ID F168B_HUMAN Reviewed; 195 AA. AC A1KXE4; Q2TAZ6; Q6NZ40; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 1. DT 24-JAN-2024, entry version 116. DE RecName: Full=Myelin-associated neurite-outgrowth inhibitor; DE Short=Mani; DE AltName: Full=p20; GN Name=FAM168B; Synonyms=KIAA0280L, MANI; 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), HOMODIMERIZATION, INTERACTION WITH RP CDC27; PRDX6 AND RBM6, AND TISSUE SPECIFICITY. RX PubMed=20716133; DOI=10.1111/j.1582-4934.2010.01134.x; RA Mishra M., Akatsu H., Heese K.; RT "The novel protein MANI modulates neurogenesis and neurite-cone growth."; RL J. Cell. Mol. Med. 15:1713-1725(2011). 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Eye; 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 ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [5] RP INTERACTION WITH DAZAP2; FAM168A; TMTC1 AND YPEL2. RX PubMed=22771904; DOI=10.1016/j.febslet.2012.06.043; RA Mishra M., Lee S., Lin M.K., Yamashita T., Heese K.; RT "Characterizing the neurite outgrowth inhibitory effect of Mani."; RL FEBS Lett. 586:3018-3023(2012). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6, AND IDENTIFICATION BY MASS RP 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: Inhibitor of neuronal axonal outgrowth. Acts as a negative CC regulator of CDC42 and STAT3 and a positive regulator of STMN2. CC Positive regulator of CDC27. {ECO:0000250|UniProtKB:D4AEP3}. CC -!- SUBUNIT: May form homodimers. May interact with DAZAP2, FAM168A, PRDX6, CC RBM6, TMTC1 and YPEL2. Interacts with CDC27. CC {ECO:0000269|PubMed:20716133, ECO:0000269|PubMed:22771904}. CC -!- INTERACTION: CC A1KXE4-2; P21549: AGXT; NbExp=3; IntAct=EBI-12193763, EBI-727098; CC A1KXE4-2; Q03989: ARID5A; NbExp=3; IntAct=EBI-12193763, EBI-948603; CC A1KXE4-2; O95817: BAG3; NbExp=3; IntAct=EBI-12193763, EBI-747185; CC A1KXE4-2; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-12193763, EBI-1383687; CC A1KXE4-2; O75909-2: CCNK; NbExp=3; IntAct=EBI-12193763, EBI-12010594; CC A1KXE4-2; P33240: CSTF2; NbExp=3; IntAct=EBI-12193763, EBI-711360; CC A1KXE4-2; Q9H0L4: CSTF2T; NbExp=3; IntAct=EBI-12193763, EBI-747012; CC A1KXE4-2; Q9H6Z9: EGLN3; NbExp=3; IntAct=EBI-12193763, EBI-1175354; CC A1KXE4-2; Q92567-2: FAM168A; NbExp=3; IntAct=EBI-12193763, EBI-11978259; CC A1KXE4-2; Q8WU58: FAM222B; NbExp=3; IntAct=EBI-12193763, EBI-2807642; CC A1KXE4-2; P22607: FGFR3; NbExp=3; IntAct=EBI-12193763, EBI-348399; CC A1KXE4-2; O75593: FOXH1; NbExp=3; IntAct=EBI-12193763, EBI-1759806; CC A1KXE4-2; Q12951-2: FOXI1; NbExp=3; IntAct=EBI-12193763, EBI-12018822; CC A1KXE4-2; Q9BZE0: GLIS2; NbExp=3; IntAct=EBI-12193763, EBI-7251368; CC A1KXE4-2; Q13227: GPS2; NbExp=3; IntAct=EBI-12193763, EBI-713355; CC A1KXE4-2; P17482: HOXB9; NbExp=3; IntAct=EBI-12193763, EBI-745290; CC A1KXE4-2; Q9ULV5-2: HSF4; NbExp=3; IntAct=EBI-12193763, EBI-12056251; CC A1KXE4-2; O14901: KLF11; NbExp=3; IntAct=EBI-12193763, EBI-948266; CC A1KXE4-2; Q6PEX3: KRTAP26-1; NbExp=3; IntAct=EBI-12193763, EBI-3957672; CC A1KXE4-2; Q14847-2: LASP1; NbExp=3; IntAct=EBI-12193763, EBI-9088686; CC A1KXE4-2; Q71SY5: MED25; NbExp=3; IntAct=EBI-12193763, EBI-394558; CC A1KXE4-2; Q8IXL7-2: MSRB3; NbExp=3; IntAct=EBI-12193763, EBI-10699187; CC A1KXE4-2; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-12193763, EBI-5662487; CC A1KXE4-2; Q14511-2: NEDD9; NbExp=3; IntAct=EBI-12193763, EBI-11746523; CC A1KXE4-2; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-12193763, EBI-2811583; CC A1KXE4-2; P32242: OTX1; NbExp=3; IntAct=EBI-12193763, EBI-740446; CC A1KXE4-2; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-12193763, EBI-11022007; CC A1KXE4-2; P78337: PITX1; NbExp=3; IntAct=EBI-12193763, EBI-748265; CC A1KXE4-2; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-12193763, EBI-1389308; CC A1KXE4-2; Q96HA1-2: POM121; NbExp=3; IntAct=EBI-12193763, EBI-11956563; CC A1KXE4-2; P0CG20: PRR35; NbExp=3; IntAct=EBI-12193763, EBI-11986293; CC A1KXE4-2; Q9BTL3: RAMAC; NbExp=3; IntAct=EBI-12193763, EBI-744023; CC A1KXE4-2; O43251-10: RBFOX2; NbExp=3; IntAct=EBI-12193763, EBI-11963050; CC A1KXE4-2; Q9BQY4: RHOXF2; NbExp=3; IntAct=EBI-12193763, EBI-372094; CC A1KXE4-2; Q01974: ROR2; NbExp=3; IntAct=EBI-12193763, EBI-6422642; CC A1KXE4-2; Q7Z3H4: SAMD7; NbExp=3; IntAct=EBI-12193763, EBI-12148649; CC A1KXE4-2; Q7Z5V6-2: SAXO4; NbExp=3; IntAct=EBI-12193763, EBI-12000762; CC A1KXE4-2; P14678-2: SNRPB; NbExp=3; IntAct=EBI-12193763, EBI-372475; CC A1KXE4-2; P09234: SNRPC; NbExp=3; IntAct=EBI-12193763, EBI-766589; CC A1KXE4-2; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-12193763, EBI-11959123; CC A1KXE4-2; Q9NQB0-10: TCF7L2; NbExp=3; IntAct=EBI-12193763, EBI-11746252; CC A1KXE4-2; Q96A09: TENT5B; NbExp=3; IntAct=EBI-12193763, EBI-752030; CC A1KXE4-2; Q01085-2: TIAL1; NbExp=3; IntAct=EBI-12193763, EBI-11064654; CC A1KXE4-2; Q08117-2: TLE5; NbExp=3; IntAct=EBI-12193763, EBI-11741437; CC A1KXE4-2; O43711: TLX3; NbExp=3; IntAct=EBI-12193763, EBI-3939165; CC A1KXE4-2; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-12193763, EBI-2514383; CC A1KXE4-2; O95231: VENTX; NbExp=3; IntAct=EBI-12193763, EBI-10191303; CC A1KXE4-2; Q14119: VEZF1; NbExp=3; IntAct=EBI-12193763, EBI-11980193; CC A1KXE4-2; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-12193763, EBI-11957216; CC A1KXE4-2; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-12193763, EBI-2559305; CC A1KXE4-2; Q64LD2-2: WDR25; NbExp=3; IntAct=EBI-12193763, EBI-12032042; CC A1KXE4-2; Q96K80: ZC3H10; NbExp=3; IntAct=EBI-12193763, EBI-742550; CC A1KXE4-2; Q15915: ZIC1; NbExp=3; IntAct=EBI-12193763, EBI-11963196; CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:D4AEP3}. Cell membrane CC {ECO:0000250|UniProtKB:Q80XQ8}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:Q80XQ8}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q80XQ8}. Note=Expressed in neuronal cell bodies CC and axonal fibers. {ECO:0000250|UniProtKB:Q80XQ8}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=A1KXE4-1; Sequence=Displayed; CC Name=2; CC IsoId=A1KXE4-2; Sequence=VSP_032508; CC -!- TISSUE SPECIFICITY: Expressed in the brain, within neuronal axonal CC fibers and associated with myelin sheets (at protein level). Expression CC tends to be lower in the brain of Alzheimer disease patients compared CC to healthy individuals (at protein level). CC {ECO:0000269|PubMed:20716133}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:D4AEP3}. CC -!- SIMILARITY: Belongs to the FAM168 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY253283; AAP79599.1; -; mRNA. DR EMBL; CH471250; EAW51267.1; -; Genomic_DNA. DR EMBL; BC066347; AAH66347.1; -; mRNA. DR EMBL; BC110642; AAI10643.1; -; mRNA. DR CCDS; CCDS42755.1; -. [A1KXE4-1] DR RefSeq; NP_001009993.2; NM_001009993.3. [A1KXE4-1] DR RefSeq; NP_001308672.1; NM_001321743.1. [A1KXE4-1] DR RefSeq; NP_001308673.1; NM_001321744.1. [A1KXE4-1] DR RefSeq; NP_001308674.1; NM_001321745.1. [A1KXE4-1] DR RefSeq; NP_001308675.1; NM_001321746.1. [A1KXE4-1] DR RefSeq; NP_001308676.1; NM_001321747.1. [A1KXE4-1] DR RefSeq; NP_001308677.1; NM_001321748.1. [A1KXE4-1] DR RefSeq; XP_016858816.1; XM_017003327.1. [A1KXE4-1] DR AlphaFoldDB; A1KXE4; -. DR BioGRID; 126221; 56. DR IntAct; A1KXE4; 58. DR MINT; A1KXE4; -. DR STRING; 9606.ENSP00000374565; -. DR GlyCosmos; A1KXE4; 1 site, No reported glycans. DR GlyGen; A1KXE4; 1 site. DR iPTMnet; A1KXE4; -. DR PhosphoSitePlus; A1KXE4; -. DR BioMuta; FAM168B; -. DR EPD; A1KXE4; -. DR jPOST; A1KXE4; -. DR MassIVE; A1KXE4; -. DR MaxQB; A1KXE4; -. DR PaxDb; 9606-ENSP00000387051; -. DR PeptideAtlas; A1KXE4; -. DR ProteomicsDB; 124; -. [A1KXE4-1] DR ProteomicsDB; 125; -. [A1KXE4-2] DR Pumba; A1KXE4; -. DR Antibodypedia; 50282; 60 antibodies from 15 providers. DR DNASU; 130074; -. DR Ensembl; ENST00000389915.4; ENSP00000374565.3; ENSG00000152102.18. [A1KXE4-1] DR Ensembl; ENST00000409185.5; ENSP00000387051.1; ENSG00000152102.18. [A1KXE4-1] DR GeneID; 130074; -. DR KEGG; hsa:130074; -. DR MANE-Select; ENST00000389915.4; ENSP00000374565.3; NM_001009993.4; NP_001009993.2. DR UCSC; uc002tsd.4; human. [A1KXE4-1] DR AGR; HGNC:27016; -. DR CTD; 130074; -. DR DisGeNET; 130074; -. DR GeneCards; FAM168B; -. DR HGNC; HGNC:27016; FAM168B. DR HPA; ENSG00000152102; Low tissue specificity. DR MIM; 620078; gene. DR neXtProt; NX_A1KXE4; -. DR OpenTargets; ENSG00000152102; -. DR PharmGKB; PA162387098; -. DR VEuPathDB; HostDB:ENSG00000152102; -. DR eggNOG; ENOG502QQDS; Eukaryota. DR GeneTree; ENSGT00390000005140; -. DR HOGENOM; CLU_065824_1_0_1; -. DR InParanoid; A1KXE4; -. DR OMA; MYPAANP; -. DR OrthoDB; 5315493at2759; -. DR PhylomeDB; A1KXE4; -. DR TreeFam; TF331128; -. DR PathwayCommons; A1KXE4; -. DR SignaLink; A1KXE4; -. DR BioGRID-ORCS; 130074; 15 hits in 1163 CRISPR screens. DR ChiTaRS; FAM168B; human. DR GenomeRNAi; 130074; -. DR Pharos; A1KXE4; Tdark. DR PRO; PR:A1KXE4; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; A1KXE4; Protein. DR Bgee; ENSG00000152102; Expressed in lateral globus pallidus and 212 other cell types or tissues. DR ExpressionAtlas; A1KXE4; baseline and differential. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR InterPro; IPR029247; FAM168A/MANI. DR PANTHER; PTHR31844:SF2; MYELIN-ASSOCIATED NEURITE-OUTGROWTH INHIBITOR; 1. DR PANTHER; PTHR31844; MYELIN-ASSOCIATED NEURITE-OUTGROWTH INHIBITOR-RELATED; 1. DR Pfam; PF14944; TCRP1; 2. DR Genevisible; A1KXE4; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cell membrane; Cell projection; KW Cytoplasm; Glycoprotein; Membrane; Phosphoprotein; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1..195 FT /note="Myelin-associated neurite-outgrowth inhibitor" FT /id="PRO_0000325978" FT TOPO_DOM 1..18 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 19..42 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 43..142 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 143..164 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 165..195 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 6 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 46 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 78..195 FT /note="NPYQTAVYPVRSAYPQQSPYAQQGTYYTQPLYAAPPHVIHHTTVVQPNGMPA FT TVYPAPIPPPRGNGVTMGMVAGTTMAMSAGTLLTAHSPTPVAPHPVTVPTYRAPGTPTY FT SYVPPQW -> QAVPMSPCADQWARQLGQISGQPFVLLAGLLCWPHGEALESLMDCN FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_032508" FT CONFLICT 7 FT /note="P -> L (in Ref. 3; AAI10643)" FT /evidence="ECO:0000305" SQ SEQUENCE 195 AA; 20324 MW; 27A0D0D74AB44A10 CRC64; MNPVYSPGSS GVPYANAKGI GYPAGFPMGY AAAAPAYSPN MYPGANPTFQ TGYTPGTPYK VSCSPTSGAV PPYSSSPNPY QTAVYPVRSA YPQQSPYAQQ GTYYTQPLYA APPHVIHHTT VVQPNGMPAT VYPAPIPPPR GNGVTMGMVA GTTMAMSAGT LLTAHSPTPV APHPVTVPTY RAPGTPTYSY VPPQW //