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Gene Model: Hlcs

NomenclatureGenomic Location
SymbolHlcsChromosome1
NameHolocarboxylase synthetaseLinkage mapunknown
SpeciesDracomimus familiarisGenome Coordinates1: 46 Mbp

Molecular Function

Post-translational modification of specific protein by attachment of biotin. Acts on various carboxylases such as acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl CoA carboxylase, and 3-methylcrotonyl CoA carboxylase

ATP + biotin + apo-[methylmalonyl-CoA:pyruvate carboxytransferase] = AMP + diphosphate + [methylmalonyl-CoA:pyruvate carboxytransferase].

ATP + biotin + apo-[propionyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [propionyl-CoA:carbon-dioxide ligase (ADP-forming)].

ATP + biotin + apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)].

ATP + biotin + apo-[acetyl-CoA:carbon-dioxide ligase (ADP-forming)] = AMP + diphosphate + [acetyl-CoA:carbon-dioxide ligase (ADP-forming)].

Molecular Function Terms:

binding
   carboxylic acid binding
      monocarboxylic acid binding
         biotin binding
   nucleotide binding
      purine nucleotide binding
         adenyl nucleotide binding
            adenyl ribonucleotide binding
               ATP binding
   protein binding
      enzyme binding
   vitamin binding
      biotin binding

catalytic activity
   ligase activity
      ligase activity, forming carbon-nitrogen bonds
         biotin-protein ligase activity

Human Disease Association

Defects in HLCS are the cause of holocarboxylase synthetase deficiency (HLCS deficiency) [MIM:253270]; also known as biotin-responsive multiple carboxylase deficiency. HLCS deficiency is a neonatal form of multiple carboxylase deficiency, an autosomal recessive disorder characterized by metabolic ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites and dermatitis. Clinical and biochemical symptoms improve dramatically with administration of biotin.

Predicted Transcript
     1 ATGGAAGATAGACTCCAAATGGATAATGGAATGGTTCCTCAAAAAATTATGTCTGTGCAC
    61 CTACAGATGTCAAAGCTGGAAGAATTAGATCAATTATCAAATATGCAGCATGGAGAATGG
   121 ACTCAAGAGCCTCCTTTTGTGACAGCTACTAAACCAGAAGTAAAAACTGCTGATTGTGCA
   181 GGAGATGATGAGGAAGAGGAGAAAGGAACAGAATATCCTGAAAAACTTGAGCAAGTATCT
   241 GAAAGAGAGGTGGATACTGGTGAACATCATCACCTGCATCTTTCTAGCTGCCACGAGTGC
   301 TTAGAACTGGAAAACAGCACAATTGAGTCTGTTAAATTTGCTTCTGTAGAAAACATTCCA
   361 GAACTTCCTGATGATTACAGTTGCAATTTGGAAGGCGTTAATAGTGACTGTCCAACAGAA
   421 TATCTGAAAAGAATAAGCCTTTCTGGGAAGCCTCCCAATATTTTAGTCTATGTTGGTTCT
   481 GACACTGAAAAAGTGAAATTTGAAGAAATAAAATCAGTCATTTTGGAATGCATTGATTTT
   541 AACTCGTATACTATCTACCAGTTGTTAGAGAAACATGTTTTAAGTGTTCCTTGGGTTCAT
   601 AATGCACTACTATTAATCATTGCTACATCAGAGCCTATCACAGATGCAGTGTCTAAACAA
   661 TTTTTAACTTTCATGTCAGAAGGTGGGAAAATTTTGGGACTTTCATCTTTTTTCACTTTT
   721 GGTGGTATACGTGTAAAGAGTAAACAAGAATTAATTGGCACAGTTCAAGCTTTTGTGTTT
   781 TCAAATGCTGAGAACAGTGAAATTAAACTCAATGTGCTAGCTAGTGGGAAAATATTTGAG
   841 AAAGAAATTGTGGAAGAACCTAACTTTCTGAAGCCACTAGGTTTCTTGGACAGTCCAGAT
   901 AAAGATATGTTGATCATCCAGCTGCCGTGTGGAAATAATGGAGGAGAAGCCATACTCTGT
   961 CAGGCACATTTAGAGGTTAATATCCAAAGTTTGTCTAATAGATCTAAAGATGACTTCAAT
  1021 TTACTCAAATTAAGCAATGCTAAAAGATACAAAGTTCTTACCAATATCCTGACCCAACTT
  1081 GGCTTGAATTGTCAAATGAGTGAAGTTCCTCCATTAACTCCTATTTACCTCCTTTCATCA
  1141 AATAAGGAAAACCACAGTTCTCTTCTGGAATGGTTAGGAAAAAATGTGAATGCAGCAGGA
  1141 AATAAGGAAAACCACAGTTCTCTTCTGGAATGGTTAGGAAAAAATGTGAATGCAGCAGGA
  1201 ATAATTACTTCCAGCAAAGTGTCCCTTAAGTTTGTATCATCTTGCAGCATGGAGACAGAA
  1261 ATAACACCCTCATTCATGCCAGTCATCACTGAGATGAAAGCTTTCTCATCTGTAAATTTC
  1321 AGCCTCGACCGATACAAGAAGAATCTACATACACAGAACCTTGGGAAAGTGGTTCTATTT
  1381 ACTGAGGTTACATCAACCACAATGGATTTGCTTGATGGGTTGATATACAAGATACCACAG
  1441 GAAATCGGTCTTATAGCAATTGCTGTTCAACAGACTCAAGGGAAAGGTCGTGGTGGAAAT
  1501 GCTTGGCTGAGTCCTGTGGGAGCTGCTTTATCCACCATTCATATCACCATTCCTTTAACA
  1561 TCCCAACTGGGTCAAAGAATTCCATTTATTCAGCATCTGGTTTCTTTAGCAGTTGTGGAG
  1621 GCTGTTAGATCCATACCTGGGTACCAGGATATTGATCTTCGAGTGAAATGGCCAAATGAT
  1681 ATTTATTACAGTGATCTTATGAAGCTTGGTGGTATTCTAGTGAATTCCACACTAACTGGA
  1741 AATACATTCCACATACTTATTGGCTGTGGATTTAACGTGAATAACAACAATCCTACTATA
  1801 TGCATCAATGATCTCATTATTGAGCACAATAAGACAAAGAATACAAATTTAAAACCTTTA
  1861 AGTGTTGACTGTCTAATTGCAAGAAGTGTGACAGTGCTGGAAAATCTGATCAGTACTTTT
  1921 CAAGAGAAAGGACCTAATGGTGTTCTTCCCTTGTATTATAAGTACTGGATACATAGTGGT
  1981 AAGCAAGTCCAGTTAGGAAGCGATGAAGGGCCAATGGCTTGGATTGTCGGAGTAGATGAT
  2041 TCTGGTTTCCTGCAAGTTCACGAGGAAGGCAAAGGCGTAGTAACTGTGCACCCAGATGGC
  2101 AATTCTTTTGACATGCTGAGAAACCTTATAATTCCAAAGCAGCGATAA

Predicted Protein Product
MEDRLQMDNGMVPQKIMSVHLQMSKLEELDQLSNMQHGEWTQEPPFVTATKPEVKTADCA
GDDEEEEKGTEYPEKLEQVSEREVDTGEHHHLHLSSCHECLELENSTIESVKFASVENIP
ELPDDYSCNLEGVNSDCPTEYLKRISLSGKPPNILVYVGSDTEKVKFEEIKSVILECIDF
NSYTIYQLLEKHVLSVPWVHNALLLIIATSEPITDAVSKQFLTFMSEGGKILGLSSFFTF
GGIRVKSKQELIGTVQAFVFSNAENSEIKLNVLASGKIFEKEIVEEPNFLKPLGFLDSPD
KDMLIIQLPCGNNGGEAILCQAHLEVNIQSLSNRSKDDFNLLKLSNAKRYKVLTNILTQL
GLNCQMSEVPPLTPIYLLSSNKENHSSLLEWLGKNVNAAGIITSSKVSLKFVSSCSMETE
ITPSFMPVITEMKAFSSVNFSLDRYKKNLHTQNLGKVVLFTEVTSTTMDLLDGLIYKIPQ
EIGLIAIAVQQTQGKGRGGNAWLSPVGAALSTIHITIPLTSQLGQRIPFIQHLVSLAVVE
AVRSIPGYQDIDLRVKWPNDIYYSDLMKLGGILVNSTLTGNTFHILIGCGFNVNNNNPTI
CINDLIIEHNKTKNTNLKPLSVDCLIARSVTVLENLISTFQEKGPNGVLPLYYKYWIHSG
KQVQLGSDEGPMAWIVGVDDSGFLQVHEEGKGVVTVHPDGNSFDMLRNLIIPKQR
Protein Alignment to Mouse
sp|Q920N2|BPL1_MOUSE Biotin--protein ligase OS=Mus musculus GN=Hlcs PE=1 SV=1
      MGI:894646 Hlcs holocarboxylase synthetase (biotin- [propriony-Coenzyme A-carboxylase (ATP-hydrolysing)] ligase) (Chr 16)
        Length = 722

 Score = 1936 (686.6 bits), Expect = 6.3e-211, Sum P(2) = 6.3e-211
 Identities = 372/614 (60%), Positives = 477/614 (77%)

Query:   105 NSTIESVKFASVENIPELPDDYSCNLEGVNSD-CPTEYLKRISLSGKPPNILVYVGSDTE 163
             NSTI+SV+ AS ENIP+LP D+S  +EG   + CP    KR+++SGK PNIL+YVGS +E
Sbjct:   114 NSTIDSVRSASAENIPDLPCDHS-GVEGAAGELCPERKGKRVNISGKAPNILLYVGSGSE 172

Query:   164 KV--KFEEIKSVILECIDFNSYTIYQLLEKHVLSVPWVHNALLLIIATSEPITDAVSKQF 221
             +   + ++++SV+ +C+D +SYT+Y LLE   L  PW  N LLL+IA+ +PI   +  +F
Sbjct:   173 EALGRLQQVRSVLTDCVDTDSYTLYHLLEDSALRDPWSDNCLLLVIASRDPIPKDIQHKF 232

Query:   222 LTFMSEGGKILGLSSFFTFGGIRVKSKQELIGTVQAFVFSNAENSEIKLNVLASGKIFEK 281
             + ++S+GGK+LGLSS FT GG RV  +  L  TVQ  VFS A+ +E++L+VL+SG ++E 
Sbjct:   233 MAYLSQGGKVLGLSSPFTLGGFRVTRRDVLRNTVQNLVFSKADGTEVRLSVLSSGYVYE- 291

Query:   282 EIVEEPNFLKPLGFLDSPDKDMLIIQLPCGNNGGEAILCQAHLEVNIQSLSNRSKDDFNL 341
                E P+  +  G L++ DKD +I+ +P G  GGEA+LCQ HLE+   +   ++ DDFN+
Sbjct:   292 ---EGPSLGRLQGHLENEDKDKMIVHVPFGTLGGEAVLCQVHLELPPGASLVQTADDFNV 348

Query:   342 LKLSNAKRYKVLTNILTQLGLNCQMSEVPPLTPIYLLSSNKENHSSLLEWLGKNVNAAGI 401
             LK SN +R++VL  ILT LGL+C   +VP LTP+YLL + +E     ++WLG++ +  GI
Sbjct:   349 LKSSNVRRHEVLKEILTALGLSCDAPQVPALTPLYLLLAAEETQDPFMQWLGRHTDPEGI 408

Query:   402 ITSSKVSLKFVSSCSMETEITPSFMPVITEMKAFSSVNFSLDRYKKNLHTQNLGKVVLFT 461
             I SSK+SL+FVSS + E EITPS MPV+T+ +AFSS +FSL+ Y++NL T  LGKV+LF 
Sbjct:   409 IKSSKLSLQFVSSYTSEAEITPSSMPVVTDPEAFSSEHFSLETYRQNLQTTRLGKVILFA 468

Query:   462 EVTSTTMDLLDGLIYKIPQEIGLIAIAVQQTQGKGRGGNAWLSPVGAALSTIHITIPLTS 521
             EVTSTTM LLDGL++++PQE+GLIAIAV+QTQGKGRG NAWLSPVG ALST+ + IPL S
Sbjct:   469 EVTSTTMSLLDGLMFEMPQEMGLIAIAVRQTQGKGRGPNAWLSPVGCALSTLLVFIPLRS 528

Query:   522 QLGQRIPFIQHLVSLAVVEAVRSIPGYQDIDLRVKWPNDIYYSDLMKLGGILVNSTLTGN 581
             QLGQRIPF+QHL+SLAVVEAVRSIPGY+DI+LRVKWPNDIYYSDLMK+GG+LVNSTL G 
Sbjct:   529 QLGQRIPFVQHLMSLAVVEAVRSIPGYEDINLRVKWPNDIYYSDLMKIGGVLVNSTLMGE 588

Query:   582 TFHILIGCGFXXXXXXPTICINDLIIEHNKTKNTNLKPLSVDCLIARSVTVLENLISTFQ 641
             TF+ILIGCGF      PTICINDLI EHNK     LKPL  DCLIAR+VTVLE LI  FQ
Sbjct:   589 TFYILIGCGFNVTNSNPTICINDLIEEHNKQHGAGLKPLRADCLIARAVTVLEKLIDRFQ 648

Query:   642 EKGPNGVLPLYYKYWIHSGKQVQLGSDEGPMAWIVGVDDSGFLQVHEEGKGVVTVHPDGN 701
             ++GP+GVLPLYYKYW+H G+QV+LGS EGP A IVG+DDSGFLQVH+E  GVVTVHPDGN
Sbjct:   649 DQGPDGVLPLYYKYWVHGGQQVRLGSTEGPQASIVGLDDSGFLQVHQEDGGVVTVHPDGN 708

Query:   702 SFDMLRNLIIPKQR 715
             SFDMLRNLI+PK++
Sbjct:   709 SFDMLRNLIVPKRQ 722

 Score = 119 (46.9 bits), Expect = 6.3e-211, Sum P(2) = 6.3e-211
 Identities = 28/57 (49%), Positives = 36/57 (63%)

Query:     1 MEDRLQMDNGMVPQKIMSVHLQMSKLEELDQLSNMQHGEWTQEPPFVTATKPEVKTA 57
             MEDRLQMDNG++ QKI+SVHL+   L+EL + S+ Q     Q PP      PE + A
Sbjct:     1 MEDRLQMDNGLIAQKIVSVHLKDPALKELGKASDKQ----VQGPPPGPEASPEAQPA 53