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Protein

WASH complex subunit FAM21A

Gene

FAM21A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 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. Plays a role in fluid-phase endocytosis, a process exploited by vaccinia intracellular mature virus (IMV) to enter cells. As a result, may facilitate the penetration of IMV into cells (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

BioCyciZFISH:G66-31017-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
WASH complex subunit FAM21ACurated
Gene namesi
Name:FAM21AImported
Synonyms:FAM21BImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:23416. FAM21A.

Subcellular locationi

  • Early endosome membrane By similarity
  • Cell membrane By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000099290.
PharmGKBiPA134877872.
PA134902481.

Polymorphism and mutation databases

BioMutaiFAM21A.
FAM21B.
DMDMi166971548.
166971555.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003172991 – 1341WASH complex subunit FAM21AAdd BLAST1341

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei539PhosphoserineCombined sources1
Modified residuei1054PhosphoserineCombined sources1
Modified residuei1087PhosphoserineCombined sources1
Modified residuei1114PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ641Q2.
MaxQBiQ641Q2.
PaxDbiQ641Q2.
PeptideAtlasiQ641Q2.
PRIDEiQ641Q2.

PTM databases

iPTMnetiQ641Q2.
PhosphoSitePlusiQ641Q2.

Expressioni

Gene expression databases

BgeeiENSG00000152726.
CleanExiHS_FAM21A.
HS_FAM21B.
ExpressionAtlasiQ641Q2. baseline and differential.
GenevisibleiQ641Q2. HS.

Organism-specific databases

HPAiHPA047844.
HPA060975.

Interactioni

Subunit structurei

Component of the WASH core complex also described as WASH regulatory complex SHRC composed of WASH (WASH1, WASH2P or WASH3P), FAM21 (FAM21A or FAM21C), 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; indicative for an association of the WASH core complex with the CCC complex (By similarity).By similarity

Protein-protein interaction databases

BioGridi132390. 34 interactors.
IntActiQ641Q2. 19 interactors.
STRINGi9606.ENSP00000351259.

Structurei

3D structure databases

ProteinModelPortaliQ641Q2.
SMRiQ641Q2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 220Sufficient for interaction with KIAA1033/SWIP, KIAA0196/strumpellin and CCDC53; required for interaction with WASH1By similarityAdd BLAST220
Regioni356 – 600Sufficient for interaction with CCDC93By similarityAdd BLAST245
Regioni357 – 1341Interaction with VPS35By similarityAdd BLAST985
Regioni937 – 1341Interaction with phospholipidsBy similarityAdd BLAST405
Regioni1029 – 1047Required for interaction with F-actin-capping protein subunit alpha (CAPZA1 or CAPZA2 or CAPZA3)By similarityAdd BLAST19

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi367 – 378LFa 1By similarityAdd BLAST12
Motifi411 – 419LFa 2By similarity9
Motifi450 – 463LFa 3By similarityAdd BLAST14
Motifi482 – 491LFa 4By similarity10
Motifi537 – 548LFa 5By similarityAdd BLAST12
Motifi572 – 583LFa 6By similarityAdd BLAST12
Motifi617 – 629LFa 7By similarityAdd BLAST13
Motifi664 – 674LFa 8By similarityAdd BLAST11
Motifi690 – 702LFa 9By similarityAdd BLAST13
Motifi726 – 738LFa 10By similarityAdd BLAST13
Motifi803 – 817LFa 11By similarityAdd BLAST15
Motifi839 – 847LFa 12By similarity9
Motifi856 – 862LFa 13By similarity7
Motifi878 – 888LFa 14By similarityAdd BLAST11
Motifi1129 – 1136LFa 15By similarity8
Motifi1171 – 1185LFa 16By similarityAdd BLAST15
Motifi1201 – 1209LFa 17By similarity9
Motifi1234 – 1240LFa 18By similarity7
Motifi1262 – 1270LFa 19By similarity9
Motifi1290 – 1299LFa 20By similarity10
Motifi1330 – 1338LFa 21By similarity9

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.
InParanoidiQ641Q2.
KOiK18462.
OMAiHSDNDQN.
OrthoDBiEOG091G05P8.
PhylomeDBiQ641Q2.
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: Q641Q2-1) [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
MMNRTTPDQE LAPASEPVWE RPWSVEEIRR SSQSWSLAAD AGLLQFLQEF
60 70 80 90 100
SQQTISRTHE IKKQVDGLIR ETKATDCRLH NVFNDFLMLS NTQFIENRVY
110 120 130 140 150
DEEVEEPVLK AEAEKTEQEK TREQKEVDLI PKVQEAVNYG LQVLDSAFEQ
160 170 180 190 200
LDIKAGNSDS EEDDANGRVE LILEPKDLYI DRPLPYLIGS KLFMEQEDVG
210 220 230 240 250
LGELSSEEGS VGSDRGSIVD TEEEKEEEES DEDFAHHSDN EQNRHTTQMS
260 270 280 290 300
DEEEDDDGCD LFADSEKEEE DIEDIEENTR PKRSRPTSFA DELAARIKGD
310 320 330 340 350
AVGRVDEEPT TLPSGEAKPR KTLKEKKERR TPSDDEEDNL FAPPKLTDED
360 370 380 390 400
FSPFGSGGGL FSGGKGLFDD EDEESDLFTE APQDRQAGAS VKEESSSSKP
410 420 430 440 450
GKKIPAGAVS VFLGDTDVFG AASVPSMKEP QKPEQPTPRK SPYGPPPTGL
460 470 480 490 500
FDDDDGDDDD DFFSAPHSKP SKTGKVQSTA DIFGDEEGDL FKEKAVASPE
510 520 530 540 550
ATVSQTDENK ARAEKKVTLS SSKNLKPSSE TKTQKGLFSD EEDSEDLFSS
560 570 580 590 600
QSASKLKGAS LLPGKLPTLV SLFDDEDEED NLFGGTAAKK QTLCLQAQRE
610 620 630 640 650
EKAKASELSK KKASALLFSS DEEDQWNIPA SQTHLASDSR SKGEPRDSGT
660 670 680 690 700
LQSQEAKAVK KTSLFEEDEE DDLFAIAKDS QKKTQRVSLL FEDDVDSGGS
710 720 730 740 750
LFGSPPTSVP PATKKKETVS EAPPLLFSDE EEKEAQLGVK SVDKKVESAK
760 770 780 790 800
ESLKFGRTDV AESEKEGLLT RSAQETVKHS DLFSSSSPWD KGTKPRTKTV
810 820 830 840 850
LSLFDEEEDK MEDQNIIQAP QKEVGKGRDP DAHPKSTGVF QDEELLFSHK
860 870 880 890 900
LQKDNDPDVD LFAGTKKTKL LEPSVGSLFG DDEDDDLFSS AKSQPLVQEK
910 920 930 940 950
KRVVKKDHSV DSFKNQKHPE SIQGSKEKGI WKPETPQDSS GLAPFKTKEP
960 970 980 990 1000
STRIGKIQAN LAINPAALLP TAASQISEVK PVLPELAFPS SEHRRSHGLE
1010 1020 1030 1040 1050
SVPVLPGSGE AGVSFDLPAQ ADTLHSANKS RVKMRGKRRP QTRAARRLAA
1060 1070 1080 1090 1100
QESSETEDMS VPRGPIAQWA DGAISPNGHR PQLRAASGED STEEALAAAA
1110 1120 1130 1140 1150
APWEGGPVPG VDRSPFAKSL GHSRGEADLF DSGDIFSTGT GSQSVERTKP
1160 1170 1180 1190 1200
KAKIAENPAN PPVGGKAKSP MFPALGEASS DDDLFQSAKP KPAKKTNPFP
1210 1220 1230 1240 1250
LLEDEDDLFT DQKVKKNETK SNSQQDVILT TQDIFEDDIF ATEAIKPSQK
1260 1270 1280 1290 1300
TREKEKTLES NLFDDNIDIF ADLTVKPKEK SKKKVEAKSI FDDDMDDIFS
1310 1320 1330 1340
SGIQAKTTKP KSRSAQAAPE PRFEHKVSNI FDDPLNAFGG Q
Length:1,341
Mass (Da):147,184
Last modified:February 5, 2008 - v3
Checksum:i8F0F755EB1493EA7
GO
Isoform 2 (identifier: Q641Q2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     938-958: Missing.

Show »
Length:1,320
Mass (Da):144,941
Checksum:i64417D36898CFFBF
GO

Sequence cautioni

The sequence CAI17187 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti342A → T in CAI17187 (PubMed:15164054).Curated1
Sequence conflicti444G → E in AAH75815 (PubMed:15489334).Curated1
Sequence conflicti569L → S in CAI17187 (PubMed:15164054).Curated1
Sequence conflicti698G → R in CAI17187 (PubMed:15164054).Curated1
Sequence conflicti816I → T in AAH75815 (PubMed:15489334).Curated1
Sequence conflicti997H → Y in AAH82258 (PubMed:15489334).Curated1
Sequence conflicti1198P → T in CAI17187 (PubMed:15164054).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030948938 – 958Missing in isoform 2. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL442003 Genomic DNA. No translation available.
AL450382 Genomic DNA. No translation available.
AL954360 Genomic DNA. Translation: CAI17187.1. Sequence problems.
BC075815 mRNA. Translation: AAH75815.1.
BC082258 mRNA. Translation: AAH82258.2.
CCDSiCCDS41527.1. [Q641Q2-1]
CCDS76303.1. [Q641Q2-2]
RefSeqiNP_001005751.1. NM_001005751.2. [Q641Q2-1]
NP_001278327.1. NM_001291398.1. [Q641Q2-2]
UniGeneiHs.365286.
Hs.449662.
Hs.645272.

Genome annotation databases

EnsembliENST00000282633; ENSP00000282633; ENSG00000099290. [Q641Q2-1]
ENST00000351071; ENSP00000344037; ENSG00000099290. [Q641Q2-2]
GeneIDi387680.
KEGGihsa:387680.
UCSCiuc001jjb.4. human. [Q641Q2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL442003 Genomic DNA. No translation available.
AL450382 Genomic DNA. No translation available.
AL954360 Genomic DNA. Translation: CAI17187.1. Sequence problems.
BC075815 mRNA. Translation: AAH75815.1.
BC082258 mRNA. Translation: AAH82258.2.
CCDSiCCDS41527.1. [Q641Q2-1]
CCDS76303.1. [Q641Q2-2]
RefSeqiNP_001005751.1. NM_001005751.2. [Q641Q2-1]
NP_001278327.1. NM_001291398.1. [Q641Q2-2]
UniGeneiHs.365286.
Hs.449662.
Hs.645272.

3D structure databases

ProteinModelPortaliQ641Q2.
SMRiQ641Q2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi132390. 34 interactors.
IntActiQ641Q2. 19 interactors.
STRINGi9606.ENSP00000351259.

PTM databases

iPTMnetiQ641Q2.
PhosphoSitePlusiQ641Q2.

Polymorphism and mutation databases

BioMutaiFAM21A.
FAM21B.
DMDMi166971548.
166971555.

Proteomic databases

EPDiQ641Q2.
MaxQBiQ641Q2.
PaxDbiQ641Q2.
PeptideAtlasiQ641Q2.
PRIDEiQ641Q2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282633; ENSP00000282633; ENSG00000099290. [Q641Q2-1]
ENST00000351071; ENSP00000344037; ENSG00000099290. [Q641Q2-2]
GeneIDi387680.
KEGGihsa:387680.
UCSCiuc001jjb.4. human. [Q641Q2-1]

Organism-specific databases

CTDi387680.
GeneCardsiFAM21A.
H-InvDBHIX0008825.
HIX0025987.
HGNCiHGNC:23416. FAM21A.
HPAiHPA047844.
HPA060975.
neXtProtiNX_Q641Q2.
OpenTargetsiENSG00000099290.
PharmGKBiPA134877872.
PA134902481.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEJH. Eukaryota.
ENOG4110AMY. LUCA.
GeneTreeiENSGT00510000047694.
HOGENOMiHOG000112469.
HOVERGENiHBG055529.
InParanoidiQ641Q2.
KOiK18462.
OMAiHSDNDQN.
OrthoDBiEOG091G05P8.
PhylomeDBiQ641Q2.
TreeFamiTF329309.

Enzyme and pathway databases

BioCyciZFISH:G66-31017-MONOMER.

Miscellaneous databases

GenomeRNAii387680.
PROiQ641Q2.

Gene expression databases

BgeeiENSG00000152726.
CleanExiHS_FAM21A.
HS_FAM21B.
ExpressionAtlasiQ641Q2. baseline and differential.
GenevisibleiQ641Q2. HS.

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 nameiFA21A_HUMAN
AccessioniPrimary (citable) accession number: Q641Q2
Secondary accession number(s): A2A3S2
, A2A3U6, Q5SNT6, Q6DHY0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: November 2, 2016
This is version 96 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

In human, FAM21 has undergone evolutionary duplication, with 4 highly homologous family members existing, including FAM21A, FAM21B, FAM21C, and an N-terminally truncated FAM21D form.

Caution

A FAM21C construct with FAM21A-specific sequence insertions has been used in a number of experiments; the results are included in the FAM21C entry.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  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.