MACIR_HUMAN
ID MACIR_HUMAN Reviewed; 206 AA.
AC Q96GV9;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Macrophage immunometabolism regulator;
GN Name=MACIR {ECO:0000312|HGNC:HGNC:25052}; Synonyms=C5orf30;
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].
RC TISSUE=Astrocyte;
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].
RA Mural R.J., Istrail S., Sutton G.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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-167, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-167, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH UNC119 AND UNC119B.
RX PubMed=22085962; DOI=10.1101/gad.173443.111;
RA Wright K.J., Baye L.M., Olivier-Mason A., Mukhopadhyay S., Sang L.,
RA Kwong M., Wang W., Pretorius P.R., Sheffield V.C., Sengupta P.,
RA Slusarski D.C., Jackson P.K.;
RT "An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary
RT cilium.";
RL Genes Dev. 25:2347-2360(2011).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25 AND SER-167, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25; SER-140 AND SER-167, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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).
RN [10]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=26316022; DOI=10.1073/pnas.1501947112;
RA Muthana M., Hawtree S., Wilshaw A., Linehan E., Roberts H., Khetan S.,
RA Adeleke G., Wright F., Akil M., Fearon U., Veale D., Ciani B., Wilson A.G.;
RT "C5orf30 is a negative regulator of tissue damage in rheumatoid
RT arthritis.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:11618-11623(2015).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INDUCTION.
RX PubMed=30659109; DOI=10.4049/jimmunol.1801155;
RA Dorris E.R., Tazzyman S.J., Moylett J., Ramamoorthi N., Hackney J.,
RA Townsend M., Muthana M., Lewis M.J., Pitzalis C., Wilson A.G.;
RT "The Autoimmune Susceptibility Gene C5orf30 Regulates Macrophage-Mediated
RT Resolution of Inflammation.";
RL J. Immunol. 202:1069-1078(2019).
CC -!- FUNCTION: Regulates the macrophage function, by enhancing the
CC resolution of inflammation and wound repair functions mediated by M2
CC macrophages (PubMed:30659109). The regulation of macrophage function
CC is, due at least in part, to its ability to inhibit glycolysis
CC (PubMed:30659109). May also play a role in trafficking of proteins via
CC its interaction with UNC119 and UNC119B cargo adapters: may help the
CC release of UNC119 and UNC119B cargo or the recycling of UNC119 and
CC UNC119B (PubMed:22085962). May play a role in ciliary membrane
CC localization via its interaction with UNC119B and protein transport
CC into photoreceptor cells (PubMed:22085962).
CC {ECO:0000269|PubMed:22085962, ECO:0000269|PubMed:30659109}.
CC -!- SUBUNIT: Interacts with UNC119 and UNC119B; interaction preferentially
CC takes place when UNC119 and UNC119B are unliganded with myristoylated
CC proteins. {ECO:0000269|PubMed:22085962}.
CC -!- INTERACTION:
CC Q96GV9; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-2350695, EBI-371922;
CC Q96GV9; Q92993: KAT5; NbExp=3; IntAct=EBI-2350695, EBI-399080;
CC Q96GV9; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-2350695, EBI-11742507;
CC Q96GV9; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-2350695, EBI-302345;
CC Q96GV9; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-2350695, EBI-9090795;
CC Q96GV9; Q13077: TRAF1; NbExp=3; IntAct=EBI-2350695, EBI-359224;
CC Q96GV9; P61981: YWHAG; NbExp=4; IntAct=EBI-2350695, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22085962,
CC ECO:0000269|PubMed:30659109}. Cell projection, cilium
CC {ECO:0000269|PubMed:22085962}. Note=Localizes to the transition zone
CC and proximal cilium in addition to being found throughout the
CC cytoplasm. {ECO:0000269|PubMed:22085962}.
CC -!- TISSUE SPECIFICITY: High expression in normal macrophages, monocytes,
CC and cultured rheumatoid arthritis synovial fibroblasts (RASFs), with
CC lower expression in B- and T-cells, and little to no expression in
CC other tissues and cell lines. {ECO:0000269|PubMed:26316022}.
CC -!- INDUCTION: Up-regulated by hypoxia in cultured rheumatoid arthritis
CC synovial fibroblasts (PubMed:26316022). Down-regulated by TNF in
CC cultured rheumatoid arthritis synovial fibroblasts (PubMed:26316022).
CC Down-regulated by the inflammatory mediators LPS and TNF in primary
CC monocyte-derived macrophages via a c-Jun N-terminal kinase mediated
CC mechanism (PubMed:30659109). {ECO:0000269|PubMed:26316022,
CC ECO:0000269|PubMed:30659109}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:18669648,
CC ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692,
CC ECO:0000269|PubMed:23186163, ECO:0000269|PubMed:30659109}.
CC -!- SIMILARITY: Belongs to the UNC119-binding protein family.
CC {ECO:0000305}.
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DR EMBL; AK090558; BAC03478.1; -; mRNA.
DR EMBL; CH471086; EAW49075.1; -; Genomic_DNA.
DR EMBL; BC009203; AAH09203.1; -; mRNA.
DR CCDS; CCDS4095.1; -.
DR RefSeq; NP_001303897.1; NM_001316968.1.
DR RefSeq; NP_001303898.1; NM_001316969.1.
DR RefSeq; NP_149988.1; NM_033211.3.
DR AlphaFoldDB; Q96GV9; -.
DR BioGRID; 124702; 28.
DR IntAct; Q96GV9; 21.
DR STRING; 9606.ENSP00000326110; -.
DR iPTMnet; Q96GV9; -.
DR PhosphoSitePlus; Q96GV9; -.
DR BioMuta; C5orf30; -.
DR EPD; Q96GV9; -.
DR jPOST; Q96GV9; -.
DR MassIVE; Q96GV9; -.
DR MaxQB; Q96GV9; -.
DR PaxDb; Q96GV9; -.
DR PeptideAtlas; Q96GV9; -.
DR PRIDE; Q96GV9; -.
DR ProteomicsDB; 76669; -.
DR Antibodypedia; 52940; 7 antibodies from 7 providers.
DR DNASU; 90355; -.
DR Ensembl; ENST00000319933.7; ENSP00000326110.2; ENSG00000181751.10.
DR Ensembl; ENST00000510890.1; ENSP00000421270.1; ENSG00000181751.10.
DR Ensembl; ENST00000515669.5; ENSP00000422836.1; ENSG00000181751.10.
DR GeneID; 90355; -.
DR KEGG; hsa:90355; -.
DR MANE-Select; ENST00000319933.7; ENSP00000326110.2; NM_033211.4; NP_149988.1.
DR UCSC; uc003kog.2; human.
DR CTD; 90355; -.
DR DisGeNET; 90355; -.
DR GeneCards; MACIR; -.
DR HGNC; HGNC:25052; MACIR.
DR HPA; ENSG00000181751; Tissue enhanced (brain).
DR MIM; 616608; gene.
DR neXtProt; NX_Q96GV9; -.
DR OpenTargets; ENSG00000181751; -.
DR VEuPathDB; HostDB:ENSG00000181751; -.
DR eggNOG; ENOG502QRGS; Eukaryota.
DR GeneTree; ENSGT00390000005782; -.
DR HOGENOM; CLU_082309_0_0_1; -.
DR InParanoid; Q96GV9; -.
DR OMA; LHMNSNY; -.
DR OrthoDB; 1190422at2759; -.
DR PhylomeDB; Q96GV9; -.
DR TreeFam; TF331553; -.
DR PathwayCommons; Q96GV9; -.
DR SignaLink; Q96GV9; -.
DR BioGRID-ORCS; 90355; 21 hits in 1051 CRISPR screens.
DR ChiTaRS; C5orf30; human.
DR GenomeRNAi; 90355; -.
DR Pharos; Q96GV9; Tdark.
DR PRO; PR:Q96GV9; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q96GV9; protein.
DR Bgee; ENSG00000181751; Expressed in middle temporal gyrus and 192 other tissues.
DR Genevisible; Q96GV9; HS.
DR GO; GO:0035869; C:ciliary transition zone; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0010631; P:epithelial cell migration; IEA:Ensembl.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IBA:GO_Central.
DR GO; GO:0010633; P:negative regulation of epithelial cell migration; IEA:Ensembl.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; IBA:GO_Central.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR InterPro; IPR029219; UNC119-bd.
DR PANTHER; PTHR31224; PTHR31224; 1.
DR Pfam; PF15435; UNC119_bdg; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell projection; Cilium; Cilium biogenesis/degradation;
KW Cytoplasm; Inflammatory response; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..206
FT /note="Macrophage immunometabolism regulator"
FT /id="PRO_0000316776"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
SQ SEQUENCE 206 AA; 23083 MW; 5D52D27AC5CA7A85 CRC64;
MEVDINGESR STLTTLPFPG AEANSPGKAE AEKPRCSSTP CSPMRRTVSG YQILHMDSNY
LVGFTTGEEL LKLAQKCTGG EESKAEAMPS LRSKQLDAGL ARSSRLYKTR SRYYQPYEIP
AVNGRRRRRM PSSGDKCTKS LPYEPYKALH GPLPLCLLKG KRAHSKSLDY LNLDKMIKEP
ADTEVLQYQL QHLTLRGDRV FARNNT
