Reviewed, UniProtKB/Swiss-Prot P63128 (POK4_HUMAN)

Names and origin

Protein names	Recommended name:     HERV-K_6q14.1 provirus ancestral Gag-Pol polyprotein Alternative name(s):     HERV-K109 Gag-Pol protein     HERV-K(C6) Gag-Pol protein Cleaved into the following 5 chains:     1- Recommended name:             Matrix protein     2- Recommended name:             Capsid protein     3- Recommended name:             Nucleocapsid protein     4- Recommended name:             Protease               EC=3.4.23.16         Alternative name(s):             Retropepsin             PR     5- Recommended name:             Reverse transcriptase/ribonuclease H               EC=2.7.7.49               EC=2.7.7.7               EC=3.1.26.4         Alternative name(s):             p66 RT
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	1117 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Inferred from homology.

General annotation (Comments)

Function	The products of the Gag polyproteins of infectious retroviruses perform highly complex orchestrated tasks during the assembly, budding, maturation, and infection stages of the viral replication cycle. During viral assembly, the proteins form membrane associations and self-associations that ultimately result in budding of an immature virion from the infected cell. Gag precursors also function during viral assembly to selectively bind and package two plus strands of genomic RNA. Endogenous Gag proteins may have kept, lost or modified their original function during evolution By similarity. Early post-infection, the reverse transcriptase converts the viral RNA genome into double-stranded viral DNA. The RNase H domain of the reverse transcriptase performs two functions. It degrades the RNA template and specifically removes the RNA primer from the RNA/DNA hybrid. Following nuclear import, the integrase catalyzes the insertion of the linear, double-stranded viral DNA into the host cell chromosome. Endogenous Pol proteins may have kept, lost or modified their original function during evolution By similarity.
Catalytic activity	Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro. Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). Endonucleolytic cleavage to 5'-phosphomonoester.
Subcellular location	Cell membrane. Note: Cytoplasmic membrane (in a transfection system) By similarity.
Domain	The LPQG motifs are catalytically important and conserved among many retroviruses. HERV-K Gag polyprotein contains regions homologous to the matrix (MA), capsid (CA) and nucleocapsid (NC) proteins from infectious retroviruses. Evidence suggests that HERV-K(HML-2) Gag polyprotein can be cleaved into mature MA, CA and NC under certain circumstances. However, the exact boundaries as well as the size of processed Gag proteins have not been precisely determined yet.
Post-translational modification	Myristoylation is essential for retroviral assembly. Alteration of the glycine residue leads to a block in the budding of particles and an accumulation of Gag inside the cell By similarity. Specific enzymatic cleavages may yield mature proteins Potential.
Sequence similarities	Belongs to the beta type-B retroviral polymerase family. HERV class-II K(HML-2) subfamily. Contains 2 CCHC-type zinc fingers. Contains 1 G-patch domain. Contains 1 peptidase A2 domain. Contains 1 reverse transcriptase domain.
Caution	Truncated; frameshift leads to premature stop codon.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Ribosomal frameshifting
Domain	Repeat Zinc-finger
Ligand	Metal-binding RNA-binding Zinc
Molecular function	Hydrolase Nucleotidyltransferase Protease RNA-directed DNA polymerase Transferase
PTM	Lipoprotein Myristate
Technical term	Complete proteome ERV Multifunctional enzyme Transposable element
Gene Ontology (GO)
Biological process	RNA-dependent DNA replication Inferred from electronic annotation. Source: InterPro dUTP metabolic process Inferred from electronic annotation. Source: InterPro proteolysis Inferred from electronic annotation. Source: InterPro viral reproduction Inferred from electronic annotation. Source: InterPro
Cellular component	intracellular Inferred from electronic annotation. Source: InterPro plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell viral capsid Inferred from electronic annotation. Source: InterPro
Molecular function	DNA-directed DNA polymerase activity Inferred from electronic annotation. Source: EC RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA-directed DNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW aspartic-type endopeptidase activity Inferred from electronic annotation. Source: InterPro ribonuclease H activity Inferred from electronic annotation. Source: EC structural molecule activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]

Note: This protein is synthesized as Gag-Pro and Gag-Pro-Pol polyprotein precursors. These polyproteins are thought, by similarity with type-B retroviruses, to be generated by -1 frameshifts occurring at the Gag-Pro and Pro-Pol genes boundaries.

Isoform 1 (identifier: P63128-1)

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: P63126-1)

The sequence of this isoform can be found in the external entry P63126-1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Gag-Pro polyprotein is produced from conventional translation of the gag ORF.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Potential
	Chain	2 – 1117	1116	HERV-K_6q14.1 provirus ancestral Gag-Pol polyprotein		PRO_0000186764
Regions
	Domain	58 – 195	138	Reverse transcriptase
	Domain	800 – 875	76	Peptidase A2
	Domain	890 – 936	47	G-patch
	Zinc finger	544 – 561	18	CCHC-type 1
	Zinc finger	580 – 597	18	CCHC-type 2
	Compositional bias	168 – 257	90	Pro-rich
	Compositional bias	611 – 666	56	Gln-rich
Sites
	Active site	805	1	By similarity
Amino acid modifications
	Lipidation	2	1	N-myristoyl glycine Potential

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: F7614F482B4117DD	FASTA	1,117	123,620
	10 20 30 40 50 60 MGQTKSKIKS KYASYLSFIK ILLKRGGVKV STKNLIKLFQ IIEQFCPWFP EQGTLDLKDW 70 80 90 100 110 120 KRIGKELKQA GRKGNIIPLT VWNDWAIIKA ALEPFQTEED SISVSDAPGS GIIDCNEKTR 130 140 150 160 170 180 KKSQKETESL HCEYVAEPVM AQSTQNVDYN QLQEVIYPET LKLEGKGPEL VGPSESKPRG 190 200 210 220 230 240 TSPLPAGQVP VTLQPQKQVK ENKTQPPVAY QYWPPAELQY RPPPESQYGY PGMPPAPQGR 250 260 270 280 290 300 APYPQPPTRR LNPTAPPSRQ GSELHEIIDK SRKEGDTEAW QFPVTLEPMP PGEGAQEGEP 310 320 330 340 350 360 PTVEARYKSF SIKILKDMKE GVKQYGPNSP YMRTLLDSIA HGHRLIPYDW EILAKSSLSP 370 380 390 400 410 420 SQFLQFKTWW IDGVQEQVRR NRAANPPVNI DADQLLGIGQ NWSTISQQAL MQNEAIEQVR 430 440 450 460 470 480 AICLRAWEKI QDPGSTCPSF NTVRQGSKEP YPDFVARLQD VAQKSIADEK ARKVIVELMA 490 500 510 520 530 540 YENANPECQS AIKPLKGKVP AGSDVISEYV KACDGIGGAM HKAMLMAQAI TGVVLGGQVR 550 560 570 580 590 600 TFGGKCYNCG QIGHLKKNCP VLNKQNITIQ ATTTGREPPD LCPRCKKGKH WASQCRSKFD 610 620 630 640 650 660 KNGQPLSGNE QRGQPQAPQQ TGAFPIQPFV PQGFQGQQPP LSQVFQGISQ LPQYNNCPPP 670 680 690 700 710 720 QVAVQQVDLC TIQAVSLLPG EPPQKIPTGV YGPLPEGTVG LILGRSSLNL KGVQIHTSVV 730 740 750 760 770 780 DSDYKGEIQL VISSSVPWSA SPGDRIAQLL LLPYIKGGNS EIKRIGGLGS TDPTGKAAYW 790 800 810 820 830 840 ASQVSENRPV CKAIIQGKQF EGLVDTGADV SIIALNQWPK NWPKQKAVTG LVGIGTASEV 850 860 870 880 890 900 YQSMEILHCL GPDNQESTVQ PMITSIPLNL WGRDLLQQWG AEITMPAPLY SPTSQKIMTK 910 920 930 940 950 960 RGYIPGKGLG KNEDGIKIPF EAKINQKREG IGYPFLGAAT IEPPKPIPLT WKTEKPVWVN 970 980 990 1000 1010 1020 QWPLPKQKLE ALHLLANEQL EKGHIEPSFS PWNSPVFVIQ KKSGKWRMLT DLRAVNAVIQ 1030 1040 1050 1060 1070 1080 PMGPLQPGLP SPAMIPKDWP LIIIDLKDCF FTIPLAEQDC EKFAFTIPAI NNKEPATRFQ 1090 1100 1110 WKVLPQGMLN SPTICQTFVG RALQPVKVFR LLYYSLY
	Isoform 2. See P63126.	FASTA	–	–

References

[1]	"Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans." Barbulescu M., Turner G., Seaman M.I., Deinard A.S., Kidd K.K., Lenz J. Curr. Biol. 9:861-868(1999) [PubMed: 10469592] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Web resources

Human Endogenous Retrovirus Database (HERVd)

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF164615 Genomic DNA. Translation: AAD51799.1. Sequence problems.
IPI	IPI00454612.
3D structure databases
ModBase	Search...
Phylogenomic databases
HOVERGEN	P63128.
Enzyme and pathway databases
BRENDA	2.7.7.49. 247. 2.7.7.7. 247. 3.1.26.4. 247. 3.4.23.16. 247.
Gene expression databases
Genevestigator	P63128.
Family and domain databases
InterPro	IPR003322. B_retro_matrix_N. IPR008180. DeoxyUTP_pyroPase_dom. IPR000467. G_patch. IPR000721. Gag_p24. IPR001995. Peptidase_A2_cat. IPR021109. Peptidase_aspartic. IPR001969. Peptidase_aspartic_AS. IPR009007. Peptidase_aspartic_catalytic. IPR008916. Retrov_capsid_C. IPR008919. Retrov_capsid_N. IPR010999. Retrovr_matrix_N. IPR000477. Reverse_transcriptase. IPR013084. Znf_CCH_retrovir. IPR001878. Znf_CCHC. [Graphical view]
Gene3D	G3DSA:2.40.70.10. Pept_Aspartc_cat. 1 hit. G3DSA:1.10.1200.30. Retrov_capsid_C. 1 hit. G3DSA:1.10.375.10. Retrov_capsid_N. 1 hit. G3DSA:4.10.60.10. Znf_CCH_retrovir. 1 hit.
Pfam	PF00692. dUTPase. 1 hit. PF01585. G-patch. 1 hit. PF02337. Gag_p10. 1 hit. PF00607. Gag_p24. 1 hit. PF00078. RVT_1. 1 hit. PF00098. zf-CCHC. 2 hits. [Graphical view]
ProDom	PD004265. B_retro_matrix_N. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00443. G_patch. 1 hit. SM00343. ZnF_C2HC. 2 hits. [Graphical view]
PROSITE	PS50175. ASP_PROT_RETROV. 1 hit. PS00141. ASP_PROTEASE. 1 hit. PS50174. G_PATCH. 1 hit. PS50878. RT_POL. 1 hit. PS50158. ZF_CCHC. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POK4_HUMAN

Accession

Primary (citable) accession number: P63128
Secondary accession number(s): Q9UKH4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 46 of the entry and version 3 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.