P07202 (PERT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thyroid peroxidase
Short name=TPO
EC=1.11.1.8

Gene names

Name:

TPO

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	933 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T3 and T4.
Catalytic activity	2 iodide + H2O2 + 2 H+ = 2 iodine + 2 H2O.
Cofactor	Binds 1 calcium ion per heterodimer By similarity. Binds 1 heme B (iron-protoporphyrin IX) group covalently per heterodimer By similarity.
Pathway	Hormone biosynthesis; thyroid hormone biosynthesis.
Subunit structure	Interacts with DUOX1, DUOX2 and CYBA. Ref.10
Subcellular location	Membrane; Single-pass type I membrane protein. Isoform 3: Cell surface.
Post-translational modification	Glycosylated. Heme is covalently bound through a H2O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface. Cleaved in its N-terminal part.
Involvement in disease	Note=An alternative splicing in the thyroperoxidase mRNA can cause Graves' disease. Ref.9 Defects in TPO are the cause of congenital hypothyroidism due to dyshormonogenesis type 2A (CHDH2A) [MIM:274500]; also called genetic defect in thyroid hormonogenesis 2A or thyroid hormone organification defect II. CHDH2A is due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete. Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26
Sequence similarities	Belongs to the peroxidase family. XPO subfamily. Contains 1 EGF-like domain. Contains 1 Sushi (CCP/SCR) domain.

Ontologies

Keywords
Biological process	Hydrogen peroxide Thyroid hormones biosynthesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Congenital hypothyroidism Disease mutation
Domain	EGF-like domain Signal Sushi Transmembrane Transmembrane helix
Ligand	Calcium Heme Iron Metal-binding
Molecular function	Oxidoreductase Peroxidase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	hormone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW hydrogen peroxide catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cell surface Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iodide peroxidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P07202-1)

Also known as: TPO1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P07202-2)

Also known as: TPO2;

The sequence of this isoform differs from the canonical sequence as follows:
     534-590: Missing.

Note: Lacks exon 10. Found in normal thyroid tissues as well as Graves'tissues. Rapidly degraded after synthesis, does not reach the cell surface. Inactive.

Isoform 3 (identifier: P07202-3)

Also known as: TPO3; Graves' disease; TPOzaninelli;

The sequence of this isoform differs from the canonical sequence as follows:
     874-933: TRTGTKSTLP...RDTHRLPRAL → RVLGWKAGIL...SAGRLFSQHG

Note: Lacks exon 16. Found in normal thyroid tissues as well as Graves'tissues. Found at the cell surface. Active.

Isoform 4 (identifier: P07202-4)

Also known as: TPO4;

The sequence of this isoform differs from the canonical sequence as follows:
     796-839: Missing.

Note: Lacks exon 14. Active.

Isoform 5 (identifier: P07202-5)

Also known as: TPO5;

The sequence of this isoform differs from the canonical sequence as follows:
     274-446: Missing.

Note: Lacks exon 8. Does not fold correctly. Does not reach the cell surface.

Isoform 6 (identifier: P07202-6)

Also known as: TPO6;

The sequence of this isoform differs from the canonical sequence as follows:
     534-590: Missing.
     669-933: Missing.

Note: Lacks exons 10, 12, 13, 14 and 16.

Isoform 2-3 (identifier: P07202-7)

The sequence of this isoform differs from the canonical sequence as follows:
     534-590: Missing.
     874-933: TRTGTKSTLP...RDTHRLPRAL → RVLGWKAGIL...SAGRLFSQHG

Note: Lacks exons 10 and 16.

Isoform 2-4 (identifier: P07202-8)

The sequence of this isoform differs from the canonical sequence as follows:
     534-590: Missing.
     796-839: Missing.

Note: Lacks exons 10 and 14.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 14	14	Potential
	Chain	15 – 933	919	Thyroid peroxidase		PRO_0000023662
Regions
	Topological domain	15 – 846	832	Extracellular Potential
	Transmembrane	847 – 871	25	Helical; Potential
	Topological domain	872 – 933	62	Cytoplasmic Potential
	Domain	740 – 795	56	Sushi
	Domain	796 – 839	44	EGF-like; calcium-binding Potential
Sites
	Active site	239	1	Proton acceptor By similarity
	Metal binding	240	1	Calcium By similarity
	Metal binding	321	1	Calcium By similarity
	Metal binding	323	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	325	1	Calcium By similarity
	Metal binding	327	1	Calcium By similarity
	Metal binding	494	1	Iron (heme axial ligand) By similarity
	Binding site	238	1	Heme (covalent; via 2 links) By similarity
	Binding site	399	1	Heme (covalent; via 2 links) By similarity
	Site	396	1	Transition state stabilizer By similarity
Amino acid modifications
	Glycosylation	129	1	N-linked (GlcNAc...) Potential
	Glycosylation	307	1	N-linked (GlcNAc...) Potential
	Glycosylation	342	1	N-linked (GlcNAc...) Potential
	Glycosylation	569	1	N-linked (GlcNAc...) Potential
	Disulfide bond	142 ↔ 158		By similarity
	Disulfide bond	259 ↔ 269		By similarity
	Disulfide bond	263 ↔ 286		By similarity
	Disulfide bond	598 ↔ 655		By similarity
	Disulfide bond	696 ↔ 721		By similarity
	Disulfide bond	800 ↔ 814		By similarity
	Disulfide bond	808 ↔ 823		By similarity
	Disulfide bond	825 ↔ 838		By similarity
Natural variations
	Alternative sequence	274 – 446	173	Missing in isoform 5.		VSP_007268
	Alternative sequence	534 – 590	57	Missing in isoform 2, isoform 2-3, isoform 2-4 and isoform 6.		VSP_004665
	Alternative sequence	669 – 933	265	Missing in isoform 6.		VSP_007270
	Alternative sequence	796 – 839	44	Missing in isoform 4 and isoform 2-4.		VSP_007269
	Alternative sequence	874 – 933	60	TRTGT…LPRAL → RVLGWKAGILTGCREPSEGK VAGHCRTASCSQNHRTTLFQ TQANRKSAGRLFSQHG in isoform 3 and isoform 2-3.		VSP_004666
	Natural variant	53	1	A → P in CHDH2A. Ref.19		VAR_021622
	Natural variant	240	1	D → N in CHDH2A; loss of activity. Ref.15		VAR_021623
	Natural variant	257	1	A → S. [dbSNP:rs4927611] Ref.11 Ref.5 Ref.6		VAR_006057
	Natural variant	307	1	N → T in CHDH2A. Ref.23		VAR_021624
	Natural variant	326	1	A → T in CHDH2A. Ref.16		VAR_021625
	Natural variant	373	1	A → S. [dbSNP:rs2280132] Ref.11		VAR_006058
	Natural variant	378	1	E → K in CHDH2A. Ref.25		VAR_025784
	Natural variant	398	1	S → T. [dbSNP:rs2175977] Ref.11		VAR_006059
	Natural variant	433	1	V → M in CHDH2A. Ref.23		VAR_021626
	Natural variant	447	1	I → F in CHDH2A. Ref.12 Ref.16		VAR_015375
	Natural variant	453	1	Y → D in CHDH2A. Ref.11 Ref.16 Ref.26		VAR_006060
	Natural variant	458	1	L → P in CHDH2A. Ref.17		VAR_021627
	Natural variant	491	1	R → H in CHDH2A. Ref.17		VAR_021628
	Natural variant	493	1	G → S in CHDH2A. Ref.20		VAR_021629
	Natural variant	499	1	P → L in CHDH2A. Ref.23		VAR_021630
	Natural variant	527	1	W → C in CHDH2A. Ref.16		VAR_021631
	Natural variant	533	1	G → C in CHDH2A; partial defect; expression slightly lower in efficiency and more degenerative than wild-type enzyme. Ref.22		VAR_027229
	Natural variant	574 – 575	2	Missing in CHDH2A; partial defect; expressed on the plasma membrane surface at less than half the rate of wild-type enzyme.		VAR_027230
	Natural variant	590	1	G → S in CHDH2A. Ref.11		VAR_027231
	Natural variant	618	1	V → M. [dbSNP:rs10189135]		VAR_027232
	Natural variant	648	1	R → Q in CHDH2A. Ref.14		VAR_013138
	Natural variant	660	1	Q → E in CHDH2A. Ref.13		VAR_021632
	Natural variant	665	1	R → W in CHDH2A; fails to localize to the plasma membrane. Ref.18		VAR_021633
	Natural variant	693	1	R → W in CHDH2A. Ref.16 Ref.24		VAR_021634
	Natural variant	706	1	M → V. [dbSNP:rs13431173]		VAR_027233
	Natural variant	725	1	T → P. [dbSNP:rs732609] Ref.11 Ref.6 Ref.1 Ref.2 Ref.7		VAR_006061
	Natural variant	771	1	G → R in CHDH2A; fails to localize to the plasma membrane. Ref.18		VAR_021635
	Natural variant	793	1	L → P. [dbSNP:rs28991293]		VAR_027234
	Natural variant	796	1	D → Y in CHDH2A. Ref.20		VAR_021636
	Natural variant	799	1	E → K in CHDH2A. Ref.11 Ref.14 Ref.16		VAR_006062
	Natural variant	808	1	C → R in CHDH2A. Ref.23		VAR_021637
	Natural variant	839	1	V → I in CHDH2A. Ref.21		VAR_027235
	Natural variant	846	1	R → W. [dbSNP:rs28913014]		VAR_027236
	Natural variant	847	1	V → A. [dbSNP:rs1126799] Ref.6 Ref.1 Ref.2 Ref.7		VAR_027237
Experimental info
	Sequence conflict	70	1	P → G in AAA61217. Ref.5
	Sequence conflict	354	1	A → G Ref.5
	Sequence conflict	354	1	A → G Ref.8
	Sequence conflict	371	1	A → R in AAA61215. Ref.1
	Sequence conflict	371	1	A → R in AAA61216. Ref.1
	Sequence conflict	381	1	I → N Ref.5
	Sequence conflict	381	1	I → N Ref.8
	Sequence conflict	574	1	D → N in CAA68467. Ref.2
	Sequence conflict	732	1	W → C in AAN11302. Ref.7
	Sequence conflict	748	1	V → M Ref.2
	Sequence conflict	748	1	V → M Ref.7
	Sequence conflict	816	1	N → S in AAL74416. Ref.6
	Sequence conflict	872	1	R → K Ref.2
	Sequence conflict	872	1	R → K Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (TPO1) [UniParc]. Last modified November 13, 2007. Version 4. Checksum: F67C5F1A4AEE0B29	FASTA	933	102,963
	10 20 30 40 50 60 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 70 80 90 100 110 120 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 130 140 150 160 170 180 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 190 200 210 220 230 240 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 250 260 270 280 290 300 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 310 320 330 340 350 360 QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 370 380 390 400 410 420 RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 430 440 450 460 470 480 LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 490 500 510 520 530 540 VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGGLDPLIR 550 560 570 580 590 600 GLLARPAKLQ VQDQLMNEEL TERLFVLSNS STLDLASINL QRGRDHGLPG YNEWREFCGL 610 620 630 640 650 660 PRLETPADLS TAIASRSVAD KILDLYKHPD NIDVWLGGLA ENFLPRARTG PLFACLIGKQ 670 680 690 700 710 720 MKALRDGDWF WWENSHVFTD AQRRELEKHS LSRVICDNTG LTRVPMDAFQ VGKFPEDFES 730 740 750 760 770 780 CDSITGMNLE AWRETFPQDD KCGFPESVEN GDFVHCEESG RRVLVYSCRH GYELQGREQL 790 800 810 820 830 840 TCTQEGWDFQ PPLCKDVNEC ADGAHPPCHA SARCRNTKGG FQCLCADPYE LGDDGRTCVD 850 860 870 880 890 900 SGRLPRVTWI SMSLAALLIG GFAGLTSTVI CRWTRTGTKS TLPISETGGG TPELRCGKHQ 910 920 930 AVGTSPQRAA AQDSEQESAG MEGRDTHRLP RAL
	Isoform 2 (TPO2). Checksum: F4CF0D050608F808	FASTA	876	96,699
	10 20 30 40 50 60 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 70 80 90 100 110 120 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 130 140 150 160 170 180 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 190 200 210 220 230 240 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 250 260 270 280 290 300 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 310 320 330 340 350 360 QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 370 380 390 400 410 420 RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 430 440 450 460 470 480 LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 490 500 510 520 530 540 VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGYNEWREF 550 560 570 580 590 600 CGLPRLETPA DLSTAIASRS VADKILDLYK HPDNIDVWLG GLAENFLPRA RTGPLFACLI 610 620 630 640 650 660 GKQMKALRDG DWFWWENSHV FTDAQRRELE KHSLSRVICD NTGLTRVPMD AFQVGKFPED 670 680 690 700 710 720 FESCDSITGM NLEAWRETFP QDDKCGFPES VENGDFVHCE ESGRRVLVYS CRHGYELQGR 730 740 750 760 770 780 EQLTCTQEGW DFQPPLCKDV NECADGAHPP CHASARCRNT KGGFQCLCAD PYELGDDGRT 790 800 810 820 830 840 CVDSGRLPRV TWISMSLAAL LIGGFAGLTS TVICRWTRTG TKSTLPISET GGGTPELRCG 850 860 870 KHQAVGTSPQ RAAAQDSEQE SAGMEGRDTH RLPRAL
	Isoform 3 (TPO3) (Graves' disease) (TPOzaninelli). Checksum: 423AC29EEB27277B	FASTA	929	102,771
	10 20 30 40 50 60 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 70 80 90 100 110 120 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 130 140 150 160 170 180 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 190 200 210 220 230 240 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 250 260 270 280 290 300 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 310 320 330 340 350 360 QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 370 380 390 400 410 420 RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 430 440 450 460 470 480 LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 490 500 510 520 530 540 VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGGLDPLIR 550 560 570 580 590 600 GLLARPAKLQ VQDQLMNEEL TERLFVLSNS STLDLASINL QRGRDHGLPG YNEWREFCGL 610 620 630 640 650 660 PRLETPADLS TAIASRSVAD KILDLYKHPD NIDVWLGGLA ENFLPRARTG PLFACLIGKQ 670 680 690 700 710 720 MKALRDGDWF WWENSHVFTD AQRRELEKHS LSRVICDNTG LTRVPMDAFQ VGKFPEDFES 730 740 750 760 770 780 CDSITGMNLE AWRETFPQDD KCGFPESVEN GDFVHCEESG RRVLVYSCRH GYELQGREQL 790 800 810 820 830 840 TCTQEGWDFQ PPLCKDVNEC ADGAHPPCHA SARCRNTKGG FQCLCADPYE LGDDGRTCVD 850 860 870 880 890 900 SGRLPRVTWI SMSLAALLIG GFAGLTSTVI CRWRVLGWKA GILTGCREPS EGKVAGHCRT 910 920 ASCSQNHRTT LFQTQANRKS AGRLFSQHG
	Isoform 4 (TPO4). Checksum: F9C575FC93A450C8	FASTA	889	98,327
	10 20 30 40 50 60 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 70 80 90 100 110 120 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 130 140 150 160 170 180 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 190 200 210 220 230 240 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 250 260 270 280 290 300 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 310 320 330 340 350 360 QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 370 380 390 400 410 420 RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 430 440 450 460 470 480 LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 490 500 510 520 530 540 VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGGLDPLIR 550 560 570 580 590 600 GLLARPAKLQ VQDQLMNEEL TERLFVLSNS STLDLASINL QRGRDHGLPG YNEWREFCGL 610 620 630 640 650 660 PRLETPADLS TAIASRSVAD KILDLYKHPD NIDVWLGGLA ENFLPRARTG PLFACLIGKQ 670 680 690 700 710 720 MKALRDGDWF WWENSHVFTD AQRRELEKHS LSRVICDNTG LTRVPMDAFQ VGKFPEDFES 730 740 750 760 770 780 CDSITGMNLE AWRETFPQDD KCGFPESVEN GDFVHCEESG RRVLVYSCRH GYELQGREQL 790 800 810 820 830 840 TCTQEGWDFQ PPLCKDSGRL PRVTWISMSL AALLIGGFAG LTSTVICRWT RTGTKSTLPI 850 860 870 880 SETGGGTPEL RCGKHQAVGT SPQRAAAQDS EQESAGMEGR DTHRLPRAL
	Isoform 5 (TPO5). Checksum: 3C6150EA7E602B78	FASTA	760	84,581
	10 20 30 40 50 60 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 70 80 90 100 110 120 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 130 140 150 160 170 180 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 190 200 210 220 230 240 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 250 260 270 280 290 300 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQIITLRDY IPRILGPEAF QQYVGPYEGY 310 320 330 340 350 360 DSTANPTVSN VFSTAAFRFG HATIHPLVRR LDASFQEHPD LPGLWLHQAF FSPWTLLRGG 370 380 390 400 410 420 GLDPLIRGLL ARPAKLQVQD QLMNEELTER LFVLSNSSTL DLASINLQRG RDHGLPGYNE 430 440 450 460 470 480 WREFCGLPRL ETPADLSTAI ASRSVADKIL DLYKHPDNID VWLGGLAENF LPRARTGPLF 490 500 510 520 530 540 ACLIGKQMKA LRDGDWFWWE NSHVFTDAQR RELEKHSLSR VICDNTGLTR VPMDAFQVGK 550 560 570 580 590 600 FPEDFESCDS ITGMNLEAWR ETFPQDDKCG FPESVENGDF VHCEESGRRV LVYSCRHGYE 610 620 630 640 650 660 LQGREQLTCT QEGWDFQPPL CKDVNECADG AHPPCHASAR CRNTKGGFQC LCADPYELGD 670 680 690 700 710 720 DGRTCVDSGR LPRVTWISMS LAALLIGGFA GLTSTVICRW TRTGTKSTLP ISETGGGTPE 730 740 750 760 LRCGKHQAVG TSPQRAAAQD SEQESAGMEG RDTHRLPRAL
	Isoform 6 (TPO6). Checksum: 7AD0B6FA3206066A	FASTA	611	67,293
	10 20 30 40 50 60 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 70 80 90 100 110 120 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 130 140 150 160 170 180 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 190 200 210 220 230 240 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 250 260 270 280 290 300 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 310 320 330 340 350 360 QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 370 380 390 400 410 420 RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 430 440 450 460 470 480 LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 490 500 510 520 530 540 VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGYNEWREF 550 560 570 580 590 600 CGLPRLETPA DLSTAIASRS VADKILDLYK HPDNIDVWLG GLAENFLPRA RTGPLFACLI 610 GKQMKALRDG D
	Isoform 2-3. Checksum: 3EDC31BFE86C24E2	FASTA	872	96,507
	10 20 30 40 50 60 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 70 80 90 100 110 120 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 130 140 150 160 170 180 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 190 200 210 220 230 240 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 250 260 270 280 290 300 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 310 320 330 340 350 360 QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 370 380 390 400 410 420 RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 430 440 450 460 470 480 LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 490 500 510 520 530 540 VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGYNEWREF 550 560 570 580 590 600 CGLPRLETPA DLSTAIASRS VADKILDLYK HPDNIDVWLG GLAENFLPRA RTGPLFACLI 610 620 630 640 650 660 GKQMKALRDG DWFWWENSHV FTDAQRRELE KHSLSRVICD NTGLTRVPMD AFQVGKFPED 670 680 690 700 710 720 FESCDSITGM NLEAWRETFP QDDKCGFPES VENGDFVHCE ESGRRVLVYS CRHGYELQGR 730 740 750 760 770 780 EQLTCTQEGW DFQPPLCKDV NECADGAHPP CHASARCRNT KGGFQCLCAD PYELGDDGRT 790 800 810 820 830 840 CVDSGRLPRV TWISMSLAAL LIGGFAGLTS TVICRWRVLG WKAGILTGCR EPSEGKVAGH 850 860 870 CRTASCSQNH RTTLFQTQAN RKSAGRLFSQ HG
	Isoform 2-4. Checksum: 7C6D17A3B62C1D7D	FASTA	832	92,063
	10 20 30 40 50 60 MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV DTAMYATMQR 70 80 90 100 110 120 NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA MKRKVNLKTQ QSQHPTDALS 130 140 150 160 170 180 EDLLSIIANM SGCLPYMLPP KCPNTCLANK YRPITGACNN RDHPRWGASN TALARWLPPV 190 200 210 220 230 240 YEDGFSQPRG WNPGFLYNGF PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD 250 260 270 280 290 300 IAFTPQSTSK AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 310 320 330 340 350 360 QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL RVHARLRDSG 370 380 390 400 410 420 RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV PSLTALHTLW LREHNRLAAA 430 440 450 460 470 480 LKALNAHWSA DAVYQEARKV VGALHQIITL RDYIPRILGP EAFQQYVGPY EGYDSTANPT 490 500 510 520 530 540 VSNVFSTAAF RFGHATIHPL VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGYNEWREF 550 560 570 580 590 600 CGLPRLETPA DLSTAIASRS VADKILDLYK HPDNIDVWLG GLAENFLPRA RTGPLFACLI 610 620 630 640 650 660 GKQMKALRDG DWFWWENSHV FTDAQRRELE KHSLSRVICD NTGLTRVPMD AFQVGKFPED 670 680 690 700 710 720 FESCDSITGM NLEAWRETFP QDDKCGFPES VENGDFVHCE ESGRRVLVYS CRHGYELQGR 730 740 750 760 770 780 EQLTCTQEGW DFQPPLCKDS GRLPRVTWIS MSLAALLIGG FAGLTSTVIC RWTRTGTKST 790 800 810 820 830 LPISETGGGT PELRCGKHQA VGTSPQRAAA QDSEQESAGM EGRDTHRLPR AL

References

[1]	"Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs." Kimura S., Kotani T., McBride O.W., Umeki K., Hirai K., Nakayama T., Ohtaki S. Proc. Natl. Acad. Sci. U.S.A. 84:5555-5559(1987) [PubMed: 3475693] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS PRO-725 AND ALA-847.
[2]	"Complete nucleotide sequence of the human thyroperoxidase-microsomal antigen cDNA." Libert F., Ruel J., Ludgate M., Swillens S., Alexander N., Vassart G., Dinsart C. Nucleic Acids Res. 15:6735-6735(1987) [PubMed: 3453124] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS PRO-725 AND ALA-847. Tissue: Thyroid.
[3]	"Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase gene." Kimura S., Hong Y.S., Kotani T., Ohtaki S., Kikkawa F. Biochemistry 28:4481-4489(1989) [PubMed: 2548579] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]	"Nucleotide sequence of the alternatively spliced human thyroid peroxidase cDNA, TPO-2." Barnett P.S., Banga J.P., Watkins J., Huang G.C., Gluckman D.R.B., Page M.J., McGregor A.M. Nucleic Acids Res. 18:670-670(1990) [PubMed: 2308857] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Thyroid.
[5]	Rapoport B. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-257. Tissue: Thyroid.
[6]	"Homo sapiens thyroid peroxidase (TPO) variant mRNA, alternatively spliced sequence." Hennen G.P., Igout A., Melen L.B. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), VARIANTS SER-257; PRO-725 AND ALA-847. Tissue: Thyroid.
[7]	"Increasing diversity of human thyroperoxidase generated by alternative splicing. Characterization by molecular cloning of new transcripts with single- and multispliced mRNAs." Ferrand M., Le Fourn V., Franc J.-L. J. Biol. Chem. 278:3793-3800(2003) [PubMed: 12454013] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6; 2-3 AND 2-4), VARIANTS PRO-725 AND ALA-847. Tissue: Thyroid.
[8]	"Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase." Seto P., Hirayu H., Magnusson R.P., Gestautas J., Portmann L., Degroot L.J., Rapoport B. J. Clin. Invest. 80:1205-1208(1987) [PubMed: 3654979] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 217-496.
[9]	"Evidence for an alternate splicing in the thyroperoxidase messenger from patients with Graves' disease." Zanelli E., Henry M., Charvet B., Malthiery Y. Biochem. Biophys. Res. Commun. 170:735-741(1990) [PubMed: 2383265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 670-933 (ISOFORM 3), ALTERNATIVE SPLICING IN GRAVES' DISEASE. Tissue: Thyroid.
[10]	"Identification of a novel partner of duox: EFP1, a thioredoxin-related protein." Wang D., De Deken X., Milenkovic M., Song Y., Pirson I., Dumont J.E., Miot F. J. Biol. Chem. 280:3096-3103(2005) [PubMed: 15561711] [Abstract] Cited for: INTERACTION WITH DUOX1; DUOX2 AND CYBA.
[11]	"Identification of five novel inactivating mutations in the human thyroid peroxidase gene by denaturing gradient gel electrophoresis." Bikker H., Vulsma T., Baas F., de Vijlder J.J.M. Hum. Mutat. 6:9-16(1995) [PubMed: 7550241] [Abstract] Cited for: VARIANTS CHDH2A ASP-453; SER-590 AND LYS-799, VARIANTS SER-257; SER-373; THR-398 AND PRO-725.
[12]	"Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects." Bikker H., Baas F., De Vijlder J.J.M. J. Clin. Endocrinol. Metab. 82:649-653(1997) [PubMed: 9024270] [Abstract] Cited for: VARIANT CHDH2A PHE-447.
[13]	"A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect." Santos C.L.S., Bikker H., Rego K.G.M., Nascimento A.C., Tambascia M., De Vijlder J.J.M., Medeiros-Neto G. Clin. Endocrinol. (Oxf.) 51:165-172(1999) [PubMed: 10468986] [Abstract] Cited for: VARIANT CHDH2A GLU-660.
[14]	"Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping." Pannain S., Weiss R.E., Jackson C.E., Dian D., Beck J.C., Sheffield V.C., Cox N., Refetoff S. J. Clin. Endocrinol. Metab. 84:1061-1071(1999) [PubMed: 10084596] [Abstract] Cited for: VARIANTS CHDH2A GLN-648 AND LYS-799.
[15]	"A novel mutation in the human thyroid peroxidase gene resulting in a total iodide organification defect." Kotani T., Umeki K., Yamamoto I., Maesaka H., Tachibana K., Ohtaki S. J. Endocrinol. 160:267-273(1999) [PubMed: 9924196] [Abstract] Cited for: VARIANT CHDH2A ASN-240, CHARACTERIZATION OF VARIANT CHDH2A ASN-240.
[16]	"Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update)." Bakker B., Bikker H., Vulsma T., de Randamie J.S.E., Wiedijk B.M., De Vijlder J.J.M. J. Clin. Endocrinol. Metab. 85:3708-3712(2000) [PubMed: 11061528] [Abstract] Cited for: VARIANTS CHDH2A THR-326; PHE-447; ASP-453; CYS-527; TRP-693 AND LYS-799.
[17]	"Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism." Ambrugger P., Stoeva I., Biebermann H., Torresani T., Leitner C., Grueters A. Eur. J. Endocrinol. 145:19-24(2001) [PubMed: 11415848] [Abstract] Cited for: VARIANTS CHDH2A PRO-458 AND HIS-491.
[18]	"Two novel missense mutations in the thyroid peroxidase gene, R665W and G771R, result in a localization defect and cause congenital hypothyroidism." Umeki K., Kotani T., Kawano J., Suganuma T., Yamamoto I., Aratake Y., Furujo M., Ichiba Y. Eur. J. Endocrinol. 146:491-498(2002) [PubMed: 11916616] [Abstract] Cited for: VARIANTS CHDH2A TRP-665 AND ARG-771, CHARACTERIZATION OF VARIANTS CHDH2A TRP-665 AND ARG-771.
[19]	"High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase gene in Taiwanese patients with total iodide organification defect, and evidence for a founder effect." Niu D.-M., Hwang B., Chu Y.-K., Liao C.-J., Wang P.-L., Lin C.-Y. J. Clin. Endocrinol. Metab. 87:4208-4212(2002) [PubMed: 12213873] [Abstract] Cited for: VARIANT CHDH2A PRO-53.
[20]	"Mutation analysis of thyroid peroxidase gene in Chinese patients with total iodide organification defect: identification of five novel mutations." Wu J.-Y., Shu S.-G., Yang C.-F., Lee C.-C., Tsai F.-J. J. Endocrinol. 172:627-635(2002) [PubMed: 11874711] [Abstract] Cited for: VARIANTS CHDH2A SER-493 AND TYR-796.
[21]	"Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach." Calaciura F., Miscio G., Coco A., Leonardi D., Cisternino C., Regalbuto C., Bozzali M., Maiorana R., Ranieri A., Carta A., Buscema M., Trischitta V., Sava L., Tassi V. Thyroid 12:945-951(2002) [PubMed: 12490071] [Abstract] Cited for: VARIANT CHDH2A ILE-839.
[22]	"Partial iodide organification defect caused by a novel mutation of the thyroid peroxidase gene in three siblings." Kotani T., Umeki K., Kawano J., Suganuma T., Hishinuma A., Ieiri T., Harada S. Clin. Endocrinol. (Oxf.) 59:198-206(2003) [PubMed: 12864797] [Abstract] Cited for: VARIANTS CHDH2A CYS-533 AND ASP-574-575-LEU DEL, CHARACTERIZATION OF VARIANTS CHDH2A CYS-533 AND ASP-574-575-LEU DEL.
[23]	"Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect." Rivolta C.M., Esperante S.A., Gruneiro-Papendieck L., Chiesa A., Moya C.M., Domene S., Varela V., Targovnik H.M. Hum. Mutat. 22:259-259(2003) [PubMed: 12938097] [Abstract] Cited for: VARIANTS CHDH2A THR-307; MET-433; LEU-499 AND ARG-808.
[24]	"Monoallelic expression of mutant thyroid peroxidase allele causing total iodide organification defect." Fugazzola L., Cerutti N., Mannavola D., Vannucchi G., Fallini C., Persani L., Beck-Peccoz P. J. Clin. Endocrinol. Metab. 88:3264-3271(2003) [PubMed: 12843174] [Abstract] Cited for: VARIANT CHDH2A TRP-693.
[25]	"Two novel mutations in the thyroid peroxidase gene with goitrous hypothyroidism." Tajima T., Tsubaki J., Fujieda K. Endocr. J. 52:643-645(2005) [PubMed: 16284446] [Abstract] Cited for: VARIANT CHDH2A LYS-378.
[26]	"Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes." Pfarr N., Borck G., Turk A., Napiontek U., Keilmann A., Mueller-Forell W., Kopp P., Pohlenz J. J. Clin. Endocrinol. Metab. 91:2678-2681(2006) [PubMed: 16684826] [Abstract] Cited for: VARIANT CHDH2A ASP-453.
+	Additional computationally mapped references.

Web resources

Wikipedia

Thyroid peroxidase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	J02969 mRNA. Translation: AAA61215.1. J02970 mRNA. Translation: AAA61216.1. Y00406 mRNA. Translation: CAA68467.1. M25715 , M25702, M25703, M25704, M25705, M25706, M25707, M25708, M25709, M25710, M25711, M25712, M25713, M25714 Genomic DNA. Translation: AAA97517.1. X17358 mRNA. Translation: CAA35235.1. M17755 mRNA. Translation: AAA61217.2. AF439430 mRNA. Translation: AAL74416.1. AF533528 mRNA. Translation: AAN04471.1. AY136822 mRNA. Translation: AAN11302.1. AF533529 mRNA. Translation: AAN04472.1. AF533530 mRNA. Translation: AAN04473.1. AF533531 mRNA. Translation: AAN04474.1. M55702 mRNA. Translation: AAA61219.1. M55702 mRNA. Translation: AAA61218.1.
IPI	IPI00232922. IPI00232923. IPI00232924. IPI00289572. IPI00289573. IPI00289575. IPI00289576. IPI00335186.
PIR	OPHUIT. A32413.
RefSeq	NP_000538.3. NP_783650.1. NP_783652.1. NP_783653.1.
UniGene	Hs.467554.
3D structure databases
ProteinModelPortal	P07202.
SMR	P07202. Positions 131-735, 741-839.
ModBase	Search...
Protein-protein interaction databases
STRING	P07202.
Protein family/group databases
PeroxiBase	3318. HsTPO01.
Proteomic databases
PRIDE	P07202.
Genome annotation databases
Ensembl	ENST00000329066; ENSP00000329869; ENSG00000115705; Homo sapiens. [Genome view]
GeneID	7173.
KEGG	hsa:7173.
UCSC	uc002qwr.1. human. uc002qwt.1. human. uc002qwu.1. human. uc002qwv.1. human.
Organism-specific databases
CTD	7173.
GeneCards	GC02P001396.
HGNC	HGNC:12015. TPO.
HPA	CAB009587. HPA007987.
MIM	274500. phenotype. 606765. gene.
Orphanet	442. Hypothyroidism, congenital. 95716. Thyroid dyshormonogenesis, familial.
PharmGKB	PA36694.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG000071.
InParanoid	P07202.
OMA	IMETSIQ.
PhylomeDB	P07202.
Enzyme and pathway databases
BRENDA	1.11.1.8. 247.
Reactome	REACT_13. Metabolism of amino acids and derivatives. REACT_15314. Hormone biosynthesis.
Gene expression databases
ArrayExpress	P07202.
Bgee	P07202.
Genevestigator	P07202.
GermOnline	ENSG00000115705. Homo sapiens.
Family and domain databases
InterPro	IPR016060. Complement_control_module. IPR013032. EGF-like_reg_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR000742. EGF_3. IPR001881. EGF_Ca-bd. IPR013091. EGF_Ca-bd_2. IPR018097. EGF_Ca-bd_CS. IPR010255. Haem_peroxidase. IPR002007. Haem_peroxidase_animal. IPR019791. Haem_peroxidase_animal_sg. IPR000436. Sushi_SCR_CCP. [Graphical view]
Gene3D	G3DSA:2.10.70.10. Complement_control_module. 1 hit. G3DSA:1.10.640.10. Haem_peroxidase_animal. 1 hit.
Pfam	PF03098. An_peroxidase. 1 hit. PF07645. EGF_CA. 1 hit. [Graphical view]
PRINTS	PR00457. ANPEROXIDASE.
SMART	SM00032. CCP. 1 hit. SM00179. EGF_CA. 1 hit. [Graphical view]
SUPFAM	SSF57535. Complement_control_module. 1 hit. SSF48113. Peroxidase_super. 1 hit.
PROSITE	PS00010. ASX_HYDROXYL. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. PS01187. EGF_CA. 1 hit. PS00435. PEROXIDASE_1. 1 hit. PS00436. PEROXIDASE_2. False negative. PS50292. PEROXIDASE_3. 1 hit. PS50923. SUSHI. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00389. Carbimazole. DB00763. Methimazole. DB00550. Propylthiouracil.
NextBio	28112.
SOURCE	Search...

Entry information

Entry name

PERT_HUMAN

Accession

Primary (citable) accession number: P07202
Secondary accession number(s): P09934 , P09935, Q8IUL0, Q8NF94, Q8NF95, Q8NF96, Q8NF97, Q8TCI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	November 13, 2007
Last modified:	August 10, 2010
This is version 150 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.