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Protein

WASH complex subunit FAM21A

Gene

FAM21A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at transcript 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

  1. lipid binding Source: UniProtKB-KW

GO - Biological processi

  1. protein transport Source: UniProtKB-KW
  2. retrograde transport, endosome to Golgi Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Lipid-binding

Names & Taxonomyi

Protein namesi
Recommended name:
WASH complex subunit FAM21A
Gene namesi
Name:FAM21A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:23416. FAM21A.

Subcellular locationi

  1. Early endosome membrane By similarity
  2. Cell membrane By similarity

GO - Cellular componenti

  1. early endosome Source: UniProtKB
  2. early endosome membrane Source: UniProtKB-SubCell
  3. plasma membrane Source: UniProtKB-SubCell
  4. WASH complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134902481.

Polymorphism and mutation databases

BioMutaiFAM21A.
DMDMi166971555.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13411341WASH complex subunit FAM21APRO_0000317299Add
BLAST

Proteomic databases

MaxQBiQ641Q2.
PaxDbiQ641Q2.
PRIDEiQ641Q2.

Expressioni

Gene expression databases

BgeeiQ641Q2.
CleanExiHS_FAM21A.
ExpressionAtlasiQ641Q2. baseline.
GenevestigatoriQ641Q2.

Organism-specific databases

HPAiHPA047844.

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. 10 interactions.
STRINGi9606.ENSP00000282633.

Structurei

3D structure databases

ProteinModelPortaliQ641Q2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 220220Sufficient for interaction with KIAA1033/SWIP, KIAA0196/strumpellin and CCDC53; required for interaction with WASH1By similarityAdd
BLAST
Regioni356 – 600245Sufficient for interaction with CCDC93By similarityAdd
BLAST
Regioni357 – 1341985Interaction with VPS35By similarityAdd
BLAST
Regioni937 – 1341405Interaction with phospholipidsBy similarityAdd
BLAST
Regioni1029 – 104719Required for interaction with F-actin-capping protein subunit alpha (CAPZA1 or CAPZA2 or CAPZA3)By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi367 – 37812LFa 1By similarityAdd
BLAST
Motifi411 – 4199LFa 2By similarity
Motifi450 – 46314LFa 3By similarityAdd
BLAST
Motifi482 – 49110LFa 4By similarity
Motifi537 – 54812LFa 5By similarityAdd
BLAST
Motifi572 – 58312LFa 6By similarityAdd
BLAST
Motifi617 – 62913LFa 7By similarityAdd
BLAST
Motifi664 – 67411LFa 8By similarityAdd
BLAST
Motifi690 – 70213LFa 9By similarityAdd
BLAST
Motifi726 – 73813LFa 10By similarityAdd
BLAST
Motifi803 – 81715LFa 11By similarityAdd
BLAST
Motifi839 – 8479LFa 12By similarity
Motifi856 – 8627LFa 13By similarity
Motifi878 – 88811LFa 14By similarityAdd
BLAST
Motifi1129 – 11368LFa 15By similarity
Motifi1171 – 118515LFa 16By similarityAdd
BLAST
Motifi1201 – 12099LFa 17By similarity
Motifi1234 – 12407LFa 18By similarity
Motifi1262 – 12709LFa 19By similarity
Motifi1290 – 129910LFa 20By similarity
Motifi1330 – 13389LFa 21By similarity

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

eggNOGiNOG76301.
GeneTreeiENSGT00510000047694.
HOGENOMiHOG000112469.
HOVERGENiHBG055529.
InParanoidiQ641Q2.
KOiK18462.
OMAiHSDNDQN.
OrthoDBiEOG7GBFWP.
PhylomeDBiQ641Q2.
TreeFamiTF329309.

Family and domain databases

InterProiIPR027308. FAM21.
IPR029341. FAM21/CAPZIP.
[Graphical view]
PANTHERiPTHR21669:SF4. PTHR21669:SF4. 1 hit.
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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti444 – 4441G → E in AAH75815 (PubMed:15489334).Curated
Sequence conflicti816 – 8161I → T in AAH75815 (PubMed:15489334).Curated
Sequence conflicti997 – 9971H → Y in AAH82258 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei938 – 95821Missing in isoform 2. 1 PublicationVSP_030948Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL442003, AL450382 Genomic DNA. Translation: CAM17004.1.
AL450382, AL442003 Genomic DNA. Translation: CAM22317.1.
BC075815 mRNA. Translation: AAH75815.1.
BC082258 mRNA. Translation: AAH82258.2.
CCDSiCCDS41527.1. [Q641Q2-1]
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.3. human. [Q641Q2-1]
uc010qhi.2. human. [Q641Q2-2]

Polymorphism and mutation databases

BioMutaiFAM21A.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL442003, AL450382 Genomic DNA. Translation: CAM17004.1.
AL450382, AL442003 Genomic DNA. Translation: CAM22317.1.
BC075815 mRNA. Translation: AAH75815.1.
BC082258 mRNA. Translation: AAH82258.2.
CCDSiCCDS41527.1. [Q641Q2-1]
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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi132390. 10 interactions.
STRINGi9606.ENSP00000282633.

Polymorphism and mutation databases

BioMutaiFAM21A.
DMDMi166971555.

Proteomic databases

MaxQBiQ641Q2.
PaxDbiQ641Q2.
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.3. human. [Q641Q2-1]
uc010qhi.2. human. [Q641Q2-2]

Organism-specific databases

CTDi387680.
GeneCardsiGC10P051827.
H-InvDBHIX0008825.
HGNCiHGNC:23416. FAM21A.
HPAiHPA047844.
neXtProtiNX_Q641Q2.
PharmGKBiPA134902481.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG76301.
GeneTreeiENSGT00510000047694.
HOGENOMiHOG000112469.
HOVERGENiHBG055529.
InParanoidiQ641Q2.
KOiK18462.
OMAiHSDNDQN.
OrthoDBiEOG7GBFWP.
PhylomeDBiQ641Q2.
TreeFamiTF329309.

Miscellaneous databases

GenomeRNAii387680.
NextBioi101504.
PROiQ641Q2.

Gene expression databases

BgeeiQ641Q2.
CleanExiHS_FAM21A.
ExpressionAtlasiQ641Q2. baseline.
GenevestigatoriQ641Q2.

Family and domain databases

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

Publicationsi

  1. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Eye and Spleen.

Entry informationi

Entry nameiFA21A_HUMAN
AccessioniPrimary (citable) accession number: Q641Q2
Secondary accession number(s): A2A3S2, A2A3U6, Q6DHY0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: April 29, 2015
This is version 81 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

External Data

Dasty 3

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 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.