ZFN2B_HUMAN
ID ZFN2B_HUMAN Reviewed; 257 AA.
AC Q8WV99; Q8NB98;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=AN1-type zinc finger protein 2B {ECO:0000305};
DE AltName: Full=Arsenite-inducible RNA-associated protein-like protein {ECO:0000305};
DE Short=AIRAP-like protein {ECO:0000305};
DE Flags: Precursor;
GN Name=ZFAND2B {ECO:0000312|HGNC:HGNC:25206};
GN Synonyms=AIRAPL {ECO:0000303|PubMed:21896481};
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] (ISOFORM 2).
RC TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [4]
RP INTERACTION WITH VCP, AND VIM MOTIF.
RX PubMed=21896481; DOI=10.1074/jbc.m111.274472;
RA Stapf C., Cartwright E., Bycroft M., Hofmann K., Buchberger A.;
RT "The general definition of the p97/valosin-containing protein (VCP)-
RT interacting motif (VIM) delineates a new family of p97 cofactors.";
RL J. Biol. Chem. 286:38670-38678(2011).
RN [5]
RP UBIQUITIN-BINDING, AND INTERACTION WITH BAG6; DERL1; FAF2; NPLOC4; UFD1 AND
RP VCP.
RX PubMed=24160817; DOI=10.1042/bj20130710;
RA Glinka T., Alter J., Braunstein I., Tzach L., Wei Sheng C., Geifman S.,
RA Edelmann M.J., Kessler B.M., Stanhill A.;
RT "Signal-peptide-mediated translocation is regulated by a p97-AIRAPL
RT complex.";
RL Biochem. J. 457:253-261(2014).
RN [6]
RP INTERACTION WITH BAG6 AND VCP.
RX PubMed=26337389; DOI=10.1091/mbc.e15-02-0085;
RA Braunstein I., Zach L., Allan S., Kalies K.U., Stanhill A.;
RT "Proteasomal degradation of preemptive quality control (pQC) substrates is
RT mediated by an AIRAPL-p97 complex.";
RL Mol. Biol. Cell 26:3719-3727(2015).
RN [7]
RP FUNCTION, INTERACTION WITH IGF1R, AND INDUCTION.
RX PubMed=26692333; DOI=10.1038/nm.4013;
RA Osorio F.G., Soria-Valles C., Santiago-Fernandez O., Bernal T.,
RA Mittelbrunn M., Colado E., Rodriguez F., Bonzon-Kulichenko E., Vazquez J.,
RA Porta-de-la-Riva M., Ceron J., Fueyo A., Li J., Green A.R., Freije J.M.,
RA Lopez-Otin C.;
RT "Loss of the proteostasis factor AIRAPL causes myeloid transformation by
RT deregulating IGF-1 signaling.";
RL Nat. Med. 22:91-96(2016).
RN [8]
RP STRUCTURE BY NMR OF 93-142 IN COMPLEX WITH ZINC IONS.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the ZF-AN1 domain from human hypothetical protein
RT LOC130617.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Plays a role in protein homeostasis by regulating both the
CC translocation and the ubiquitin-mediated proteasomal degradation of
CC nascent proteins at the endoplasmic reticulum. It is involved in the
CC regulation of signal-mediated translocation of proteins into the
CC endoplasmic reticulum. It also plays a role in the ubiquitin-mediated
CC proteasomal degradation of proteins for which signal-mediated
CC translocation to the endoplasmic reticulum has failed. May therefore
CC function in the endoplasmic reticulum stress-induced pre-emptive
CC quality control, a mechanism that selectively attenuates the
CC translocation of newly synthesized proteins into the endoplasmic
CC reticulum and reroutes them to the cytosol for proteasomal degradation
CC (By similarity). By controlling the steady-state expression of the
CC IGF1R receptor, indirectly regulates the insulin-like growth factor
CC receptor signaling pathway (PubMed:26692333).
CC {ECO:0000250|UniProtKB:Q91X58, ECO:0000269|PubMed:26692333}.
CC -!- SUBUNIT: Binds 'Lys-48'-linked polyubiquitin chains of ubiquitinated
CC proteins (PubMed:24160817). Associates with the proteasome complex;
CC upon exposure to arsenite (By similarity). Interacts (via VIM motif)
CC with VCP; the interaction is direct (PubMed:21896481, PubMed:24160817,
CC PubMed:26337389). Interacts with BAG6 (PubMed:24160817,
CC PubMed:26337389). Interacts with IGF1R (nascent precursor form)
CC (PubMed:26692333). Interacts with DERL1, FAF2, NPLOC4 and UFD1;
CC probably through VCP (PubMed:24160817). {ECO:0000250|UniProtKB:Q91X58,
CC ECO:0000269|PubMed:21896481, ECO:0000269|PubMed:24160817,
CC ECO:0000269|PubMed:26337389, ECO:0000269|PubMed:26692333}.
CC -!- INTERACTION:
CC Q8WV99; Q9H672-2: ASB7; NbExp=3; IntAct=EBI-747823, EBI-12104328;
CC Q8WV99; Q15038: DAZAP2; NbExp=10; IntAct=EBI-747823, EBI-724310;
CC Q8WV99; G3V162: TARDBP; NbExp=3; IntAct=EBI-747823, EBI-10177881;
CC Q8WV99; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-747823, EBI-10173939;
CC Q8WV99; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-747823, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q91X58}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q91X58}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WV99-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WV99-2; Sequence=VSP_018001;
CC -!- INDUCTION: Down-regulated by the miRNA miR-125a-3p in myelo-
CC proliferative neoplasms. {ECO:0000269|PubMed:26692333}.
CC -!- DOMAIN: The UIM domains specifically bind 'Lys-48'-linked ubiquitin
CC polymers. The UIM domains mediate interaction with polyubiquitinated
CC proteins. {ECO:0000250|UniProtKB:Q91X58}.
CC -!- PTM: Phosphorylated by MAPK14. Phosphorylation has no effect on
CC association with the proteasome complex.
CC {ECO:0000250|UniProtKB:Q91X58}.
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DR EMBL; AK091345; BAC03642.1; -; mRNA.
DR EMBL; BC018415; AAH18415.1; -; mRNA.
DR CCDS; CCDS2435.1; -. [Q8WV99-1]
DR RefSeq; NP_001257927.1; NM_001270998.1. [Q8WV99-1]
DR RefSeq; NP_001257928.1; NM_001270999.1.
DR RefSeq; NP_620157.1; NM_138802.2. [Q8WV99-1]
DR RefSeq; XP_016858857.1; XM_017003368.1. [Q8WV99-1]
DR PDB; 1X4V; NMR; -; A=93-142.
DR PDBsum; 1X4V; -.
DR AlphaFoldDB; Q8WV99; -.
DR SMR; Q8WV99; -.
DR BioGRID; 126246; 47.
DR IntAct; Q8WV99; 21.
DR MINT; Q8WV99; -.
DR STRING; 9606.ENSP00000289528; -.
DR GlyGen; Q8WV99; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8WV99; -.
DR PhosphoSitePlus; Q8WV99; -.
DR BioMuta; ZFAND2B; -.
DR DMDM; 74730823; -.
DR EPD; Q8WV99; -.
DR jPOST; Q8WV99; -.
DR MassIVE; Q8WV99; -.
DR MaxQB; Q8WV99; -.
DR PaxDb; Q8WV99; -.
DR PeptideAtlas; Q8WV99; -.
DR PRIDE; Q8WV99; -.
DR ProteomicsDB; 74766; -. [Q8WV99-1]
DR ProteomicsDB; 74767; -. [Q8WV99-2]
DR Antibodypedia; 51845; 203 antibodies from 15 providers.
DR DNASU; 130617; -.
DR Ensembl; ENST00000289528.10; ENSP00000289528.5; ENSG00000158552.13. [Q8WV99-1]
DR Ensembl; ENST00000409206.5; ENSP00000386824.1; ENSG00000158552.13. [Q8WV99-2]
DR Ensembl; ENST00000409336.5; ENSP00000386898.1; ENSG00000158552.13. [Q8WV99-1]
DR Ensembl; ENST00000409594.5; ENSP00000386399.1; ENSG00000158552.13. [Q8WV99-2]
DR Ensembl; ENST00000444522.6; ENSP00000411334.3; ENSG00000158552.13. [Q8WV99-1]
DR GeneID; 130617; -.
DR KEGG; hsa:130617; -.
DR MANE-Select; ENST00000289528.10; ENSP00000289528.5; NM_138802.3; NP_620157.1.
DR UCSC; uc002vjz.3; human. [Q8WV99-1]
DR CTD; 130617; -.
DR DisGeNET; 130617; -.
DR GeneCards; ZFAND2B; -.
DR HGNC; HGNC:25206; ZFAND2B.
DR HPA; ENSG00000158552; Low tissue specificity.
DR MIM; 613474; gene.
DR neXtProt; NX_Q8WV99; -.
DR OpenTargets; ENSG00000158552; -.
DR PharmGKB; PA142670527; -.
DR VEuPathDB; HostDB:ENSG00000158552; -.
DR eggNOG; KOG3183; Eukaryota.
DR GeneTree; ENSGT00940000159648; -.
DR HOGENOM; CLU_061621_2_0_1; -.
DR InParanoid; Q8WV99; -.
DR OMA; NENIVWE; -.
DR OrthoDB; 1422113at2759; -.
DR PhylomeDB; Q8WV99; -.
DR TreeFam; TF314219; -.
DR PathwayCommons; Q8WV99; -.
DR SignaLink; Q8WV99; -.
DR BioGRID-ORCS; 130617; 10 hits in 1086 CRISPR screens.
DR ChiTaRS; ZFAND2B; human.
DR EvolutionaryTrace; Q8WV99; -.
DR GenomeRNAi; 130617; -.
DR Pharos; Q8WV99; Tbio.
DR PRO; PR:Q8WV99; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8WV99; protein.
DR Bgee; ENSG00000158552; Expressed in lower esophagus mucosa and 166 other tissues.
DR ExpressionAtlas; Q8WV99; baseline and differential.
DR Genevisible; Q8WV99; HS.
DR GO; GO:0031225; C:anchored component of membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000502; C:proteasome complex; IEA:Ensembl.
DR GO; GO:0036435; F:K48-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0045047; P:protein targeting to ER; IMP:UniProtKB.
DR GO; GO:0043567; P:regulation of insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006616; P:SRP-dependent cotranslational protein targeting to membrane, translocation; IMP:MGI.
DR Gene3D; 4.10.1110.10; -; 2.
DR InterPro; IPR035896; AN1-like_Znf.
DR InterPro; IPR003903; UIM_dom.
DR InterPro; IPR000058; Znf_AN1.
DR Pfam; PF02809; UIM; 2.
DR Pfam; PF01428; zf-AN1; 2.
DR SMART; SM00726; UIM; 2.
DR SMART; SM00154; ZnF_AN1; 2.
DR SUPFAM; SSF118310; SSF118310; 2.
DR PROSITE; PS50330; UIM; 2.
DR PROSITE; PS51039; ZF_AN1; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Endoplasmic reticulum; Lipoprotein;
KW Membrane; Metal-binding; Methylation; Phosphoprotein; Prenylation;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..254
FT /note="AN1-type zinc finger protein 2B"
FT /id="PRO_0000232876"
FT PROPEP 255..257
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:Q91X58"
FT /id="PRO_0000444335"
FT DOMAIN 197..216
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 221..240
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT ZN_FING 4..52
FT /note="AN1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT ZN_FING 94..142
FT /note="AN1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT REGION 141..151
FT /note="VCP/p97-interacting motif (VIM)"
FT /evidence="ECO:0000269|PubMed:21896481"
FT REGION 153..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 254..257
FT /note="CAAX motif"
FT /evidence="ECO:0000250|UniProtKB:Q91X58"
FT BINDING 10
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 15
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 25
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 28
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 33
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 36
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 42
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 132
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91X58"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91X58"
FT MOD_RES 254
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250|UniProtKB:Q91X58"
FT LIPID 254
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q91X58"
FT VAR_SEQ 177..257
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018001"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:1X4V"
FT HELIX 124..127
FT /evidence="ECO:0007829|PDB:1X4V"
SQ SEQUENCE 257 AA; 28023 MW; E87D47744157F48C CRC64;
MEFPDLGAHC SEPSCQRLDF LPLKCDACSG IFCADHVAYA QHHCGSAYQK DIQVPVCPLC
NVPVPVARGE PPDRAVGEHI DRDCRSDPAQ QKRKIFTNKC ERAGCRQREM MKLTCERCSR
NFCIKHRHPL DHDCSGEGHP TSRAGLAAIS RAQAVASTST VPSPSQTMPS CTSPSRATTR
SPSWTAPPVI ALQNGLSEDE ALQRALEMSL AETKPQVPSC QEEEDLALAQ ALSASEAEYQ
RQQAQSRSSK PSNCSLC
