PSD1_HUMAN
ID PSD1_HUMAN Reviewed; 1024 AA.
AC A5PKW4; B1AKX7; D3DR87; Q15673; Q8IVG0;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=PH and SEC7 domain-containing protein 1;
DE AltName: Full=Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6;
DE Short=Exchange factor for ARF6;
DE AltName: Full=Exchange factor for ARF6 A;
DE AltName: Full=Pleckstrin homology and SEC7 domain-containing protein 1;
GN Name=PSD;
GN Synonyms=EFA6, EFA6A {ECO:0000303|PubMed:23603394}, KIAA2011, PSD1, TYL;
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] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9417912; DOI=10.1006/geno.1997.5022;
RA Perletti L., Talarico D., Trecca D., Ronchetti D., Fracchiolla N.S.,
RA Maiolo A.T., Neri A.;
RT "Identification of a novel gene, PSD, adjacent to NFKB2/lyt-10, which
RT contains Sec7 and pleckstrin-homology domains.";
RL Genomics 46:251-259(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Nagase T., Kikuno R., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-621 AND
RP 765-ARG-LYS-766.
RX PubMed=23603394; DOI=10.1016/j.febslet.2013.03.042;
RA Ueda T., Hanai A., Takei T., Kubo K., Ohgi M., Sakagami H., Takahashi S.,
RA Shin H.W., Nakayama K.;
RT "EFA6 activates Arf6 and participates in its targeting to the Flemming body
RT during cytokinesis.";
RL FEBS Lett. 587:1617-1623(2013).
CC -!- FUNCTION: Guanine nucleotide exchange factor for ARF6
CC (PubMed:23603394). Induces cytoskeletal remodeling (By similarity).
CC {ECO:0000250|UniProtKB:Q5DTT2, ECO:0000269|PubMed:23603394}.
CC -!- SUBUNIT: Interacts with ACTN1. Interacts (ARF6-bound form) with KCNK1;
CC does not interact with KCNK1 in the absence of ARF6 (By similarity).
CC {ECO:0000250|UniProtKB:Q5DTT2}.
CC -!- INTERACTION:
CC A5PKW4; P70398: Usp9x; Xeno; NbExp=3; IntAct=EBI-719999, EBI-2214043;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23603394}. Cell
CC projection, ruffle membrane {ECO:0000269|PubMed:23603394}. Cleavage
CC furrow {ECO:0000269|PubMed:23603394}. Note=Distributed uniformly on the
CC plasma membrane, as well as throughout the cytoplasm during metaphase.
CC Subsequently concentrated at patches in the equatorial region at the
CC onset of cytokinesis, and becomes distributed in the equatorial region
CC concurrent with cleavage furrow ingression. In later cytokinesis
CC phases, fades away from the cleavage furrow and becomes uniformly
CC distributed throughout the plasma membrane.
CC {ECO:0000269|PubMed:23603394}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms may exist.;
CC Name=1;
CC IsoId=A5PKW4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A5PKW4-2; Sequence=VSP_031186;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed in the brain.
CC {ECO:0000269|PubMed:9417912}.
CC -!- SIMILARITY: Belongs to the PSD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC23107.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X99688; CAA68002.1; -; mRNA.
DR EMBL; AB095931; BAC23107.1; ALT_INIT; mRNA.
DR EMBL; AL121928; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49693.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49694.1; -; Genomic_DNA.
DR EMBL; BC142643; AAI42644.1; -; mRNA.
DR EMBL; BC142689; AAI42690.1; -; mRNA.
DR CCDS; CCDS31272.1; -. [A5PKW4-1]
DR CCDS; CCDS73187.1; -. [A5PKW4-2]
DR PIR; G01205; G01205.
DR RefSeq; NP_001257894.1; NM_001270965.1. [A5PKW4-1]
DR RefSeq; NP_001257895.1; NM_001270966.1. [A5PKW4-2]
DR RefSeq; NP_002770.3; NM_002779.4. [A5PKW4-1]
DR RefSeq; XP_011538270.1; XM_011539968.1. [A5PKW4-1]
DR RefSeq; XP_011538271.1; XM_011539969.2. [A5PKW4-1]
DR RefSeq; XP_016871922.1; XM_017016433.1. [A5PKW4-1]
DR RefSeq; XP_016871923.1; XM_017016434.1. [A5PKW4-1]
DR AlphaFoldDB; A5PKW4; -.
DR SMR; A5PKW4; -.
DR BioGRID; 111641; 4.
DR IntAct; A5PKW4; 13.
DR MINT; A5PKW4; -.
DR STRING; 9606.ENSP00000020673; -.
DR ChEMBL; CHEMBL4523105; -.
DR DrugCentral; A5PKW4; -.
DR iPTMnet; A5PKW4; -.
DR PhosphoSitePlus; A5PKW4; -.
DR BioMuta; PSD; -.
DR jPOST; A5PKW4; -.
DR MassIVE; A5PKW4; -.
DR PaxDb; A5PKW4; -.
DR PeptideAtlas; A5PKW4; -.
DR PRIDE; A5PKW4; -.
DR ProteomicsDB; 723; -. [A5PKW4-1]
DR ProteomicsDB; 724; -. [A5PKW4-2]
DR Antibodypedia; 31428; 54 antibodies from 17 providers.
DR DNASU; 5662; -.
DR Ensembl; ENST00000020673.6; ENSP00000020673.5; ENSG00000059915.17. [A5PKW4-1]
DR Ensembl; ENST00000406432.5; ENSP00000384830.1; ENSG00000059915.17. [A5PKW4-1]
DR Ensembl; ENST00000611678.4; ENSP00000481250.1; ENSG00000059915.17. [A5PKW4-2]
DR GeneID; 5662; -.
DR KEGG; hsa:5662; -.
DR MANE-Select; ENST00000020673.6; ENSP00000020673.5; NM_002779.5; NP_002770.3.
DR UCSC; uc001kvg.3; human. [A5PKW4-1]
DR CTD; 5662; -.
DR DisGeNET; 5662; -.
DR GeneCards; PSD; -.
DR HGNC; HGNC:9507; PSD.
DR HPA; ENSG00000059915; Tissue enhanced (brain, intestine).
DR MIM; 602327; gene.
DR neXtProt; NX_A5PKW4; -.
DR OpenTargets; ENSG00000059915; -.
DR PharmGKB; PA33854; -.
DR VEuPathDB; HostDB:ENSG00000059915; -.
DR eggNOG; KOG0932; Eukaryota.
DR GeneTree; ENSGT00940000155061; -.
DR HOGENOM; CLU_011021_4_0_1; -.
DR InParanoid; A5PKW4; -.
DR OMA; PLRCYHE; -.
DR OrthoDB; 301851at2759; -.
DR PhylomeDB; A5PKW4; -.
DR TreeFam; TF319755; -.
DR PathwayCommons; A5PKW4; -.
DR SignaLink; A5PKW4; -.
DR BioGRID-ORCS; 5662; 13 hits in 1070 CRISPR screens.
DR ChiTaRS; PSD; human.
DR GenomeRNAi; 5662; -.
DR Pharos; A5PKW4; Tchem.
DR PRO; PR:A5PKW4; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; A5PKW4; protein.
DR Bgee; ENSG00000059915; Expressed in right frontal lobe and 120 other tissues.
DR ExpressionAtlas; A5PKW4; baseline and differential.
DR Genevisible; A5PKW4; HS.
DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0098999; C:extrinsic component of postsynaptic endosome membrane; IEA:Ensembl.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IEA:Ensembl.
DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR CDD; cd00171; Sec7; 1.
DR Gene3D; 1.10.1000.11; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041681; PH_9.
DR InterPro; IPR001605; PH_dom-spectrin-type.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR023394; Sec7_C_sf.
DR InterPro; IPR000904; Sec7_dom.
DR InterPro; IPR035999; Sec7_dom_sf.
DR Pfam; PF15410; PH_9; 1.
DR Pfam; PF01369; Sec7; 1.
DR PRINTS; PR00683; SPECTRINPH.
DR SMART; SM00233; PH; 1.
DR SMART; SM00222; Sec7; 1.
DR SUPFAM; SSF48425; SSF48425; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50190; SEC7; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Coiled coil;
KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1024
FT /note="PH and SEC7 domain-containing protein 1"
FT /id="PRO_0000318298"
FT DOMAIN 512..706
FT /note="SEC7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00189"
FT DOMAIN 756..869
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 25..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 113..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 246..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 976..1024
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 898..924
FT /evidence="ECO:0000255"
FT COMPBIAS 69..92
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..315
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..342
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..368
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 439..463
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 479..493
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 522..536
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 985..1009
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DTT2"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DTT2"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DTT2"
FT VAR_SEQ 1..379
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9417912"
FT /id="VSP_031186"
FT MUTAGEN 621
FT /note="E->K: Loss of GEF activity, loss of ARF6
FT localization to the cleavage furrow and, later in
FT cytokinesis, to the midbody ring."
FT /evidence="ECO:0000269|PubMed:23603394"
FT MUTAGEN 765..766
FT /note="RK->EE: Loss of localization to the plasma membrane
FT during interphase and to the cleavage furrow during
FT cytokinesis. No effect on ARF6 localization to the cleavage
FT furrow and, later in cytokinesis, to the midbody ring."
FT /evidence="ECO:0000269|PubMed:23603394"
FT CONFLICT 109
FT /note="A -> T (in Ref. 1; CAA68002 and 5; AAI42690)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="A -> T (in Ref. 1; CAA68002)"
FT /evidence="ECO:0000305"
FT CONFLICT 537
FT /note="E -> D (in Ref. 1; CAA68002)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1024 AA; 109543 MW; 74583FEAAB0E4E01 CRC64;
MAQGAMRFCS EGDCAISPPR CPRRWLPEGP VPQSPPASMY GSTGSLLRRV AGPGPRGREL
GRVTAPCTPL RGPPSPRVAP SPWAPSSPTG QPPPGAQSSV VIFRFVEKAS VRPLNGLPAP
GGLSRSWDLG GVSPPRPTPA LGPGSNRKLR LEASTSDPLP ARGGSALPGS RNLVHGPPAP
PQVGADGLYS SLPNGLGGPP ERLATLFGGP ADTGFLNQGD TWSSPREVSS HAQRIARAKW
EFFYGSLDPP SSGAKPPEQA PPSPPGVGSR QGSGVAVGRA AKYSETDLDT VPLRCYRETD
IDEVLAEREE ADSAIESQPS SEGPPGTAYP PAPRPGPLPG PHPSLGSGNE DEDDDEAGGE
EDVDDEVFEA SEGARPGSRM PLKSPVPFLP GTSPSADGPD SFSCVFEAIL ESHRAKGTSY
TSLASLEALA SPGPTQSPFF TFELPPQPPA PRPDPPAPAP LAPLEPDSGT SSAADGPWTQ
RGEEEEAEAR AKLAPGREPP SPCHSEDSLG LGAAPLGSEP PLSQLVSDSD SELDSTERLA
LGSTDTLSNG QKADLEAAQR LAKRLYRLDG FRKADVARHL GKNNDFSKLV AGEYLKFFVF
TGMTLDQALR VFLKELALMG ETQERERVLA HFSQRYFQCN PEALSSEDGA HTLTCALMLL
NTDLHGHNIG KRMTCGDFIG NLEGLNDGGD FPRELLKALY SSIKNEKLQW AIDEEELRRS
LSELADPNPK VIKRISGGSG SGSSPFLDLT PEPGAAVYKH GALVRKVHAD PDCRKTPRGK
RGWKSFHGIL KGMILYLQKE EYKPGKALSE TELKNAISIH HALATRASDY SKRPHVFYLR
TADWRVFLFQ APSLEQMQSW ITRINVVAAM FSAPPFPAAV SSQKKFSRPL LPSAATRLSQ
EEQVRTHEAK LKAMASELRE HRAAQLGKKG RGKEAEEQRQ KEAYLEFEKS RYSTYAALLR
VKLKAGSEEL DAVEAALAQA GSTEDGLPPS HSSPSLQPKP SSQPRAQRHS SEPRPGAGSG
RRKP
