ID   AFTIN_MOUSE             Reviewed;         931 AA.
AC   Q80WT5; Q5SSE6; Q99KJ1;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   29-MAR-2005, sequence version 2.
DT   24-JAN-2024, entry version 144.
DE   RecName: Full=Aftiphilin;
GN   Name=Aftph; Synonyms=Afth;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J; TISSUE=Brain, and Mammary gland;
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA   Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA   Thibault P.;
RT   "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL   Immunity 30:143-154(2009).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Component of clathrin-coated vesicles (By similarity).
CC       Component of the aftiphilin/p200/gamma-synergin complex, which plays
CC       roles in AP1G1/AP-1-mediated protein trafficking including the
CC       trafficking of transferrin from early to recycling endosomes, and the
CC       membrane trafficking of furin and the lysosomal enzyme cathepsin D
CC       between the trans-Golgi network (TGN) and endosomes (By similarity).
CC       {ECO:0000250|UniProtKB:Q6ULP2}.
CC   -!- SUBUNIT: Self-associates (By similarity). Interacts with GGA1 (via GAE
CC       domain) (By similarity). Interacts with GGA3 (via GAE domain), AP1G1
CC       (via GAE domain) and AP1G2 (via GAE domain) (By similarity). Component
CC       of the aftiphilin/p200/gamma-synergin complex, at least composed of
CC       AFTPH/aftiphilin, HEATR5B/p200a and SYNRG/gamma-synergin, which plays a
CC       role in the AP1G1/AP-1-mediated protein trafficking from early to
CC       recycling endosomes (By similarity). Within the complex interacts with
CC       HEATR5B/p200a and SYNRG/gamma-synergin; the interactions are direct (By
CC       similarity). Interacts with AP1G1/AP-1; the interaction is required to
CC       recruit AFTPH/aftiphilin to the perinuclear region of the cell (By
CC       similarity). Interacts with CLTCL1/Clathrin (By similarity).
CC       {ECO:0000250|UniProtKB:Q6ULP2}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6ULP2}.
CC       Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q6ULP2}.
CC       Cytoplasmic vesicle, clathrin-coated vesicle
CC       {ECO:0000250|UniProtKB:Q6ULP2}. Note=Co-localizes with AP1G1/AP-1 in
CC       the cytoplasm (By similarity). Recruited to the perinuclear region by
CC       AP1G1/AP-1 (By similarity). {ECO:0000250|UniProtKB:Q6ULP2}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q80WT5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q80WT5-2; Sequence=VSP_013242;
CC   -!- DOMAIN: The WXXF motifs mediate binding of accessory proteins to the
CC       ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions.
CC       Selective binding to the GAE domains of AP-1 or to the alpha-ear domain
CC       of AP-2 is tuned by the acidic context surrounding the motif and the
CC       properties of the second residue of the motif itself (By similarity).
CC       {ECO:0000250}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAI24910.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAI25738.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AL663115; CAI25737.1; -; Genomic_DNA.
DR   EMBL; AL645599; CAI25737.1; JOINED; Genomic_DNA.
DR   EMBL; AL663115; CAI25738.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AL645599; CAI25738.1; JOINED; Genomic_DNA.
DR   EMBL; AL645599; CAI24909.1; -; Genomic_DNA.
DR   EMBL; AL663115; CAI24909.1; JOINED; Genomic_DNA.
DR   EMBL; AL645599; CAI24910.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AL663115; CAI24910.1; JOINED; Genomic_DNA.
DR   EMBL; BC004630; AAH04630.1; -; mRNA.
DR   EMBL; BC052036; AAH52036.1; -; mRNA.
DR   CCDS; CCDS24459.1; -. [Q80WT5-2]
DR   CCDS; CCDS70146.1; -. [Q80WT5-1]
DR   RefSeq; NP_001239432.1; NM_001252503.2.
DR   RefSeq; NP_001277474.1; NM_001290545.1. [Q80WT5-1]
DR   RefSeq; NP_852076.1; NM_181411.4. [Q80WT5-2]
DR   AlphaFoldDB; Q80WT5; -.
DR   BioGRID; 229758; 3.
DR   MINT; Q80WT5; -.
DR   STRING; 10090.ENSMUSP00000121612; -.
DR   GlyGen; Q80WT5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q80WT5; -.
DR   PhosphoSitePlus; Q80WT5; -.
DR   SwissPalm; Q80WT5; -.
DR   EPD; Q80WT5; -.
DR   jPOST; Q80WT5; -.
DR   MaxQB; Q80WT5; -.
DR   PaxDb; 10090-ENSMUSP00000036778; -.
DR   PeptideAtlas; Q80WT5; -.
DR   ProteomicsDB; 285621; -. [Q80WT5-1]
DR   ProteomicsDB; 285622; -. [Q80WT5-2]
DR   Pumba; Q80WT5; -.
DR   Antibodypedia; 30831; 117 antibodies from 22 providers.
DR   DNASU; 216549; -.
DR   Ensembl; ENSMUST00000035350.12; ENSMUSP00000036778.6; ENSMUSG00000049659.16. [Q80WT5-2]
DR   Ensembl; ENSMUST00000146722.9; ENSMUSP00000121612.3; ENSMUSG00000049659.16. [Q80WT5-1]
DR   GeneID; 216549; -.
DR   KEGG; mmu:216549; -.
DR   UCSC; uc007idh.3; mouse. [Q80WT5-2]
DR   UCSC; uc056yjx.1; mouse. [Q80WT5-1]
DR   AGR; MGI:1923012; -.
DR   CTD; 54812; -.
DR   MGI; MGI:1923012; Aftph.
DR   VEuPathDB; HostDB:ENSMUSG00000049659; -.
DR   eggNOG; ENOG502QPXF; Eukaryota.
DR   GeneTree; ENSGT00940000154186; -.
DR   HOGENOM; CLU_017041_0_0_1; -.
DR   InParanoid; Q80WT5; -.
DR   OMA; SDQHLYQ; -.
DR   OrthoDB; 5402549at2759; -.
DR   PhylomeDB; Q80WT5; -.
DR   TreeFam; TF331532; -.
DR   BioGRID-ORCS; 216549; 3 hits in 76 CRISPR screens.
DR   ChiTaRS; Aftph; mouse.
DR   PRO; PR:Q80WT5; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; Q80WT5; Protein.
DR   Bgee; ENSMUSG00000049659; Expressed in dentate gyrus of hippocampal formation granule cell and 243 other cell types or tissues.
DR   ExpressionAtlas; Q80WT5; baseline and differential.
DR   GO; GO:0030121; C:AP-1 adaptor complex; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0032588; C:trans-Golgi network membrane; IBA:GO_Central.
DR   GO; GO:0030276; F:clathrin binding; ISO:MGI.
DR   GO; GO:0046907; P:intracellular transport; IBA:GO_Central.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   InterPro; IPR046359; Aftin-like.
DR   InterPro; IPR029205; Clathrin-bd.
DR   PANTHER; PTHR16156:SF9; AFTIPHILIN; 1.
DR   PANTHER; PTHR16156; AFTIPHILIN A-RELATED; 1.
DR   Pfam; PF15045; Clathrin_bdg; 1.
DR   Genevisible; Q80WT5; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Cytoplasmic vesicle; Phosphoprotein;
KW   Protein transport; Reference proteome; Repeat; Transport.
FT   CHAIN           1..931
FT                   /note="Aftiphilin"
FT                   /id="PRO_0000064489"
FT   REGION          1..49
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          371..454
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          494..561
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          599..636
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          821..825
FT                   /note="Clathrin-binding"
FT                   /evidence="ECO:0000255"
FT   MOTIF           28..31
FT                   /note="WXXF motif 1"
FT   MOTIF           433..436
FT                   /note="WXXF motif 2"
FT   MOTIF           476..479
FT                   /note="WXXF motif 3"
FT   MOTIF           712..714
FT                   /note="CLTCL1/Clathrin-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q6ULP2"
FT   COMPBIAS        379..393
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        405..425
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        518..532
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        535..561
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        602..627
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         151
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6ULP2"
FT   MOD_RES         395
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT   MOD_RES         613
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6ULP2"
FT   VAR_SEQ         815..841
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_013242"
SQ   SEQUENCE   931 AA;  101131 MW;  FE1C64F3B7270620 CRC64;
     MEPDIIRMYS SSPPPLDNGA EDDEEDEFGE FGGFSEVSPS GVGFVDFDTP DYTRPKEDFV
     PSNHFMPIHE YSEDVDSLTS FKSVQNGNDK DITAELSTPV KSQSDVVLST TSKEMIPSKT
     LDPSIDGMES LEDLDKVVVQ GPSTGQLRSF SPGDFRTDKN IVHQTKQLES CNGEKPPCLE
     ILTNGFAGLE TVNPQGTDDL DNVADSKGSK PLNTCGTECI LESAASHATE FADFSTFSQT
     ERTQLEEIEC PVLNDGDTLT IQGNSKGPRV KELNCVKEVT LDGSFEDTGN TEREHQVCVS
     EIHAVADRGL SVEKQDLQTL QQDEFLNSRI QSEAWSLVDS SENSEAITKE RCKMEKNDLF
     ASKCADLSMD SVKTSDVNEI GSSKEENRKL TNPKSPDPDP TGQNALDDSA ASMKNGDSGN
     GFVTCHDTNE DDFGDFGTAN GTTPPFVTST QDSMSDVTFE DSSEHFLHLS EPGDDFGEFE
     DTNAVSCQEE MRFTESDLRQ TSDGLSEECP LAGESGGKDS KPDSKLKNGQ DSEFGDFDSV
     PNTQGSAFQD SDDFADFSSA GPSQAVDWNA FEDEQKDGCS WAAFGDQQET ESHHLKEVWQ
     SQRTDETMGT LGTPKMHSVS SAASKGAVAS GHLQEPGTSV QTALLNRLER IFEACFPSVF
     VPDVEEEVSS LKHLLETHSS PAKTREALAD RGELRGVWTE LQDIHDAHGL RYQWGGSHSN
     KKLLCSLGID TRNILFTGNK KQPVIVPMYA AGLGMLEPTK EPLKPLSAAE KIASIGQTTV
     MTPEINTCTS DPFQESLPPV QFDWSSSGLT NPLDASGGST LLNLDFFGPV DDSSSSSSTI
     PGVDPELYEL TTAKLETSTS SLRVTDAFAK LMSTVEKTST STRKPKREEH LSEEAMKVIA
     SLPDLTFMHA KVLMFPATLT PSMSSQEQAD A
//