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Protein

WASH complex subunit FAM21

Gene

Fam21

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-4P), phosphatidylinositol 5-phosphate (PtdIns-5P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, SDCCAG3, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1, CCDC93 and C16orf62 homolog (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
WASH complex subunit FAM21
Gene namesi
Name:Fam21
Synonyms:D6Wsu116e, Kiaa0592
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:106463. Fam21.

Subcellular locationi

  • Early endosome membrane By similarity
  • Cell membrane By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003174331 – 1334WASH complex subunit FAM21Add BLAST1334

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei157PhosphoserineCombined sources1
Modified residuei159PhosphoserineCombined sources1
Modified residuei204PhosphoserineBy similarity1
Modified residuei205PhosphoserineBy similarity1
Modified residuei209PhosphoserineBy similarity1
Modified residuei284PhosphoserineCombined sources1
Modified residuei322PhosphothreonineCombined sources1
Modified residuei388PhosphoserineCombined sources1
Modified residuei533PhosphoserineCombined sources1
Modified residuei538PhosphoserineBy similarity1
Modified residuei613PhosphoserineCombined sources1
Modified residuei614PhosphoserineCombined sources1
Modified residuei723PhosphoserineCombined sources1
Modified residuei747PhosphoserineCombined sources1
Modified residuei752PhosphoserineCombined sources1
Modified residuei783PhosphoserineBy similarity1
Modified residuei798PhosphoserineCombined sources1
Modified residuei870PhosphoserineCombined sources1
Modified residuei873PhosphoserineCombined sources1
Modified residuei1049PhosphoserineBy similarity1
Modified residuei1067PhosphoserineBy similarity1
Modified residuei1084PhosphoserineBy similarity1
Modified residuei1109PhosphoserineBy similarity1
Modified residuei1169PhosphoserineCombined sources1
Modified residuei1172PhosphoserineCombined sources1
Modified residuei1173PhosphoserineCombined sources1
Modified residuei1333PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6PGL7.
PaxDbiQ6PGL7.
PeptideAtlasiQ6PGL7.
PRIDEiQ6PGL7.

PTM databases

iPTMnetiQ6PGL7.
PhosphoSitePlusiQ6PGL7.

Expressioni

Gene expression databases

BgeeiENSMUSG00000024104.
ExpressionAtlasiQ6PGL7. baseline and differential.
GenevisibleiQ6PGL7. MM.

Interactioni

Subunit structurei

Component of the WASH core complex also described as WASH regulatory complex SHRC composed of WASH1, FAM21, KIAA1033/ SWIP, KIAA0196/strumpellin and CCDC53; in the complex interacts (via N-terminus) directly with WASH1. The WASH core complex associates with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex. Interacts with VPS35; mediates the association with the retromer CSC complex. Interacts with FKBP15. Interacts with CCDC93, CCDC22, C16orf62 homolog; indicative for an association of the WASH core complex with the CCC complex (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ6PGL7. 3 interactors.
MINTiMINT-1864605.
STRINGi10090.ENSMUSP00000038983.

Structurei

3D structure databases

ProteinModelPortaliQ6PGL7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 219Sufficient for interaction with KIAA1033/SWIP, KIAA0196/strumpellin and CCDC53; required for interaction with WASH1By similarityAdd BLAST219
Regioni347 – 594Sufficient for interaction with CCDC93By similarityAdd BLAST248
Regioni348 – 1334Interaction with VPS35By similarityAdd BLAST987
Regioni932 – 1334Interaction with phospholipidsBy similarityAdd BLAST403
Regioni1024 – 1042Required for interaction with F-actin-capping protein subunit alpha (CAPZA1 or CAPZA2 or CAPZA3)By similarityAdd BLAST19

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi358 – 368LFa 1By similarityAdd BLAST11
Motifi441 – 457LFa 2By similarityAdd BLAST17
Motifi476 – 485LFa 3By similarity10
Motifi531 – 542LFa 4By similarityAdd BLAST12
Motifi566 – 577LFa 5By similarityAdd BLAST12
Motifi658 – 670LFa 6By similarityAdd BLAST13
Motifi686 – 698LFa 7By similarityAdd BLAST13
Motifi835 – 843LFa 8By similarity9
Motifi852 – 858LFa 9By similarity7
Motifi874 – 884LFa 10By similarityAdd BLAST11
Motifi1124 – 1131LFa 11By similarity8
Motifi1164 – 1178LFa 12By similarityAdd BLAST15
Motifi1194 – 1202LFa 13By similarity9
Motifi1227 – 1233LFa 14By similarity7
Motifi1255 – 1263LFa 15By similarity9
Motifi1283 – 1292LFa 16By similarity10
Motifi1323 – 1331LFa 17By similarity9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi221 – 228Poly-Glu8
Compositional biasi443 – 453Poly-AspAdd BLAST11
Compositional biasi661 – 665Poly-Asp5
Compositional biasi780 – 783Poly-Ser4

Domaini

The LFa (leucine-phenylalanine-acidic) motif bind directly to VPS35 of retromer CSC; adjacent motifs can act cooperatively to bind multiple CSCs, although there is significant variability in the affinities of different motifs for retromer.By similarity

Sequence similaritiesi

Belongs to the FAM21 family.Curated

Phylogenomic databases

eggNOGiENOG410IEJH. Eukaryota.
ENOG4110AMY. LUCA.
GeneTreeiENSGT00510000047694.
HOGENOMiHOG000112469.
HOVERGENiHBG055529.
InParanoidiQ6PGL7.
KOiK18462.
OMAiHSDNDQN.
OrthoDBiEOG091G05P8.
PhylomeDBiQ6PGL7.
TreeFamiTF329309.

Family and domain databases

InterProiIPR027308. FAM21.
IPR029341. FAM21/CAPZIP.
[Graphical view]
PANTHERiPTHR21669:SF4. PTHR21669:SF4. 2 hits.
PfamiPF15255. CAP-ZIP_m. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6PGL7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNRTSPDSER PPASEPVWER PWSVEEIRRS SQNWSLAADA GLLQFLQEFS
60 70 80 90 100
QQTISRTHEI KKQVDGLIQE TKATHCRLHN VFNDFLMLSN TQFIENRVYD
110 120 130 140 150
EEVEEQVLKA EAEKAEQEKT REQKEIDLIP KVQEAVNYGL QVLDSAFEQL
160 170 180 190 200
DIKAGNSDSE EDDANERVDL ILEPKDLYID RPLPYLIGSK LFMEQEDVGL
210 220 230 240 250
GELSSEEGSV GSDRGSIVDS EDEKEEEESD EDFASHSDND QNQHTTQISD
260 270 280 290 300
EEEDDDGDLF ADSEKEGDDI EDIEESAKSK RPTSFADELA ARIKGDISNQ
310 320 330 340 350
RKEGQTDGKP QKTVKEKKER RTPADDEEDI LFPPPTLTDE DFSPFGSRGG
360 370 380 390 400
LFSNGQGLFD DEDESDLFKE APRARPAQAP VSEELPPSPK PGKKIPAGAV
410 420 430 440 450
SVLLGHPDVS GSTSAPSLKE LQKHGQPTPG KSSHLPTPAG LFDDDDNDND
460 470 480 490 500
EDDNNFFMPS SSKPSKTDKV KSTAIIFDDD EGDLFKEKAE ALPAASVSQT
510 520 530 540 550
HESKTRADKT IALPSSKNLK LVSETKTQKG LFSDEEDSED LFSSQSSSKP
560 570 580 590 600
KSASLPSSQP PTSVSLFGDE DEEDSLFGSA AAKKQTSSLQ PQSQEKAKPS
610 620 630 640 650
EQPSKKTSAL LFSSDEEDQW NIADSHTKLA SDNKSKGELW DSGATQGQEA
660 670 680 690 700
KAVKKTNLFE DDDDDEVDLF AIAKDSQKKT QRTSLLFEDD AESGSSLFGL
710 720 730 740 750
PPTSVPSATT KKESVPKVPL LFSDEEDSEV PSGVKPEDLK VDNARVSPEV
760 770 780 790 800
GSADVASIAQ KEGLLPASDQ EAGGPSDIFS SSSPLDKGAK GRTRTVLSLF
810 820 830 840 850
DEDEDKVEDE SSTCAPQDGR EKGLKTDSRP KSTGVFQDEE LLFSHKLQKD
860 870 880 890 900
NDPDVDLFAG TKKIRSSVPS GGSLFGDDED DDLFSSAKTQ PVVPEKKGTL
910 920 930 940 950
KKDHPVSLKN QDPLDSTQGS KEKSTWKTEP AQDSSGLTPF KSREPSSRIG
960 970 980 990 1000
KIQANLAINP AALLPTVALQ IPGTKPVSSE LAFPSSEPGR SHILESVPTL
1010 1020 1030 1040 1050
PGSVEAGVSF DLPAQADTLH SANKSRVKVR GKRRPQTRAA RRLAAQESSE
1060 1070 1080 1090 1100
AEDVTVDRGP VAQLSSSPVL PNGHQPLLQP RMASGQTSSE TATAPPWEGG
1110 1120 1130 1140 1150
PVLSAADRSF FVKSRPQTGN EADLFDSGDI FPKSRGSQSV EGAGVMAGEP
1160 1170 1180 1190 1200
PSHSSGGRKE KSLAFPDLSE GSSTEDLFQS VKPRAAKNRN PFPLLEDEED
1210 1220 1230 1240 1250
LFADPRGKKN ERKPDSHQDS VSKTHDIFED DIFATEAIKP FPKKREKGRT
1260 1270 1280 1290 1300
LEPNLFDDNI DIFADLTVKP KEKSKKKVAA KSMFDDDTDD IFSSGLQAKA
1310 1320 1330
SKPKSQSAEA ASEQRSEHKV ASIFDDPLNA FGSQ
Length:1,334
Mass (Da):145,311
Last modified:July 5, 2004 - v1
Checksum:iAD35C3FFAC27C159
GO
Isoform 2 (identifier: Q6PGL7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     866-952: SSVPSGGSLF...REPSSRIGKI → V

Note: No experimental confirmation available.
Show »
Length:1,248
Mass (Da):136,082
Checksum:i410A9852587F5DB7
GO

Sequence cautioni

The sequence AAH49979 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti385L → S in AAH49979 (PubMed:15489334).Curated1
Sequence conflicti556P → S in AAH49979 (PubMed:15489334).Curated1
Sequence conflicti630A → V in BAC65602 (PubMed:12693553).Curated1
Sequence conflicti910N → S in BAC29966 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030949866 – 952SSVPS…RIGKI → V in isoform 2. 1 PublicationAdd BLAST87

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK122320 Transcribed RNA. Translation: BAC65602.2.
AK163765 mRNA. Translation: BAE37485.1.
AK038318 mRNA. Translation: BAC29966.1.
BC049979 mRNA. Translation: AAH49979.1. Sequence problems.
BC056942 mRNA. Translation: AAH56942.1.
CCDSiCCDS20450.1. [Q6PGL7-1]
RefSeqiNP_080861.2. NM_026585.3. [Q6PGL7-1]
UniGeneiMm.28524.

Genome annotation databases

EnsembliENSMUST00000036759; ENSMUSP00000038983; ENSMUSG00000024104. [Q6PGL7-1]
GeneIDi28006.
KEGGimmu:28006.
UCSCiuc009djs.2. mouse. [Q6PGL7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK122320 Transcribed RNA. Translation: BAC65602.2.
AK163765 mRNA. Translation: BAE37485.1.
AK038318 mRNA. Translation: BAC29966.1.
BC049979 mRNA. Translation: AAH49979.1. Sequence problems.
BC056942 mRNA. Translation: AAH56942.1.
CCDSiCCDS20450.1. [Q6PGL7-1]
RefSeqiNP_080861.2. NM_026585.3. [Q6PGL7-1]
UniGeneiMm.28524.

3D structure databases

ProteinModelPortaliQ6PGL7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ6PGL7. 3 interactors.
MINTiMINT-1864605.
STRINGi10090.ENSMUSP00000038983.

PTM databases

iPTMnetiQ6PGL7.
PhosphoSitePlusiQ6PGL7.

Proteomic databases

EPDiQ6PGL7.
PaxDbiQ6PGL7.
PeptideAtlasiQ6PGL7.
PRIDEiQ6PGL7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000036759; ENSMUSP00000038983; ENSMUSG00000024104. [Q6PGL7-1]
GeneIDi28006.
KEGGimmu:28006.
UCSCiuc009djs.2. mouse. [Q6PGL7-1]

Organism-specific databases

CTDi28006.
MGIiMGI:106463. Fam21.
RougeiSearch...

Phylogenomic databases

eggNOGiENOG410IEJH. Eukaryota.
ENOG4110AMY. LUCA.
GeneTreeiENSGT00510000047694.
HOGENOMiHOG000112469.
HOVERGENiHBG055529.
InParanoidiQ6PGL7.
KOiK18462.
OMAiHSDNDQN.
OrthoDBiEOG091G05P8.
PhylomeDBiQ6PGL7.
TreeFamiTF329309.

Miscellaneous databases

PROiQ6PGL7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024104.
ExpressionAtlasiQ6PGL7. baseline and differential.
GenevisibleiQ6PGL7. MM.

Family and domain databases

InterProiIPR027308. FAM21.
IPR029341. FAM21/CAPZIP.
[Graphical view]
PANTHERiPTHR21669:SF4. PTHR21669:SF4. 2 hits.
PfamiPF15255. CAP-ZIP_m. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFAM21_MOUSE
AccessioniPrimary (citable) accession number: Q6PGL7
Secondary accession number(s): Q3TQ99
, Q80TW8, Q80UQ4, Q8CAP0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 82 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.