ID   CMAH_HUMAN              Reviewed;         501 AA.
AC   Q9Y471; C1K3L2; O95250; Q5TD41; Q5TD42; Q5TD43; Q5TD44; Q68DC3; Q9UEE7;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   29-APR-2015, sequence version 4.
DT   24-JAN-2024, entry version 136.
DE   RecName: Full=Inactive cytidine monophosphate-N-acetylneuraminic acid hydroxylase {ECO:0000305|PubMed:9751737};
DE            Short=CMP-NeuAc hydroxylase-like protein;
DE   AltName: Full=Cytidine monophosphate-N-acetylneuraminic acid hydroxylase pseudogene;
GN   Name=CMAHP; Synonyms=CMAH;
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), AND LACK OF ENZYME ACTIVITY.
RX   PubMed=9751737; DOI=10.1073/pnas.95.20.11751;
RA   Chou H.-H., Takematsu H., Diaz S., Iber J., Nickerson E., Wright K.L.,
RA   Muchmore E.A., Nelson D.L., Warren S.T., Varki A.;
RT   "A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-
RT   Pan divergence.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:11751-11756(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, LACK OF ENZYME ACTIVITY,
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=19890979; DOI=10.1002/stem.250;
RA   Nystedt J., Anderson H., Hirvonen T., Impola U., Jaatinen T., Heiskanen A.,
RA   Blomqvist M., Satomaa T., Natunen J., Saarinen J., Lehenkari P., Valmu L.,
RA   Laine J.;
RT   "Human CMP-N-acetylneuraminic acid hydroxylase is a novel stem cell marker
RT   linked to stem cell-specific mechanisms.";
RL   Stem Cells 28:258-267(2010).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), LACK OF ENZYME
RP   ACTIVITY, AND TISSUE SPECIFICITY.
RX   PubMed=9624188; DOI=10.1074/jbc.273.25.15866;
RA   Irie A., Koyama S., Kozutsumi Y., Kawasaki T., Suzuki A.;
RT   "The molecular basis for the absence of N-glycolylneuraminic acid in
RT   humans.";
RL   J. Biol. Chem. 273:15866-15871(1998).
RN   [5]
RP   ENZYME INACTIVATION.
RX   PubMed=11562455; DOI=10.1073/pnas.191268198;
RA   Hayakawa T., Satta Y., Gagneux P., Varki A., Takahata N.;
RT   "Alu-mediated inactivation of the human CMP-N-acetylneuraminic acid
RT   hydroxylase gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:11399-11404(2001).
RN   [6]
RP   ENZYME INACTIVATION.
RX   PubMed=12192086; DOI=10.1073/pnas.182257399;
RA   Chou H.-H., Hayakawa T., Diaz S., Krings M., Indriati E., Leakey M.,
RA   Paabo S., Satta Y., Takahata N., Varki A.;
RT   "Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to
RT   brain expansion during human evolution.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:11736-11741(2002).
CC   -!- FUNCTION: Sialic acids are components of carbohydrate chains of
CC       glycoconjugates and are involved in cell-cell recognition and cell-
CC       pathogen interactions. That protein has no CMP-N-acetylneuraminate
CC       monooxygenase activity and is not able to convert CMP-N-
CC       acetylneuraminic acid (CMP-Neu5Ac) into its hydroxylated derivative
CC       CMP-N-glycolylneuraminic acid (CMP-Neu5Gc), a sialic acid abundantly
CC       expressed at the surface of many cells in vertebrates (PubMed:9624188).
CC       However, it may play a role in Wnt signaling (PubMed:19890979).
CC       {ECO:0000269|PubMed:19890979, ECO:0000269|PubMed:9624188,
CC       ECO:0000303|PubMed:11562455, ECO:0000303|PubMed:12192086,
CC       ECO:0000303|PubMed:9751737}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19890979}. Note=May
CC       localize to membranes, nucleus and cytoskeleton.
CC       {ECO:0000269|PubMed:19890979}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9Y471-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9Y471-4; Sequence=VSP_057565, VSP_057566;
CC   -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in thymus. Not
CC       expressed in brain. May be expressed in adult stem cells (at protein
CC       level) (PubMed:19890979). {ECO:0000269|PubMed:19890979,
CC       ECO:0000269|PubMed:9624188}.
CC   -!- SIMILARITY: Belongs to the CMP-Neu5Ac hydroxylase family.
CC       {ECO:0000305}.
CC   -!- CAUTION: An Alu-mediated mutation of this gene occured in a common
CC       ancestor of Homo sapiens and Homo sapiens neanderthalis, approximately
CC       2.1-2.2 million years ago, before brain expansion. It is generally
CC       accepted that the product of this gene, if any, is catalytically
CC       inactive as suggested by the absence of CMP-Neu5Gc sialic acid in
CC       human, while it is abundantly expressed at the surface of many cells in
CC       other vertebrates. The gene is however, significantly transcribed and
CC       the product described here might be expressed in vivo
CC       (PubMed:19890979). The putative protein is N-terminally truncated
CC       compared to orthologs and lacks a region probably essential to the CMP-
CC       N-acetylneuraminate monooxygenase activity.
CC       {ECO:0000269|PubMed:19890979, ECO:0000305|PubMed:11562455,
CC       ECO:0000305|PubMed:12192086, ECO:0000305|PubMed:9624188,
CC       ECO:0000305|PubMed:9751737}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC68881.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR   EMBL; AF074480; AAC68881.1; ALT_SEQ; mRNA.
DR   EMBL; FJ794466; ACN93797.1; -; mRNA.
DR   EMBL; AL133268; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AB009668; BAA31198.1; -; Genomic_DNA.
DR   EMBL; D86324; BAA31160.1; -; mRNA.
DR   AlphaFoldDB; Q9Y471; -.
DR   IntAct; Q9Y471; 1.
DR   iPTMnet; Q9Y471; -.
DR   PhosphoSitePlus; Q9Y471; -.
DR   BioMuta; HGNC:2098; -.
DR   DMDM; 223590237; -.
DR   MassIVE; Q9Y471; -.
DR   PeptideAtlas; Q9Y471; -.
DR   AGR; HGNC:2098; -.
DR   GeneCards; CMAHP; -.
DR   HGNC; HGNC:2098; CMAHP.
DR   MIM; 603209; gene.
DR   neXtProt; NX_Q9Y471; -.
DR   InParanoid; Q9Y471; -.
DR   PhylomeDB; Q9Y471; -.
DR   TreeFam; TF331273; -.
DR   BRENDA; 1.14.18.2; 2681.
DR   PathwayCommons; Q9Y471; -.
DR   ChiTaRS; CMAHP; human.
DR   Pharos; Q9Y471; Tdark.
DR   PRO; PR:Q9Y471; -.
DR   Proteomes; UP000005640; Unplaced.
DR   RNAct; Q9Y471; Protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0030338; F:CMP-N-acetylneuraminate monooxygenase activity; IBA:GO_Central.
DR   GO; GO:0046381; P:CMP-N-acetylneuraminate metabolic process; IBA:GO_Central.
DR   GO; GO:0030111; P:regulation of Wnt signaling pathway; IMP:UniProtKB.
DR   Gene3D; 3.60.15.10; Ribonuclease Z/Hydroxyacylglutathione hydrolase-like; 1.
DR   InterPro; IPR027033; Cnh.
DR   InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR   PANTHER; PTHR46522; CYTIDINE MONOPHOSPHATE-N-ACETYLNEURAMINIC ACID HYDROXYLASE; 1.
DR   PANTHER; PTHR46522:SF3; INACTIVE CYTIDINE MONOPHOSPHATE-N-ACETYLNEURAMINIC ACID HYDROXYLASE; 1.
DR   Pfam; PF13483; Lactamase_B_3; 1.
DR   SUPFAM; SSF56281; Metallo-hydrolase/oxidoreductase; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Reference proteome.
FT   CHAIN           1..501
FT                   /note="Inactive cytidine monophosphate-N-acetylneuraminic
FT                   acid hydroxylase"
FT                   /id="PRO_0000127801"
FT   VAR_SEQ         478..486
FT                   /note="VILQFSTER -> AILQECKTT (in isoform 2)"
FT                   /id="VSP_057565"
FT   VAR_SEQ         487..501
FT                   /note="Missing (in isoform 2)"
FT                   /id="VSP_057566"
FT   CONFLICT        87
FT                   /note="I -> V (in Ref. 4; BAA31160)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        181
FT                   /note="I -> T (in Ref. 4; BAA31160)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        241
FT                   /note="R -> W (in Ref. 4; BAA31160)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        310
FT                   /note="R -> P (in Ref. 4; BAA31160)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        478
FT                   /note="V -> A (in Ref. 2; ACN93797 and 1; AAC68881)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   501 AA;  58380 MW;  7C340A121B5ACA4D CRC64;
     MDENNGLLLL ELNPPNPWDL QPRSPEELAF GEVQITYLTH ACMDLKLGDK RMVFDPWLIG
     PAFARGWWLL HEPPSDWLER LCQADLIYIS HLHSDHLSYP TLKKLAGRRP DIPIYVGNTE
     RPVFWNLNQS GVQLTNINVV PFGIWQQVDK NLRFMILMDG VHPEMDTCII VEYKGHKILN
     IVDCTRPNGG RLPMKVALMM SDFAGGASGF PMTFSGGKFT EEWKAQFIKT ERKKLLNYKA
     RLVKNLQPRI YCPFAGYFVE SHPSDKYIKE TNTKNDPNEL NNLIKKNSDV ITWTPRPGAT
     LDLGRMLKDR TDSKGIIEPP EGTKIYKDSW DFEPYLEILN AALGDEIFLH SSWIKEYFTW
     AGFKDYNLVV RMIETDEDFN PFPGGYDYLV DFLDLSFPKE RPQREHPYEE IHSRVDVIRH
     VVKNGLLWDE LYIGFQTRLQ RDPDIYHHLF WNHFQIKLPL TPPNWKSFLM CCEQNGPVIL
     QFSTERTNEP NRNKFSVENK A
//