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Table 6 Problematic Pfam domains that picked up false-positive hits and missed false-negative hits in HMMER2 searches due to the inclusion of TM segments

From: Not all transmembrane helices are born equal: Towards the extension of the sequence homology concept to membrane proteins

Domain name

Validated TM helices, reference(s)

HMM TM sequence

x c

x Φ

z-score

PF01537.9 : Herpes_glycop_D (Herpesvirus glycoprotein D)

372-393, ref. [80]

VIIGIVVLALLIGAIIVGVVYY

1.20

4.72

-19.34

PF03381.7 : CDC50 (ligand-effect modulator 3/CDC50)

318-340, ref. [81]

PFLGIAYLVVGGLCLVLGIVFLI

1.66

2.78

-7.37

PF00690.18 : Cation_ATPase_N (Cation transporter/ATPase, N-terminus)

66-87, ref. [82]

DPLVLLLLAAAIISALDFVLGG

1.68

2.38

-6.83

PF00482.11 : GSPII_F (Bacterial type II secretion system protein F domain)

118-136, ref. [83]

LLLIVALLILLLLLAILLP

0.55

10.89

-53.23

PF01569.13 : PAP2 (type 2 phosphatidic acid phosphatase)

129-143, 156-172, ref. [84]

LLGLLLLLLALLVGLSRVY, LAGALLGALIAALVLLFVR

1.23, 1.44

4.48, 2.35

-18.43, -11.49

PF01001.11 : HCV_NS4b (Hepatitis C virus non-structural protein NS4b)

124-143, 156-179, ref. [85]

RVLVDVLGGYEAAVNAASLT, DLVNLLPALLSPGASVVGVALALI

2.50, 2.14

4.98, 1.45

3.50, -1.08

PF08510.4 : PIG-P (phosphatidylinositol N-acetylGlucosaminyl transferase subunit P)

8-24, 44-67, ref. [86]

GFVLYILSQLAFILYLLWAF, YWALAIPIYLLVALIFGYVVYFLY

2.19, 1.85

5.77, 5.35

-3.99, -6.72

PF01105.15 : EMP24_GP25L (Endoplasmic recticulum and golgi apparatus trafficking proteins)

142-162, ref. [87]

WWSIIQLLVLVGVSVFQVYYL

1.71

4.83

-8.09

PF04387.6 : PTPLA (protein tyrosine phosphatase-like protein)

89-106, 138-155, refs. [88, 89]

YTLFIVLYPLGVTSELLTVY, LIIALMLIYIPGFYQLYSH

2.34, 2.47

2.87, 3.28

-0.79, -0.99

PF01299.9 : Lamp (Lysosome-associated membrane glycoprotein)

304-327, ref. [90]

LIPIAVGAALAGLVLIVLIAYLIG

1.44

3.50

-12.34

PF02416.8 : MttA_Hcf106 (sec-independent translocation mechanism protein)

1-19, refs. [91, 92]

IGIPELLIILVVALLLFGP

1.20

5.42

-20.07

PF00672.17 : HAMP (cytoplasmic helical linker domain)

1-15, ref. [93]

LLLVLLIALLLALLLALLL

0.73

10.01

-43.85

PF01544.10 : CorA (CorA-like Mg2+ transporter protein)

342-362, 377-401, ref. [94]

LLTVGTTIFAPLTLIAGIYGM, YGYPLVLGLMAILAIVLFLIILSYF

2.36, 1.65

1.70, 7.03

-0.25, -11.97

PF00558.11 : Vpu (Vpu protein)

6-28, ref. [95]

IIGLIALIVALIILAIVVWTIVI

1.04

8.09

-28.92

PF04901.5 : RAMP (Receptor activity modifying family)

85-106, ref. [96]

VLLPLIVVPITLTLLLTALVVW

1.31

8.50

-21.96

  1. The first column lists the fifteen problematic Pfam domains from our previous work [1] where they picked up significant false hits or missed true hits due to the inclusion of TM segments in the model. These domains were compiled from supplementary Tables S1, S2 and S3 of [1]. The second column gives the regions of the validated TM in the Pfam HMM (hidden markov models) models with respect to the given references. In a nutshell, the HMM sequences were aligned to the sequences provided in the literatures for the demarcation of the TM segments in the HMM models. The third column denotes the emitted HMM sequence of the TM segments. The last three columns give the complexity x c , hydrophobicity xΦ measures and subsequent z-scores of the TM segments. Note that the complex TM segments are highlighted in bold italic.