WASC2_RAT
ID WASC2_RAT Reviewed; 1328 AA.
AC Q80X08;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=WASH complex subunit 2 {ECO:0000312|RGD:735230};
GN Name=Washc2 {ECO:0000312|RGD:735230}; Synonyms=Fam21;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Majda B.T., Meloni B.P., Knuckey N.W.;
RT "The isolation and sequencing of a novel rat brain cDNA.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157; SER-159; SER-204;
RP SER-205; SER-209; SER-384; SER-387; SER-531; SER-536; SER-610; SER-611;
RP SER-720; SER-744; SER-780 AND SER-1060, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Acts as a component of the WASH core complex that functions
CC as a nucleation-promoting factor (NPF) at the surface of endosomes,
CC where it recruits and activates the Arp2/3 complex to induce actin
CC polymerization, playing a key role in the fission of tubules that serve
CC as transport intermediates during endosome sorting. Mediates the
CC recruitment of the WASH core complex to endosome membranes via binding
CC to phospholipids and VPS35 of the retromer CSC. Mediates the
CC recruitment of the F-actin-capping protein dimer to the WASH core
CC complex probably promoting localized F-actin polymerization needed for
CC vesicle scission. Via its C-terminus binds various phospholipids, most
CC strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P),
CC phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol
CC 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma
CC membrane trafficking and recycling of SNX27-retromer-dependent cargo
CC proteins, such as GLUT1. Required for the association of DNAJC13,
CC ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the
CC endosomal recruitment of CCC and retriever complexes subunits COMMD1
CC and CCDC93 as well as the retrievere complex subunit VPS35L.
CC {ECO:0000250|UniProtKB:Q9Y4E1}.
CC -!- SUBUNIT: Component of the WASH core complex also described as WASH
CC regulatory complex (SHRC) composed of WASHC1, WASHC2, WASHC3, WASHC4
CC and WASHC5; in the complex interacts (via N-terminus) directly with
CC WASHC1. The WASH core complex associates with the F-actin-capping
CC protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a
CC transient or substoichiometric manner which was initially described as
CC WASH complex. Interacts with VPS35; mediates the association with the
CC retromer CSC complex. Interacts with FKBP15. Interacts with CCDC93,
CC CCDC22, VPS35L; indicative for an association of the WASH core complex
CC with the CCC and retriever complexes (By similarity). Directly
CC interacts with TBC1D23 (By similarity). {ECO:0000250|UniProtKB:Q641Q2,
CC ECO:0000250|UniProtKB:Q9Y4E1}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000250|UniProtKB:Q9Y4E1}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9Y4E1}.
CC -!- DOMAIN: The LFa (leucine-phenylalanine-acidic) motif bind directly to
CC VPS35 of retromer CSC; adjacent motifs can act cooperatively to bind
CC multiple CSCs, although there is significant variability in the
CC affinities of different motifs for retromer.
CC {ECO:0000250|UniProtKB:Q9Y4E1}.
CC -!- SIMILARITY: Belongs to the FAM21 family. {ECO:0000305}.
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DR EMBL; AY257251; AAP31854.1; -; mRNA.
DR RefSeq; NP_954677.1; NM_199207.1.
DR AlphaFoldDB; Q80X08; -.
DR SMR; Q80X08; -.
DR STRING; 10116.ENSRNOP00000015620; -.
DR iPTMnet; Q80X08; -.
DR PhosphoSitePlus; Q80X08; -.
DR jPOST; Q80X08; -.
DR PaxDb; Q80X08; -.
DR PRIDE; Q80X08; -.
DR GeneID; 297530; -.
DR KEGG; rno:297530; -.
DR UCSC; RGD:735230; rat.
DR CTD; 253725; -.
DR RGD; 735230; Washc2c.
DR eggNOG; ENOG502QTIY; Eukaryota.
DR InParanoid; Q80X08; -.
DR OrthoDB; 131637at2759; -.
DR PhylomeDB; Q80X08; -.
DR PRO; PR:Q80X08; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0071203; C:WASH complex; ISS:UniProtKB.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISO:RGD.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISO:RGD.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISO:RGD.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISO:RGD.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISO:RGD.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISO:RGD.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISO:RGD.
DR GO; GO:1905394; F:retromer complex binding; ISO:RGD.
DR GO; GO:0032456; P:endocytic recycling; ISO:RGD.
DR GO; GO:2000813; P:negative regulation of barbed-end actin filament capping; ISO:RGD.
DR GO; GO:0036010; P:protein localization to endosome; ISS:UniProtKB.
DR GO; GO:1900024; P:regulation of substrate adhesion-dependent cell spreading; ISO:RGD.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS:UniProtKB.
DR InterPro; IPR029341; FAM21/CAPZIP.
DR Pfam; PF15255; CAP-ZIP_m; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endosome; Membrane; Phosphoprotein; Reference proteome;
KW Transport.
FT CHAIN 1..1328
FT /note="WASH complex subunit 2"
FT /id="PRO_0000317434"
FT REGION 1..219
FT /note="Sufficient for interaction with WASHC3, WASHC4 and
FT WASHC5; required for interaction with WASHC1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT REGION 201..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 346..592
FT /note="Sufficient for interaction with CCDC93"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT REGION 347..1328
FT /note="Interaction with VPS35"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT REGION 675..830
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 863..940
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 925..1328
FT /note="Interaction with phospholipids"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT REGION 991..1088
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1017..1035
FT /note="Required for interaction with F-actin-capping
FT protein subunit alpha (CAPZA1 or CAPZA2 or CAPZA3)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT REGION 1115..1210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1289..1310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 357..367
FT /note="LFa 1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 440..455
FT /note="LFa 2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 474..483
FT /note="LFa 3"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 529..540
FT /note="LFa 4"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 564..575
FT /note="LFa 5"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 655..667
FT /note="LFa 6"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 683..695
FT /note="LFa 7"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 832..840
FT /note="LFa 8"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 849..855
FT /note="LFa 9"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 871..881
FT /note="LFa 10"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 1117..1124
FT /note="LFa 11"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 1157..1171
FT /note="LFa 12"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 1187..1195
FT /note="LFa 13"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 1220..1226
FT /note="LFa 14"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 1249..1257
FT /note="LFa 15"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 1277..1286
FT /note="LFa 16"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT MOTIF 1317..1325
FT /note="LFa 17"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4E1"
FT COMPBIAS 248..270
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..286
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..327
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 405..432
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 453..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 470..485
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 507..526
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 541..562
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..596
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 611..625
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 684..700
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 715..730
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 770..785
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 896..921
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 922..940
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1018..1032
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1052..1066
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1182..1210
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
FT MOD_RES 321
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 610
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 611
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 744
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 749
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
FT MOD_RES 780
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 795
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
FT MOD_RES 867
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
FT MOD_RES 870
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
FT MOD_RES 1042
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q641Q2"
FT MOD_RES 1060
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1077
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q641Q2"
FT MOD_RES 1102
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q641Q2"
FT MOD_RES 1162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
FT MOD_RES 1165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
FT MOD_RES 1327
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PGL7"
SQ SEQUENCE 1328 AA; 145149 MW; 5621384568E4478E CRC64;
MNRTSPDSEQ PPASEPVWER PWSVEEIRRS SQNWSLAADA GLLQFLQEFS QQTISRTHEI
KKQVDGLIQE TKATHCRLHN VFNDFLMLSN TQFIENRVYD EEVEDQALKT EAEKAEQEKT
REQKEIDLIP KVQEAVNYGL QVLDSAFEQL DIKAGNSDSE EEDANERVEL ILEPKDLYID
RPLPYLIGSK LFMEQEDVGL GELSSEEGSV GSDRGSIVDS EDEKEEEESD DFASHSDNEQ
NQHITQMSDE EEDDDADLFA DSEKEGDDIE DIEESAKSKR PTSFADELAA RIKGDVSNQR
KEGHTDGKPQ RTVKEKKERR TPADDEEDIL FPPPTLTDED FSPFGSRGGL FSDRQGLFDD
DDESDLFKEA PRGQPAQGPV SEESPPSPKP GKKIPAGAVS VFLGYTDVSG STSAPSLKEF
QKHEQSTPGK SPHLPAPTGL FDDDDNDSDE DDNFFMPSSS KPSKTDKVKP TTIIFDDDEG
DLFKEKTTAL PAASVSQTDE NKARTDKTIT LPSSKNPKLV SETKTQKGLF SDEEDSEDLF
SSQSSSKTKS ASVLSSQPPA SVSLFGDEDE EDNLFGSAAA KKQTSSLPPQ SQEKAKPSEQ
PPKKASALFS SDEEDQWSVA DSQTKLASER KSKGERWDAG TNQGQEAKAV KKTNLFEEED
DDGVDLFAIA KDSQKKTQRT SLLFEDDTDS GSSLFSLPPT SVPPAATKKE SIPKVPLLFS
DEEDSEVPSG VKPVDLKAEN AAASPEVGSA DVANVAQKEG LLPTSDQEAG GPSDIFSSSS
PLDKGAKGRT KTVLSLFDED EDKVEDDSNT CAPQGGLEKG VKTDRRPKST GVFQDEELLF
SHKLQKDNDP DVDLFAGTKK TRLSMPSGGS LFGDDDDDDL FSTAKTQPAQ PVVPEKKGTL
RKDHKPPELT EGSKEKSTWK AETAQDSSGL TPFKSREPSS RIGKIQANLA INPATLLPSV
APQIPGAKPA SCELAFPSSE PARSHIREAV PTLPGSEEAG VSFDLPAQAD TLHSANKGRV
KVRGKRRPQT RAARRLAAQE SSEAEDVTID RGPVTQLSSS PVLPNGHQPL LQPRMASGET
SSEKAMAVPW EGGPVLSAVD RSFFVKSLPQ TGNEAHLFDS GDIFPKSTGS QSMEGASVKA
GETPAHSSAG RKEKSLVFPD LSEASGVDDL FQSAKPRPTK KRNPFPLLED EEDLFADQKG
KKNQWKSDSH QDVVSKTQDI FEDDIFATEA IKKPFPKKRE KERTLEPNLF DDNIDIFADL
TVKPKEKPKK KVTAKSMFDD DTDDIFSSGL QAKASKPKSQ SAEAVSELRS ENKVSNIFDD
PLNAFGSQ
