AKTIP_HUMAN
ID AKTIP_HUMAN Reviewed; 292 AA.
AC Q9H8T0; Q503B1; Q53H38;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=AKT-interacting protein {ECO:0000305};
DE AltName: Full=Ft1;
DE AltName: Full=Fused toes protein homolog;
GN Name=AKTIP {ECO:0000312|HGNC:HGNC:16710};
GN Synonyms=FTS {ECO:0000303|PubMed:32073997};
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 1).
RC TISSUE=Ovary;
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=Placenta;
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Dermoid cancer;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin;
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 [6]
RP FUNCTION, INTERACTION WITH AKT1, AND SUBCELLULAR LOCATION.
RX PubMed=14749367; DOI=10.1128/mcb.24.4.1493-1504.2004;
RA Remy I., Michnick S.W.;
RT "Regulation of apoptosis by the Ft1 protein, a new modulator of protein
RT kinase B/Akt.";
RL Mol. Cell. Biol. 24:1493-1504(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE FHF COMPLEX,
RP FUNCTION, ASSOCIATION WITH THE HOPS COMPLEX, AND MUTAGENESIS OF
RP 106-TRP-PHE-107.
RX PubMed=18799622; DOI=10.1091/mbc.e08-05-0473;
RA Xu L., Sowa M.E., Chen J., Li X., Gygi S.P., Harper J.W.;
RT "An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal
RT clustering by the homotypic vacuolar protein sorting complex.";
RL Mol. Biol. Cell 19:5059-5071(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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).
RN [9]
RP FUNCTION, INTERACTION WITH HOOK1; FHIP1A AND FHIP1B, AND MUTAGENESIS OF
RP 106-TRP-PHE-107.
RX PubMed=32073997; DOI=10.1091/mbc.e19-11-0658;
RA Mattera R., Williamson C.D., Ren X., Bonifacino J.S.;
RT "The FTS-Hook-FHIP (FHF) complex interacts with AP-4 to mediate perinuclear
RT distribution of AP-4 and its cargo ATG9A.";
RL Mol. Biol. Cell 31:963-979(2020).
CC -!- FUNCTION: Component of the FTS/Hook/FHIP complex (FHF complex)
CC (PubMed:32073997). The FHF complex may function to promote vesicle
CC trafficking and/or fusion via the homotypic vesicular protein sorting
CC complex (the HOPS complex). Regulates apoptosis by enhancing
CC phosphorylation and activation of AKT1. Increases release of TNFSF6 via
CC the AKT1/GSK3B/NFATC1 signaling cascade. FHF complex promotes the
CC distribution of AP-4 complex to the perinuclear area of the cell
CC (PubMed:32073997). {ECO:0000269|PubMed:14749367,
CC ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:32073997}.
CC -!- SUBUNIT: Component of the FTS/Hook/FHIP complex (FHF complex), composed
CC of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of
CC proteins HOOK1, HOOK2, and HOOK3. Interacts directly with HOOK1, HOOK2
CC and HOOK3 (PubMed:18799622, PubMed:32073997). The FHF complex
CC associates with the homotypic vesicular sorting complex (the HOPS
CC complex) (PubMed:18799622). Also interacts with AKT1. May interact with
CC FHIP1A (PubMed:32073997). {ECO:0000269|PubMed:14749367,
CC ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:32073997}.
CC -!- INTERACTION:
CC Q9H8T0; Q9UJC3: HOOK1; NbExp=6; IntAct=EBI-711399, EBI-746704;
CC Q9H8T0; Q96ED9: HOOK2; NbExp=3; IntAct=EBI-711399, EBI-743290;
CC Q9H8T0; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-711399, EBI-10961706;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14749367}. Cell
CC membrane {ECO:0000269|PubMed:14749367}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14749367}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H8T0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H8T0-2; Sequence=VSP_037631;
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. FTS
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC -!- CAUTION: Lacks the conserved Cys residue necessary for ubiquitin-
CC conjugating enzyme E2 activity. {ECO:0000305}.
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DR EMBL; AK023320; BAB14524.1; -; mRNA.
DR EMBL; CR457308; CAG33589.1; -; mRNA.
DR EMBL; AK222743; BAD96463.1; -; mRNA.
DR EMBL; CH471092; EAW82805.1; -; Genomic_DNA.
DR EMBL; BC001134; AAH01134.1; -; mRNA.
DR EMBL; BC095401; AAH95401.1; -; mRNA.
DR CCDS; CCDS10749.1; -. [Q9H8T0-1]
DR CCDS; CCDS76866.1; -. [Q9H8T0-2]
DR RefSeq; NP_001012398.1; NM_001012398.2. [Q9H8T0-1]
DR RefSeq; NP_001295254.1; NM_001308325.1. [Q9H8T0-2]
DR RefSeq; NP_071921.1; NM_022476.3. [Q9H8T0-1]
DR RefSeq; XP_005256152.1; XM_005256095.4. [Q9H8T0-2]
DR RefSeq; XP_005256153.1; XM_005256096.4. [Q9H8T0-2]
DR RefSeq; XP_005256154.1; XM_005256097.4. [Q9H8T0-2]
DR RefSeq; XP_005256155.1; XM_005256098.4. [Q9H8T0-2]
DR RefSeq; XP_016879053.1; XM_017023564.1. [Q9H8T0-1]
DR RefSeq; XP_016879054.1; XM_017023565.1. [Q9H8T0-1]
DR RefSeq; XP_016879055.1; XM_017023566.1. [Q9H8T0-1]
DR AlphaFoldDB; Q9H8T0; -.
DR SMR; Q9H8T0; -.
DR BioGRID; 122157; 103.
DR CORUM; Q9H8T0; -.
DR IntAct; Q9H8T0; 36.
DR STRING; 9606.ENSP00000378152; -.
DR iPTMnet; Q9H8T0; -.
DR PhosphoSitePlus; Q9H8T0; -.
DR BioMuta; AKTIP; -.
DR DMDM; 54035954; -.
DR EPD; Q9H8T0; -.
DR jPOST; Q9H8T0; -.
DR MassIVE; Q9H8T0; -.
DR MaxQB; Q9H8T0; -.
DR PaxDb; Q9H8T0; -.
DR PeptideAtlas; Q9H8T0; -.
DR PRIDE; Q9H8T0; -.
DR ProteomicsDB; 81239; -. [Q9H8T0-1]
DR ProteomicsDB; 81240; -. [Q9H8T0-2]
DR Antibodypedia; 28404; 281 antibodies from 28 providers.
DR DNASU; 64400; -.
DR Ensembl; ENST00000300245.8; ENSP00000300245.4; ENSG00000166971.17. [Q9H8T0-2]
DR Ensembl; ENST00000394657.12; ENSP00000378152.6; ENSG00000166971.17. [Q9H8T0-1]
DR Ensembl; ENST00000570004.5; ENSP00000455874.1; ENSG00000166971.17. [Q9H8T0-1]
DR GeneID; 64400; -.
DR KEGG; hsa:64400; -.
DR MANE-Select; ENST00000394657.12; ENSP00000378152.6; NM_022476.4; NP_071921.1.
DR UCSC; uc002ehk.4; human. [Q9H8T0-1]
DR CTD; 64400; -.
DR DisGeNET; 64400; -.
DR GeneCards; AKTIP; -.
DR HGNC; HGNC:16710; AKTIP.
DR HPA; ENSG00000166971; Low tissue specificity.
DR MIM; 608483; gene.
DR neXtProt; NX_Q9H8T0; -.
DR OpenTargets; ENSG00000166971; -.
DR PharmGKB; PA162376210; -.
DR VEuPathDB; HostDB:ENSG00000166971; -.
DR eggNOG; KOG0429; Eukaryota.
DR GeneTree; ENSGT00390000010125; -.
DR HOGENOM; CLU_083049_0_0_1; -.
DR InParanoid; Q9H8T0; -.
DR OMA; WGFPEWR; -.
DR PhylomeDB; Q9H8T0; -.
DR TreeFam; TF314386; -.
DR PathwayCommons; Q9H8T0; -.
DR SignaLink; Q9H8T0; -.
DR BioGRID-ORCS; 64400; 86 hits in 1042 CRISPR screens.
DR ChiTaRS; AKTIP; human.
DR GeneWiki; AKTIP; -.
DR GenomeRNAi; 64400; -.
DR Pharos; Q9H8T0; Tbio.
DR PRO; PR:Q9H8T0; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9H8T0; protein.
DR Bgee; ENSG00000166971; Expressed in secondary oocyte and 206 other tissues.
DR ExpressionAtlas; Q9H8T0; baseline and differential.
DR Genevisible; Q9H8T0; HS.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0070695; C:FHF complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0045022; P:early endosome to late endosome transport; IMP:UniProtKB.
DR GO; GO:0007032; P:endosome organization; IMP:UniProtKB.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; IMP:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:1905719; P:protein localization to perinuclear region of cytoplasm; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cell membrane; Cytoplasm; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..292
FT /note="AKT-interacting protein"
FT /id="PRO_0000082609"
FT DOMAIN 74..222
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT REGION 1..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 256
FT /note="Q -> QK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT /id="VSP_037631"
FT MUTAGEN 106..107
FT /note="WF->AA: Impairs interaction with FHIP1B, HOOK1,
FT HOOK2 and HOOK3."
FT /evidence="ECO:0000269|PubMed:18799622,
FT ECO:0000269|PubMed:32073997"
FT CONFLICT 212
FT /note="K -> N (in Ref. 5; AAH95401)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 292 AA; 33128 MW; 3DD4E32980463324 CRC64;
MNPFWSMSTS SVRKRSEGEE KTLTGDVKTS PPRTAPKKQL PSIPKNALPI TKPTSPAPAA
QSTNGTHASY GPFYLEYSLL AEFTLVVKQK LPGVYVQPSY RSALMWFGVI FIRHGLYQDG
VFKFTVYIPD NYPDGDCPRL VFDIPVFHPL VDPTSGELDV KRAFAKWRRN HNHIWQVLMY
ARRVFYKIDT ASPLNPEAAV LYEKDIQLFK SKVVDSVKVC TARLFDQPKI EDPYAISFSP
WNPSVHDEAR EKMLTQKKPE EQHNKSVHVA GLSWVKPGSV QPFSKEEKTV AT
