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LMX1A_HUMAN
ID   LMX1A_HUMAN             Reviewed;         382 AA.
AC   Q8TE12; B3KXP6; Q0VDB5; Q5VWG4; Q8TE11;
DT   27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   03-AUG-2022, entry version 167.
DE   RecName: Full=LIM homeobox transcription factor 1-alpha;
DE   AltName: Full=LIM/homeobox protein 1.1;
DE            Short=LMX-1.1;
DE   AltName: Full=LIM/homeobox protein LMX1A;
GN   Name=LMX1A;
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 [GENOMIC DNA], ALTERNATIVE SPLICING, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=12062816; DOI=10.1016/s0378-1119(02)00582-6;
RA   Thameem F., Wolford J.K., Wang J., German M.S., Bogardus C., Prochazka M.;
RT   "Cloning, expression and genomic structure of human LMX1A, and variant
RT   screening in Pima Indians.";
RL   Gene 290:217-225(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LMX1A-4AB).
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   [6]
RP   INVOLVEMENT IN DFNA7, VARIANTS DFNA7 SER-97 AND LEU-241, AND VARIANT
RP   LYS-126.
RX   PubMed=29754270; DOI=10.1007/s00439-018-1880-5;
RG   DOOFNL Consortium;
RA   Wesdorp M., de Koning Gans P.A.M., Schraders M., Oostrik J., Huynen M.A.,
RA   Venselaar H., Beynon A.J., van Gaalen J., Piai V., Voermans N.,
RA   van Rossum M.M., Hartel B.P., Lelieveld S.H., Wiel L., Verbist B.,
RA   Rotteveel L.J., van Dooren M.F., Lichtner P., Kunst H.P.M., Feenstra I.,
RA   Admiraal R.J.C., Yntema H.G., Hoefsloot L.H., Pennings R.J.E., Kremer H.;
RT   "Heterozygous missense variants of LMX1A lead to nonsyndromic hearing
RT   impairment and vestibular dysfunction.";
RL   Hum. Genet. 137:389-400(2018).
RN   [7]
RP   VARIANT THR-369.
RX   PubMed=29971487; DOI=10.1007/s00439-018-1899-7;
RA   Schrauwen I., Chakchouk I., Liaqat K., Jan A., Nasir A., Hussain S.,
RA   Nickerson D.A., Bamshad M.J., Ullah A., Ahmad W., Leal S.M.;
RT   "A variant in LMX1A causes autosomal recessive severe-to-profound hearing
RT   impairment.";
RL   Hum. Genet. 137:471-478(2018).
CC   -!- FUNCTION: Acts as a transcriptional activator by binding to an A/T-rich
CC       sequence, the FLAT element, in the insulin gene promoter. Required for
CC       development of the roof plate and, in turn, for specification of dorsal
CC       cell fates in the CNS and developing vertebrae (By similarity).
CC       {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q8TE12; P62993: GRB2; NbExp=3; IntAct=EBI-10692065, EBI-401755;
CC       Q8TE12-2; Q86V38: ATN1; NbExp=3; IntAct=EBI-25846312, EBI-11954292;
CC       Q8TE12-2; Q92876: KLK6; NbExp=3; IntAct=EBI-25846312, EBI-2432309;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8TE12-1; Sequence=Displayed;
CC       Name=LMX1A-4AB;
CC         IsoId=Q8TE12-2; Sequence=VSP_003112;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is expressed in many tissues. Not found
CC       in heart, liver, spleen and testis. Relatively highly expressed in
CC       fetal brain. Isoform LMX1A-4AB is expressed in testis.
CC       {ECO:0000269|PubMed:12062816}.
CC   -!- DISEASE: Deafness, autosomal dominant, 7 (DFNA7) [MIM:601412]: A form
CC       of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC       results from damage to the neural receptors of the inner ear, the nerve
CC       pathways to the brain, or the area of the brain that receives sound
CC       information. DFNA7 is a progressive form with highly variable age at
CC       onset and severity, even within families. The age at onset ranges from
CC       congenital to mid-adulthood. {ECO:0000269|PubMed:29754270}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
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DR   EMBL; AY078398; AAL82892.1; -; Genomic_DNA.
DR   EMBL; AY078391; AAL82892.1; JOINED; Genomic_DNA.
DR   EMBL; AY078392; AAL82892.1; JOINED; Genomic_DNA.
DR   EMBL; AY078393; AAL82892.1; JOINED; Genomic_DNA.
DR   EMBL; AY078394; AAL82892.1; JOINED; Genomic_DNA.
DR   EMBL; AY078395; AAL82892.1; JOINED; Genomic_DNA.
DR   EMBL; AY078396; AAL82892.1; JOINED; Genomic_DNA.
DR   EMBL; AY078397; AAL82892.1; JOINED; Genomic_DNA.
DR   EMBL; AY078398; AAL82893.1; -; Genomic_DNA.
DR   EMBL; AY078396; AAL82893.1; JOINED; Genomic_DNA.
DR   EMBL; AY078397; AAL82893.1; JOINED; Genomic_DNA.
DR   EMBL; AK127724; BAG54558.1; -; mRNA.
DR   EMBL; AL160058; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL390730; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471067; EAW90744.1; -; Genomic_DNA.
DR   EMBL; BC119743; AAI19744.1; -; mRNA.
DR   EMBL; BC119744; AAI19745.1; -; mRNA.
DR   CCDS; CCDS1247.1; -. [Q8TE12-1]
DR   RefSeq; NP_001167540.1; NM_001174069.1. [Q8TE12-1]
DR   RefSeq; NP_796372.1; NM_177398.3. [Q8TE12-1]
DR   AlphaFoldDB; Q8TE12; -.
DR   SMR; Q8TE12; -.
DR   BioGRID; 110194; 6.
DR   IntAct; Q8TE12; 4.
DR   STRING; 9606.ENSP00000340226; -.
DR   GlyGen; Q8TE12; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8TE12; -.
DR   PhosphoSitePlus; Q8TE12; -.
DR   BioMuta; LMX1A; -.
DR   DMDM; 27923801; -.
DR   MassIVE; Q8TE12; -.
DR   PaxDb; Q8TE12; -.
DR   PeptideAtlas; Q8TE12; -.
DR   PRIDE; Q8TE12; -.
DR   ProteomicsDB; 74389; -. [Q8TE12-1]
DR   Antibodypedia; 20523; 221 antibodies from 28 providers.
DR   DNASU; 4009; -.
DR   Ensembl; ENST00000294816.6; ENSP00000294816.2; ENSG00000162761.14. [Q8TE12-1]
DR   Ensembl; ENST00000342310.7; ENSP00000340226.3; ENSG00000162761.14. [Q8TE12-1]
DR   Ensembl; ENST00000367893.4; ENSP00000356868.4; ENSG00000162761.14. [Q8TE12-1]
DR   GeneID; 4009; -.
DR   KEGG; hsa:4009; -.
DR   MANE-Select; ENST00000342310.7; ENSP00000340226.3; NM_177398.4; NP_796372.1.
DR   UCSC; uc001gcz.3; human. [Q8TE12-1]
DR   CTD; 4009; -.
DR   DisGeNET; 4009; -.
DR   GeneCards; LMX1A; -.
DR   HGNC; HGNC:6653; LMX1A.
DR   HPA; ENSG00000162761; Tissue enriched (choroid).
DR   MalaCards; LMX1A; -.
DR   MIM; 600298; gene.
DR   MIM; 601412; phenotype.
DR   neXtProt; NX_Q8TE12; -.
DR   OpenTargets; ENSG00000162761; -.
DR   PharmGKB; PA30416; -.
DR   VEuPathDB; HostDB:ENSG00000162761; -.
DR   eggNOG; KOG0490; Eukaryota.
DR   GeneTree; ENSGT00940000157774; -.
DR   HOGENOM; CLU_027802_0_0_1; -.
DR   InParanoid; Q8TE12; -.
DR   OMA; SXAEPLF; -.
DR   OrthoDB; 737134at2759; -.
DR   PhylomeDB; Q8TE12; -.
DR   TreeFam; TF315442; -.
DR   PathwayCommons; Q8TE12; -.
DR   SignaLink; Q8TE12; -.
DR   SIGNOR; Q8TE12; -.
DR   BioGRID-ORCS; 4009; 16 hits in 1094 CRISPR screens.
DR   ChiTaRS; LMX1A; human.
DR   GeneWiki; LMX1A; -.
DR   GenomeRNAi; 4009; -.
DR   Pharos; Q8TE12; Tbio.
DR   PRO; PR:Q8TE12; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q8TE12; protein.
DR   Bgee; ENSG00000162761; Expressed in apex of heart and 61 other tissues.
DR   Genevisible; Q8TE12; HS.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:ParkinsonsUK-UCL.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR   GO; GO:0021953; P:central nervous system neuron differentiation; IEA:Ensembl.
DR   GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR   GO; GO:0021542; P:dentate gyrus development; IEA:Ensembl.
DR   GO; GO:0071542; P:dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR   GO; GO:0007613; P:memory; IEA:Ensembl.
DR   GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR   GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR   GO; GO:0042048; P:olfactory behavior; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0001558; P:regulation of cell growth; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0050808; P:synapse organization; IEA:Ensembl.
DR   CDD; cd00086; homeodomain; 1.
DR   CDD; cd09370; LIM1_Lmx1a; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR042688; Lmx1a_LIM1.
DR   InterPro; IPR001781; Znf_LIM.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF00412; LIM; 2.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00132; LIM; 2.
DR   SUPFAM; SSF46689; SSF46689; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR   PROSITE; PS50023; LIM_DOMAIN_2; 2.
PE   1: Evidence at protein level;
KW   Activator; Alternative splicing; Deafness; Developmental protein;
KW   Disease variant; DNA-binding; Homeobox; LIM domain; Metal-binding;
KW   Non-syndromic deafness; Nucleus; Reference proteome; Repeat; Transcription;
KW   Transcription regulation; Zinc.
FT   CHAIN           1..382
FT                   /note="LIM homeobox transcription factor 1-alpha"
FT                   /id="PRO_0000075825"
FT   DOMAIN          33..92
FT                   /note="LIM zinc-binding 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT   DOMAIN          92..154
FT                   /note="LIM zinc-binding 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT   DNA_BIND        195..254
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          161..208
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          252..285
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        165..195
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        255..281
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..249
FT                   /note="Missing (in isoform LMX1A-4AB)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_003112"
FT   VARIANT         97
FT                   /note="C -> S (in DFNA7; unknown pathological
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:29754270"
FT                   /id="VAR_083732"
FT   VARIANT         126
FT                   /note="E -> K"
FT                   /evidence="ECO:0000269|PubMed:29754270"
FT                   /id="VAR_083733"
FT   VARIANT         241
FT                   /note="V -> L (in DFNA7)"
FT                   /evidence="ECO:0000269|PubMed:29754270"
FT                   /id="VAR_083734"
FT   VARIANT         369
FT                   /note="I -> T (found in autosomal recessive sensorineural
FT                   hearing loss; unknown pathological significance)"
FT                   /evidence="ECO:0000269|PubMed:29971487"
FT                   /id="VAR_083735"
SQ   SEQUENCE   382 AA;  42747 MW;  55424762757FF5FD CRC64;
     MLDGLKMEEN FQSAIDTSAS FSSLLGRAVS PKSVCEGCQR VILDRFLLRL NDSFWHEQCV
     QCASCKEPLE TTCFYRDKKL YCKYDYEKLF AVKCGGCFEA IAPNEFVMRA QKSVYHLSCF
     CCCVCERQLQ KGDEFVLKEG QLLCKGDYEK ERELLSLVSP AASDSGKSDD EESLCKSAHG
     AGKGTAEEGK DHKRPKRPRT ILTTQQRRAF KASFEVSSKP CRKVRETLAA ETGLSVRVVQ
     VWFQNQRAKM KKLARRQQQQ QQDQQNTQRL SSAQTNGGGS AGMEGIMNPY TALPTPQQLL
     AIEQSVYSSD PFRQGLTPPQ MPGDHMHPYG AEPLFHDLDS DDTSLSNLGD CFLATSEAGP
     LQSRVGNPID HLYSMQNSYF TS
 
 
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