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   24-JAN-2024, entry version 171.
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; Q05DH4: FHIP1A; NbExp=3; IntAct=EBI-711399, EBI-21303726;
CC       Q9H8T0; Q9UJC3: HOOK1; NbExp=8; IntAct=EBI-711399, EBI-746704;
CC       Q9H8T0; Q96ED9: HOOK2; NbExp=6; IntAct=EBI-711399, EBI-743290;
CC       Q9H8T0; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-711399, EBI-10961706;
CC       Q9H8T0; Q86VS8: HOOK3; NbExp=3; IntAct=EBI-711399, EBI-1777078;
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; 106.
DR   ComplexPortal; CPX-2353; FTS-Hook-FHIP cargo adaptor complex, FHIP1A-HOOK1/3 variant.
DR   ComplexPortal; CPX-2356; FTS-Hook-FHIP cargo adaptor complex, FHIP1B-HOOK1/3 variant.
DR   ComplexPortal; CPX-2357; FTS-Hook-FHIP cargo adaptor complex, FHIP2A-HOOK2 variant.
DR   ComplexPortal; CPX-2359; FTS-Hook-FHIP cargo adaptor complex, FHIP2B-HOOK1/2/3 variant.
DR   CORUM; Q9H8T0; -.
DR   IntAct; Q9H8T0; 38.
DR   STRING; 9606.ENSP00000300245; -.
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; 9606-ENSP00000378152; -.
DR   PeptideAtlas; Q9H8T0; -.
DR   ProteomicsDB; 81239; -. [Q9H8T0-1]
DR   ProteomicsDB; 81240; -. [Q9H8T0-2]
DR   Pumba; Q9H8T0; -.
DR   Antibodypedia; 28404; 310 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   AGR; HGNC:16710; -.
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; QVLKYMQ; -.
DR   OrthoDB; 8595at2759; -.
DR   PhylomeDB; Q9H8T0; -.
DR   TreeFam; TF314386; -.
DR   PathwayCommons; Q9H8T0; -.
DR   SignaLink; Q9H8T0; -.
DR   BioGRID-ORCS; 64400; 87 hits in 1120 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 208 other cell types or tissues.
DR   ExpressionAtlas; Q9H8T0; baseline and differential.
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:0019788; F:NEDD8 transferase 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:0045116; P:protein neddylation; IBA:GO_Central.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1.
DR   InterPro; IPR000608; UBQ-conjugat_E2.
DR   InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR   PANTHER; PTHR24067:SF294; PROTEIN CROSSBRONX-RELATED; 1.
DR   PANTHER; PTHR24067; UBIQUITIN-CONJUGATING ENZYME E2; 1.
DR   Pfam; PF00179; UQ_con; 1.
DR   SMART; SM00212; UBCc; 1.
DR   SUPFAM; SSF54495; UBC-like; 1.
DR   PROSITE; PS50127; UBC_2; 1.
DR   Genevisible; Q9H8T0; HS.
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
//