MS4A3_HUMAN
ID MS4A3_HUMAN Reviewed; 214 AA.
AC Q96HJ5; A8MTP8; Q8NHW2;
DT 04-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Membrane-spanning 4-domains subfamily A member 3;
DE AltName: Full=CD20 antigen-like protein;
DE AltName: Full=Hematopoietic-specific transmembrane protein 4;
DE Short=HTm4;
GN Name=MS4A3; Synonyms=CD20L, HTM4;
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 1).
RC TISSUE=Hematopoietic;
RX PubMed=7524084; DOI=10.1073/pnas.91.21.10178;
RA Adra C.N., Lelias J.-M., Kobayashi H., Kaghad M., Morrison P., Rowley J.D.,
RA Lim B.;
RT "Cloning of the cDNA for a hematopoietic cell-specific protein related to
RT CD20 and the beta subunit of the high-affinity IgE receptor: evidence for a
RT family of proteins with four membrane-spanning regions.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:10178-10182(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Bone marrow;
RA Xie C., Yuan H.F., Xie X.Y., Li Y.H., Shi W., Wang D.M., Li H.M., Yue W.,
RA Bai C.X., Zhang R., Pei X.T.;
RT "Cloning and function analysis of the transcript variant of human
RT hematopoietic cell-specific protein HTm4.";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Shirakawa T., Yang X., Lyengar A., Sayegh M., Scadden D., Adra C.;
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Epidermal carcinoma, and Lung;
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, AND INTERACTION WITH CDKN3.
RX PubMed=11781350; DOI=10.1172/jci14025;
RA Donato J.-L., Ko J., Kutok J.L., Cheng T., Shirakawa T., Mao X.-Q.,
RA Beach D., Scadden D.T., Sayegh M.H., Adra C.N.;
RT "Human HTm4 is a hematopoietic cell cycle regulator.";
RL J. Clin. Invest. 109:51-58(2002).
RN [7]
RP INTERACTION WITH CDKN3.
RX PubMed=15671017; DOI=10.1074/jbc.m413437200;
RA Chinami M., Yano Y., Yang X., Salahuddin S., Moriyama K., Shiroishi M.,
RA Turner H., Shirakawa T., Adra C.N.;
RT "Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase
RT (KAP).Cdk2.cyclin A complex enhances the phosphatase activity of KAP,
RT dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2.";
RL J. Biol. Chem. 280:17235-17242(2005).
CC -!- FUNCTION: Hematopoietic modulator for the G1-S cell cycle transition.
CC Modulates the level of phosphorylation of cyclin-dependent kinase 2
CC (CDK2) through its direct binding to cyclin-dependent kinase inhibitor
CC 3 (CDKN3/KAP). {ECO:0000269|PubMed:11781350}.
CC -!- SUBUNIT: Interacts with CDKN3. Interacts with CDKN3-CDK2 complexes
CC through its binding to CDKN3; this interaction facilitates dissociation
CC of cyclin A from CDKN3-CDK2 complexes. {ECO:0000269|PubMed:11781350,
CC ECO:0000269|PubMed:15671017}.
CC -!- INTERACTION:
CC Q96HJ5; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-12806656, EBI-10827839;
CC Q96HJ5; Q99437: ATP6V0B; NbExp=5; IntAct=EBI-12806656, EBI-3904417;
CC Q96HJ5; O95393: BMP10; NbExp=3; IntAct=EBI-12806656, EBI-3922513;
CC Q96HJ5; Q12983: BNIP3; NbExp=3; IntAct=EBI-12806656, EBI-749464;
CC Q96HJ5; Q8WVX3-2: C4orf3; NbExp=3; IntAct=EBI-12806656, EBI-12003442;
CC Q96HJ5; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-12806656, EBI-9083477;
CC Q96HJ5; P19397: CD53; NbExp=3; IntAct=EBI-12806656, EBI-6657396;
CC Q96HJ5; P21854: CD72; NbExp=3; IntAct=EBI-12806656, EBI-307924;
CC Q96HJ5; O95832: CLDN1; NbExp=3; IntAct=EBI-12806656, EBI-723889;
CC Q96HJ5; P56747: CLDN6; NbExp=5; IntAct=EBI-12806656, EBI-12955011;
CC Q96HJ5; P52803: EFNA5; NbExp=3; IntAct=EBI-12806656, EBI-1753674;
CC Q96HJ5; P54852: EMP3; NbExp=3; IntAct=EBI-12806656, EBI-3907816;
CC Q96HJ5; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-12806656, EBI-711490;
CC Q96HJ5; Q01628: IFITM3; NbExp=3; IntAct=EBI-12806656, EBI-7932862;
CC Q96HJ5; P24593: IGFBP5; NbExp=3; IntAct=EBI-12806656, EBI-720480;
CC Q96HJ5; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-12806656, EBI-12070086;
CC Q96HJ5; Q16617: NKG7; NbExp=3; IntAct=EBI-12806656, EBI-3919611;
CC Q96HJ5; P60201-2: PLP1; NbExp=3; IntAct=EBI-12806656, EBI-12188331;
CC Q96HJ5; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-12806656, EBI-11721828;
CC Q96HJ5; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-12806656, EBI-8652744;
CC Q96HJ5; O43765: SGTA; NbExp=3; IntAct=EBI-12806656, EBI-347996;
CC Q96HJ5; Q9Y267: SLC22A14; NbExp=4; IntAct=EBI-12806656, EBI-12824155;
CC Q96HJ5; Q9NY91: SLC5A4; NbExp=3; IntAct=EBI-12806656, EBI-12409133;
CC Q96HJ5; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-12806656, EBI-8640191;
CC Q96HJ5; Q9BZL3: SMIM3; NbExp=3; IntAct=EBI-12806656, EBI-741850;
CC Q96HJ5; Q9UNK0: STX8; NbExp=3; IntAct=EBI-12806656, EBI-727240;
CC Q96HJ5; Q9Y6I9: TEX264; NbExp=4; IntAct=EBI-12806656, EBI-10329860;
CC Q96HJ5; Q96CE8: TM4SF18; NbExp=3; IntAct=EBI-12806656, EBI-13351685;
CC Q96HJ5; P55061: TMBIM6; NbExp=3; IntAct=EBI-12806656, EBI-1045825;
CC Q96HJ5; Q6UX40: TMEM107; NbExp=3; IntAct=EBI-12806656, EBI-12845616;
CC Q96HJ5; Q9NV12: TMEM140; NbExp=3; IntAct=EBI-12806656, EBI-2844246;
CC Q96HJ5; Q6ZP80: TMEM182; NbExp=5; IntAct=EBI-12806656, EBI-10255122;
CC Q96HJ5; A2RU14: TMEM218; NbExp=5; IntAct=EBI-12806656, EBI-10173151;
CC Q96HJ5; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-12806656, EBI-11528917;
CC Q96HJ5; Q8N0U8: VKORC1L1; NbExp=3; IntAct=EBI-12806656, EBI-11337915;
CC Q96HJ5; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-12806656, EBI-751210;
CC Q96HJ5; O95159: ZFPL1; NbExp=3; IntAct=EBI-12806656, EBI-718439;
CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Multi-pass
CC membrane protein {ECO:0000250}. Cytoplasm, perinuclear region
CC {ECO:0000250}. Note=Located in the perinuclear area.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96HJ5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96HJ5-2; Sequence=VSP_007109;
CC Name=3;
CC IsoId=Q96HJ5-3; Sequence=VSP_045798;
CC -!- TISSUE SPECIFICITY: Expressed specifically in hematopoietic cells and
CC tissues.
CC -!- DOMAIN: The C-terminal region is required for binding to CDKN3-CDK2
CC complexes and the modulation of CDKN3 activity.
CC -!- SIMILARITY: Belongs to the MS4A family. {ECO:0000305}.
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DR EMBL; L35848; AAA62319.1; -; mRNA.
DR EMBL; AY095480; AAM23312.1; -; mRNA.
DR EMBL; AY258289; AAP14648.1; -; Genomic_DNA.
DR EMBL; AP000790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008487; AAH08487.1; -; mRNA.
DR EMBL; BG494288; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS31567.1; -. [Q96HJ5-1]
DR CCDS; CCDS31568.1; -. [Q96HJ5-2]
DR CCDS; CCDS41651.1; -. [Q96HJ5-3]
DR PIR; I59258; I59258.
DR RefSeq; NP_001026836.1; NM_001031666.1. [Q96HJ5-3]
DR RefSeq; NP_001026979.1; NM_001031809.1. [Q96HJ5-2]
DR RefSeq; NP_006129.4; NM_006138.4. [Q96HJ5-1]
DR AlphaFoldDB; Q96HJ5; -.
DR SMR; Q96HJ5; -.
DR BioGRID; 107370; 39.
DR IntAct; Q96HJ5; 37.
DR STRING; 9606.ENSP00000278865; -.
DR iPTMnet; Q96HJ5; -.
DR PhosphoSitePlus; Q96HJ5; -.
DR BioMuta; MS4A3; -.
DR DMDM; 29611825; -.
DR EPD; Q96HJ5; -.
DR MassIVE; Q96HJ5; -.
DR PaxDb; Q96HJ5; -.
DR PeptideAtlas; Q96HJ5; -.
DR PRIDE; Q96HJ5; -.
DR Antibodypedia; 14413; 169 antibodies from 23 providers.
DR DNASU; 932; -.
DR Ensembl; ENST00000278865.8; ENSP00000278865.3; ENSG00000149516.14. [Q96HJ5-1]
DR Ensembl; ENST00000358152.6; ENSP00000350872.2; ENSG00000149516.14. [Q96HJ5-2]
DR Ensembl; ENST00000395032.6; ENSP00000378473.2; ENSG00000149516.14. [Q96HJ5-3]
DR Ensembl; ENST00000534744.1; ENSP00000434117.1; ENSG00000149516.14. [Q96HJ5-2]
DR GeneID; 932; -.
DR KEGG; hsa:932; -.
DR MANE-Select; ENST00000278865.8; ENSP00000278865.3; NM_006138.5; NP_006129.4.
DR UCSC; uc001nom.4; human. [Q96HJ5-1]
DR CTD; 932; -.
DR DisGeNET; 932; -.
DR GeneCards; MS4A3; -.
DR HGNC; HGNC:7317; MS4A3.
DR HPA; ENSG00000149516; Tissue enriched (bone).
DR MIM; 606498; gene.
DR neXtProt; NX_Q96HJ5; -.
DR OpenTargets; ENSG00000149516; -.
DR PharmGKB; PA31112; -.
DR VEuPathDB; HostDB:ENSG00000149516; -.
DR eggNOG; ENOG502T41X; Eukaryota.
DR GeneTree; ENSGT00940000162383; -.
DR HOGENOM; CLU_091032_6_2_1; -.
DR InParanoid; Q96HJ5; -.
DR OMA; QRHFFFF; -.
DR OrthoDB; 1239340at2759; -.
DR PhylomeDB; Q96HJ5; -.
DR TreeFam; TF335157; -.
DR PathwayCommons; Q96HJ5; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q96HJ5; -.
DR BioGRID-ORCS; 932; 9 hits in 1075 CRISPR screens.
DR GeneWiki; MS4A3; -.
DR GenomeRNAi; 932; -.
DR Pharos; Q96HJ5; Tbio.
DR PRO; PR:Q96HJ5; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96HJ5; protein.
DR Bgee; ENSG00000149516; Expressed in bone marrow and 83 other tissues.
DR ExpressionAtlas; Q96HJ5; baseline and differential.
DR Genevisible; Q96HJ5; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:InterPro.
DR InterPro; IPR007237; CD20-like.
DR InterPro; IPR030417; MS4A.
DR InterPro; IPR030419; MS4A3.
DR PANTHER; PTHR23320; PTHR23320; 1.
DR PANTHER; PTHR23320:SF74; PTHR23320:SF74; 1.
DR Pfam; PF04103; CD20; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Membrane; Receptor; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..214
FT /note="Membrane-spanning 4-domains subfamily A member 3"
FT /id="PRO_0000158632"
FT TOPO_DOM 1..49
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 50..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..81
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 146..175
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..214
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..123
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045798"
FT VAR_SEQ 53..98
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_007109"
FT CONFLICT 24
FT /note="A -> T (in Ref. 1; AAA62319)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="Q -> H (in Ref. 1; AAA62319)"
FT /evidence="ECO:0000305"
FT CONFLICT 38
FT /note="D -> N (in Ref. 1; AAA62319)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 214 AA; 22933 MW; D30C276213DB8F3D CRC64;
MASHEVDNAE LGSASAHGTP GSEAGPEELN TSVYQPIDGS PDYQKAKLQV LGAIQILNAA
MILALGVFLG SLQYPYHFQK HFFFFTFYTG YPIWGAVFFC SSGTLSVVAG IKPTRTWIQN
SFGMNIASAT IALVGTAFLS LNIAVNIQSL RSCHSSSESP DLCNYMGSIS NGMVSLLLIL
TLLELCVTIS TIAMWCNANC CNSREEISSP PNSV
