ID   MARH3_HUMAN             Reviewed;         253 AA.
AC   Q86UD3; A8K264; B9EJE7;
DT   15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   22-FEB-2023, entry version 156.
DE   RecName: Full=E3 ubiquitin-protein ligase MARCHF3;
DE            EC=2.3.2.27;
DE   AltName: Full=Membrane-associated RING finger protein 3;
DE   AltName: Full=Membrane-associated RING-CH protein III;
DE            Short=MARCH-III;
DE   AltName: Full=RING finger protein 173;
DE   AltName: Full=RING-type E3 ubiquitin transferase MARCHF3 {ECO:0000305};
GN   Name=MARCHF3 {ECO:0000312|HGNC:HGNC:28728}; Synonyms=MARCH3, RNF173;
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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-68.
RC   TISSUE=Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain;
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   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=16428329; DOI=10.1093/jb/mvj012;
RA   Fukuda H., Nakamura N., Hirose S.;
RT   "MARCH-III is a novel component of endosomes with properties similar to
RT   those of MARCH-II.";
RL   J. Biochem. 139:137-145(2006).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237 AND SER-243, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase which may be involved in
CC       endosomal trafficking. E3 ubiquitin ligases accept ubiquitin from an E2
CC       ubiquitin-conjugating enzyme in the form of a thioester and then
CC       directly transfer the ubiquitin to targeted substrates.
CC       {ECO:0000250|UniProtKB:Q5XIE5}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC         [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC         cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC         EC=2.3.2.27;
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with MARCHF2 and STX6. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q86UD3; Q9BQE5: APOL2; NbExp=3; IntAct=EBI-2341065, EBI-4290634;
CC       Q86UD3; Q969F0: FATE1; NbExp=3; IntAct=EBI-2341065, EBI-743099;
CC       Q86UD3; P61086: UBE2K; NbExp=3; IntAct=EBI-2341065, EBI-473850;
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
CC       {ECO:0000269|PubMed:16428329}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:16428329}. Early endosome membrane
CC       {ECO:0000269|PubMed:16428329}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:16428329}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q86UD3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q86UD3-2; Sequence=VSP_055451, VSP_055452;
CC   -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC       activity. {ECO:0000255|PROSITE-ProRule:PRU00623}.
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DR   EMBL; AK290129; BAF82818.1; -; mRNA.
DR   EMBL; AC004507; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC005221; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC093532; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC137794; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471062; EAW62412.1; -; Genomic_DNA.
DR   EMBL; CH471062; EAW62413.1; -; Genomic_DNA.
DR   EMBL; BC047569; AAH47569.1; -; mRNA.
DR   EMBL; BC146948; AAI46949.1; -; mRNA.
DR   EMBL; BC146964; AAI46965.1; -; mRNA.
DR   CCDS; CCDS4141.1; -. [Q86UD3-1]
DR   RefSeq; NP_848545.1; NM_178450.4. [Q86UD3-1]
DR   AlphaFoldDB; Q86UD3; -.
DR   SMR; Q86UD3; -.
DR   BioGRID; 125416; 42.
DR   IntAct; Q86UD3; 11.
DR   MINT; Q86UD3; -.
DR   STRING; 9606.ENSP00000309141; -.
DR   TCDB; 8.A.159.1.9; the march ubiquitin ligase (march) family.
DR   iPTMnet; Q86UD3; -.
DR   PhosphoSitePlus; Q86UD3; -.
DR   BioMuta; MARCH3; -.
DR   DMDM; 59798460; -.
DR   MassIVE; Q86UD3; -.
DR   PaxDb; Q86UD3; -.
DR   PeptideAtlas; Q86UD3; -.
DR   Antibodypedia; 25757; 171 antibodies from 27 providers.
DR   DNASU; 115123; -.
DR   Ensembl; ENST00000308660.6; ENSP00000309141.5; ENSG00000173926.6. [Q86UD3-1]
DR   Ensembl; ENST00000515241.1; ENSP00000421979.1; ENSG00000173926.6. [Q86UD3-2]
DR   GeneID; 115123; -.
DR   KEGG; hsa:115123; -.
DR   MANE-Select; ENST00000308660.6; ENSP00000309141.5; NM_178450.5; NP_848545.1.
DR   UCSC; uc003kuf.4; human. [Q86UD3-1]
DR   AGR; HGNC:28728; -.
DR   CTD; 115123; -.
DR   DisGeNET; 115123; -.
DR   GeneCards; MARCHF3; -.
DR   HGNC; HGNC:28728; MARCHF3.
DR   HPA; ENSG00000173926; Low tissue specificity.
DR   MIM; 613333; gene.
DR   neXtProt; NX_Q86UD3; -.
DR   OpenTargets; ENSG00000173926; -.
DR   VEuPathDB; HostDB:ENSG00000173926; -.
DR   eggNOG; KOG1609; Eukaryota.
DR   GeneTree; ENSGT00940000159206; -.
DR   HOGENOM; CLU_096532_0_0_1; -.
DR   InParanoid; Q86UD3; -.
DR   OMA; TYCELCH; -.
DR   OrthoDB; 1342875at2759; -.
DR   PhylomeDB; Q86UD3; -.
DR   TreeFam; TF319557; -.
DR   PathwayCommons; Q86UD3; -.
DR   SignaLink; Q86UD3; -.
DR   SIGNOR; Q86UD3; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 115123; 30 hits in 1108 CRISPR screens.
DR   ChiTaRS; MARCH3; human.
DR   GenomeRNAi; 115123; -.
DR   Pharos; Q86UD3; Tbio.
DR   PRO; PR:Q86UD3; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q86UD3; protein.
DR   Bgee; ENSG00000173926; Expressed in pancreatic ductal cell and 145 other tissues.
DR   Genevisible; Q86UD3; HS.
DR   GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR   CDD; cd16699; RING_CH-C4HC3_MARCH2_like; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR011016; Znf_RING-CH.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR46065; E3 UBIQUITIN-PROTEIN LIGASE MARCH 2/3 FAMILY MEMBER; 1.
DR   PANTHER; PTHR46065:SF2; E3 UBIQUITIN-PROTEIN LIGASE MARCHF3; 1.
DR   Pfam; PF12906; RINGv; 1.
DR   SMART; SM00744; RINGv; 1.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   PROSITE; PS51292; ZF_RING_CH; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasmic vesicle; Endocytosis; Endosome; Membrane;
KW   Metal-binding; Phosphoprotein; Reference proteome; Transferase;
KW   Transmembrane; Transmembrane helix; Ubl conjugation pathway; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..253
FT                   /note="E3 ubiquitin-protein ligase MARCHF3"
FT                   /id="PRO_0000055927"
FT   TRANSMEM        145..165
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        182..202
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   ZN_FING         63..123
FT                   /note="RING-CH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   BINDING         71
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   BINDING         74
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   BINDING         87
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   BINDING         89
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   BINDING         97
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   BINDING         100
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   BINDING         113
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   BINDING         116
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT   MOD_RES         237
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         243
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         132..138
FT                   /note="WLRNPGP -> VSKWGTS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_055451"
FT   VAR_SEQ         139..253
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_055452"
FT   VARIANT         68
FT                   /note="R -> Q (in dbSNP:rs34821177)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_053639"
SQ   SEQUENCE   253 AA;  28504 MW;  6E090675CEBC8A88 CRC64;
     MTTSRCSHLP EVLPDCTSSA APVVKTVEDC GSLVNGQPQY VMQVSAKDGQ LLSTVVRTLA
     TQSPFNDRPM CRICHEGSSQ EDLLSPCECT GTLGTIHRSC LEHWLSSSNT SYCELCHFRF
     AVERKPRPLV EWLRNPGPQH EKRTLFGDMV CFLFITPLAT ISGWLCLRGA VDHLHFSSRL
     EAVGLIALTV ALFTIYLFWT LVSFRYHCRL YNEWRRTNQR VILLIPKSVN VPSNQPSLLG
     LHSVKRNSKE TVV
//