ID   SESQ2_HUMAN             Reviewed;         259 AA.
AC   Q6ICB4; Q3SXQ3; Q8N6L9;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   24-JAN-2024, entry version 137.
DE   RecName: Full=Sesquipedalian-2 {ECO:0000305|PubMed:20133602};
DE            Short=Ses2 {ECO:0000305|PubMed:20133602};
DE   AltName: Full=27 kDa inositol polyphosphate phosphatase interacting protein B;
DE            Short=IPIP27B;
DE   AltName: Full=PH domain-containing endocytic trafficking adaptor 2 {ECO:0000305};
GN   Name=PHETA2 {ECO:0000312|HGNC:HGNC:27161};
GN   Synonyms=FAM109B {ECO:0000312|HGNC:HGNC:27161};
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].
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA   Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA   Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA   Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA   Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA   Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA   Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA   Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA   Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA   Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA   Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA   Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA   Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA   Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA   Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA   Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA   Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA   Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA   Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA   Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA   Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA   Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA   Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA   Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA   Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA   Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA   Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA   McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA   Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA   Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA   Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA   Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-188.
RC   TISSUE=Colon;
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   [4]
RP   INTERACTION WITH OCRL, F&H MOTIF, AND SUBCELLULAR LOCATION.
RX   PubMed=20133602; DOI=10.1073/pnas.0914658107;
RA   Swan L.E., Tomasini L., Pirruccello M., Lunardi J., De Camilli P.;
RT   "Two closely related endocytic proteins that share a common OCRL-binding
RT   motif with APPL1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:3511-3516(2010).
RN   [5]
RP   FUNCTION, INTERACTION WITH OCRL AND INPP5B, SUBUNIT, SUBCELLULAR LOCATION,
RP   AND MUTAGENESIS OF PHE-224; HIS-228 AND 234-GLU-ILE-235.
RX   PubMed=21233288; DOI=10.1091/mbc.e10-08-0730;
RA   Noakes C.J., Lee G., Lowe M.;
RT   "The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in
RT   the endocytic pathway.";
RL   Mol. Biol. Cell 22:606-623(2011).
CC   -!- FUNCTION: Plays a role in endocytic trafficking. Required for receptor
CC       recycling from endosomes, both to the trans-Golgi network and the
CC       plasma membrane. {ECO:0000269|PubMed:21233288}.
CC   -!- SUBUNIT: Forms homodimers and heterodimers with PHETA1. Interacts with
CC       OCRL and INPP5B. {ECO:0000269|PubMed:20133602,
CC       ECO:0000269|PubMed:21233288}.
CC   -!- INTERACTION:
CC       Q6ICB4; Q5SYC1: CLVS2; NbExp=3; IntAct=EBI-11081747, EBI-12357161;
CC       Q6ICB4; Q01968-2: OCRL; NbExp=6; IntAct=EBI-11081747, EBI-11749425;
CC       Q6ICB4; Q8N4B1-4: PHETA1; NbExp=5; IntAct=EBI-11081747, EBI-14131832;
CC       Q6ICB4; Q9NW61: PLEKHJ1; NbExp=4; IntAct=EBI-11081747, EBI-1057560;
CC   -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:21233288}.
CC       Recycling endosome {ECO:0000269|PubMed:21233288}. Golgi apparatus,
CC       trans-Golgi network {ECO:0000269|PubMed:21233288}. Cytoplasmic vesicle,
CC       clathrin-coated vesicle {ECO:0000269|PubMed:21233288}. Note=Also found
CC       on macropinosomes. Not detected in late endosomes, nor in lysosomes.
CC       {ECO:0000269|PubMed:20133602, ECO:0000269|PubMed:21233288}.
CC   -!- DOMAIN: The F&H motif, an approximately 12-13 amino-acid sequence
CC       centered around Phe and His residues, is essential for binding to OCRL
CC       and INPP5B. {ECO:0000250|UniProtKB:Q8N4B1}.
CC   -!- MISCELLANEOUS: Was named after 'sesquipedalian', an unnecessarily long
CC       description of a simple thing. {ECO:0000305|PubMed:20133602}.
CC   -!- SIMILARITY: Belongs to the sesquipedalian family. {ECO:0000305}.
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DR   EMBL; CR456454; CAG30340.1; -; mRNA.
DR   EMBL; Z99716; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; Z82192; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC029776; AAH29776.1; -; mRNA.
DR   EMBL; BC104175; AAI04176.1; -; mRNA.
DR   EMBL; BC104176; AAI04177.1; -; mRNA.
DR   CCDS; CCDS33655.1; -.
DR   RefSeq; NP_001002034.2; NM_001002034.2.
DR   RefSeq; XP_005261430.1; XM_005261373.3.
DR   AlphaFoldDB; Q6ICB4; -.
DR   SMR; Q6ICB4; -.
DR   BioGRID; 127287; 15.
DR   ELM; Q6ICB4; -.
DR   IntAct; Q6ICB4; 9.
DR   MINT; Q6ICB4; -.
DR   STRING; 9606.ENSP00000312753; -.
DR   iPTMnet; Q6ICB4; -.
DR   PhosphoSitePlus; Q6ICB4; -.
DR   BioMuta; FAM109B; -.
DR   DMDM; 74757717; -.
DR   EPD; Q6ICB4; -.
DR   jPOST; Q6ICB4; -.
DR   MassIVE; Q6ICB4; -.
DR   MaxQB; Q6ICB4; -.
DR   PaxDb; 9606-ENSP00000312753; -.
DR   PeptideAtlas; Q6ICB4; -.
DR   ProteomicsDB; 66383; -.
DR   Pumba; Q6ICB4; -.
DR   Antibodypedia; 270; 41 antibodies from 11 providers.
DR   DNASU; 150368; -.
DR   Ensembl; ENST00000321753.8; ENSP00000312753.3; ENSG00000177096.9.
DR   GeneID; 150368; -.
DR   KEGG; hsa:150368; -.
DR   MANE-Select; ENST00000321753.8; ENSP00000312753.3; NM_001002034.3; NP_001002034.2.
DR   UCSC; uc003bbz.4; human.
DR   AGR; HGNC:27161; -.
DR   CTD; 150368; -.
DR   DisGeNET; 150368; -.
DR   GeneCards; PHETA2; -.
DR   HGNC; HGNC:27161; PHETA2.
DR   HPA; ENSG00000177096; Low tissue specificity.
DR   MIM; 614240; gene.
DR   neXtProt; NX_Q6ICB4; -.
DR   OpenTargets; ENSG00000177096; -.
DR   PharmGKB; PA143485467; -.
DR   VEuPathDB; HostDB:ENSG00000177096; -.
DR   eggNOG; ENOG502QQ94; Eukaryota.
DR   GeneTree; ENSGT00940000162686; -.
DR   HOGENOM; CLU_060423_0_1_1; -.
DR   InParanoid; Q6ICB4; -.
DR   OMA; WELQGPT; -.
DR   OrthoDB; 5483476at2759; -.
DR   PhylomeDB; Q6ICB4; -.
DR   TreeFam; TF326731; -.
DR   PathwayCommons; Q6ICB4; -.
DR   SignaLink; Q6ICB4; -.
DR   BioGRID-ORCS; 150368; 15 hits in 1148 CRISPR screens.
DR   GenomeRNAi; 150368; -.
DR   Pharos; Q6ICB4; Tbio.
DR   PRO; PR:Q6ICB4; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; Q6ICB4; Protein.
DR   Bgee; ENSG00000177096; Expressed in stromal cell of endometrium and 148 other cell types or tissues.
DR   ExpressionAtlas; Q6ICB4; baseline and differential.
DR   GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IEA:GOC.
DR   GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR   GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR   GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR   GO; GO:0007032; P:endosome organization; IMP:UniProtKB.
DR   GO; GO:0001881; P:receptor recycling; IMP:UniProtKB.
DR   GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   InterPro; IPR045188; Boi1/Boi2-like.
DR   InterPro; IPR011993; PH-like_dom_sf.
DR   InterPro; IPR001849; PH_domain.
DR   PANTHER; PTHR22902; SESQUIPEDALIAN; 1.
DR   PANTHER; PTHR22902:SF15; SESQUIPEDALIAN-2; 1.
DR   Pfam; PF00169; PH; 1.
DR   SMART; SM00233; PH; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   Genevisible; Q6ICB4; HS.
PE   1: Evidence at protein level;
KW   Coiled coil; Cytoplasmic vesicle; Endosome; Golgi apparatus;
KW   Reference proteome.
FT   CHAIN           1..259
FT                   /note="Sesquipedalian-2"
FT                   /id="PRO_0000254133"
FT   DOMAIN          17..121
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT   COILED          124..149
FT                   /evidence="ECO:0000255"
FT   MOTIF           223..235
FT                   /note="F&H"
FT   VARIANT         188
FT                   /note="A -> G (in dbSNP:rs1807493)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_028822"
FT   MUTAGEN         224
FT                   /note="F->A: Loss of OCRL-binding."
FT                   /evidence="ECO:0000269|PubMed:21233288"
FT   MUTAGEN         228
FT                   /note="H->A: Loss of OCRL-binding."
FT                   /evidence="ECO:0000269|PubMed:21233288"
FT   MUTAGEN         234..235
FT                   /note="EI->AA: Loss of OCRL-binding."
FT                   /evidence="ECO:0000269|PubMed:21233288"
SQ   SEQUENCE   259 AA;  28338 MW;  F82FDD0D2314BB0F CRC64;
     MKLNERSVAH YALSDSPADH MGFLRTWGGP GTPPTPSGTG RRCWFVLKGN LLFSFESREG
     RAPLSLVVLE GCTVELAEAP VPEEFAFAIC FDAPGVRPHL LAAEGPAAQE AWVKVLSRAS
     FGYMRLVVRE LESQLQDARQ SLALQRRSSW KSVASRCKPQ APNHRAAGLE NGHCLSKDSS
     PVGLVEEAGS RSAGWGLAEW ELQGPASLLL GKGQSPVSPE TSCFSTLHDW YGQEIVELRQ
     CWQKRAQGSH SKCEEQDRP
//