMBL; AP001350; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471076; EAW73811.1; -; Genomic_DNA.
DR   EMBL; BC051743; AAH51743.1; -; mRNA.
DR   EMBL; AF310246; AAL09963.1; ALT_FRAME; mRNA.
DR   CCDS; CCDS31553.1; -. [Q96JP5-1]
DR   RefSeq; NP_001183980.1; NM_001197051.1.
DR   RefSeq; NP_444251.1; NM_053023.4. [Q96JP5-1]
DR   PDB; 2M9A; NMR; -; A=370-456.
DR   PDBsum; 2M9A; -.
DR   AlphaFoldDB; Q96JP5; -.
DR   SMR; Q96JP5; -.
DR   BioGRID; 123322; 149.
DR   CORUM; Q96JP5; -.
DR   IntAct; Q96JP5; 33.
DR   MINT; Q96JP5; -.
DR   STRING; 9606.ENSP00000339030; -.
DR   ChEMBL; CHEMBL4739701; -.
DR   GlyGen; Q96JP5; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q96JP5; -.
DR   PhosphoSitePlus; Q96JP5; -.
DR   BioMuta; ZFP91; -.
DR   DMDM; 60416377; -.
DR   EPD; Q96JP5; -.
DR   jPOST; Q96JP5; -.
DR   MassIVE; Q96JP5; -.
DR   MaxQB; Q96JP5; -.
DR   PaxDb; 9606-ENSP00000339030; -.
DR   PeptideAtlas; Q96JP5; -.
DR   ProteomicsDB; 76999; -. [Q96JP5-1]
DR   ProteomicsDB; 77000; -. [Q96JP5-2]
DR   Pumba; Q96JP5; -.
DR   Antibodypedia; 14324; 225 antibodies from 24 providers.
DR   DNASU; 80829; -.
DR   Ensembl; ENST00000316059.7; ENSP00000339030.5; ENSG00000186660.15. [Q96JP5-1]
DR   GeneID; 80829; -.
DR   KEGG; hsa:80829; -.
DR   MANE-Select; ENST00000316059.7; ENSP00000339030.5; NM_053023.5; NP_444251.1.
DR   UCSC; uc001nmx.5; human. [Q96JP5-1]
DR   AGR; HGNC:14983; -.
DR   DisGeNET; 80829; -.
DR   GeneCards; ZFP91; -.
DR   HGNC; HGNC:14983; ZFP91.
DR   HPA; ENSG00000186660; Low tissue specificity.
DR   MIM; 619289; gene.
DR   neXtProt; NX_Q96JP5; -.
DR   OpenTargets; ENSG00000186660; -.
DR   PharmGKB; PA37955; -.
DR   VEuPathDB; HostDB:ENSG00000186660; -.
DR   eggNOG; KOG1721; Eukaryota.
DR   GeneTree; ENSGT00940000156393; -.
DR   HOGENOM; CLU_034557_0_0_1; -.
DR   InParanoid; Q96JP5; -.
DR   OMA; TYKPHLD; -.
DR   OrthoDB; 5359713at2759; -.
DR   PhylomeDB; Q96JP5; -.
DR   TreeFam; TF332664; -.
DR   PathwayCommons; Q96JP5; -.
DR   SignaLink; Q96JP5; -.
DR   SIGNOR; Q96JP5; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 80829; 31 hits in 1182 CRISPR screens.
DR   ChiTaRS; ZFP91; human.
DR   GeneWiki; ZFP91; -.
DR   GenomeRNAi; 80829; -.
DR   Pharos; Q96JP5; Tbio.
DR   PRO; PR:Q96JP5; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q96JP5; Protein.
DR   Bgee; ENSG00000186660; Expressed in tibialis anterior and 197 other cell types or tissues.
DR   ExpressionAtlas; Q96JP5; baseline and differential.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR   GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IDA:UniProtKB.
DR   GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 4.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR24409; ZINC FINGER PROTEIN 142; 1.
DR   PANTHER; PTHR24409:SF334; ZINC FINGER PROTEIN 653; 1.
DR   Pfam; PF00096; zf-C2H2; 3.
DR   SMART; SM00355; ZnF_C2H2; 5.
DR   SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 3.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
DR   Genevisible; Q96JP5; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Direct protein sequencing;
KW   Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW   Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|Ref.5"
FT   CHAIN           2..570
FT                   /note="E3 ubiquitin-protein ligase ZFP91"
FT                   /id="PRO_0000047312"
FT   ZN_FING         311..336
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         342..366
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         372..394
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         400..422
FT                   /note="C2H2-type 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         430..453
FT                   /note="C2H2-type 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          1..306
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          338..368
FT                   /note="Interaction with MAP3K14/NIK"
FT                   /evidence="ECO:0000269|PubMed:20682767"
FT   COMPBIAS        1..16
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        115..132
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        171..186
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        207..222
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        223..271
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        290..306
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         83
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q62511"
FT   MOD_RES         103
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q62511"
FT   VAR_SEQ         526..529
FT                   /note="VSLM -> SIHR (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12738986"
FT                   /id="VSP_012686"
FT   VAR_SEQ         530..570
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12738986"
FT                   /id="VSP_012687"
FT   VARIANT         37
FT                   /note="V -> I (in dbSNP:rs17854702)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_032454"
FT   VARIANT         207
FT                   /note="S -> G (in dbSNP:rs8373)"
FT                   /evidence="ECO:0000269|Ref.6"
FT                   /id="VAR_021889"
FT   MUTAGEN         344
FT                   /note="C->A: Abolishes ubiquitination of MAP3K14/NIK; when
FT                   associated with A-349."
FT                   /evidence="ECO:0000269|PubMed:20682767"
FT   MUTAGEN         349
FT                   /note="C->A: Abolishes ubiquitination of MAP3K14/NIK; when
FT                   associated with A-344."
FT                   /evidence="ECO:0000269|PubMed:20682767"
FT   CONFLICT        74
FT                   /note="A -> V (in Ref. 6; AAL09963)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        206
FT                   /note="Missing (in Ref. 4; AAH51743)"
FT                   /evidence="ECO:0000305"
FT   STRAND          381..383
FT                   /evidence="ECO:0007829|PDB:2M9A"
FT   HELIX           384..390
FT                   /evidence="ECO:0007829|PDB:2M9A"
FT   HELIX           391..393
FT                   /evidence="ECO:0007829|PDB:2M9A"
FT   STRAND          395..397
FT                   /evidence="ECO:0007829|PDB:2M9A"
FT   STRAND          408..411
FT                   /evidence="ECO:0007829|PDB:2M9A"
FT   HELIX           412..423
FT                   /evidence="ECO:0007829|PDB:2M9A"
FT   STRAND          426..429
FT                   /evidence="ECO:0007829|PDB:2M9A"
FT   TURN            433..435
FT                   /evidence="ECO:0007829|PDB:2M9A"
FT   HELIX           442..452
FT                   /evidence="ECO:0007829|PDB:2M9A"
SQ   SEQUENCE   570 AA;  63445 MW;  476F4C21DD453522 CRC64;
     MPGETEEPRP PEQQDQEGGE AAKAAPEEPQ QRPPEAVAAA PAGTTSSRVL RGGRDRGRAA
     AAAAAAAVSR RRKAEYPRRR RSSPSARPPD VPGQQPQAAK SPSPVQGKKS PRLLCIEKVT
     TDKDPKEEKE EEDDSALPQE VSIAASRPSR GWRSSRTSVS RHRDTENTRS SRSKTGSLQL
     ICKSEPNTDQ LDYDVGEEHQ SPGGISSEEE EEEEEEMLIS EEEIPFKDDP RDETYKPHLE
     RETPKPRRKS GKVKEEKEKK EIKVEVEVEV KEEENEIRED EEPPRKRGRR RKDDKSPRLP
     KRRKKPPIQY VRCEMEGCGT VLAHPRYLQH HIKYQHLLKK KYVCPHPSCG RLFRLQKQLL
     RHAKHHTDQR DYICEYCARA FKSSHNLAVH RMIHTGEKPL QCEICGFTCR QKASLNWHMK
     KHDADSFYQF SCNICGKKFE KKDSVVAHKA KSHPEVLIAE ALAANAGALI TSTDILGTNP
     ESLTQPSDGQ GLPLLPEPLG NSTSGECLLL EAEGMSKSYC SGTERVSLMA DGKIFVGSGS
     SGGTEGLVMN SDILGATTEV LIEDSDSAGP
//