FAF2_HUMAN
ID FAF2_HUMAN Reviewed; 445 AA.
AC Q96CS3; O94963; Q8IUF2; Q9BRP2; Q9BVM7;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=FAS-associated factor 2;
DE AltName: Full=Protein ETEA;
DE AltName: Full=UBX domain-containing protein 3B;
DE AltName: Full=UBX domain-containing protein 8;
GN Name=FAF2; Synonyms=ETEA, KIAA0887, UBXD8, UBXN3B;
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], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=T-cell;
RX PubMed=12372427; DOI=10.1016/s0006-291x(02)02380-x;
RA Imai Y., Nakada A., Hashida R., Sugita Y., Tanaka T., Tsujimoto G.,
RA Matsumoto K., Akasawa A., Saito H., Oshida T.;
RT "Cloning and characterization of the highly expressed ETEA gene from blood
RT cells of atopic dermatitis patients.";
RL Biochem. Biophys. Res. Commun. 297:1282-1290(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Muscle;
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 3-445.
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [4]
RP IDENTIFICATION IN A COMPLEX WITH SEL1L, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=18711132; DOI=10.1073/pnas.0805371105;
RA Mueller B., Klemm E.J., Spooner E., Claessen J.H., Ploegh H.L.;
RT "SEL1L nucleates a protein complex required for dislocation of misfolded
RT glycoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12325-12330(2008).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=19773358; DOI=10.1242/jcs.054700;
RA Zehmer J.K., Bartz R., Bisel B., Liu P., Seemann J., Anderson R.G.W.;
RT "Targeting sequences of UBXD8 and AAM-B reveal that the ER has a direct
RT role in the emergence and regression of lipid droplets.";
RL J. Cell Sci. 122:3694-3702(2009).
RN [7]
RP INTERACTION WITH YOD1.
RX PubMed=19818707; DOI=10.1016/j.molcel.2009.09.016;
RA Ernst R., Mueller B., Ploegh H.L., Schlieker C.;
RT "The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to
RT facilitate protein dislocation from the ER.";
RL Mol. Cell 36:28-38(2009).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-167, 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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP FUNCTION, INTERACTION WITH PNPLA2 AND UBAC2, AND SUBCELLULAR LOCATION.
RX PubMed=23297223; DOI=10.1073/pnas.1213738110;
RA Olzmann J.A., Richter C.M., Kopito R.R.;
RT "Spatial regulation of UBXD8 and p97/VCP controls ATGL-mediated lipid
RT droplet turnover.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:1345-1350(2013).
RN [11]
RP INTERACTION WITH ZFAND2B.
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 [12]
RP FUNCTION, AND INTERACTION WITH UBQLN2.
RX PubMed=24215460; DOI=10.1111/jnc.12606;
RA Xia Y., Yan L.H., Huang B., Liu M., Liu X., Huang C.;
RT "Pathogenic mutation of UBQLN2 impairs its interaction with UBXD8 and
RT disrupts endoplasmic reticulum-associated protein degradation.";
RL J. Neurochem. 129:99-106(2014).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP FUNCTION.
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 [16]
RP INTERACTION WITH LMBR1L.
RX PubMed=31073040; DOI=10.1126/science.aau0812;
RA Choi J.H., Zhong X., McAlpine W., Liao T.C., Zhang D., Fang B., Russell J.,
RA Ludwig S., Nair-Gill E., Zhang Z., Wang K.W., Misawa T., Zhan X., Choi M.,
RA Wang T., Li X., Tang M., Sun Q., Yu L., Murray A.R., Moresco E.M.Y.,
RA Beutler B.;
RT "LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling.";
RL Science 364:0-0(2019).
RN [17]
RP STRUCTURE BY NMR OF 3-56.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the novel identified UBA-like domain in the N-
RT terminal of human ETEA protein.";
RL Submitted (JUN-2006) to the PDB data bank.
CC -!- FUNCTION: Plays an important role in endoplasmic reticulum-associated
CC degradation (ERAD) that mediates ubiquitin-dependent degradation of
CC misfolded endoplasmic reticulum proteins (PubMed:18711132,
CC PubMed:24215460). By controlling the steady-state expression of the
CC IGF1R receptor, indirectly regulates the insulin-like growth factor
CC receptor signaling pathway (PubMed:26692333). Involved in inhibition of
CC lipid droplet degradation by binding to phospholipase PNPL2 and
CC inhibiting its activity by promoting dissociation of PNPL2 from its
CC endogenous activator, ABHD5 which inhibits the rate of triacylglycerol
CC hydrolysis (PubMed:23297223). {ECO:0000269|PubMed:18711132,
CC ECO:0000269|PubMed:23297223, ECO:0000269|PubMed:24215460,
CC ECO:0000269|PubMed:26692333}.
CC -!- SUBUNIT: Identified in a complex that contains SEL1L, OS9, FAF2/UBXD8,
CC UBE2J1/UBC6E and AUP1 (PubMed:18711132). Interacts with YOD1
CC (PubMed:19818707). Interacts (via N-terminus) with UBQLN2 (via C-
CC terminus) (PubMed:24215460). Interacts with PNPLA2 and UBAC2
CC (PubMed:23297223). Interacts with ZFAND2B; probably through VCP
CC (PubMed:24160817). Interacts with LMBR1L (PubMed:31073040).
CC {ECO:0000269|PubMed:18711132, ECO:0000269|PubMed:19818707,
CC ECO:0000269|PubMed:23297223, ECO:0000269|PubMed:24160817,
CC ECO:0000269|PubMed:24215460, ECO:0000305|PubMed:31073040}.
CC -!- INTERACTION:
CC Q96CS3; Q8NBM4: UBAC2; NbExp=7; IntAct=EBI-1055805, EBI-724045;
CC Q96CS3; P55072: VCP; NbExp=13; IntAct=EBI-1055805, EBI-355164;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12372427}. Lipid
CC droplet {ECO:0000269|PubMed:19773358, ECO:0000269|PubMed:23297223}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:18711132,
CC ECO:0000269|PubMed:23297223}.
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in brain.
CC {ECO:0000269|PubMed:12372427}.
CC -!- MISCELLANEOUS: Up-regulated in T-cells and eosinophils from patients
CC with atopic dermatitis.
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DR EMBL; AB088120; BAC22491.1; -; mRNA.
DR EMBL; BC001069; AAH01069.2; -; mRNA.
DR EMBL; BC006145; AAH06145.2; -; mRNA.
DR EMBL; BC014001; AAH14001.2; -; mRNA.
DR EMBL; AB020694; BAA74910.1; -; mRNA.
DR CCDS; CCDS34296.1; -.
DR RefSeq; NP_055428.1; NM_014613.2.
DR PDB; 2DAM; NMR; -; A=3-56.
DR PDBsum; 2DAM; -.
DR AlphaFoldDB; Q96CS3; -.
DR BMRB; Q96CS3; -.
DR SMR; Q96CS3; -.
DR BioGRID; 116806; 413.
DR CORUM; Q96CS3; -.
DR DIP; DIP-46261N; -.
DR IntAct; Q96CS3; 171.
DR MINT; Q96CS3; -.
DR STRING; 9606.ENSP00000261942; -.
DR GlyGen; Q96CS3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96CS3; -.
DR MetOSite; Q96CS3; -.
DR PhosphoSitePlus; Q96CS3; -.
DR SwissPalm; Q96CS3; -.
DR BioMuta; FAF2; -.
DR DMDM; 74731375; -.
DR EPD; Q96CS3; -.
DR jPOST; Q96CS3; -.
DR MassIVE; Q96CS3; -.
DR MaxQB; Q96CS3; -.
DR PaxDb; Q96CS3; -.
DR PeptideAtlas; Q96CS3; -.
DR PRIDE; Q96CS3; -.
DR ProteomicsDB; 76214; -.
DR Antibodypedia; 29092; 208 antibodies from 35 providers.
DR DNASU; 23197; -.
DR Ensembl; ENST00000261942.7; ENSP00000261942.6; ENSG00000113194.13.
DR GeneID; 23197; -.
DR KEGG; hsa:23197; -.
DR MANE-Select; ENST00000261942.7; ENSP00000261942.6; NM_014613.3; NP_055428.1.
DR UCSC; uc003mej.4; human.
DR CTD; 23197; -.
DR DisGeNET; 23197; -.
DR GeneCards; FAF2; -.
DR HGNC; HGNC:24666; FAF2.
DR HPA; ENSG00000113194; Low tissue specificity.
DR MIM; 616935; gene.
DR neXtProt; NX_Q96CS3; -.
DR OpenTargets; ENSG00000113194; -.
DR PharmGKB; PA162385570; -.
DR VEuPathDB; HostDB:ENSG00000113194; -.
DR eggNOG; KOG1363; Eukaryota.
DR GeneTree; ENSGT00940000157197; -.
DR HOGENOM; CLU_047924_0_0_1; -.
DR InParanoid; Q96CS3; -.
DR OMA; HTLFWAC; -.
DR OrthoDB; 1251507at2759; -.
DR PhylomeDB; Q96CS3; -.
DR TreeFam; TF314172; -.
DR PathwayCommons; Q96CS3; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR SignaLink; Q96CS3; -.
DR BioGRID-ORCS; 23197; 296 hits in 1080 CRISPR screens.
DR ChiTaRS; FAF2; human.
DR EvolutionaryTrace; Q96CS3; -.
DR GenomeRNAi; 23197; -.
DR Pharos; Q96CS3; Tbio.
DR PRO; PR:Q96CS3; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q96CS3; protein.
DR Bgee; ENSG00000113194; Expressed in parotid gland and 201 other tissues.
DR ExpressionAtlas; Q96CS3; baseline and differential.
DR Genevisible; Q96CS3; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0034098; C:VCP-NPL4-UFD1 AAA ATPase complex; IDA:BHF-UCL.
DR GO; GO:0035473; F:lipase binding; IDA:MGI.
DR GO; GO:0055102; F:lipase inhibitor activity; IDA:MGI.
DR GO; GO:0043130; F:ubiquitin binding; IDA:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:BHF-UCL.
DR GO; GO:0034389; P:lipid droplet organization; IMP:MGI.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:UniProtKB.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR006577; UAS.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR001012; UBX_dom.
DR Pfam; PF00789; UBX; 1.
DR SMART; SM00594; UAS; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50033; UBX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Coiled coil; Cytoplasm; Endoplasmic reticulum;
KW Lipid droplet; Reference proteome; Unfolded protein response.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..445
FT /note="FAS-associated factor 2"
FT /id="PRO_0000244064"
FT DOMAIN 12..48
FT /note="UBA"
FT DOMAIN 357..439
FT /note="UBX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00215"
FT REGION 299..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 275..350
FT /evidence="ECO:0000255"
FT COMPBIAS 300..353
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 167
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT HELIX 11..24
FT /evidence="ECO:0007829|PDB:2DAM"
FT HELIX 29..39
FT /evidence="ECO:0007829|PDB:2DAM"
FT HELIX 43..52
FT /evidence="ECO:0007829|PDB:2DAM"
SQ SEQUENCE 445 AA; 52623 MW; D5510BCB0623096B CRC64;
MAAPEERDLT QEQTEKLLQF QDLTGIESMD QCRHTLEQHN WNIEAAVQDR LNEQEGVPSV
FNPPPSRPLQ VNTADHRIYS YVVSRPQPRG LLGWGYYLIM LPFRFTYYTI LDIFRFALRF
IRPDPRSRVT DPVGDIVSFM HSFEEKYGRA HPVFYQGTYS QALNDAKREL RFLLVYLHGD
DHQDSDEFCR NTLCAPEVIS LINTRMLFWA CSTNKPEGYR VSQALRENTY PFLAMIMLKD
RRMTVVGRLE GLIQPDDLIN QLTFIMDANQ TYLVSERLER EERNQTQVLR QQQDEAYLAS
LRADQEKERK KREERERKRR KEEEVQQQKL AEERRRQNLQ EEKERKLECL PPEPSPDDPE
SVKIIFKLPN DSRVERRFHF SQSLTVIHDF LFSLKESPEK FQIEANFPRR VLPCIPSEEW
PNPPTLQEAG LSHTEVLFVQ DLTDE
